***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background : The Women 's Health Initiative r and omized trial found greater coronary heart disease ( CHD ) risk in women assigned to estrogen/progestin therapy  than in those assigned to placebo . Observational studies had previously suggested reduced CHD risk in hormone users . Methods : Using data from the observational Nurses ’ Health Study , we emulated the design and intention-to-treat ( ITT ) analysis of the r and omized trial . The observational study was conceptualized as a sequence of “ trials , ” in which eligible women were classified as initiators or noninitiators of estrogen/progestin therapy . Results : The ITT hazard ratios ( HRs ) ( 95 % confidence intervals ) of CHD for initiators versus noninitiators were 1.42 ( 0.92–2.20 ) for the first 2 years , and 0.96 ( 0.78–1.18 ) for the entire follow-up . The ITT HRs were 0.84 ( 0.61–1.14 ) in women within 10 years of menopause , and 1.12 ( 0.84–1.48 ) in the others ( P value for interaction = 0.08 ) . These ITT estimates are similar to those from the Women 's Health Initiative . Because the ITT approach causes severe treatment misclassification , we also estimated adherence-adjusted effects by inverse probability weighting . The HRs were 1.61 ( 0.97–2.66 ) for the first 2 years , and 0.98 ( 0.66–1.49 ) for the entire follow-up . The HRs were 0.54 ( 0.19–1.51 ) in women within 10 years after menopause , and 1.20 ( 0.78–1.84 ) in others ( P value for interaction = 0.01 ) . We also present comparisons between these estimates and previously reported Nurses ’ Health Study estimates . Conclusions : Our findings suggest that the discrepancies between the Women 's Health Initiative and Nurses ’ Health Study ITT estimates could be largely explained by differences in the distribution of time since menopause and length of follow-up Background A large prospect i ve study in patients with type 2 diabetes ( T2D ) , the German D2C cohort , is presently being enumerated to investigate risk factors of incident cancer in diabetic patients . Study setting A disease management program was offered , on a voluntary basis , to all T2D patients who were members of a statutory health insurance fund in Germany . This first feasibility report uses data from 26.742 T2D patients , who were 40 to 79 years old , resided in the Muenster District , and who were enrolled between June 2003 and July 2008 . Cancer cases were identified through the regional Cancer Registry . Methods Invasive cancer cases were identified using probabilistic record linkage procedures and pseudonymised personal identifiers . Censoring date was December 31 , 2008 . We included only first cancers , leaving 12.650 male and 14.092 female T2D with a total of 88.778 person-years ( py ) . We computed st and ardised incidence ratios ( SIR ) for external comparisons and we employed Cox regression models and hazard ratios ( HR ) within the cohort . Results We identified 759 first cancers among male T2D patients ( 18.7 per 1,000 py ) and 605 among females ( 12.7 per 1,000 py ) . The risk of any incident cancer in T2D was raised ( SIR = 1.14 ; 95 % confidence interval [ 1.10 - 1.21 ] ) , in particular for cancer of the liver ( SIR = 1.94 [ 1.15 - 2.94 ] ) and pancreas ( SIR = 1.45 [ 1.07 - 1.92 ] ) . SIRs decreased markedly with time after T2D diagnosis . In Cox models , adjusting for diabetes duration , body mass index and sex , insulin therapy was related to higher cancer risk ( HR = 1.25 [ 1.17 - 1.33 ] ) . No effect was seen for metformin . Discussion Our study demonstrates feasibility of record linkage between DMP and cancer registries . These first cohort results confirm previous reports . It is envisaged to enhance this cohort by inclusion of further regions of the state , expansion of the follow-up times , and collection of a more detailed medication history Aims /hypothesisObservational and mechanistic studies have suggested a possible relationship between treatment with metformin and decreased incidence of cancer in participants with type 2 diabetes . We extracted data for malignancies from the ADOPT ( A Diabetes Outcome Progression Trial ) and RECORD ( Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes ) r and omised controlled clinical trials , in which the efficacy and /or safety of metformin was assessed in comparison with sulfonylureas and rosiglitazone . Methods Neoplasm occurrences were collected as adverse events in these studies . We review ed and re-analysed the individual participant data in both studies for serious adverse events , malignancies reported as adverse events and related neoplasms of special interest . Results In ADOPT , 50 participants ( 3.4 % ) on  metformin  and 55 ( 3.8 % ) on each of rosiglitazone and glibenclamide ( known as glyburide in the USA and Canada ) developed serious adverse event malignancies ( excluding non-melanoma skin cancers ) . This corresponds to 1.03 , 1.12 and 1.31 per 100 person-years , giving hazard ratios for metformin of 0.92 ( 95 % CI 0.63–1.35 ) vs rosiglitazone and 0.78 ( 0.53–1.14 ) vs glibenclamide . In RECORD , on a background of sulfonylurea , 69 ( 6.1 % ) participants developed malignant neoplasms in the metformin group , compared with 56 ( 5.1 % ) in the rosiglitazone group ( HR 1.22 [ 0.86–1.74 ] ) . On a background of metformin , 74 ( 6.7 % ) participants in the sulfonylurea group developed malignant neoplasms , compared with 57 ( 5.1 % ) in the rosiglitazone group ( HR 1.33 [ 0.94–1.88 ] ) . Conclusions /interpretationThe malignancy rates in these two r and omised controlled clinical trials do not support a view that metformin offers any particular protection against malignancy compared with rosiglitazone . However , they do not refute the possibility of a difference compared with sulfonylureas OBJECTIVE The antidiabetic properties of metformin are mediated through its ability to activate the AMP-activated protein kinase ( AMPK ) . Activation of AMPK can suppress tumor formation and inhibit cell growth in addition to lowering blood glucose levels . We tested the hypothesis that metformin reduces the risk of cancer in people with type 2 diabetes . RESEARCH DESIGN AND METHODS In an observational cohort study using record-linkage data bases and based in Tayside , Scotl and , U.K. , we identified people with type 2 diabetes who were new users of metformin in 1994–2003 . We also identified a set of diabetic comparators , individually matched to the metformin users by year of diabetes diagnosis , who had never used metformin . In a survival analysis we calculated hazard ratios for diagnosis of cancer , adjusted for baseline characteristics of the two groups using Cox regression . RESULTS Cancer was diagnosed among 7.3 % of 4,085 metformin users compared with 11.6 % of 4,085 comparators  , with median times to cancer of 3.5 and 2.6 years , respectively ( P < 0.001 ) . The unadjusted hazard ratio ( 95 % CI ) for cancer was 0.46 ( 0.40–0.53 ) . After adjusting for sex , age , BMI , A1C , deprivation , smoking , and other drug use , there was still a significantly reduced risk of cancer associated with metformin : 0.63 ( 0.53–0.75 ) . CONCLUSIONS These results suggest that metformin use may be associated with a reduced risk of cancer . A r and omized trial is needed to assess whether metformin is protective in a population at high risk for cancer There is growing evidence that patients with type 2 diabetes mellitus have increased  cancer risk . We examined the association between diabetes , cancer , and cancer-related mortality  and hypothesized that insulin sensitizers lower cancer-related mortality . Participants in the Diabetes Cardiovascular Risk and Evaluation : Targets and Essential Data for Commitment of Treatment study , a nationwide cross-sectional and prospect i ve epidemiological study , were recruited from German primary care practice s. In the cross-sectional study , subjects with type 2 diabetes mellitus had a higher prevalence of malignancies ( 66/1308 , 5.1 % ) compared to nondiabetic subjects ( 185/6211 , 3.0 % ) ( odds ratio , 1.64 ; 95 % confidence interval , 1.12 - 2.41 ) before and after adjustment for age , sex , hemoglobin A(1c ) , smoking status , and body mass index . Patients on  metformin had a lower prevalence of malignancies , comparable with that among nondiabetic patients , whereas those on any other oral combination treatment had a 2-fold higher risk for malignancies even after adjusting for possible confounders ; inclusion of metformin in these regimens decreased the prevalence of malignancies . In the prospect i ve analyses , diabetic patients in general and diabetic patients treated with insulin ( either as monotherapy or in combination with other treatments ) had a 2- and 4-fold , respectively , higher mortality rate than nondiabetic patients , even after adjustment for potential confounders ( incidence of cancer deaths in patients with type 2 diabetes mellitus [ 2.6 % ] vs the incidence of cancer deaths in patients without type 2 diabetes mellitus [ 1.2 % ] ) . Our results suggest that diabetes and medications for diabetes , with the exception of the insulin sensitizer metformin , increase cancer risk and mortality OBJECTIVE Meta-analyses of epidemiologic studies have suggested that metformin may reduce cancer incidence , but r and omized controlled trials did not support this hypothesis . RESEARCH DESIGN AND METHODS A retrospective cohort study , Clinical Practice Research Data link , was design ed to investigate the association between use of metformin compared with other antidiabetes medications and cancer risk by emulating an intention-to-treat analysis as in a trial . A total of 95,820 participants with type 2 diabetes who started taking metformin and other oral antidiabetes medications within 12 months of their diagnosis ( initiators ) were followed up for first incident cancer diagnosis without regard to any subsequent changes in pharmacotherapy . Cox proportional hazards models were used to estimate multivariable-adjusted hazard ratios ( HR ) and 95 % CI . RESULTS A total of 51,484 individuals ( 54 % ) were metformin initiators and 18,264 ( 19 % ) were sulfonylurea initiators , and 3,805 first incident cancers were diagnosed during a median follow-up time of 5.1 years . Compared with initiators of sulfonylurea , initiators of metformin had a similar incidence of total cancer ( HR 0.96 ; 95 % CI 0.89–1.04 ) and colorectal ( HR 0.92 ; 95 % CI 0.76–1.13 ) , prostate ( HR 1.02 ; 95 % CI 0.83–1.25 ) , lung ( HR 0.85 ; 95 % CI 0.68–1.07 ) , or postmenopausal breast ( HR 1.03 ; 95 % CI 0.82–1.31 ) cancer or any other cancer . CONCLUSIONS In this large study , individuals with diabetes who used metformin  had a similar risk of developing cancer compared with those who used sulfonylureas Summary Background Co-trimoxazole prophylaxis can reduce mortality from untreated HIV infection in Africa ; whether benefits occur alongside combination antiretroviral therapy ( ART ) is unclear . We estimated the effect of prophylaxis after ART initiation in adults . Methods Participants in our observational analysis were from the DART r and omised trial of management strategies in HIV-infected , symptomatic , previously untreated African adults starting triple-drug ART with CD4 counts lower than 200 cells per μL.  Co-trimoxazole prophylaxis was not routinely used or r and omly allocated , but was variably prescribed by clinicians . We estimated effects on clinical outcomes , CD4 cell count , and body-mass index ( BMI ) using marginal structural models to adjust for time-dependent confounding by indication . DART was registered , number IS RCT N13968779 . Findings 3179 participants contributed 14 214 years of follow-up ( 8128 [ 57 % ] person-years on co-trimoxazole ) . Time-dependent predictors of co-trimoxazole use were current CD4 cell count , haemog 
    Output:
    
The studies least likely to be affected by bias did not support a causal effect of metformin on cancer risk