Scoring the Value Assessment Framework for China: A Factorial Survey.

OBJECTIVES: This study aimed to develop the scoring functions for the recently developed value assessment framework (VAF) for China, which comprises 12 attributes. METHODS: We implemented a factorial survey among Chinese healthcare stakeholders from July to September 2022. A total of 240 hypothetical drug value profiles described by the VAF were grouped into 60 blocks and randomly assigned to respondents. Each respondent was assigned with 1 block, each presented in 3 disease scenarios of different levels of severity. For each profile, respondents were asked to assess the drug's value on a scale from 0 (lowest) to 10 (highest) and make 1 of the 3 insurance recommendations: cover, to be negotiated for coverage, or reject. Linear and logistic mixed-effects models were used to develop scoring functions for aggregating the value attributes. RESULTS: A total of 365 respondents participated in the survey. 3968 responses from 331 respondents were included in the analysis. Most of the included respondents were under 45 (n = 256, 77.3%), females (n = 208, 62.8%), living in urban areas (n = 296, 89.4%), and with a bachelor's degree or higher (n = 303, 91.5%). Health benefits and safety carried more weights than other attributes in the scoring functions across disease scenarios. The value and probability of entering negotiation or receiving insurance coverage for the attribute profiles for severe/critical disease were higher than for mild/moderate disease. CONCLUSIONS: The scoring functions of the VAF can be used to assess the value of a drug and its probability of entering negotiation or receiving insurance coverage in China.

In adults with acute HF, high-intensity care vs. usual care reduced a composite of death or HF readmission at 180 d.

SOURCE CITATION: Mebazaa A, Davison B, Chioncel O, et al. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022;400:1938-52. 36356631.

In acute HF in the ED, a risk-based management algorithm vs. usual care reduced a composite clinical outcome at 30 d.

SOURCE CITATION: Lee DS, Straus SE, Farkouh ME, et al. Trial of an intervention to improve acute heart failure outcomes. N Engl J Med. 2023;388:22-32. 36342109.

Baseline factors associated with self-reported disease flares following COVID-19 vaccination among adults with systemic rheumatic disease: results from the COVID-19 global rheumatology alliance vaccine survey.

OBJECTIVE: To examine the frequency of, and risk factors for, disease flare following COVID-19 vaccination in patients with systemic rheumatic disease (SRD). METHODS: An international study was conducted from 2 April to 16 August 2021, using an online survey of 5619 adults with SRD for adverse events following COVID-19 vaccination, including flares of disease requiring a change in treatment. We examined risk factors identified a priori based on published associations with SRD activity and SARS-CoV-2 severity, including demographics, SRD type, comorbidities, vaccine type, cessation of immunosuppressive medications around vaccination and history of reactions to non-COVID-19 vaccines, using multivariable logistic regression. RESULTS: Flares requiring a change in treatment following COVID-19 vaccination were reported by 4.9% of patients. Compared with rheumatoid arthritis, certain SRD, including systemic lupus erythematosus (OR 1.51, 95% CI 1.03, 2.20), psoriatic arthritis (OR 1.95, 95% CI 1.20, 3.18) and polymyalgia rheumatica (OR 1.94, 95% CI 1.08, 2.48) were associated with higher odds of flare, while idiopathic inflammatory myopathies were associated with lower odds for flare (OR 0.54, 95% CI 0.31-0.96). The Oxford-AstraZeneca vaccine was associated with higher odds of flare relative to the Pfizer-BioNTech vaccine (OR 1.44, 95% CI 1.07, 1.95), as were a prior reaction to a non-COVID-19 vaccine (OR 2.50, 95% CI 1.76, 3.54) and female sex (OR 2.71, 95% CI 1.55, 4.72). CONCLUSION: SRD flares requiring changes in treatment following COVID-19 vaccination were uncommon in this large international study. Several potential risk factors, as well as differences by disease type, warrant further examination in prospective cohorts.

What Is Value in Health and Healthcare? A Systematic Literature Review of Value Assessment Frameworks.

OBJECTIVES: This study aimed to investigate how value is defined and measured in existing value assessment frameworks (VAFs) in healthcare. METHODS: We searched PubMed, Embase, the Cochrane Library, and Centre for Reviews and Dissemination from 2008 to 2019. We also performed backward citation chaining of included studies and previously published systematic reviews. Studies reporting the development of a VAF in healthcare were included. For each included framework, we extracted and compared the context, target users, intended use, methods used to identify value attributes, description of the attributes, and attribute scoring approaches. RESULTS: Of the 8151 articles screened, 57 VAFs were included. The value attributes included in 55 VAFs were grouped into 9 categories: health benefits (n = 53, 96%), affordability (n = 45, 82%), societal impact (n = 42, 76%), burden of disease (n = 36, 65%), quality of evidence (n = 32, 58%), cost-effectiveness (n = 31, 56%), ethics and equity (n = 27, 49%), unmet needs (n = 21, 38%), and innovation (n = 15, 27%). The remaining 2 VAFs used broad attributes or user-defined attributes. Literature review was the main approach to identify value attributes in 36 VAFs. Patient or public was engaged through the development of only 11 VAFs. Weighting has been used to score 29 VAFs, of which 19 used the methods of multicriteria decision analysis. CONCLUSIONS: There are substantial variations in defining and measuring value. A noticeable weakness of existing VAFs is that patient or public engagement was generally very limited or missing in framework development process. Existing VAFs tend to aggregate multiple value attributes into a single index for decision making.

Understanding health professional role integration in complex adaptive systems: a multiple-case study of physician assistants in Ontario, Canada.

BACKGROUND: To meet the complex needs of healthcare delivery, the Ministry of Health and Long Term Care (MOHLTC) introduced Physician Assistants (PAs) into the Ontario health care system in 2006 with the goal of helping to increase access to care, decrease wait times, improve continuity of care and provide a flexible addition to the healthcare workforce. The characterization of healthcare organizations as complex adaptive systems (CAS) may offer insight into the relationships and interactions that optimize and restrict successful PA integration. The aim of this study is to explore the integration of PAs across multiple case settings and to understand the role of PAs within complex adaptive systems. METHODS: An exploratory, multiple-case study was used to examine PA role integration in four settings: family medicine, emergency medicine, general surgery, and inpatient medicine. Interviews were conducted with 46 healthcare providers and administrators across 13 hospitals and 6 family medicine clinics in Ontario, Canada. Analysis was conducted in three phases including an inductive thematic analysis within each of the four cases, a cross-case thematic analysis, and a broader, deductive exploration of cross-case patterns pertaining to specific complexity theory principles of interest. RESULTS: Forty-six health care providers were interviewed across 19 different healthcare sites. Support for PA contributions across various health care settings, the importance of role awareness, supervisory relationship attributes, and role vulnerability are interconnected and dynamic. Findings represent the experiences of PAs and other healthcare providers, and demonstrate how the PAs willingness to work and ability to build relationships allows for the establishment of interprofessional, collaborative, and person-centered care. As a self-organizing agent in complex adaptive systems (i.e., health organizations), PA role exploration revealed patterns of team behavior, non-linear interconnections, open relationships, dynamic systems, and the legacy of role implementation as defined by complexity theory. CONCLUSIONS: By exploring the role of PAs across multiple sites, the complexity theory lens concurrently fosters an awareness of emerging patterns, relationships and non-linear interactions within the defined context of the Ontario healthcare system. By establishing collaborative, interprofessional care models in hospital and community settings, PAs are making a significant contribution to Ontario healthcare settings.

Evaluation of online clinical pharmacology curriculum resources for medical students.

AIMS: To identify and evaluate clinical pharmacology (CP) online curricular (e-Learning) resources that are internationally available for medical students. METHODS: Literature searches of Medline, EMBASE and ERIC databases and an online survey of faculty members of international English language medical schools, were used to identify CP e-Learning resources. Resources that were accessible online in English and aimed to improve the quality of prescribing specific medications were then evaluated using a summary percentage score for comprehensiveness, usability and quality, and for content suitability. RESULTS: Our literature searches and survey of 252 faculty (40.7% response rate) in 219 medical schools identified 22 and 59 resources respectively. After screening and removing duplicates, 8 eligible resources remained for evaluation. Mean total score was 53% (standard deviation = 13). The Australian National Prescribing Curriculum, ranked highest with a score of 77%, based primarily on very good ratings for usability, quality and suitable content. CONCLUSION: Using a novel method and evaluation metric to identify, classify, and rate English language CP e-Learning resources, the National Prescribing Curriculum was the highest ranked open access resource. Future work is required to implement and evaluate its effectiveness on prescribing competence.

Direct comparative effectiveness and safety between non-vitamin K antagonist oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation: a systematic review and meta-analysis of observational studies.

The non-vitamin K antagonist oral anticoagulants (NOACs) have been increasingly prescribed in clinical practice for stroke prevention in patients with nonvalvular atrial fibrillation (AF). Direct comparisons between NOACs in trials are lacking, leaving an important clinical decision-making gap. We aimed to perform a systematic review and meta-analysis to summarize the evidence of observational studies for direct comparative effectiveness and safety amongst NOACs in patients with AF. Conference proceedings and electronic databases including MEDLINE, CINAHL, EMBASE and PUBMED were systematically searched. We included observational studies directly comparing individual NOACs in patients with nonvalvular AF who were aged ≥ 18 years for stroke prevention. Primary outcome included effectiveness outcome (stroke or systemic embolism) and safety outcome (major bleeding). Data were extracted in duplicated by two reviewers independently. A random-effects meta-analysis was conducted to synthesize the data from included observational studies. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to rate the overall quality of evidence for each outcome. Fifteen studies were included for qualitative synthesis, twelve studies for meta-analyses. It was found that rivaroxaban and dabigatran were similar with regard to risk of stroke or systemic embolism (Hazard ratio [HR] = 1.00, 95% CI 0.91-1.10; evidence quality: low), but rivaroxaban was associated with higher risk of major bleeding (HR = 1.39, 95% CI 1.28-1.50; evidence quality: moderate). Compared with apixaban, a significantly higher risk of major bleeding was observed with rivaroxaban (HR = 1.71, 95% CI 1.51-1.94; evidence quality: low). Apixaban was associated with lower risk of major bleeding, in comparison with dabigatran (HR = 0.80, 95% CI 0.68-0.95; evidence quality: low). No differences in risk of stroke or systemic embolism was observed between rivaroxaban versus apixaban, and apixaban versus dabigatran. In this study, apixaban was found to have the most favorable safety profile amongst the three NOACs. No significant difference was observed in risk of stroke or systemic embolism between the NOACs. Such findings may provide some decision-making support for physicians regarding their choices amongst NOACs in patients with AF.Registration PROSPERO (identifier: CRD42016052908).

Safety and efficacy of active and passive immunotherapy in mild-to-moderate Alzheimer's disease: A systematic review and network meta-analysis.

OBJECTIVE: The objective of this study was to systematically review and conduct a direct and network meta-analysis of randomized controlled trials that have examined the clinical safety and efficacy of using passive and active immunotherapies in Alzheimer's disease (AD). RESEARCH QUESTIONS: (1) Is amyloid-based immunotherapy in patients with mild-to-moderate AD associated with more efficacy benefits compared to placebo? (2) Which immunotherapy agent is associated with more comparative benefit? (3) Is passive or active immunotherapy associated with more benefits? DATA SOURCES: A systematic review of published randomized controlled trials was performed in MEDLINE, EMBASE, PubMed and Cochrane library. Review methods and meta-analysis: Two reviewers independently selected the studies, extracted the data and assessed risk of bias. Important AD cognitive scales as clinical efficacy outcomes were ADAS-cog, CDR and MMSE whereas edema, neoplasms and mortality were included as safety outcomes. A direct comparison meta-analysis using a random effect model and a network (direct and indirect) comparison was conducted to calculate mean differences in treatment effects, SUCRA and ranking probabilities for each medicine per safety and efficacy outcome. Quality of network results were assessed using GRADE methodology. PRINCIPLE FINDINGS: Thirteen RCT-assessed patients with mild-to-moderate AD were included in the final analysis. The results showed that immunotherapies compared with placebo produced a statistically, but not clinically significant, improvement in ADAS-cog (MD=-0.39; 95% CI -0.42, -0.35, P=0.00) and MMSE. In terms of safety, the rate of ARIA-E was significantly higher with monoclonal antibodies. Solanezumab and AN1792 (vaccine) were the drugs of choice both from efficacy and safety perspectives. CONCLUSION: In terms of efficacy, the review showed a statistically, but not clinically significant, improvement in favor of immunotherapy versus placebo. Further clinical trials are required to demonstrate any cognitive benefits of immunotherapies in mild-to-moderate AD.

Obstructive sleep apnea and orthodontics: An American Association of Orthodontists White Paper.

The Board of Trustees of the American Association of Orthodontists asked a panel of medical and dental experts in sleep medicine and dental sleep medicine to create a document designed to offer guidance to practicing orthodontists on the suggested role of the specialty of orthodontics in the management of obstructive sleep apnea. This White Paper presents a summary of the Task Force's findings and recommendations.

Minimally important difference and predictors of change in quality of life in type 2 diabetes: A community-based survey in China.

BACKGROUND: To identify the minimally important difference (MID) of the EQ-5D-3L and determinants of change in quality of life (QoL) as measured by the EQ-5D-3L over 1 year for Chinese type 2 diabetic patients (T2DPs). METHODS: Clinically diagnosed T2DPs were recruited from 66 community health centres in five Chinese cities using a multistage quota sampling method between December 2010 and October 2011. Demographics, diabetes-related information, and health-related behaviours were collected at baseline. The EQ-5D-3L was administered at baseline and at 12 months. Anchor-based and distribution-based approaches were employed to estimate MIDs. Using the MIDs as cut-points, we identified the change in EQ-5D-3L-measured QoL into "worsening," "no change," and "bettering." Logistic and ordered logistic regressions were conducted for those who reported best possible EQ-5D health state ("best possible HS") and impaired EQ-5D health states ("impaired HS") at baseline, respectively. Explanatory variables included demographics, diabetes-related information, and health-related behaviours. RESULTS: A total of 1958 patients (54.9% female, mean age 61.2 years, mean diabetes duration 7.9 years) were included in our analysis. MIDs of the EQ-5D-3L for deterioration and improvement were estimated as -0.066 to -0.003, and 0.049 to 0.077, respectively. For the impaired HS group, older age, lower education, and less exercise were significant predictors for worsening in QoL; whereas, those predictors were older age, female gender, and lower income for the best possible HS group. CONCLUSIONS: Minimally important differences for deterioration and improvement were estimated for the EQ-5D-3L. Age, gender, education, income, and exercise were significant determinants of QoL change for Chinese T2DPs.

A systematic review of comparisons between protocols or registrations and full reports in primary biomedical research.

BACKGROUND: Prospective study protocols and registrations can play a significant role in reducing incomplete or selective reporting of primary biomedical research, because they are pre-specified blueprints which are available for the evaluation of, and comparison with, full reports. However, inconsistencies between protocols or registrations and full reports have been frequently documented. In this systematic review, which forms part of our series on the state of reporting of primary biomedical, we aimed to survey the existing evidence of inconsistencies between protocols or registrations (i.e., what was planned to be done and/or what was actually done) and full reports (i.e., what was reported in the literature); this was based on findings from systematic reviews and surveys in the literature. METHODS: Electronic databases, including CINAHL, MEDLINE, Web of Science, and EMBASE, were searched to identify eligible surveys and systematic reviews. Our primary outcome was the level of inconsistency (expressed as a percentage, with higher percentages indicating greater inconsistency) between protocols or registration and full reports. We summarized the findings from the included systematic reviews and surveys qualitatively. RESULTS: There were 37 studies (33 surveys and 4 systematic reviews) included in our analyses. Most studies (n = 36) compared protocols or registrations with full reports in clinical trials, while a single survey focused on primary studies of clinical trials and observational research. High inconsistency levels were found in outcome reporting (ranging from 14% to 100%), subgroup reporting (from 12% to 100%), statistical analyses (from 9% to 47%), and other measure comparisons. Some factors, such as outcomes with significant results, sponsorship, type of outcome and disease speciality were reported to be significantly related to inconsistent reporting. CONCLUSIONS: We found that inconsistent reporting between protocols or registrations and full reports of primary biomedical research is frequent, prevalent and suboptimal. We also identified methodological issues such as the need for consensus on measuring inconsistency across sources for trial reports, and more studies evaluating transparency and reproducibility in reporting all aspects of study design and analysis. A joint effort involving authors, journals, sponsors, regulators and research ethics committees is required to solve this problem.

Item reduction and validation of the Chinese version of diabetes quality-of-life measure (DQOL).

BACKGROUND: The Diabetes Quality-of-Life (DQOL) Measure is a 46-item diabetes-specific quality of life instrument. The original English version of the DQOL has been translated into Chinese after cultural adaption, and the Chinese DQOL has been validated in the Chinese diabetic patient population and used in diabetes-related studies. There are two recognized problems with the Chinese DQOL: 1) the instrument is too long, and 2) the non-response rate of certain items is relatively high. This study aimed to develop and validate a short version for the Chinese DQOL. METHODS: Item reduction was conducted based on the classical test theory (CTT) and item response theory (IRT), each combined with exploratory factor analysis (EFA). The confirmatory factor analysis (CFA) and Spearman correlation coefficient were employed in validating the short versions. RESULTS: Both the study sample (n = 2,886) and the validation sample (n = 2,286) were from a longitudinal observation study of Chinese type 2 diabetic patients. The CTT kept 32 items, and the IRT kept 24 items from the original 46-item version. The two short versions were comparable in psychometric properties. CONCLUSION: The 24-item IRT-based short version of the Chinese DQOL was selected as the preferred short version because it imposes a lower burden on patients without compromising the psychometric properties of the instrument.

Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: Evidence on the long-term clinical benefits of individual members of angiotensin II receptor blockers is limited given the lack of head-to-head studies. We conducted a network meta-analysis to determine the comparative efficacy of different members within this drug class with respect to outcomes of (i) blood pressure reduction (at 24 and 52 weeks) and (ii) prevention of cardiovascular disease (>104 weeks). METHODS: A systematic literature review was conducted - Protocol registration: (PROSPERO - CRD42014007067) - to identify relevant literature from the following databases: Cochrane Library, PubMed, Medline and EMBASE; searched from inception to July 2016. Randomised controlled trials (RCTs) were included if they reported long-term effectiveness relating to blood pressure, mortality, myocardial infarction or stroke. Eligible studies included those with placebo or specific active-treatment comparators (either another angiotensin II receptor blockers or hydrochlorothiazide). A Bayesian random-effects network model was used to combine direct within-trial comparisons between treatment groups with indirect evidence from other trials. RESULTS: Thirty-six studies were identified, representing 28 unique trials. Blood pressure reduction, based on 12 studies (n=807) with fixed dosing regimen, was found to be similar amongst members of the angiotensin receptor blocker drug class at both 24 and 52 weeks. A network meta-analysis of five studies (n=16,716) with a treat-to-target approach found that prevention of all-cause mortality, stroke and myocardial infarction was similar across the angiotensin-receptor blockers therapies initiated. CONCLUSIONS: Current evidence is insufficient to show differences in any members within the angiotensin II receptor blocker drug class with respect to blood pressuring lowering effects or a reduction in cardiovascular diseases.

A scoping review of comparisons between abstracts and full reports in primary biomedical research.

BACKGROUND: Evidence shows that research abstracts are commonly inconsistent with their corresponding full reports, and may mislead readers. In this scoping review, which is part of our series on the state of reporting of primary biomedical research, we summarized the evidence from systematic reviews and surveys, to investigate the current state of inconsistent abstract reporting, and to evaluate factors associated with improved reporting by comparing abstracts and their full reports. METHODS: We searched EMBASE, Web of Science, MEDLINE, and CINAHL from January 1st 1996 to September 30th 2016 to retrieve eligible systematic reviews and surveys. Our primary outcome was the level of inconsistency between abstracts and corresponding full reports, which was expressed as a percentage (with a lower percentage indicating better reporting) or categorized rating (such as major/minor difference, high/medium/low inconsistency), as reported by the authors. We used medians and interquartile ranges to describe the level of inconsistency across studies. No quantitative syntheses were conducted. Data from the included systematic reviews or surveys was summarized qualitatively. RESULTS: Seventeen studies that addressed this topic were included. The level of inconsistency was reported to have a median of 39% (interquartile range: 14% - 54%), and to range from 4% to 78%. In some studies that separated major from minor inconsistency, the level of major inconsistency ranged from 5% to 45% (median: 19%, interquartile range: 7% - 31%), which included discrepancies in specifying the study design or sample size, designating a primary outcome measure, presenting main results, and drawing a conclusion. A longer time interval between conference abstracts and the publication of full reports was found to be the only factor which was marginally or significantly associated with increased likelihood of reporting inconsistencies. CONCLUSIONS: This scoping review revealed that abstracts are frequently inconsistent with full reports, and efforts are needed to improve the consistency of abstract reporting in the primary biomedical community.

Reduction in targeted potentially inappropriate medication use in elderly inpatients: a pragmatic randomized controlled trial.

PURPOSE: The use of potentially inappropriate medications (PIMs) in hospitalized older adults is a complex problem, but the use of computerized alert systems (CAS) has shown some potential. The study's objective is to assess the change in PIM use with a CAS-based pharmacist-physician intervention model compared to usual clinical care. METHODS: Pragmatic single-site randomized controlled trial was conducted at a university teaching hospital. Hospitalizations identified with selected Beers or STOPP criteria were randomized to usual clinical care or to the CAS-based pharmacist-physician intervention. The primary outcome was PIM drug cessation or dosage decrease. Clinical relevance of the CAS alerts was assessed. RESULTS: Analyses included 231 patients who had 128 and 126 hospitalizations in the control and intervention groups, respectively. Patients had a mean age of 81, and 60% were female. In the intervention compared to the control group, drug cessation or dosage decrease were more frequent at 48 h post-alert (45.8 vs 15.9%; absolute difference 30.0%; 95%CI 13.8 to 46.1%) and at discharge from the hospital (48.1 vs 27.3%; absolute difference 20.8%; 95%CI 4.6 to 37.0%). In a post hoc analysis of all alerts, regardless of their clinical relevance, the absolute difference in drug cessation or dosage decrease between the intervention and control groups was 16.2% (95%CI 2.9 to 29.6%) at 48 h and 8.0% (95%CI -4.0 to 20.0%) at discharge from the hospital. CONCLUSIONS: In hospitalized older adults, a CAS-based pharmacist-physician intervention, compared to usual clinical care, resulted in significant higher number of drug cessation and dosage reductions for targeted PIMs.

Systematic Review of Clinical Practice Guidelines for Failed Antidepressant Treatment Response in Major Depressive Disorder, Dysthymia, and Subthreshold Depression in Adults.

OBJECTIVE: This systematic review critically evaluated clinical practice guidelines (CPGs) for treating adults with major depressive disorder, dysthymia, or subthreshold or minor depression for recommendations following inadequate response to first-line treatment with selective serotonin reuptake inhibitors (SSRIs). METHOD: Searches for CPGs (January 2004 to November 2014) in English included 7 bibliographic databases and grey literature sources using CPG and depression as the keywords. Two raters selected CPGs on depression with a national scope. Data extraction included definitions of adequate response and recommended treatment options. Two raters assessed quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument. RESULTS: From 46,908 citations, 3167 were screened at full text. From these 21 CPG were applicable to adults in primary care and outpatient settings. Five CPGs consider patients with dysthymia or subthreshold or minor depression. None provides recommendations for those who do not respond to first-line SSRI treatment. For adults with MDD, most CPGs do not define an "inadequate response" or provide specific suggestions regarding how to choose alternative medications when switching to an alternative antidepressant. There is variability between CPGs in recommending combination strategies. AGREE II ratings for stakeholder involvement in CPG development, editorial independence, and rigor of development are domains in which depression guidelines are often less robust. CONCLUSIONS: About half of patients with depression require second-line treatment to achieve remission. Consistency and clarity in guidelines for second-line treatment of depression are therefore important for clinicians but lacking in most current guidelines. This may reflect a paucity of primary studies upon which to base conclusions.

An overview of osteoporosis and frailty in the elderly.

Osteoporosis and osteoporotic fractures remain significant public health challenges worldwide. Recently the concept of frailty in relation to osteoporosis in the elderly has been increasingly accepted, with emerging studies measuring frailty as a predictor of osteoporotic fractures. In this overview, we reviewed the relationship between frailty and osteoporosis, described the approaches to measuring the grades of frailty, and presented current studies and future research directions investigating osteoporosis and frailty in the elderly. It is concluded that measuring the grades of frailty in the elderly could assist in the assessment, management and decision-making for osteoporosis and osteoporotic fractures at a clinical research level and at a health care policy level.

Risk factors for mortality in patients admitted to intensive care units with pneumonia.

BACKGROUND: Despite the high mortality in patients with pneumonia admitted to an ICU, data on risk factors for death remain limited. METHODS: In this secondary analysis of PROTECT (Prophylaxis for Thromboembolism in Critical Care Trial), we focused on the patients admitted to ICU with a primary diagnosis of pneumonia. The primary outcome for this study was 90-day hospital mortality and the secondary outcome was 90-day ICU mortality. Cox regression model was conducted to examine the relationship between baseline and time-dependent variables and hospital and ICU mortality. RESULTS: Six hundred sixty seven patients admitted with pneumonia (43.8 % females) were included in our analysis, with a mean age of 60.7 years and mean APACHE II score of 21.3. During follow-up, 111 patients (16.6 %) died in ICU and in total, 149 (22.3 %) died in hospital. Multivariable analysis demonstrated significant independent risk factors for hospital mortality including male sex (hazard ratio (HR) = 1.5, 95 % confidence interval (CI): 1.1 - 2.2, p-value = 0.021), higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value < 0.001 for per-5 point increase), chronic heart failure (HR = 2.9, 95 % CI: 1.6 - 5.4, p-value = 0.001), and dialysis (time-dependent effect: HR = 2.7, 95 % CI: 1.3 - 5.7, p-value = 0.008). Higher APACHE II score (HR = 1.2, 95 % CI: 1.1 - 1.4, p-value = 0.002 for per-5 point increase) and chronic heart failure (HR = 2.6, 95 % CI: 1.3 - 5.0, p-value = 0.004) were significantly related to risk of death in the ICU. CONCLUSION: In this study using data from a multicenter thromboprophylaxis trial, we found that male sex, higher APACHE II score on admission, chronic heart failure, and dialysis were independently associated with risk of hospital mortality in patients admitted to ICU with pneumonia. While high illness severity score, presence of a serious comorbidity (heart failure) and need for an advanced life support (dialysis) are not unexpected risk factors of mortality, male sex might necessitate further exploration. More studies are warranted to clarify the effect of these risk factors on survival in critically ill patients admitted to ICU with pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182143 .

Comparison of treatment effect estimates of non-vitamin K antagonist oral anticoagulants versus warfarin between observational studies using propensity score methods and randomized controlled trials.

Emerging observational studies using propensity score (PS) methods assessed real-world comparative effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin in patients with non-valvular atrial fibrillation (AF). We aimed to compare treatment effect estimates of NOACs between PS studies and randomized controlled trials (RCTs). Electronic databases and conference proceedings were searched systematically. Primary outcomes included stroke or systemic embolism (SE) and major bleeding. A random-effects meta-analysis was performed to synthesize the data by pooling the PS- and RCT-derived hazard ratios (HRs) separately. The ratio of HRs (RHR) from the ratio of PS-derived HRs relative to RCT-derived HRs was used to determine whether there was a difference between estimates from PS studies and RCTs. There were 10 PS studies and 5 RCTs included for analysis. No significant difference of treatment effect estimates between the PS studies and RCTs was observed: RHR 1.11, 95 % CI 0.98-1.23 for stroke or SE; RHR 1.07, 95 % CI 0.87-1.34 for major bleeding. A significant association between NOACs and risk of stroke or SE was observed: HR 0.88, 95 % CI 0.83-0.94 for the PS studies; HR 0.79, 95 % CI 0.72-0.87 for the RCTs. However, no relationship between NOACs and risk of major bleeding was found: HR 0.91, 95 % CI 0.79-1.05 for the PS studies; HR 0.85, 95 % CI 0.73-1.00 for the RCTs. In this study, treatment effect estimates of NOACs versus warfarin in patients with non-valvular AF from PS studies are found to be in agreement with those from RCTs.