***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: OBJECTIVE To assess the subjective health status , quality of life , and functional ability of patients whose intensive care stay was prolonged and to compare their quality of life with that of the general population . DESIGN Inception cohort study . SETTING Twenty-three-bed multidisciplinary intensive care unit ( ICU ) in a tertiary care center . PATIENTS A consecutive sample of 718 patients aged > or = 18 yrs who required intensive care > or = 4 days . INTERVENTIONS None . MEASUREMENTS AND MAIN RESULTS The Nottingham Health Profile was used to compare the ICU patients with a r and om sample ( n = 2,595 ) of the general population . The quality of life and functional ability of 368 respondents ( 78.3 % of 470 survivors ) were assessed at 6 months after ICU admission . The length of the ICU stay was 13.6+/-11.8 ( median , 9 ; maximum , 81 ) days . The quality of life and its various dimensions were influenced by the diagnosis for ICU admission and age . Although problems in physical mobility and energy were prevalent among all patient groups , only a small proportion was dependent on others for the management of daily activities . Patients with trauma or respiratory failure experienced the most limitations . The quality of life of elderly patients and patients who had undergone cardiac surgery was comparable with the general population regarding emotional reactions , social isolation , and pain . CONCLUSIONS The quality of life of survivors after a prolonged intensive care stay is fairly good , although not comparable with that of the general population . The psychosocial aspects of the quality of life are restored more rapidly than physical performance A system has been constructed to evaluate the design , implementation , and analysis of  r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials OBJECTIVES Few studies have examined the effects of caregiving on the caregivers of chronically critically ill ( CCI ) patients , and no one has examined the impact of a disease management program ( DMP ) on physical and psychological outcomes for the caregivers of CCI patients . The purpose s of this study of caregivers of CCI patients were as follows : ( 1 ) to describe the characteristics of CCI patients and caregivers and to examine the frequency of depression , subjective burden , and physical health ; ( 2 ) to examine factors related to depression after hospital discharge ; and ( 3 ) to examine the effects of a DMP on the physical health , depression , and burden of caregivers 2 months post-hospital discharge . DESIGN Prospect i ve experimental design . SETTING AND PARTICIPANTS Caregivers of 290 patients who had received > 3 days of mechanical ventilation while in the ICU of a university medical center . MEASUREMENTS Sociodemographics , caregiver burden , physical health status , and depression were measured using established tools . RESULTS Interviews of caregivers were conducted at hospital discharge and 2 months later . Seventy-three percent of patients survived , completed the study period , and required caregiving 2 months later . Caregivers of patients residing in an institution reported higher depression ( p = 0.0001 ) , higher burden ( ie , disrupted schedule , p = 0.0001 ; lack of family support , p = 0.036 ) , and greater health problem scores ( p = 0.0001 ) than did caregivers of patients residing at home . The DMP did not have a statistically significant impact on any of the outcome variables . However , by 2 months , 54 % of caregivers in the experimental group had no depression or mild depression compared with 34.5 % of the control group . CONCLUSION Two months after hospital discharge , approximately 25 % of caregivers were classified as depressed with 16.7 % of the depressed group classified as moderately or severely depressed . The caregivers of CCI patients are at risk for post-hospital discharge depression , and the caregivers of institutionalized CCI patients are at highest risk of long-term negative effects from caregiving OBJECTIVE Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis , oral dosing may be unsuitable for some patients . An efficacious intravenously administered bisphosphonate could be beneficial for such patients . Ib and ronate , a potent nitrogen-containing bisphosphonate , can be administered using extended dosing intervals , either orally or by rapid intravenous injection . The aim of this study was to identify the optimal intravenous dosing regimen for ib and ronate in postmenopausal women with osteoporosis . METHODS In a r and omized , double-blind , double-dummy , phase III , noninferiority study , we compared 2 regimens of intermittent intravenous injections of ib and ronate ( 2 mg every 2 months and 3 mg every 3 months ) with a regimen of 2.5 mg of oral ib and ronate daily , the latter of which has proven antifracture efficacy . The study group comprised 1,395 women ( ages 55 - 80 years ) who were at least 5 years postmenopausal . All patients had osteoporosis ( lumbar spine [ L2-L4 ] bone mineral density [ BMD ] T score less than -2.5 ) . Participants also received daily calcium ( 500 mg ) and vitamin D ( 400 IU ) . The primary end point was change from baseline in lumbar spine BMD at 1 year . Changes in hip BMD and in the level of serum C-telopeptide of type I collagen ( CTX ) were also measured , as were safety and tolerability . RESULTS At 1 year , mean lumbar spine BMD increases were as follows : 5.1 % among 353 patients receiving 2 mg of ib and ronate every 2 months , 4.8 % among 365 patients receiving 3 mg of ib and ronate every 3 months , and 3.8 % among 377 patients receiving 2.5 mg of oral ib and ronate daily . Both of the intravenous regimens not only were noninferior , but also were superior ( P < 0.001 ) to the oral regimen . Hip BMD increases ( at all sites ) were also greater in the groups receiving medication intravenously than in the group receiving ib and ronate orally . Robust decreases in the serum CTX level were observed in all arms of the study . Both of the intravenous regimens were well tolerated and did not compromise renal function . CONCLUSION As assessed by BMD , intravenous injections of ib and ronate ( 2 mg every 2 months or 3 mg every 3 months ) are at least as effective as the regimen of 2.5 mg orally daily , which has proven antifracture efficacy , and are well tolerated Quality of life is often thought to be poor before and after intensive care unit admission . The aim of this study was to investigate changes in quality of life before and after intensive care . A prospect i ve cohort study of 300 consecutive patients admitted to intensive care was performed in a Scottish Teaching Hospital .  Quality of life was assessed premorbidly and 3 , 6 and 12 months after intensive care admission for surviving patients using SF‐36 as well as EQ‐5D scores at 12 months . The median value for age was 60.5 years and for APACHE II score , 18 . The mean length of stay was 6.7 days . SF‐36 physical component scores decreased from premorbid values at 3 months ( p = 0.05 ) and then returned to premorbid values at 12 months ( p < 0.001 ) . The mean physical scores were below the population norm at all time points but the mean mental scores were similar or higher than these population norms . Patients who died after intensive care discharge had lower quality of life scores than did survivors ( all p < 0.01 ) . Poor premorbid quality of life was demonstrated and appears to reduce after ICU discharge . For survivors there was a slow increase in physical quality of life to premorbid levels by the end of the first year but these remained lower than in the general population . ICU patients experience a considerable longer‐term burden of ill health OBJECTIVE To evaluate the long-term mortality and morbidity of critically ill elderly patients requiring intensive care .  DESIGN Prospect i ve comparison of outcome of critically ill patients aged 75 years and older with patients aged 65 to 74 years . PATIENTS Critically ill patients aged 65 years and older who required intensive care and who were recruited during a 3-month period . MAIN OUTCOME MEASURES Duration of hospitalization , hospital charges , procedures used in the intensive care unit , mortality in the hospital and during the follow-up period , and quality of life of survivors during the follow-up period . RESULTS Ninety-seven patients were included in the study ; 54 were 75 years or older and 43 were aged 65 to 74 years . No significant difference was noted between the two groups for length of stay in the hospital , hospital charges , or mortality at 1 year . Severity of illness , as assessed by Acute Physiology and Chronic Health Evaluation score at the time of intensive care unit admission , was a better predictor of survival than age . Quality of life , as assessed by activities of daily living , perceived quality of life , and Center for Epidemiologic Studies -Depression score , were not significantly different in either group at 1 , 6 , and 12 months after discharge from the hospital . Most patients in both groups described their quality of life as adequate and were willing to receive intensive care again , if necessary . CONCLUSION Age alone is not an adequate predictor of long-term survival and quality of life in critically ill elderly patients Objective : Patients who remain critically ill for prolonged periods and require tracheotomy , defined as chronic critical illness ( CCI ) , display elevated levels of bone resorption . The measurement of bone turnover markers reveals that osteoclastic bone resorption is not only enhanced but also uncoupled from osteoblastic bone formation . We examine the effect of ib and ronate on bone turnover in patients with CCI . Methods : This study is a prospect i ve , double-blind , placebo-controlled trial , in which 20 postmenopausal female participants with CCI were followed for an 11-day period after the administration of a single intravenous dose of ib and ronate ( 3 mg ) . All participants were treated with ergocalciferol ( 2000 IU daily ) , calcium carbonate ( 1250 mg daily ) , and calcitriol ( 0.25 μg daily ) . Results : The ib and ronate group showed a 34 % decrease in serum C-telopeptide ( CTX ) levels ( a marker of osteoclastic activity ) on day 6 , while the placebo group showed a 13 % increase ( P = .01 ) . By day 11 , CTX levels  in ib and ronate group were not significantly different than baseline or from the placebo group . Osteocalcin ( OCN ) levels ( a marker of osteoblast activity ) increased by 78 % compared to baseline in the ib and ronate group ( P = .01 ) and by 42 % in the placebo group ( P = .05 ) . There were no significant differences in OCN between the 2 groups throughout the study . Parathyroid hormone levels remained constant throughout the study . No adverse events were observed . Conclusion : A single dose of intravenous ib and ronate causes a significant but transient reduction in osteoclast activity in patients with CCI , which persists over a 6-day period UNLABELLED Osteoporotic fractures are associated with accelerated bone turnover and excess mortality . In a prospect i ve study of 1112 frail subjects ( 79 % female ; mean age , 86 years ) , high bone turnover was an independent predictor of  all-cause mortality . This association seemed to be mainly manifested in deaths from cardiovascular causes . INTRODUCTION Osteoporotic fractures are associated with accelerated bone turnover and excess mortality . In a prospect i ve cohort study of elderly men and women , we assessed whether the rate of bone turnover measured by markers of bone remodeling is a direct predictor of mortality . MATERIAL S AND METHODS We measured serum concentrations of the aminoterminal propeptide of type I collagen ( PINP ) , a marker of bone formation , and of the carboxyterminal telopeptide of type I collagen ( CTX-I ) , a marker of bone resorption , along with serum PTH and 25-hydroxyvitamin D [ 25(OH)D ] levels in 1112 subjects ( 79 % female ; mean age , 86 years ) living in residential care .  Co-morbidity was measured using the Implicit  Illness Severity Scale . Fracture data were vali date d by a radiology report . Mortality and causes of death were ascertained from death certificates . RESULTS Over a median follow-up of 817 days , 559 ( 50.3 % ) subjects died . In univariate analyses , time to death from all causes was significantly ( p < 0.01 ) associated with age ( HR 
    Output:
    
This systematic review found moderate evidence for a positive association between critical illness and increased bone turnover .
Findings were consistent across studies , and best- evidence analysis result ed in a conclusion that moderate evidence exists for an association between critical illness requiring admission to intensive care  and altered bone turnover .