title: Cataract Surgery Outcomes and Postoperative Patient Compliance in Limited English Proficiency Patients at a County Hospital

abstract:
Background/AimsInvestigate the role of language barriers in cataract surgery outcomes at a county hospital.

MethodsRetrospective chart review of patients who underwent cataract surgery March 2018-February 2019 at Lyndon B. Johnson Hospital. Patients who underwent cataract surgery combined with another procedure or had severe glaucoma or proliferative diabetic retinopathy were excluded. Patients were classified into limited English proficient (LEP) or English proficient (non-LEP) groups based on language preferences. Demographics, baseline ocular characteristics, intraoperative complications, postoperative BCVA (best-corrected visual acuity), complications, and compliance were recorded. The primary outcome was incidence of poor visual outcomes (BCVA<20/40) at the postoperative 1-month visit.

Results354 patients (199 [56%] LEP and 155 [44%] non-LEP) with 125 (35%) males and a mean age 66.1 ({+/-}10.9) years were included. LEP patients were about 5 years older than non-LEP patients (P<0.001) and were mostly Hispanic (172 [86%] LEP vs. 36 [26%] non-LEP, P<0.001). The baseline ocular characteristics were similar (P >0.05), except severity of cataract (125 [63%] NSC grade >2+ for LEP vs 70 [51%] for non-LEP, P =0.03). No significant differences in intraoperative complications (P =0.18), incidence of poor vision (P =0.59), postoperative cystoid macular edema (P =0.32), and compliance with the postoperative drop regimen (P =0.11) were noted.

ConclusionThere were no statistically significant differences in incidence of poor vision, complications, or compliance. However, there was a trend toward significance, showing that language barriers may lead to more advanced disease and compliance issues with postoperative medications.

SYNOPSISLanguage barriers may lead to compliance issues with postoperative medication regimens, as shown by the difference in postoperative care adherence rates between limited English proficient and English proficient patients.

category: ophthalmology


title: Worldwide Prevalence and Clinical Characteristics of RAS Mutations in Head and Neck Cancer: A Systematic Review and Meta-Analysis

abstract:
ImportanceThere is considerable variation among different studies for the prevalence of RAS mutations in head and neck cancer (HNC) patients. In light of the development of RAS inhibitors, a reliable assessment of the prevalence of RAS mutations and their correlation with the clinical features of patients with HNC is crucially needed.

ObjectiveTo assess the worldwide prevalence of HRAS, KRAS, and NRAS mutations in HNC in the relation to geographical region, anatomical site(s) of the tumor(s) and clinical features.

Data SourcesA systematic search of the PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials databases was performed to identify studies published since January 2000. Data were analyzed between June and September 2021.

Study SelectionStudies that included mutational analyses of at least one of the target genes and reported the prevalence and frequency of mutations as an outcome measure were included. Studies including less than ten patients or were conducted before year 2000 were excluded.

Data Extraction and SynthesisTwo researchers independently reviewed the literature according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. Random-effects models were applied to results with high heterogeneity. Otherwise, fixed-effects models were used for the analyses. Dichotomous variables were pooled as odds ratios (OR).

Main Outcome(s) and Measure(s)The primary outcome was mutation prevalence. Secondary outcomes included the location of the mutated codon and amino acid substitution.

ResultsThe estimated mutation rate is highest for HRAS (7%), followed by KRAS (2.89%) and NRAS (2.20%). HRAS prevalence in South Asia (15.28%) is twice as high as the global estimate. HRAS mutations are more prevalent in oral cavity and salivary gland tumors. In contrast, KRAS mutations are found more frequently in sinonasal tumors, and NRAS mutations are found chiefly in tumors of the nasopharynx. OR analyses show a significant association between HRAS mutations and a high tumor stage (OR=3.63). In addition, there is a significant association between HPV-positive status and KRAS mutations (OR=2.09).

Conclusions and RelevanceRAS mutations occur in a subset of HNC patients and their prevalence varies according to geography, tumors anatomical site, stage, and HPV status. This meta-analysis provides support for their potential as viable therapeutic targets in HNC patients.

Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the prevalence of mutations in RAS genes in head and neck cancer (HNC) with respect to anatomical site, geographical region, and clinical features?

FindingsThis meta-analysis compiles the findings of 149 studies with over 8500 HNC patients and assesses the global prevalence of mutations in the HRAS, KRAS and NRAS genes. The prevalence of RAS mutations varies between the seven major anatomical sites of HNC. The HRAS mutation rate in South Asia is double that in other geographical regions. Mutations in HRAS are associated with advanced disease, and mutations in KRAS are positively associated with HPV status.

MeaningThis study presents the most comprehensive assessment of the prevalence of RAS mutations in HNC and their correlation with geographical regions and with clinical features.

category: otolaryngology


title: Assessing and predicting neuropathic pain after spinal cord injury: a TRACK-SCI study

abstract: Neuropathic pain is one of the most common secondary complications occurring after spinal cord injury (SCI), and often surpasses motor and sensory deficits in the patient population preferences of the most important aspects to be treated. Despite the better understanding of the molecular and physiological mechanisms of neuropathic pain, reliable treatments are still lacking and exhibit wide variations in efficiency. Previous reports have suggested that the most effective pain management is early treatment. To this end, we utilized the TRACK-SCI prospective clinical research database to assess the neuropathic pain status of all enrolled patients and identify acute care variables that can predict the development of neuropathic pain 6- and 12-months post SCI. 36 out of 61 patients of our study cohort reported neuropathic pain at the chronic stages post SCI. Using multidimensional analytics and logistic regression we discovered that (1) the number of total injuries the patient sustained, (2) the injury severity score (ISS), (3) the lower limb total motor score, and (4) the sensory pin prick total score together predict the development of chronic neuropathic pain after SCI. The balanced accuracy of the corresponding logistic regression model is 74.3%, and repeated 5-fold cross validation showed an AUC of 0.708. Our study suggests a crucial role of polytrauma in chronic pain development after SCI and offers a predictive model using variables routinely collected at every hospital setting.

category: pain medicine


title: The feasibility of an objective measure of the parent-child relationship in health visiting practice: assessment of the Maternal Postnatal Attachment Scale.

abstract:
Positive parent infant relationships are key to achieving long term child outcomes. Identifying parents who may need support is difficult because of a lack of robust assessment tools. Working in partnership with health services we piloted the Maternal Postnatal Attachment Scale (MPAS) in a deprived, multi-ethnic urban community in Bradford, UK.

The pilot aimed to assess the clinical utility of MPAS to identify need for support: Was it administered to a representative group of women? Is MPAS valid for this population?

Data were linked to a cohort study in the pilot area (Born in Bradfords Better Start - BiBBS). Chi Square tests assessed sample representativeness (age, ethnicity, parity, English language, education, deprivation). Exploratory factor analysis explored MPAS validity.

563 women in BiBBS were eligible, 210 (37%) completed MPAS. No differences were found between completers and non-completers, suggestive of a representative sample. In total, 336 women completed MPAS in the pilot. MPAS had ceiling effects and a satisfactory factor structure could not be identified, indicating poor psychometric properties

Health visitors were successful in administering MPAS to a representative sample, but poor psychometric robustness indicates that MPAS is unsuitable for routine use in this setting. A gap for such a measure remains.

Statement of relevance to practitionersThis research shows that:

O_LIHealth practitioners working in universal early years services were willing and able to integrate structured assessments of parent-infant relationship into their routine practice
C_LIO_LIThere is no evidence that health professionals were less likely to offer traditionally considered  hard to reach families an assessment of their parent-infant relationship
C_LIO_LIThe Maternal Postnatal Attachment Scale did not demonstrate psychometric robustness when delivered in routine, universal, health visiting services in Bradford as part of an initial assessment of parent-infant relationship, and therefore cannot be recommended for continued routine use.
C_LI

Statement of relevance to the fieldThis pilot study explores a significant gap in the field, namely how universal services can assess parent-infant relationship to facilitate timely signposting to appropriate services, in a preventative model, to those families that may benefit. This study contributes to the evidence base by assessing if health professionals working in a universal service can offer an assessment to a representative group of families, including families who may be considered hard to reach as well as providing psychometric evidence on the Maternal Postnatal Attachment Scale. We did not find good evidence for the psychometric properties of the Maternal Postnatal Attachment Scale when used in this way in Bradford. We found that health professionals offered the assessment to a representative sample of families, including those who may be at an enhanced risk of health inequalities because of their ethnicity, age, education, and wider socioeconomic circumstances.

This evidence is important for measure/tool selection for community studies. The findings also emphasise that practitioners can integrate tools for assessment in their practice, including with families who are at an increased risk of experiencing inequalities.

Diversity and anti-racist scholarshipThis study was designed and executed in a very diverse community with approximately 60% of the population identifying as Asian/Asian British: Pakistani, and 10% of the population identifying as White: British and the remaining population identifying with a wide range of ethnicities. The health visiting service deliberately engages with the whole population in a culturally sensitive way, including ensuring staff speak key community languages and using translators as required. We included specific tests of representativeness as part of the study design and found that participants in the study were representative of the wider community in terms of ethnicity and English language comprehension.

category: public and global health


title: Machine learning for prediction of immunotherapy efficacy in non- small cell lung cancer from simple clinical and biological data

abstract:
BackgroundImmune checkpoint inhibitors (ICIs) are now a therapeutic standard in advanced non-small cell lung cancer (NSCLC), but strong predictive markers for ICIs efficacy are still lacking. We evaluated machine learning models built on simple clinical and biological data to individually predict response to ICIs.

MethodsPatients with metastatic NSCLC who received ICI in second line or later were included. We collected clinical and hematological data and studied the association of this data with disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Multiple machine learning (ML) algorithms were assessed for their ability to predict response.

ResultsOverall, 298 patients were enrolled. The overall response rate and DCR were 15.3 % and 53%, respectively. Median PFS and OS were 3.3 and 11.4 months, respectively. In multivariable analysis, DCR was significantly associated with performance status (PS) and hemoglobin level (OR 0.58, p<0.0001; OR 1.8, p<0.001). These variables were also associated with PFS and OS and ranked top in random forest-based feature importance. Neutrophils-to-lymphocytes ratio was also associated with DCR, PFS and OS. The best ML algorithm was a random forest. It could predict DCR with satisfactory efficacy based on these three variables. Ten-fold cross-validated performances were: accuracy 0.68 {+/-} 0.04, sensitivity 0.58 {+/-} 0.08; specificity 0.78 {+/-} 0.06; positive predictive value 0.70 {+/-} 0.08; negative predictive value 0.68 {+/-} 0.06; AUC 0.74 {+/-} 0.03.

ConclusionCombination of simple clinical and biological data could accurately predict disease control rate at the individual level.

Highlights- Machine learning applied to a large set of NSCLC patients could predict efficacy of immunotherapy with a 69% accuracy using simple routine data
- Hemoglobin levels and performance status were the strongest predictors and significantly associated with DCR, PFS and OS
- Neutrophils-to-lymphocyte ratio was also associated with outcome
- Benchmark of 8 machine learning models

category: oncology


title: Study of association of migraine susceptibility genes with common migraine in 200,000 exome-sequenced UK Biobank participants

abstract:
BackgroundA number of genes have been implicated in rare familial syndromes which have migraine as part of their phenotype but these genes have not previously been implicated in the common form of migraine.

MethodsAmong exome-sequenced participants in the UK Biobank we identified 7,194 migraine cases with the remaining 193,433 participants classified as controls. We investigated ten genes previously reported to be implicated in conditions with migraine as a prominent part of the phenotype and carried out gene and variant based tests for association.

ResultsWe found no evidence for association of these genes or variants with the common form of migraine seen in our subjects. In particular, a frameshift variant in KCNK18, F139Wfs*24, which had been shown to segregate with migraine with aura in a multiply affected pedigree was found in 196 (0.10%) controls as well as in 10 (0.14%) cases ({chi}2 = 0.96, 1 df, p = 0.33).

ConclusionsSince there is no other reported evidence to implicate KCNK18, we conclude that this gene and its product, TRESK, should no longer be regarded as being involved in migraine aetiology. Overall, we do not find that rare, functional variants in genes previously implicated to be involved in familial syndromes including migraine as part of the phenotype make a contribution to the commoner forms of migraine observed in this population.

category: genetic and genomic medicine


title: Acceptability of Rectal Artesunate as pre-referral treatment for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda

abstract:
BackgroundIn children below 6 years with suspected severe malaria who are several hours from facilities providing parenteral treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out. Yet to date, there is limited literature on RAS acceptability. This study aimed to determine the acceptability of RAS by health care providers and child caregivers in communities where quality assured RAS was rolled out.

MethodsThis study was nested within the comprehensive multi-country observational research project Community Access to Rectal Artesunate for Malaria (CARAMAL). The CARAMAL project was implemented in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Data from three different sources were analysed to understand RAS acceptability: Interviews with health workers during three healthcare provider surveys, with caregivers of children under 5 years of age during three household surveys, and with caregivers of children who were recently treated with RAS and enrolled in the CARAMAL Patient Surveillance System.

ResultsRAS acceptability was high among all interviewed stakeholders in the three countries. After the roll-out of RAS, 97-100% heath care providers in DRC considered RAS medication as very good or good, as well as 98-100% in Nigeria and 93-100% in Uganda. Majority of caregivers whose children had received rectal artesunate for pre-referral management of severe malaria indicated that they would want to get the medication again, if their child had the same illness (99.8% of caregivers in DRC, 100% in Nigeria and 99.9% in Uganda). Further, using data from three household surveys, 67-80% of caregivers whose children had not received RAS considered the medication as useful.

ConclusionRAS was well accepted by health workers and child caregivers in DRC, Nigeria and Uganda. Acceptability is unlikely to be an obstacle to the large-scale roll-out of RAS in the studied settings.

category: infectious diseases


title: Rapid Clinical Screening and Staging for COVID-19 Severe Outcome - A Hospitalization Study in New York City

abstract:
BackgroundWe aimed to evaluate the risk factors for Coronavirus disease 2019 (COVID-19) related severe outcome in New York State (NYS) and proposed a method that could be used to inform future work to develop clinical algorithms and predict resource needs for COVID-19 patients.

MethodsWe analyzed COVID-19 related hospital encounter and hospitalization in NYS from April 1st to November 17th, 2020, using Statewide Planning and Research Cooperative System (SPARCS) hospital discharge dataset. Logistic regression was performed to evaluate the risk factors for COVID-19 related in-hospital death using demographic variables, symptom, rapid clinical examination, and medical history of chronic co-morbid conditions. Receiver operating characteristic (ROC) curve was calculated, and cut-off points for predictors were selected to stage the risk of COVID-19 related fatal outcome.

FindingsLogistic regression analysis showed age was the greatest risk factor for COVID-19 related fatal outcome, which by itself achieved the diagnostic accuracy of 0.78 represented by the area under the ROC curve. By adding other demographic variables, dyspnea or hypoxemia and multiple chronic co-morbid conditions, the diagnostic accuracy was improved to 0.85. We selected cut-off points for predictors and provided a general recommendation to categorize the levels of risk for COVID-19 related fatal outcome.

InterpretationWe assessed risk factors associated with in-hospital COVID-19 mortality and identified cut-off points that might be used to categorize the level of risk. Further studies are warranted to evaluate laboratory tests and develop laboratory biomarkers to improve the diagnostic accuracy for early intervention.


title: Rapid Clinical Screening and Staging for COVID-19 Severe Outcome


title: Clinical Risk Factors for COVID-19 related Severe Outcome


title: Alcohol intake and hypertensive disorders of pregnancy: a negative control analysis in the ALSPAC cohort

abstract:
AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSIntroductionC_ST_ABSAlcohol intake increases blood pressure, yet estimates of associations between maternal intake and hypertensive disorders of pregnancy (HDP) are sparse and range from null to a protective effect. Here we estimated the association of maternal drinking during pregnancy with preeclampsia and gestational hypertension (separately and jointly, as HDP). We used partners alcohol intake as a negative control exposure, beverage type-specific models, and a range of sensitivity analyses to strengthen causal inference and reduce the influence of bias.

MethodsWe performed a prospective cohort study using data on self-reported alcohol intake in the UK Avon Longitudinal Study of Parents And Children (ALSPAC) and HDP ascertained from obstetric notes. Multivariable multinomial regression models were adjusted for confounders and mutually adjusted for partners or maternal alcohol intake in the negative control analysis. We also performed a beverage type analysis of the effect of beer and wine separately on HDP risk, due to different social patterning associated with different drinks. Sensitivity analyses assessed the robustness of results to assumptions of no recall bias, no residual confounding, and no selection bias.

ResultsOf the 8,999 women eligible for inclusion, 1,490 developed HDP (17%). Both maternal and partners drinking were associated with decreased HDP odds (mutually adjusted odds ratio 0.86, 95% confidence interval 0.77 to 0.96, P-value=0.008 and 0.82, 0.70 to 0.97, P=0.018, respectively). We demonstrate the validity of the negative control analyses using the same approach for smoking as the exposure. This confirmed an inverse association for maternal but not partners smoking, as expected. Estimates were more extreme for increasing levels of wine intake compared to increasing levels of beer. Multiple sensitivity analyses did not alter our conclusions.

ConclusionWe observed an inverse relationship between alcohol intake during pregnancy and risk of HDP for both maternal and, more surprisingly, partners drinking. We speculate that this is more likely to be due to common environmental exposures shared between pregnant women and their partners, rather than a true causal effect. This warrants further investigation using different study designs, including Mendelian randomisation.

category: epidemiology


title: Tajima D test accurately forecasts Omicron / COVID-19 outbreak

abstract: On 26 November 2021, the World Health Organization designated the SARS-CoV-2 variant B.1.1.529, Omicron, a variant of concern. However, the phylogenetic and evolutionary dynamics of this variant remain unclear. An analysis of the 131 Omicron variant sequences from November 9 to November 28, 2021 reveals that variants have diverged into at least 6 major subgroups. 86.3% of the cases have an insertion at amino acid 214 (INS214EPE) of the spike protein. Neutrality analysis of DH (-2.814, p<0.001) and Zengs E (0.0583, p=1.0) tests suggested that directional selection was the major driving force of Omicron variant evolution. The synonymous (Dsyn) and nonsynonymous (Dnonsyn) polymorphisms of the Omicron variant spike gene were estimated with Tajimas D statistic to eliminate homogenous effects. Both D ratio (Dnonsyn/Dsyn, 1.57) and {Delta}D (Dsyn-Dnonsyn, 0.63) indicate that purifying selection operates at present. The low nucleotide diversity (0.00008) and Tajima D value (-2.709, p<0.001) also confirms that Omicron variants had already spread in human population for more than the 6 weeks than has been reported. These results, along with our previous analysis of Delta and Lambda variants, also supports the validity of the Tajimas D test score, with a threshold value as -2.50, as an accurate predictor of new COVID-19 outbreaks.


title: Increased risk of psychiatric sequelae of COVID-19 is highest early in the clinical course

abstract:
BackgroundCOVID-19 has been shown to increase the risk of adverse mental health consequences. A recent electronic health record (EHR)-based observational study showed an almost two-fold increased risk of new-onset mental illness in the first 90 days following a diagnosis of acute COVID-19.

MethodsWe used the National COVID Cohort Collaborative, a harmonized EHR repository with 2,965,506 COVID-19 positive patients, and compared cohorts of COVID-19 patients with comparable controls. Patients were propensity score-matched to control for confounding factors. We estimated the hazard ratio (COVID-19:control) for new-onset of mental illness for the first year following diagnosis. We additionally estimated the change in risk for new-onset mental illness between the periods of 21-120 and 121-365 days following infection.

FindingsWe find a significant increase in incidence of new-onset mental disorders in the period of 21-120 days following COVID-19 (3.8%, 3.6-4.0) compared to patients with respiratory tract infections (3%, 2.8-3.2). We further show that the risk for new-onset mental illness decreases over the first year following COVID-19 diagnosis compared to other respiratory tract infections and demonstrate a reduced (non-significant) hazard ratio over the period of 121-365 days following diagnosis. Similar findings are seen for new-onset anxiety disorders but not for mood disorders.

InterpretationPatients who have recovered from COVID-19 are at an increased risk for developing new-onset mental illness, especially anxiety disorders. This risk is most prominent in the first 120 days following infection.

FundingNational Center for Advancing Translational Sciences (NCATS).


title: The prostate tissue-based telomere biomarker as a prognostic tool for metastasis and death from prostate cancer after prostatectomy

abstract:
PurposeCurrent biomarkers are inadequate prognostic predictors in localized prostate cancer making treatment decision-making challenging. Previously, we observed that the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells - the telomere biomarker - is strongly associated with progression to metastasis and prostate cancer death after prostatectomy independent of currently used pathologic indicators.

Experimental DesignWe optimized our method allowing for semi-automated telomere length determination in single cells in fixed tissue, and tested the telomere biomarker in tissue microarrays from five cohort studies of men surgically treated for clinically localized disease (N=2,255). We estimated the relative risk (RR) of progression to metastasis (N=311) and prostate cancer death (N=85) using models appropriate to each studys design adjusting for age, prostatectomy stage, and tumor grade, which then we meta-analyzed using inverse variance weights.

ResultsCompared with men who had less variable telomere length among prostate cancer cells and longer telomere length in prostate cancer-associated stromal cells, men with the combination of more variable and shorter telomere length, had 3.76-times the risk of prostate cancer death (95% CI 1.37-10.3; p=0.01) and had 2.23-times the risk of progression to metastasis (95% CI 0.99-5.02, P=0.05). The telomere biomarker was associated with prostate cancer death in men with intermediate risk disease (Grade Groups 2/3: RR=9.18, 95% CI 1.14- 74.0, p=0.037) and with PTEN intact tumors (RR=6.74, 95% CI 1.46-37.6, p=0.015).

ConclusionsThe telomere biomarker is robust and associated with poor outcome independent of current pathologic indicators in surgically-treated men.

Translational RelevanceCurrent prognostic biomarkers in localized prostate cancer are inadequate imperfect predictors; therefore, new biomarkers are needed to improve the prognostic classification and management of these patients. In a five-cohort study, we confirmed that the tissue-based telomere biomarker - the combination of more variable telomere length among prostate cancer cells and shorter telomere length in prostate cancer-associated stromal cells - was associated with progression to metastasis and prostate cancer death independent of currently used prognostic indicators after prostatectomy for clinically-localized disease. Importantly, the telomere biomarker was associated with poor outcome in men with intermediate risk disease, as well as in men with intact PTEN tumors. Thus, this tissue-based telomere biomarker has the translational potential to improve treatment and surveillance decision-making.

category: pathology


title: SARS-COV-2 INFECTION IN PRIMARY CARE: A SINGLE-CENTERED, RETROSPECTIVE, OBSERVATIONAL STUDY

abstract:
Purposeto describe the clinical characteristics of patients with confirmed SARS-CoV-2 infection in primary care and to analyze the predictive role of different risk factors on prognosis, especially living conditions.

MethodsRetrospective longitudinal observational retrospective study by reviewing medical records from a primary care center since March 1 to April 30, 2020. Case definition of confirmed SARS-CoV-2 infection, sociodemographic data, clinical characteristics, comorbidity and living conditions were collected. The statistical analysis consisted in description of the sample, comparison of prognosis groups and analysis of prognostic factors.

ResultsA sample of 70 patients with confirmed SARS-CoV-2 infection was obtained, with comorbidity mainly related to arterial hypertension, overweight/obesity, hypercholesterolemia, diabetes and chronic pulmonary pathology. Pneumonia was present in 66%. Exitus occurred in 14% of the sample. Factors associated with mortality were advanced age (84 vs 55; p<0.0001), arterial hypertension (78% vs 41%; p=0.040), asthma-COPD (56% vs 13%; p=0.008) and atrial fibrillation (56% vs 5%; p=0.001).

ConclusionsThe study reflects the clinical practice of a primary care center. This kind of studies are essential to strengthen and reorganize the Health System and to try to anticipate the medium- to long-term consequences of COVID-19 on global health.

category: primary care research


title: Metabolic phenotyping reveals a potential link between elevated faecal amino acids, diet and symptom severity in individuals with severe mental illness

abstract: The brain-gut axis is increasingly recognized as an important contributing factor in the onset and progression of severe mental illnesses such as schizophrenia spectrum disorders and bipolar disorder. This study investigates associations between levels of faecal metabolites identified using 1H-NMR, clinical parameters, and dietary components of forty-two individuals diagnosed in a transdiagnostic approach to have severe mental illness. Faecal levels of the amino acids; alanine, leucine, and valine showed a significant positive correlation with psychiatric symptom severity as well as with dairy intake. Overall, this study proposes a diet-induced link between the brain-gut axis and the severity of psychiatric symptoms, which could be valuable in the design of novel dietary or therapeutic interventions to improve psychiatric symptoms.

category: psychiatry and clinical psychology


title: Danger signs and management of suspected severe malaria cases at community level and in referral health facilities: an operational study in the Democratic Republic of the Congo

abstract:
BackgroundEvidence from one trial in Africa suggests that pre-referral Rectal Artesunate (RAS) can be a life-saving intervention for severe malaria in remote settings, where parenteral treatment is not available. Recognition of danger signs indicative of severe malaria is critical for prompt and appropriate case management.

MethodsAn observational study was conducted in the Democratic Republic of the Congo (DRC) in the frame of the multi-country CARAMAL project, to assess the effectiveness of RAS under real-world conditions. Severely ill feverish children <5 years seeking care from a community-based healthcare provider were recruited in three rural health zones into a patient surveillance system. They were subsequently followed within the healthcare system and at home after 28 days to determine care seeking, antimalarial treatment provision and health outcomes.

ResultsOverall, 66.4% of patients had iCCM general danger signs, as well as more specific danger signs. Children aged 2-5 years (aOR=1.58, 95% CI 1.20-2.08) and those presenting iCCM general danger signs were more likely to receive RAS (aOR = 2.77, 95% CI 2.04-3.77). Injectable treatment was less likely with RAS pre-referral treatment (aOR=0.21, 95% 0.13- 0.33). In the post-RAS phase, the case fatality ratio was 7.1%. Children not receiving RAS had a higher risk of dying, but this was not statistically significant (aOR = 1.50, 95% CI 0.86- 2.60). The odds of dying were reduced in patients without iCCM general danger signs, but just not statistically so (aOR = 0.64, 95% CI 0.38-1.06). Full oral therapy at a RHF was highly protective (aOR = 0.13, 95% CI 0.07-0.26), while a full treatment of severe malaria (injectable + oral) was shown to also decrease massively the odds of dying (aOR = 0.26, 95% CI 0.09- 0.79) compared to injectable treatment alone.

ConclusionsBetter understanding the determinants of successful case management, and targeted improvements of the health system (especially the provision of a full course of an oral antimalarial) are crucial for improving health oucomes of children with suspected severe malaria.


title: Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa

abstract:
ObjectivesUnder the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa.

MethodsWe examined school-level Ag and Ab status (presence/absence of Ag- and Ab- positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearsons chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3.

ResultsSchools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5).

ConclusionAnti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings.


title: Changes Over Time in COVID-19 Vaccination Inequalities in Eight Large U.S. Cities

abstract: We estimate the associations between community socioeconomic composition and changes in COVID-19 vaccination levels in eight large cities at three time points. Between March and April, low SES communities had significantly lower change in percent vaccinated than high SES communities. Between April and May, this difference was not significant. Thus, the large vaccination gap between communities during restricted vaccine eligibility did not narrow when eligibility opened up. The link between COVID-19 vaccination and community disadvantage may lead to a bifurcated recovery where advantaged communities move on from the pandemic more quickly while disadvantaged communities continue to suffer.


title: Assessing Open Science practices in physical activity behaviour change intervention evaluations

abstract:
ObjectivesConcerns on the lack of reproducibility and transparency in science have led to a range of research practice reforms, broadly referred to as  Open Science. The extent that physical activity interventions are embedding Open Science practices is currently unknown. In this study, we randomly sampled 100 reports of recent physical activity behaviour change interventions to estimate the prevalence of Open Science practices.

MethodsOne hundred reports of randomised controlled trial physical activity behaviour change interventions published between 2018-2021 were identified. Open Science practices were coded in identified reports, including: study pre-registration, protocol sharing, data-, materials- and analysis scripts-sharing, replication of a previous study, open access publication, funding sources and conflict of interest statements. Coding was performed by two independent researchers, with inter-rater reliability calculated using Krippendorffs alpha.

Results78% of the 100 reports provided details of study pre-registration and 41% provided evidence of a published protocol. 4% provided accessible open data, 8% provided open materials and 1% provided open analysis scripts. 73% of reports were published as open access and no studies were described as replication attempts. 93% of reports declared their sources of funding and 88% provided conflicts of interest statements. A Krippendorffs alpha of 0.73 was obtained across all coding.

ConclusionOpen data, materials, analysis and replication attempts are currently rare in physical activity behaviour change intervention reports, whereas funding source and conflict of interest declarations are common. Future physical activity research should increase the reproducibility of their methods and results by incorporating more Open Science practices.

category: sports medicine


title: Longitudinal prediction of motor dysfunction after stroke: a disconnectome study.

abstract: Motricity is the most commonly affected ability after a stroke. While many clinical studies attempt to predict motor symptoms at different chronic time points after a stroke, longitudinal acute-to-chronic studies remain scarce. Taking advantage of recent advances in mapping brain disconnections, we predict motor outcomes in 62 patients assessed longitudinally two weeks, three months, and one year after their stroke. Results indicate that brain disconnection patterns accurately predict motor impairments. However, disconnection patterns leading to impairment differ between the three time points and between left and right motor impairments. These results were cross-validated using resampling techniques. In sum, we demonstrated that while some neuroplasticity mechanisms exist changing the structure-function relationship, disconnection patterns prevail when predicting motor impairment at different time points after stroke.

category: neurology


title: Neuropsychiatric, cognitive and brain morphology characteristics of conversion from Mild Cognitive Impairment to Alzheimers Disease

abstract:
The impact of neuropsychiatric symptoms (NPS) on cognitive performance has been extensively reported, and this impact was better defined in the aging population. Yet a potential impact of NPS on brain morphology, cognitive performance and interactions between them in a longitudinal setting, as well as the potential of using these values as prediction of conversion - have remained questionable. We studied 156 participants with mild cognitive impairment (MCI) from the Alzheimers Disease Neuroimaging Initiative database who maintained the same level of cognitive performance after a 4-year follow-up and compared them to 119 MCI participants who converted to dementia. Additionally, we assessed the same analysis in 170 healthy controls who remained healthy at follow-up. Compared to 15 controls who converted to MCI. Their neuropsychological, neuropsychiatric, and brain morphology data underwent statistical analyses of 1) baseline comparison between the groups; (2) analysis of covariance model controlling for age, sex, education, and MMSE score, to specify the cognitive performance and brain structures that distinguish the two subgroups, and 3) used the significant ANCOVA variables to construct a binary logistic regression model that generates a probability equation for a given individual to convert to a lower cognitive performance state.

Results showed that MCI who converted to AD in comparison to those who did not convert, exhibited a higher NPS prevalence, a lower cognitive performance and a higher number of involved brain structures. Furthermore, agitation, memory and the volumes of inferior temporal, hippocampal and amygdala sizes were significant predictors of MCI to AD conversion.


title: Multidisciplinary analysis of evolution based Abiraterone treatment for metastatic castrate resistant prostate cancer

abstract:
BackgroundWe present a multidisciplinary approach to clinical trial design and analysis in a pilot study (NCT02415621) in which evolution-based mathematical models guide patient-specific dosing for Abiraterone treatment in men with castrate resistant metastatic prostate cancer.

MethodsAbiraterone plus prednisone were administered intermittently based on an evolutionary mathematical model. Outcomes are compared to historical controls and a matched contemporaneous cohort who met trial eligibility but received SOC dosing. Longitudinal cohort data allowed modification of pre-trial model parameter estimates. Model simulations of each patient using updated parameters critically evaluated trial design.

ResultsTrial patients, on average, received no abiraterone during 59% of time on treatment. Median Time to Radiographic Progression (TTP) was 30.4 months compared to 14.3 months in the contemporaneous SOC group (p<0.001). All patients in the SOC group have progressed but 4 in the adaptive cohort remain on treatment at >1800 days. Longitudinal trial data found the competition coefficient ratio (RS/SR) of sensitive and resistant populations, a critical factor in intratumoral evolution, was 2 to 3-fold higher than pre-trial estimates. Computer simulations using the corrected parameter unexpectedly demonstrated optimal cycling can reduce the resistant cells. Longitudinal data from 4 trial patients who remain on treatment are consistent with model predictions. Modeling results predict protocol changes that will allow similar outcomes in most patients.

ConclusionsAdministration of abiraterone using evolution-based mathematical models decreased drug dosing and increased radiographic TTP. Integration of mathematical models into trial design identifies novel insights into key treatment parameters and provides optimization strategies for follow-up investigations.

Article Summarysupplemental sections outline the methodology for parameter estimates from trial data, computer simulations, and comparison of simulation results and actual clinical data in every patient in both cohorts.

Statement of Translational RelevanceIntegration of evolution-based mathematical models significantly increased TTP in abiraterone therapy for mCRPC. This multidisciplinary approach represents a novel clinical trial strategy in which the treatment protocol is framed mathematically, clinical data then refines model parameterization, and simulations using the updated model predict alternative strategies to improve outcomes. Here we demonstrate the mathematical models used to design the trial can also produce novel analytic approaches. By using longitudinal trial data, key model parameters can be refined. Simulations using the updated model can then be applied to every patient in the trial. Finally, additional simulations demonstrate alternative protocols that could improve results. These analyses demonstrate evolution-based approaches may allow consistent long-term control in patients with metastatic prostate cancer.


title: Radiographic evaluation of lumbar intervertebral disc height index: an intra and inter-rater agreement and reliability study

abstract:
PurposeTo evaluate intra- and inter-rater agreement and reliability of seven reported disc height index (DHI) measurement methods on standing lateral X-ray of lumbar spine.

MethodsThe adult patients who had standing lateral X-ray of lumbar spine were recruited. Seven methods were used to measure DHI of each lumbar intervertebral disc level. Bland and Altmans Limits of Agreement (LOA) with standard difference were calculated to examine intra- and inter-rater agreements between two out of seven methods for DHI. Intra-class correlations (ICC) with 95% confidence intervals were calculated to assess intra- and inter-rater reliability.

ResultsThe intra-rater reliability in DHI measurements for 288 participants were ICCs from 0.807 (0.794, 0.812) to 0.922 (0.913, 0.946) by rater 1 (SS) and from 0.827 (0.802, 0.841) to 0.918 (0.806, 0.823) by rater 2 (XC). Method 2, 3, and 5 on all segmental levels had bias (95% CI does not include zero) or/and out of the acceptable cut-off proportion (>50%). A total of 609 outliers in 9174 segmental levels LOA range. Inter-rater reliability was good-to-excellent in all but method 2 (0.736 (0.712, 0.759)) and method 5 (0.634 (0.598, 0.667)). ICCs of related lines to good-to-excellent reliability methods was excellent in all but only indirect line in method 1 and 4 (ICCs lie in the range from 0.8 to 0.9).

ConclusionFollowing structured protocol, intra- and inter-rater reliability was good-to-excellent for most DHI measurement methods on X-ray. However, in the presence of vertebral rotation, one should exercise caution in using complicated methods to define vertebral landmarks.

category: orthopedics


title: Clinical Characteristics and Treatment Experience of Individuals with SCN8A Developmental and Epileptic Encephalopathy (SCN8A-DEE): Findings from an Online Caregiver Survey

abstract:
PurposeSCN8A developmental epileptic encephalopathy (SCN8A-DEE) is a rare and severe genetic epilepsy syndrome characterized by early-onset developmental delay, cognitive impairment, and intractable seizures. Variants in the SCN8A gene are associated with a broad phenotypic spectrum and variable disease severity. A caregiver survey, solicited by the advocacy group The Cute Syndrome Foundation (TCSF), was conducted to gather information on the demographics/disease presentation, seizure history, and treatment of patients with SCN8A-related epilepsies.

MethodsA 36-question online survey was developed to obtain de-identified data from caregivers of children with SCN8A-related epilepsy. The survey included questions on genetic diagnosis, disease manifestations/comorbidities, seizure severity/type, current/prior use of antiseizure medicines (ASMs), and best/worst treatments per caregiver perception.

ResultsIn total, 116 survey responses (87 USA, 12 Canada, 12 UK, 5 Australia) were included in the quantitative analysis. Generalized tonic/clonic was the most common seizure type at onset and time of survey; absence and partial/focal seizures were also common. Most patients (77%) were currently taking [≥]2 ASMs; 50% had previously tried and stopped [≥]4 ASMs. Sodium channel blockers (oxcarbazepine, phenytoin, lamotrigine) provided the best subjective seizure control and quality of life.

ConclusionThe SCN8A-DEE patient population is heterogeneous and difficult to treat, with high seizure burden and multiple comorbidities. The high proportion of patients who previously tried and stopped ASMs indicates a large unmet treatment need. Further collaboration between families, caregivers, patient advocates, clinicians, researchers, and industry can increase awareness and understanding of SCN8A-related epilepsies, improve clinical trial design, and potentially improve patient outcomes.

HIGHLIGHTSO_LIThis is the first survey-based study of caregiver experiences in SCN8A-DEE
C_LIO_LICaregivers report a broad range of seizure types and genetic variants in patients
C_LIO_LIPatients generally suffer from high seizure burden and multiple comorbidities
C_LIO_LIResults suggest new treatments and standardized treatment protocols are needed
C_LIO_LIPatient-centered research may improve awareness of SCN8A-DEE and patient outcomes
C_LI


title: Network Assisted Analysis of De Novo Variants Using Protein-Protein Interaction Information Identified 46 Candidate Genes for Congenital Heart Disease

abstract: De novo variants (DNVs) with deleterious effects have proved informative in identifying risk genes for early-onset diseases such as congenital heart disease (CHD). A number of statistical methods have been proposed for family-based studies or case/control studies to identify risk genes by screening genes with more DNVs than expected by chance in Whole Exome Sequencing (WES) studies. However, the statistical power is still limited for cohorts with thousands of subjects. Under the hypothesis that connected genes in protein-protein interaction (PPI) networks are more likely to share similar disease association status, we develop a Markov Random Field model that can leverage information from publicly available PPI databases to increase power in identifying risk genes. We identified 46 candidate genes with at least 1 DNV in the CHD study cohort, including 18 known human CHD genes and 35 highly expressed genes in mouse developing heart. Our results may shed new insight on the shared protein functionality among risk genes for CHD.


title: TREATMENT COSTS FOR COVID-19 PATIENTS IN A TERTIARY HOSPITAL FROM SERBIA

abstract:
IntroductionAim of our study was to identify total costs of COVID-19 inpatients treatment in an upper-middle income country from Southeast Europe.

MethodsThis retrospective, observational cost of illness study was performed from National Health Insurance Fund perspective and included a cohort of 118 males and 78 females admitted to COVID-19 ward units of a tertiary center, during the first wave of epidemics.

ResultsThe median of total costs in the non-survivors subgroup (n=43) was 3279.16 Euro (4023.34, 355.20, 9909.61) which is higher than in the survivors (n=153) subgroup 747.10 Euro (1088.21, 46.71, 3265.91). The odds ratio of Charlson Comorbidity Index total score and every 100-Euros increase of patients total hospital treatment costs for fatal outcome were 1.804 (95% confidence interval 1.408-2.311, p<0.001) and 1.050 (1.029-1.072, p<0.001), respectively.

ConclusionsDirect medical treatment costs for COVID-19 inpatients represent significant economic burden. The link between increased costs and unfavorable final outcome should be further explored.

category: health economics


title: The impact of the COVID-19 pandemic on hospital services for patients with cardiac diseases: a scoping review

abstract:
BackgroundThe repercussions of the COVID-19 pandemic concern care in many clinical areas, including cardiology. We aim to assess the impact of the COVID-19 pandemic on hospital care for cardiac patients.

MethodsScoping review. Performance indicators were extracted and collated to inform on changes in the use of health services and care provided during January - June 2020.

ResultsDatabase searches yielded 6277 articles, of which 838 articles met the inclusion criteria during initial screening. After full-text screening, 94 articles were considered for data extraction. In total, 1637 indicators were retrieved, showing large variation in the indicators and their definitions. Most of the indicators that provided information on changes in number of admissions (n=118, 88%) signalled a decrease in admissions; 88% (n=15) of the indicators showed patients delayed presentation and 40% (n=54) showed patients in a worse clinical condition. A reduction in diagnostic and treatment procedures was signalled by 95% (n=18) and 81% (n=64) of the indicators reporting on cardiac procedures, respectively. Length of stay decreased in 58% (n=21) of the indicators and acute coronary syndromes treatment times increased in 61% (n=65) of the indicators. Outpatient activity decreased in 94% (n=17) of the indicators related with outpatient care, whereas telehealth utilization increased in 100% (n=6). Outcomes worsened in 40% (n=35) of the indicators, and mortality rates increased in 52% (n=31).

ConclusionAll phases of the hospital cardiac care pathway were affected. This information could support the planning of care during the ongoing pandemic and in future events.

category: health systems and quality improvement


title: Sexual risk among pregnant women at risk of HIV infection in Cape Town, South Africa: What does alcohol have to do with it?

abstract: This study examines associations between alcohol use and HIV sexual risk among a cohort of HIV-uninfected pregnant women (n=1201) residing in a high HIV burden community in South Africa. Alcohol use was measured using a modified version of the Alcohol Use Disorder Identification Test (AUDIT). HIV sexual risk was measured through a composite variable of four risk factors: diagnosis with a STI, self-report of >1 recent sex partners, partner HIV serostatus (unknown or HIV+) and condomless sex at last sex. Any past year alcohol use prior to pregnancy was reported by half of participants (50%); 6.0% reported alcohol use during pregnancy. Alcohol use prior to pregnancy was associated with increased odds of being at high risk of HIV (aOR=1.33 for 2 risks and aOR=1.47 for 3 risks). In addition to reducing alcohol use, several other strategies to address HIV sexual risk in this population were identified.

category: hiv aids


title: Differences in bacterial colonization and mucosal responses between high and low SES children in Indonesia

abstract:
BACKGROUNDNasopharyngeal carriage of pathogenic bacteria precedes invasive disease and higher rates are found in low socioeconomic-status (SES) settings. Local immune responses are important for controlling colonization, but whether SES affects these responses is currently unknown.

OBJECTIVEExamining bacterial colonization and cytokine response in nasal mucosa of children from high and low SES.

METHODSTwenty-five cytokines were measured in nasal fluid. qPCR was performed to determine carriage and density of Haemophilus influenzae (H. influenzae), Streptococcus pneumoniae (S. pneumoniae), Moraxella catarrhalis (M. catarrhalis) and Staphylococcus aureus (S. aureus).

RESULTSThe densities of H. influenzae and S. pneumoniae were increased in low compared to the high SES (p=0.006, p=0.026), with respectively 6 and 67 times higher median densities. Densities of H. influenzae and S. pneumoniae were positively associated with levels of IL-1beta (p=0.002, p=0.008) and IL-6 (p<0.001, p=0.006). After correcting for bacterial density, IL-6 levels were increased in colonized children from high compared to low SES for both H. influenzae and S. pneumoniae (both p=0.039).

CONCLUSIONIncreased density of H. influenzae and S. pneumoniae was observed in low SES children, while IL-6 levels associated with colonization were reduced in these children, indicating that immune responses to bacterial colonization were altered by SES.


title: Polymethylation Scores for Prenatal Maternal Smoke Exposure Persist Until Age 15 and Are Detected in Saliva

abstract: Prenatal maternal smoking is associated with low birthweight, neurological disorders, and asthma in exposed children. DNA methylation signatures can function as biomarkers of prenatal smoke exposure. However, the robustness of these DNA methylation signatures across child ages, genetic ancestry groups, or tissues is not clear. Using coefficients from a meta-analysis of prenatal maternal smoke exposure and DNA methylation in newborn cord blood, we created polymethylation scores of saliva DNA methylation from children at ages 9 and 15 in the Fragile Families and Child Wellbeing study. In the full sample at age 9 (n=753), prenatal maternal smoke exposure was associated with a 0.51 (95%CI: 0.35, 0.66) standard deviation higher polymethylation score. The direction and magnitude of the association was consistent in European and African genetic ancestry samples. In the full sample at age 15 (n=747), prenatal maternal smoke exposure was associated with a 0.48 (95%CI: 0.32, 0.63) standard deviation higher polymethylation score, and the association was attenuated among the European and Admixed - Latin genetic ancestry samples. The polymethylation score classified prenatal maternal smoke exposure accurately (AUC age 9=0.77, age 15=0.77). Including the polymethylation score increased the AUC of base model covariates by 5 (95% CI: (2, 7)) percentage points, while including a single candidate site in the AHRR gene did not (P-value=0.19). Polymethylation scores for prenatal maternal smoking were portable across genetic ancestries and more accurate than an individual DNA methylation site. DNA polymethylation scores from saliva samples could serve as robust and practical clinical biomarkers of prenatal maternal smoke exposure.


title: Polymethylation Scores for Prenatal Maternal Smoke Exposure Persist Until Age 15 and Are Detected in Saliva in the Fragile Families and Child Wellbeing Cohort


title: Evaluating COVID-19 booster vaccination strategies in a partially vaccinated population: a modeling study.

abstract:
BackgroundAs evidence shows that vaccine immunity to COVID-19 wanes with time and decreases due to variants, several countries are implementing booster vaccination campaigns. The objective of this study was to analyze the morbidity and mortality burdens of different primary and booster vaccination strategies against COVID-19, using France as a case study.

MethodsWe used a deterministic, age-structured, compartmental model fitted to hospital admission data and validated against sero-prevalence data in France to analyze the impact of primary and booster vaccination strategies on morbidity and mortality assuming waning of immunity and increased virus transmissibility during winter.

FindingsStrategies prioritizing primary vaccinations were systematically more effective than strategies prioritizing boosters. Regarding booster strategies targeting different age groups, their effectiveness varied with the levels of virus transmissibility, and according to the assumed loss of immunity for each age group. If the immunity reduction affects all age groups, people aged 30 to 49 years should be boosted in priority, even for low transmissibility levels. If the immunity reduction is restricted to people older than 65 years, boosting younger people becomes effective only above certain levels of transmissibility.

InterpretationIncreasing the primary vaccination coverage should remain a priority to reduce morbidity and mortality due to COVID-19. If a plateau of primary vaccination has been reached, boosting immunity in younger age-groups could prevent more hospitalizations and deaths than boosting the immunity of older people, especially under conditions increasing SARS-CoV-2 transmissibility, or when facing new variants.

FundingThe study was partially funded by the French national research agency through project SPHINX-17-CE36-0008-0.

Research in contextO_ST_ABSEvidence before this studyC_ST_ABSMany countries have started booster vaccination programs against Covid-19, while others are still struggling to vaccinate their population. However, evidence is scarce regarding the optimal vaccination strategy to pursue in a rapidly evolving epidemiological context. A search of the literature on Nov 27 2021, using the terms (booster OR third dose) AND vaccine AND strategy AND (COVID* OR SARS*) AND (effect OR impact), returned 45 studies on PubMed and 1602 on medRxiv. However, very few studies assessed the public health impact of a booster strategy, and none of them compared different allocations strategies between primary and booster vaccinations, or investigated which age-group should be targeted for booster vaccination to maximize the public health impact of the strategy.

Added value of this studyUsing an epidemiological model able to replicate the dynamic of the SARS-CoV-2 epidemic and able to account for the use of multiple vaccines and booster, we analyzed the effectiveness of different vaccination strategies, either based on prioritization of primary vaccination versus booster, or based on the age-group targeted for the booster vaccination. We evaluated the strategies in terms of hospitalizations and deaths avoided, in various epidemic scenarios during winter 2021-2022. To our knowledge, this is the first modeling study evaluating such strategies. We found that increasing primary vaccination of all adults is always more beneficial than giving a booster dose to elderly individuals, and that the age-group to target for a booster dose for optimal effectiveness depends on the level of transmission of the virus. As the level of SARS-CoV-2 transmission increases, boosting immunity in younger age-groups becomes the most effective strategy to decrease hospitalizations and deaths in the general population.

Implications of all available evidenceCountries that have not reached the plateau of primary vaccination should focus their effort towards extending the overall primary vaccination coverage rather than boosting the immunity of fully vaccinated people, even for elderly individuals that may be facing waning immunity. When considering booster vaccination, the choice of which age groups to target should consider the level of virus transmissibility in the population. Considering the emergence of new, more transmissible SARS-CoV-2 variants, increasing the worldwide vaccination coverage should remain a priority.


title: Investigating group-based classes ("weaning workshops") to support complementary infant feeding in Irish primary care settings: A cross-sectional survey.

abstract:
ObjectiveThis study aims to 1) investigate current practice regarding  weaning workshops to support complementary infant feeding delivered within Irish primary care, 2) explore the experiences and opinions of community dietitians regarding optimal content and modes of delivery of weaning workshops, and 3) identify the key factors to be considered in the development and implementation of weaning workshops delivered within primary care.

DesignCross-sectional survey

SettingIrish primary care

Participants47 community-based dietitians

ResultsSixteen dietitians reported that workshops were run in their area with variable frequency, with ten reporting that workshops were never run in their area. Participants reported that mostly mothers of medium socioeconomic status attended weaning workshops when infants were aged between 4-7 months, and that feedback from workshop attendees was predominantly positive. Dietitians identified that key factors to be considered in future development and delivery of weaning workshops are 1) workshop characteristics such as content, timing and venue, 2) organisational characteristics such as availability of resources and multidisciplinary involvement, and 3) attendee characteristics such as socioeconomic status.

ConclusionsThis study highlights substantial variability regarding provision of weaning workshops in Ireland, and a lack of standardisation regarding the provider, content, and frequency of workshops where workshops are being delivered. The study also provides unique insights into the experiences and opinions of primary care community dietitians regarding the development and delivery of weaning workshops in terms of optimal content and delivery options. These perspectives will make a valuable contribution given the dearth of evidence in this area internationally.


title: Accessibility of Canadian COVID-19 Testing Locations for People with Disabilities During the Third Wave of the COVID-19 Pandemic

abstract:
BackgroundCanadians with disabilities make up nearly a quarter of the population yet face barriers in accessing information about COVID-19 testing accessibility across the country.

ObjectiveNo known studies evaluate the online information about the accessibility of COVID-19 testing locations. This study aimed to understand the accessibility of COVID-19 testing sites in Canada based on online information in March 2021.

MethodsKey accessibility features were identified to evaluate COVID-19 testing websites information on accessibility and data were extracted from the website to simulate the user experience of booking a COVID-19 test.

ResultsAll provinces and territories provided minimal accessibility information on their COVID-19 testing websites, except for Ontario. Out of 170 testing locations in Ontario, few had information about accessibility, with only 8.2% listing at least 3 of the 5 key accessibility features measured on their websites.

ConclusionsThis paper demonstrates that more than a year into the pandemic, there existed a clear lack of accessibility information for Canadian testing locations for people with disabilities.


title: A new indicator to measure discordance between patient reported outcomes and traditional disease activity holds promise to advance care trajectories improve care in patients with early Rheumatoid Arthritis

abstract:
ObjectiveTo unravel disease impact in early RA patients by separately quantifying patient reported (PRF), clinical (CF) and laboratory (LF) factors. We put forward a new indicator, the discordance score (DS), for early identification and prediction of unmet patient outcomes in terms of future achievement of sustained remission and RA-related quality of life (QoL).

MethodsWe obtained factor scores via factor analysis in the CareRA trial, then calculated the DS between PRF and the mean of the other scores. We computed the improvement from baseline to week 104 (%) and area-under-the-curve (AUC) across time-points per factor score and compared these between patients achieving or not achieving sustained (week 16 to 104) remission (DAS28CRP<2.6) with ANOVA. Logistic and linear regressions respectively were used to predict SR based on previous factor and discordance scores, and QoL at year 1 and 2 based on DS at week 16.

ResultsPRF, CF and LF scores improved rapidly within 8 weeks. In patients achieving SR; PRF improved 57%, CF 90% and LF 27%, compared to 32% PRF (p=0.13), 77% CF (p<0.001) and 9% LF (p=0.36) score improvement in patients not achieving SR. Patients achieving SR had an AUC of 15.7, 3.4 and 4.8 for PRF, CF and LF respectively, compared to 33.2, 10.1, and 7.2 in participants not achieving SR (p<0.001 for all). Early factor and discordance scores were associated with later stage factor scores as well as QoL and PRF scores predicted SR (p<0.005 for PRF and DS).

ConclusionsAll factor scores improved rapidly, especially in patients achieving SR. Patient-reported burden improved less extensively. Discordance scores could help in predicting the need for additional non-pharmacological interventions to achieve SR and decrease disease impact.

KEY MESSAGESO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIEarly and intensive RA drug-treatment using disease activity as a target allows rapid disease control and prevents joint destruction.
C_LIO_LIIncluding pain, fatigue and physical function when assessing patients with early RA broadens the evaluation of disease impact.
C_LI

What does this study add?O_LILeveraging patient reported outcomes (pain, fatigue and physical function) and traditional disease activity measures, we introduce a new indicator (named discordance score) for unraveling disease impact and treatment efficacy.
C_LIO_LIWe show how the discordance score stands for current unmet patient reported outcomes and could be used to predict future sustained disease contol and quality of life (1 and 2 years after baseline).
C_LIO_LIWe demonstrate this effect both in patients with and without sustained remission
C_LI

How might this impact on clinical practice or future developments?O_LIThe earlier detection of unmet needs despite good disease control could allow to perform timely interdisciplinary interventions other than medication adaptations and could promote psychosocial wellbeing for patients.
C_LI

category: rheumatology


title: A landscape of the genetic and cellular heterogeneity in Alzheimer disease

abstract:
BackgroundAlzheimer disease (AD) has substantial genetic, molecular, and cellular heterogeneity associated with its etiology. Much of our current understanding of the main AD molecular events associated with the amyloid hypothesis (APP, PSEN1 and PSEN2) and neuroimmune modulation (TREM2 and MS4A) is based on genetic studies including GWAS. However, the functional genes, downstream transcriptional ramifications, and the cell-type-specific effects of many GWAS loci remain poorly understood. Understanding these effects can point us to the cellular processes involved in AD and uncover potential therapeutic targets.

MethodsWe applied a genetic-based approach to our sample selection; our cohort included carriers of AD pathogenic mutations (APP, PSEN1), risk variants in TREM2, and the resilience variant (rs1582763) in the MS4A cluster associated with cerebrospinal fluid (CSF) soluble TREM2 levels. We performed single-nucleus RNA-sequencing (snRNA-seq) of 1,102,459 nuclei from the human parietal cortex of these carriers. Following initial unbiased clustering and cell-type annotation, we performed deep subclustering analysis per cell type to identify unique cellular transcriptional states associated with these genetic variants. We identified differentially expressed genes between cell states and genetic variant carriers/controls, and performed differential cell proportion analyses to determine key differences among these carriers. We analyzed sequencing data from human dorsolateral prefrontal cortex and mouse models to replicate the enrichment of unique cell states in genetic variant carriers. Finally, we leveraged these cell-state differential expression results to link genes in AD GWAS loci to their functional cell types.

FindingsWe identified cell-specific expression states influenced by AD genetic factors for neurons and glia. Autosomal dominant AD (ADAD) brains exhibited unique transcriptional states in all cell types. TREM2 variant carrier brains were also enriched for specific microglia and oligodendrocyte subpopulations. Carriers of the resilience MS4A variant were enriched for an altered activated-microglia expression state. We mapped AD GWAS genes to their potential functional cell types, and some, including PLCG2 and SORL1, were expressed in a broader range of brain cell types than previously reported.

InterpretationAD pathogenic, risk, or resilience variants are sufficient to alter the transcriptional and cellular landscape of human brains. Overall, our results suggest that the genetic architecture contributes to the cortical cellular heterogeneity associated with disease status, which is a critical factor to consider when designing drug trials and selecting the treatment program for AD patients. Our findings suggest that integrating genetic and single-cell molecular data facilitates our understanding of the heterogeneity of pathways, biological processes and cell types modulated by genetic risk factors for AD.

FundingUS National Institutes of Health, Hope Center, Archer foundation, Alzheimer Association, CZI.


title: Single-cell physical phenotyping of mechanically dissociated tissue biopsies for fast diagnostic assessment

abstract: Rapid and accurate histopathological diagnosis during surgery is critical for clinical decision-making. The prevalent method of intraoperative consultation pathology is time, labour and cost intensive and requires the expertise of trained pathologists. Here, we present an alternative technique for the rapid, label-free analysis of biopsy samples by sequentially assessing the physical phenotype of singularized, suspended cells in high-throughput. This new diagnostic pipeline combines enzyme-free, mechanical dissociation of tissues with real-time deformability cytometry at measurement rates of 100 - 1,000 cells/sec, and machine learning-based analysis. We show that physical phenotype parameters extracted from brightfield images of single cells can be used to distinguish subpopulations of cells in various tissues, without prior knowledge or the need for molecular markers. Further, we demonstrate the potential of our method for inflammatory bowel disease diagnostics. Using unsupervised dimensionality reduction and logistic regression, we accurately differentiate between healthy and tumorous tissue in both mouse and human biopsy samples. The method delivers results within 30 minutes, laying the groundwork for a fast and marker-free diagnostic pipeline to detect pathological changes in solid biopsies.


title: Assessment of correlations between risk factors and symptom presentation among defined at-risk groups following a confirmed COVID-19 diagnosis

abstract: This study analyzes the specific linkages between symptoms within individual COVID patients belonging to at-risk groups. The goal was to determine how strongly linked patient symptoms are within these at-risk groups to find any associations between factors such as comorbidities and COVID symptoms. In this study, de-identified patient data from the N3C database was utilized in order to link representative immunocompromised states with specific symptoms, and non-immunocompromised state with the same, to determine if the strength of the correlation changes for these at-risk groups. Multiple autoimmune disorders resulting in immunocompromised state were analyzed, to determine if severity of immune response and inflammatory action plays a role in any potential differences. An exploratory approach using statistical methods and visualization techniques appropriate to multidimensional data sets was taken. The identified correlations may allow pattern analysis in disease presentation specific to a given population, potentially informing pattern recognition, symptom presentation, and treatment approaches in patients with immune comorbidities.

category: health informatics


title: Comparison of Saliva and Mid-Turbinate Swabs for Detection of COVID-19

abstract:
BackgroundSaliva is an attractive sample for detecting SARS-CoV-2. However, contradictory reports exist concerning the sensitivity of saliva versus nasal swabs.

MethodsWe followed close contacts of COVID-19 cases for up to 14 days from last exposure and collected self-reported symptoms, mid-turbinate swabs (MTS), and saliva every two or three days. Ct values, viral load, and frequency of viral detection by MTS and saliva were compared.

Results58 contacts provided 200 saliva-MTS pairs; 14 contacts (13 with symptoms) had one or more positive samples. Saliva and MTS had similar rates of viral detection (p=0.78) and substantial agreement ({kappa}=0.83). However, sensitivity varied significantly with time since symptom onset. Early on (days -3 to 2), saliva had 12 times (95%CI: 1.2, 130) greater likelihood of viral detection and 3.2 times (95% CI: 2.8, 3.8) higher RNA copy numbers compared to MTS. After day 2 post-symptoms, there was a non-significant trend toward greater sensitivity using MTS.

ConclusionSaliva and MTS demonstrated high agreement making saliva a suitable alternative to MTS for COVID-19 detection. Saliva was more sensitive early in the infection when transmission is most likely to occur, suggesting that it may be a superior and cost-effective screening tool for COVID-19.


title: A simple model of COVID-19 explains disease severity and the effect of treatments

abstract: Considerable effort was made to better understand why some people suffer from severe COVID-19 while others remain asymptomatic. This has led to important clinical findings; people with severe COVID-19 generally experience persistently high levels of inflammation, slower viral load decay, display a dysregulated type-I interferon response, have less active natural killer cells and increased levels of neutrophil extracellular traps. How these findings are connected to the pathogenesis of COVID-19 remains unclear. We propose a mathematical model that sheds light on this issue. The model focuses on cells that trigger inflammation through molecular patterns: infected cells carrying pathogen-associated molecular patterns (PAMPs) and damaged cells producing damage-associated molecular patterns (DAMPs). The former signals the presence of pathogens while the latter signals danger such as hypoxia or the lack of nutrients. Analyses show that SARS-CoV-2 infections can lead to a self-perpetuating feedback loop between DAMP expressing cells and inflammation. It identifies the inability to quickly clear PAMPs and DAMPs as the main contributor to hyperinflammation. The model explains clinical findings and the conditional impact of treatments on disease severity. The simplicity of the model and its high level of consistency with clinical findings motivate its use for the formulation of new treatment strategies.


title: Estimating the increase in reproduction number associated with the Delta variant using local area dynamics in England

abstract:
BackgroundLocal estimates of the time-varying effective reproduction number (Rt) of COVID-19 in England became increasingly heterogeneous during April and May 2021. This may have been attributable to the spread of the Delta SARS-CoV-2 variant. This paper documents real-time analysis that aimed to investigate the association between changes in the proportion of positive cases that were S-gene positive, an indicator of the Delta variant against a background of the previously predominant Alpha variant, and the estimated time-varying Rt at the level of upper-tier local authorities (UTLA).

MethodWe explored the relationship between the proportion of samples that were S-gene positive and the Rt of test-positive cases over time from the 23 February 2021 to the 25 May 2021. Effective reproduction numbers were estimated using the EpiNow2 R package independently for each local authority using two different estimates of the generation time. We then fit a range of regression models to estimate a multiplicative relationship between S-gene positivity and weekly mean Rt estimate.

ResultsWe found evidence of an association between increased mean Rt estimates and the proportion of S-gene positives across all models evaluated with the magnitude of the effect increasing as model flexibility was decreased. Models that adjusted for either national level or NHS region level time-varying residuals were found to fit the data better, suggesting potential unexplained confounding.

ConclusionsOur results indicated that even after adjusting for time-varying residuals between NHS regions, S-gene positivity was associated with an increase in the effective reproduction number of COVID-19. These findings were robust across a range of models and generation time assumptions, though the specific effect size was variable depending on the assumptions used. The lower bound of the estimated effect indicated that the reproduction number of Delta was above 1 in almost all local authorities throughout the period of investigation.


title: Antimicrobial stewardship among Nigerian children: A pilot study of the knowledge, attitude, and practice of prescribers at two tertiary healthcare facilities in Bayelsa State.

abstract: Antimicrobial stewardship (AMS), the evidence-based use of antimicrobials, is an effective strategy in controlling antimicrobial resistance (AMR) in humans by reducing the irrational use of antimicrobials. Stewardship in children is less studied. This study assessed the knowledge, attitude, and practice of physicians prescribing antibiotics to children in Bayelsa State, Nigeria to identify gaps in AMS and possible solutions. Following ethical approval, a semi-structured questionnaire was distributed among 40 paediatricians and gynaecologists at the two public tertiary healthcare facilities in Bayelsa State - the Niger Delta University Teaching Hospital and the Federal Medical Centre - for self-completion. Responses were expressed as percentages and analyzed using Blooms cutoffs. The Capability, Opportunity, Motivation, and Behaviour (COM-B) model was employed to identify gaps for intervention in prescribing behavior with gaps in each component identified by aggregate scores <80%. Perceived approaches to improve prescribing among 14 selected options were assessed using 5-point Likert scales and options with scores >90% rated the most acceptable. Questionnaires were administered from August to September 2021. The response rate was 68% (27/40). Participants were paediatricians (81%, 22/27) and gynaecologists (19%, 5/27). Antimicrobial Susceptibility Testing (AST) was not performed before antibiotic selection nine times out of 10 (89%, 24/27). In a third (37%, 10/27) of cases, 2-3 antibiotics were prescribed. The top three antibiotics, in rank order, were: cefuroxime or amoxicillin 41% (11/27); ciprofloxacin or amoxicillin 30% (8/27), and azithromycin (33%, 9/27). Aggregate COM-B scores were: capability, 74%; opportunity, 78%; and motivation, 87%. The most acceptable (100%, 27/27) options to improving antibiotic prescribing were: availability of resistance data, availability of guidelines, readily accessible microbiological data, and easy access to infectious disease physicians. There are gaps in knowledge of AMR and opportunity for rational prescribing. There is need for antimicrobial resistance data to promote pediatric AMS at the surveyed healthcare facilities.


title: Early life infection and proinflammatory, atherogenic metabolomic and lipidomic profiles at 12 months of age: a population-based cohort study

abstract:
BackgroundThe risk of adult onset cardiovascular and metabolic (cardiometabolic) disease accrues from early life. Infection is ubiquitous in infancy and induces inflammation, a key cardiometabolic risk factor, but the relationship between infection, inflammation, and metabolic profiles in early childhood remains unexplored. We investigated relationships between infection and plasma metabolomic and lipidomic profiles at age 12 months, and mediation of these associations by inflammation.

MethodsMatched infection, metabolomics and lipidomics data were generated from 555 infants in a pre-birth longitudinal cohort. Infection data from birth to 12 months were parent-reported (total infections at age 1, 3, 6, 9, and 12 months), inflammation markers (high-sensitivity C-reactive protein, hsCRP); glycoprotein acetyls GlycA) were quantified at 12 months. Metabolic profiles were 12-month plasma nuclear magnetic resonance metabolomics (228 metabolites) and liquid-chromatography/mass-spectrometry lipidomics (776 lipids). Associations were evaluated with multivariable linear regression models.

ResultsFrequent infant infections were associated with adverse metabolomic (elevated inflammation markers, triglycerides, phenylalanine, and lower HDL cholesterol, apolipoprotein A1, and omega-3 fatty acids) and lipidomic profiles (elevated phosphatidylethanolamines and lower hexosylceramides, trihexosylceramides, and cholesteryl esters). Similar, more marked, profiles were observed with higher GlycA, but not hsCRP. GlycA, but not hsCRP, mediated a substantial proportion of the relationship between infection and metabolome/lipidome.

ConclusionsInfants with a greater infection burden from birth to 12 months had pro-inflammatory and pro-atherogenic plasma metabolomic/lipid profiles, indicative of heightened risk of cardiovascular disease, obesity, and type 2 diabetes in adults. These findings suggest potentially modifiable pathways linking early life infection and inflammation with subsequent cardiometabolic risk.

FundingThe establishment work and infrastructure for the BIS was provided by the Murdoch Childrens Research Institute (MCRI), Deakin University and Barwon Health. Subsequent funding was secured from National Health and Medical Research Council of Australia (NHMRC), The Shepherd Foundation, The Jack Brockhoff Foundation, the Scobie & Claire McKinnon Trust, the Shane OBrien Memorial Asthma Foundation, the Our Womens Our Childrens Fund Raising Committee Barwon Health, the Rotary Club of Geelong, the Minderoo Foundation, the Ilhan Food Allergy Foundation, GMHBA, Vanguard Investments Australia Ltd, and the Percy Baxter Charitable Trust, Perpetual Trustees. In-kind support was provided by the Cotton on Foundation and CreativeForce. The study sponsors were not involved in the collection, analysis, and interpretation of data; writing of the report; or the decision to submit the report for publication. Research at MCRI is supported by the Victorian Governments Operational Infrastructure Support Program. This work was also supported by NHMRC Senior Research Fellowships (1008396 to ALP; 1064629 to DB; 1045161 to RS), NHMRC Investigator Grants to ALP (1110200) and DB (1175744), NHMRC-A*STAR project grant (1149047). TM is supported by an MCRI ECR Fellowship. SB is supported by the Dutch Research Council (452173113).


title: Medical Students' Perceptions of Learning and Working on the COVID-19 Frontlines: "...a confirmation that I am in the right place professionally."

abstract:
IntroductionThe COVID-19 pandemic caused complex and enduring challenges for health care providers and medical educators and changed the medical education landscape for learners. Medical students were required to adapt and learn in a novel learning environment while universities paused their formal medical training. The current study sought to investigate medical students experiences working on a pandemic frontline to understand how they perceived this novel learning environment influenced both their learning and their developing professional identity.

MethodsWe conducted semi-structured interviews with 21 medical students who worked in a COVID-19 testing facility at the University Hospital of Basel. Using constructivist grounded theory methodology, we collected and analyzed data iteratively using a constant comparative approach to develop codes and theoretical categories.

ResultsParticipants described improvements in their technical and communication skills, consequently impacting their professional development. The presence of a perceived flat hierarchy between the physicians and medical students promoted professional identity development amongst the medical students. Most participants perceived working on the pandemic frontlines as a positive learning experience, which seemed supported by a flatter hierarchy and open communication compared to their usual learning environment.

ConclusionSince medical students reported that their work on the pandemic frontlines positively affected their learning, the need to create hands-on learning opportunities for medical students challenge curriculum developers. Medical students wish to feel like full-fledged care team members rather than observing learners. Performing simple clinical tasks and collaborative moments in a supportive learning environment may promote learning and professional development.

category: medical education


title: A phylogeny-aware GWAS framework to correct for heritable pathogen effects on infectious disease traits

abstract: Infectious diseases are a unique challenge for genome-wide association studies (GWAS) because pathogen, host, and environmental factors can all affect disease traits. Previous GWAS have successfully identified several human genetic variants associated with HIV-1 set point viral load (spVL), among other important infectious disease traits. However, these GWAS do not account for potentially confounding or extraneous pathogen effects that are heritable from donor to recipient in transmission chains. We propose a new method to consider the full genome of each patients infecting pathogen strain, remove strain-specific effects on a trait based on the pathogen phylogeny, and thus better estimate the effect of human genetic variants on infectious disease traits. In simulations, we show our method can increase GWAS power to detect truly associated host variants when pathogen effects are highly heritable, with strong phylogenetic correlations. When we apply our method to HIV-1 subtype B data from the Swiss HIV Cohort Study, we recover slightly weaker but qualitatively similar signals of association between spVL and human genetic variants in the CCR5 and major histocompatibility complex (MHC) gene regions compared to standard GWAS. Our simulation study confirms that based on the estimated heritability and selection parameters for HIV-1 subtype B spVL, standard GWAS are robust to pathogen effects. Our framework may improve GWAS for other diseases if pathogen effects are even more phylogenetically correlated amongst individuals in a cohort.


title: CHRONOSIG: Digital Triage for Secondary Mental Healthcare using Natural Language Processing - Rationale and Protocol

abstract:
BackgroundAccessing specialist secondary mental health care in the NHS in England requires a referral, usually from primary or acute care. Community mental health teams triage these referrals deciding on the most appropriate team to meet patients needs. Referrals require resource-intensive review by clinicians and often, collation and review of the patients history with services captured in their electronic health records (EHR). Triage processes are, however, opaque and often result in patients not receiving appropriate and timely access to care that is a particular concern for some minority and under-represented groups. Our project, funded by the National Institute of Health Research (NIHR) will develop a clinical decision support tool (CDST) to deliver accurate, explainable and justified triage recommendations to assist clinicians and expedite access to secondary mental health care.

MethodsOur proposed CDST will be trained on narrative free-text data combining referral documentation and historical EHR records for patients in the UK-CRIS database. This high-volume data set will enable training of end-to-end neural network natural language processing (NLP) to extract  signatures of patients who were (historically) triaged to different treatment teams. The resulting algorithm will be externally validated using data from different NHS trusts (Nottinghamshire Healthcare, Southern Health, West London and Oxford Health). We will use an explicit algorithmic fairness framework to mitigate risk of unintended harm evident in some artificial intelligence (AI) healthcare applications. Consequently, the performance of the CDST will be explicitly evaluated in simulated triage team scenarios where the tool augments clinicians decision making, in contrast to traditional "human versus AI" performance metrics.

DiscussionThe proposed CDST represents an important test-case for AI applied to real-world process improvement in mental health. The project leverages recent advances in NLP while emphasizing the risks and benefits for patients of AI-augmented clinical decision making. The projects ambition is to deliver a CDST that is scalable and can be deployed to any mental health trust in England to assist with digital triage.


title: Perceived barriers and enablers influencing physical activity in heart failure: a qualitative one-to-one interview study

abstract: In heart failure (HF), increased physical activity is associated with improved quality of life, reduced hospitalisation, and increased longevity and is an important aim of treatment. However, physical activity levels in individuals living with HF are typically extremely low. This qualitative study with one-to-one interviews systematically explores perceived clinical, environmental, and psychosocial barriers and enablers in older adults (>70 years old) living with HF. Semi-structured interviews (N = 16) based on the Theoretical Domains Framework elicited 78 belief statements describing the barriers and enablers to physical activity. Theoretical domains containing these beliefs and corresponding constructs that were both pervasive and common were deemed most relevant. These were: concerns about physical activity (Beliefs about Consequences), self-efficacy (Beliefs about Capabilities), social support (Social Influences), major health event (Environmental Context and Resources), goal behavioural (Goal), action planning (Behavioural Regulation). This work extends the limited research on the modifiable barriers and enablers for physical activity participation by individuals living with HF. The research findings provide insights for cardiologists, HF-specialist nurses, and physiotherapists to help co-design and deliver a physical activity intervention more likely to be effective for individuals living with HF.

category: cardiovascular medicine


title: The Politics of Vaccine Hesitancy in the United States

abstract:
ObjectiveWhy are Americans COVID-19 vaccine hesitant? We test social science hypotheses for vaccine hesitancy, focusing on partisanship, trust in institutions, and social-demographic characteristics of registered voters.

MethodsWe use survey data from a representative sample of American registered voters collected in November 2020 to study vaccine hesitancy, and the reasons for vaccine hesitancy, at a point in time before the vaccine was available and hence show underlying responses based on beliefs and not on clinical trial data. We use multivariate logistic regression models to test hypotheses on vaccine hesitancy.

ResultsWe find that consistently similar groups of people tend to be vaccine hesitant. Specifically, Black voters, those between the ages of 45 and 64, female voters, voters without college degrees, voters not worried about the spread of COVID-19, and voters who are concerned about government and the CDCs handling of the COVID-19 pandemic, were vaccine hesitant. We also provide intriguing results showing the nuanced reasons that the vaccine hesitant provide.

ConclusionsOur analysis allows us to establish important baseline information from a social science perspective on vaccine hesitancy at a crucial time, right before COVID-19 vaccines were beginning to be made available to adult Americans. What emerges from our analysis is a nuanced perspective on vaccine hesitancy in the United States, from this important point in the history of the COVID-19 pandemic.


title: Digital exclusion predicts worse mental health among adolescents during COVID-19

abstract:
BackgroundSocial isolation is strongly associated with poor mental health. The COVID-19 pandemic and ensuing social restrictions disrupted young peoples social interactions and resulted in several periods during which school closures necessitated online learning. We hypothesise that digitally excluded young people would demonstrate greater deterioration in their mental health than their digitally connected peers during this time.

MethodsWe analysed representative mental health data from a sample of UK 10-15-year-olds (N = 1387); Understanding Society collected the Strengths and Difficulties Questionnaire in 2017-19 and thrice during the pandemic (July 2020, November 2020 and March 2021). We employed cross-sectional methods and longitudinal latent growth curve modelling to describe trajectories of adolescent mental health for participants with and without access to a computer or a good internet connection for schoolwork.

OutcomesAdolescent mental health had a quadratic trajectory during the COVID-19 pandemic, with the highest mean Total Difficulties score around December 2020. The worsening and recovery of mental health during the pandemic was greatly pronounced among those without access to a computer, although we did not find evidence for a similar effect among those without a good internet connection.

InterpretationDigital exclusion, as indicated by lack of access to a computer, is a tractable risk factor that likely compounds other adversities facing children and young people during periods of social isolation.

FundingBritish Psychological Society; School of the Biological Sciences, University of Cambridge; NIHR Applied Research Centre; Medical Research Council; Economic and Social Research Council; and Emmanuel College, University of Cambridge.


title: Comparative efficacy of interferential therapy, bronchodilators, and body positioning on asthma control and quality of life of patients with bronchial asthma: Study protocol

abstract:
BackgroundInterferential therapy (IFT) is the application of two medium frequency currents to the skin to stimulate and activate different systems in the body using specific frequencies and frequency ranges. IFT aims to reduce myalgia in the chest and upper back, reduce muscular fatigue and induce mucus expectoration. This study is designed to compare the efficacy of IFT on asthma control and quality of life of asthma patients pre-and post-administration of bronchodilators and determine the most influential body position in its application.

MethodsForty-eight (48) patients aged 18 years and above with bronchial Asthma attending the respiratory clinic at the Lagos State University Teaching Hospital, Ikeja (LASUTH) will be assessed for the study eligibility. The study design will be a double-blinded, randomized control trial with four intervention groups and four parallel placebo control groups. IFT will be administered as an intervention to patients on short and long-acting bronchodilators in an assigned fundamental body position for 20 minutes. Six continuous outcome variables at different points will be utilized as an outcome measure. Baseline Pulmonary Function Test (PFT) will be assessed on entry into the study, Quality of life and asthma control will be evaluated every two (2) weeks of the study. Data obtained will be analyzed using descriptive and inferential statistics of repeated ANOVA; P<0.05.

DiscussionThe study outcome will compare the efficacy of IFT on Bronchial Asthma, identify its effect in different body positions, and compare the relationship between its application and the bronchodilator medication frequently used by the patients.

Trial Registrationhttps://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=10942:

PACTR202005807526130

category: respiratory medicine