Small Reduction In Risk Research Articles

Screening for Osteoporosis to Prevent Fractures: A Systematic Evidence Review for the US Preventive Services Task Force.

Fragility fractures result in significant morbidity. To review evidence on osteoporosis screening to inform the US Preventive Services Task Force. PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024. Randomized clinical trials (RCTs) and systematic reviews of screening; pharmacotherapy studies for primary osteoporosis; predictive and diagnostic accuracy studies. Two reviewers assessed titles/abstracts, full-text articles, study quality, and extracted data; when at least 2 similar studies were available, meta-analyses were conducted. Hip, clinical vertebral, major osteoporotic, and total fractures; mortality; harms; accuracy. Three RCTs and 3 systematic reviews reported benefits of screening in older, higher-risk women. Two RCTs used 2-stage screening: Fracture Risk Assessment Tool estimate with bone mineral density (BMD) testing if risk threshold exceeded. One RCT used BMD plus additional tests. Screening was associated with reduced hip (pooled relative risk [RR], 0.83 [95% CI, 0.73-0.93]; 3 RCTs; 42 009 participants) and major osteoporotic fracture (pooled RR, 0.94 [95% CI, 0.88-0.99]; 3 RCTs; 42 009 participants) compared with usual care. Corresponding absolute risk differences were 5 to 6 fewer fractures per 1000 participants screened. The discriminative accuracy of risk assessment instruments to predict fracture or identify osteoporosis varied by instrument and fracture type; most had an area under the curve between 0.60 and 0.80 to predict major osteoporotic fracture, hip fracture, or both. Calibration outcomes were limited. Compared with placebo, bisphosphonates (pooled RR, 0.67 [95% CI, 0.45-1.00]; 6 RCTs; 12 055 participants) and denosumab (RR, 0.60 [95% CI, 0.37-0.97] from the largest RCT [7808 participants]) were associated with reduced hip fractures. Compared with placebo, no statistically significant associations were observed for adverse events. Screening in higher-risk women 65 years or older was associated with a small absolute risk reduction in hip and major fractures compared with usual care. No evidence evaluated screening with BMD alone or screening in men or younger women. Risk assessment instruments, BMD alone, or both have poor to modest discrimination for predicting fracture. Osteoporosis treatment with bisphosphonates or denosumab over several years was associated with fracture reductions and no meaningful increase in adverse events.

GLP1R Gene Expression and Kidney Disease Progression

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control. To investigate the association of genetically proxied GLP-1RAs with kidney disease progression. This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024. Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project. The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression. Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status. In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.

Early Seizure Prophylaxis in Mild and Moderate Traumatic Brain Injury

Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial. To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI. PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched. Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction. The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI. A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients. Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.

Assessment of suicidality in trials of psychological interventions for depression: a meta-analysis

Psychological interventions that are efficacious as treatments for depression could indirectly affect suicide-related outcomes. We examined suicidal thoughts and behaviours as eligibility criteria, outcomes, and adverse events across trials of psychotherapy for depression. We used a publicly available meta-analytic database developed through systematic searches (updated as of May 1, 2023) to identify randomised controlled trials in which a psychological intervention for depression was compared with an inactive or non-specific control condition in adults with depression and in which any suicide-related outcomes were reported. We also identified studies in which suicide risk was an exclusion criterion. We excluded inpatient studies and trials of unguided digital interventions or collaborative care that included a psychological component. Pairs of reviewers worked independently to select studies and extract data. In a random-effects meta-analysis with robust variance estimation, we assessed the effect of the psychological intervention on suicide outcomes in trials in which suicide was explicitly assessed as an outcome with clinical scales with established psychometric properties. Risk of bias was assessed with the Cochrane risk-of-bias tool (version 2). Of the 469 randomised trials we identified in which a psychological intervention was compared with an inactive control in people with depression, 251 excluded people judged at risk of suicide. Any assessment of suicide was included in only 45 trials, 12 of which assessed suicidal ideation or risk as an outcome. These 12 trials included 3930 participants, 2795 (71%) of whom were female and 1135 (29%) of whom were male; data for age and ethnicity were not consistently reported. Psychological interventions for depression were associated with a small reduction in suicidal ideation and risk in 11 trials (one trial reported only follow-up data) after the intervention (standardised mean difference -0·31 [95% CI -0·60 to -0·03]) but not at follow-up (-0·49 [-1·31 to 0·32]). Suicide-related adverse events were reported in 25 trials, and suicide-related serious adverse events (eg, suicide attempts, deaths by suicide) were reported in 13 trials. Heterogeneity was substantial across all analyses, and prediction intervals crossed zero. Trials of psychological interventions for depression rarely report assessments of suicide. Psychological interventions might reduce suicidal ideation in patients with depression, but more randomised controlled trials are required to clarify this effect. Monitoring and reporting of suicide-related adverse events should be improved in trials of psychological interventions for depression, and future trials should incorporate outcomes related to suicidal thoughts or behaviours. None. For the Spanish translation of the abstract see Supplementary Materials section.

Partial substitution of red meat or processed meat with plant-based foods and the risk of colorectal cancer

ObjectivesShifting from animal-based to plant-based diets could reduce colorectal cancer (CRC) incidence. Currently, the impacts of these dietary shifts on CRC risk are ill-defined. Therefore, we examined partial substitutions of red or processed meat with whole grains, vegetables, fruits or a combination of these in relation to CRC risk in Finnish adults.MethodsWe pooled five Finnish cohorts, resulting in 43 788 participants aged ≥ 25 years (79% men). Diet was assessed by validated food frequency questionnaires at study enrolment. We modelled partial substitutions of red (100 g/week) or processed meat (50 g/week) with corresponding amounts of plant-based foods. Cohort-specific hazard ratios (HR) for CRC were calculated using Cox proportional hazards models and pooled together using random-effects models. Adjustments included age, sex, energy intake and other relevant confounders.ResultsDuring the median follow-up of 28.8 years, 1124 CRCs were diagnosed. We observed small risk reductions when red meat was substituted with vegetables (HR 0.97, 95% CI 0.95 − 0.99), fruits (0.97, 0.94 − 0.99), or whole grains, vegetables and fruits combined (0.97, 0.95 − 0.99). For processed meat, these substitutions yielded 1% risk reductions. Substituting red or processed meat with whole grains was associated with a decreased CRC risk only in participants with < median whole grain intake (0.92, 0.86 − 0.98; 0.96, 0.93 − 0.99, respectively; pinteraction=0.001).ConclusionsEven small, easily implemented substitutions of red or processed meat with whole grains, vegetables or fruits could lower CRC risk in a population with high meat consumption. These findings broaden our insight into dietary modifications that could foster CRC primary prevention.

Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions.

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

Saturated fat, the estimated absolute risk and certainty of risk for mortality and major cancer and cardiometabolic outcomes: an overview of systematic reviews

ObjectiveTo assess the impact of reducing saturated fat or fatty foods, or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of mortality and major cancer and cardiometabolic outcomes in adults.MethodsWe searched MEDLINE, EMBASE, CINAHL, and references of included studies for systematic reviews and meta-analyses (SRMAs) of randomized controlled trials (RCTs) and observational studies in adults published in the past 10 years. Eligible reviews investigated reducing saturated fat or fatty foods or replacing saturated fat with unsaturated fat, carbohydrate or protein, on the risk of cancer and cardiometabolic outcomes and assessed the certainty of evidence for each outcome using, for example, the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. We assessed the quality of SRMAs using a modified version of AMSTAR-2. Results were summarized as absolute estimates of effect together with the certainty of effects using a narrative synthesis approach.ResultsWe included 17 SRMAs (13 reviews of observational studies with follow-up 1 to 34 years; 4 reviews of RCTs with follow-up 1 to 17 years). The quality of two-thirds of the SRMAs was critically low to moderate; the main limitations included deficient reporting of study selection, absolute effect estimates, sources of funding, and a priori subgroups to explore heterogeneity. Our included reviews reported > 100 estimates of effect across 11 critically important cancer and cardiometabolic outcomes. High quality SRMAs consistently and predominantly reported low to very low certainty evidence that reducing or replacing saturated fat was associated with a very small risk reduction in cancer and cardiometabolic endpoints. The risk reductions where approximately divided, some being statistically significant and some being not statistically significant. However, based on 2 moderate to high quality reviews, we found moderate certainty evidence for a small but important effect that was statistically significant for two outcomes (total mortality events [20 fewer events per 1000 followed] and combined cardiovascular events [16 fewer per 1000 followed]). Conversely, 4 moderate to high quality reviews showed very small effects on total mortality, with 3 of these reviews showing non-statistically significant mortality effects.ConclusionSystematic reviews investigating the impact of SFA on mortality and major cancer and cardiometabolic outcomes almost universally suggest very small absolute changes in risk, and the data is based primarily on low and very low certainty evidence.Systematic review registrationPROSPERO CRD42020172141

Major Update: Masks for Prevention of SARS-CoV-2 in Health Care and Community Settings-Final Update of a Living, Rapid Review.

Optimal use of masks for preventing COVID-19 is unclear. To update an evidence synthesis on N95, surgical, and cloth mask effectiveness in community and health care settings for preventing SARS-CoV-2 infection. MEDLINE, EMBASE, medRxiv (3 June 2022 to 2 January 2023), and reference lists. Randomized trials of interventions to increase mask use and risk for SARS-CoV-2 infection and observational studies of mask use that controlled for potential confounders. Two investigators sequentially abstracted study data and rated quality. Three randomized trials and 21 observational studies were included. In community settings, mask use may be associated with a small reduced risk for SARS-CoV-2 infection versus no mask use, on the basis of 2 randomized trials and 7 observational studies. In routine patient care settings, surgical masks and N95 respirators may be associated with similar risk for SARS-CoV-2 infection, on the basis of 1 new randomized trial with some imprecision and 4 observational studies. Evidence from observational studies was insufficient to evaluate other mask comparisons due to methodological limitations and inconsistency. Few randomized trials, studies had methodological limitations and some imprecision, suboptimal adherence and pragmatic aspects of randomized trials potentially attenuated benefits, very limited evidence on harms, uncertain applicability to Omicron variant predominant era, meta-analysis not done due to heterogeneity, unable to formally assess for publication bias, and restricted to English-language articles. Updated evidence suggests that masks may be associated with a small reduction in risk for SARS-CoV-2 infection in community settings. Surgical masks and N95 respirators may be associated with similar infection risk in routine patient care settings, but a beneficial effect of N95 respirators cannot be ruled out. None.

Interventions to Reduce Severe Brain Injury Risk in Preterm Neonates

Interventions to reduce severe brain injury risk are the prime focus in neonatal clinical trials. To evaluate multiple perinatal interventions across clinical settings for reducing the risk of severe intraventricular hemorrhage (sIVH) and cystic periventricular leukomalacia (cPVL) in preterm neonates. MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception until September 8, 2022, using prespecified search terms and no language restrictions. Randomized clinical trials (RCTs) that evaluated perinatal interventions, chosen a priori, and reported 1 or more outcomes (sIVH, cPVL, and severe brain injury) were included. Two co-authors independently extracted the data, assessed the quality of the trials, and evaluated the certainty of the evidence using the Cochrane GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. Fixed-effects pairwise meta-analysis was used for data synthesis. The 3 prespecified outcomes were sIVH, cPVL, and severe brain injury. A total of 221 RCTs that assessed 44 perinatal interventions (6 antenatal, 6 delivery room, and 32 neonatal) were included. Meta-analysis showed with moderate certainty that antenatal corticosteroids were associated with small reduction in sIVH risk (risk ratio [RR], 0.54 [95% CI, 0.35-0.82]; absolute risk difference [ARD], -1% [95% CI, -2% to 0%]; number needed to treat [NNT], 80 [95% CI, 48-232]), whereas indomethacin prophylaxis was associated with moderate reduction in sIVH risk (RR, 0.64 [95% CI, 0.52-0.79]; ARD, -5% [95% CI, -8% to -3%]; NNT, 20 [95% CI, 13-39]). Similarly, the meta-analysis showed with low certainty that volume-targeted ventilation was associated with large reduction in risk of sIVH (RR, 0.51 [95% CI, 0.36-0.72]; ARD, -9% [95% CI, -13% to -5%]; NNT, 11 [95% CI, 7-23]). Additionally, early erythropoiesis-stimulating agents (RR, 0.68 [95% CI, 0.57-0.83]; ARD, -3% [95% CI, -4% to -1%]; NNT, 34 [95% CI, 22-67]) and prophylactic ethamsylate (RR, 0.68 [95% CI, 0.48-0.97]; ARD, -4% [95% CI, -7% to 0%]; NNT, 26 [95% CI, 13-372]) were associated with moderate reduction in sIVH risk (low certainty). The meta-analysis also showed with low certainty that compared with delayed cord clamping, umbilical cord milking was associated with a moderate increase in sIVH risk (RR, 1.82 [95% CI, 1.03-3.21]; ARD, 3% [95% CI, 0%-6%]; NNT, -30 [95% CI, -368 to -16]). Results of this study suggest that a few interventions, including antenatal corticosteroids and indomethacin prophylaxis, were associated with reduction in sIVH risk (moderate certainty), and volume-targeted ventilation, early erythropoiesis-stimulating agents, and prophylactic ethamsylate were associated with reduction in sIVH risk (low certainty) in preterm neonates. However, clinicians should carefully consider all of the critical factors that may affect applicability in these interventions, including certainty of the evidence, before applying them to clinical practice.

Abstract 2798: Simplifying selection and optimization of step-up dosing of subcutaneous Epcoritamab to mitigate CRS risk using repeated time-to-event modeling

Abstract Background: Epcoritamab, a bispecific antibody, binds to CD3 on T cells and CD20 on B cells to induce T-cell-mediated killing of CD20+ malignant B cells. For T-cell engagers, CRS is a potential adverse event. Step-up dosing (SUD) is used to mitigate potential severe CRS symptoms. Identification of optimal SUD is challenging because multiple steps of dose escalation are needed to manage CRS. Based on a dose-escalation study of epcoritamab, 2-step SUD (weekly priming and intermediate dose prior to administering the target dose) was necessary to effectively mitigate the risk of CRS. A wide range of priming (0.004-0.16 mg) and intermediate (0.0128-1.6 mg) doses for 17 combinations was explored; the 0.16/0.8/48-mg regimen was selected based on the CRS event rate. We further explored optimization of the SUD regimen using a model-based approach to inform clinical evaluation. Methods: A repeated time-to-event model was developed using pharmacokinetic and CRS event data collected in the phase 1/2 EPCORE NHL-1 monotherapy trial. The model was required to predict the onset of 1 or more CRS events (all-grade and grade ≥2) over time and to describe the impact of epcoritamab concentration on CRS risk over time and the development of tolerance after multiple doses. To capture these dynamics, the hazard function (risk of CRS event) was modeled as the product of 2 components: the first component addressed the risk of a CRS event and allowed for increasing hazard with increasing epcoritamab plasma concentrations, and the second component described the inhibition of the hazard to capture development of CRS tolerance over time after multiple doses. Simulations assessed the performance of different SUD regimens, measured by the probability of a grade ≥2 CRS event. Results: The model was able to predict the observed CRS events over time and confirmed that the SUD regimen used in the recommended phase 2 dose regimen for epcoritamab (0.16/0.8/48 mg) provided similar or better potential to reduce the risk of grade ≥2 CRS events versus other priming and intermediate dose permutations tested during dose escalation in the EPCORE NHL-1 trial. The validated model was used to further explore a large number of SUD regimens not studied in clinical trials. Based on model predictions, alternative SUD regimens can potentially lead to a small reduction in risk of grade ≥2 CRS. To further assess this, alternative SUD regimens were selected for potential clinical assessment. Conclusions: A dynamic model for CRS was successfully developed, validated, and applied to aid the optimization of an epcoritamab SUD regimen. The model-based optimization of SUD informed and narrowed down the number of doses/cohorts to be tested in clinical trials, simplified study design, and played a critical role in expediting the optimization of the epcoritamab SUD regimen. Citation Format: Tommy Li, Daniel Polhamus, Craig Thalhauser, Apurvasena Parikh, Manish Gupta, Mariana Sacchi, Steven Xu. Simplifying selection and optimization of step-up dosing of subcutaneous Epcoritamab to mitigate CRS risk using repeated time-to-event modeling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2798.

Daily composition of movement behaviors with cardiovascular disease incidence in elderly

Abstract Background Moderate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behavior (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviors as independent entities ignoring their co-dependency. This study aims to examine the association between daily composition of objectively-assessed movement behaviors (MVPA, LIPA, SB) and incident CVD in older adults. Methods Whitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age=68.9 years in 2012-2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA were extracted. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviors characterized by 10 (20 or 30) minutes greater duration in one movement behavior accompanied by decrease in another behavior, while keeping the third behavior constant, compared to reference composition. Results Of the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to individuals with daily movement behavior composition composed with MVPA at recommended 21 minutes per day (150 minutes/week), composition with additional 10 minutes of MVPA and 10 minutes less SB were associated with smaller risk reduction -8% (HR, 0.92; 95% CI, 0.87-0.99) - than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02-1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations. Conclusions An increase in MVPA duration at the expense of time in either SB or LIPA was associated with lower risk of incident CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at their current duration. Key messages Older adults should be encouraged to increase their moderate-to-vigorous physical activity or at least maintain at their current levels to lower risk of incident cardiovascular disease. Highly sedentary older adults should increase their moderate-to-vigorous physical activity by decreasing sedentary time rather than light-intensity activity to prevent cardiovascular disease.

Preoperative hair removal to reduce surgical site infection.

Preoperative hair removal to reduce surgical site infection.

Association of daily composition of physical activity and sedentary behaviour with incidence of cardiovascular disease in older adults

BackgroundModerate-to-vigorous physical activity (MVPA) is proposed as key for cardiovascular diseases (CVD) prevention. At older ages, the role of sedentary behaviour (SB) and light intensity physical activity (LIPA) remains unclear. Evidence so far is based on studies examining movement behaviours as independent entities ignoring their co-dependency. This study examines the association between daily composition of objectively-assessed movement behaviours (MVPA, LIPA, SB) and incident CVD in older adults.MethodsWhitehall II accelerometer sub-study participants free of CVD at baseline (N = 3319, 26.7% women, mean age = 68.9 years in 2012–2013) wore a wrist-accelerometer from which times in SB, LIPA, and MVPA during waking period were extracted over 7 days. Compositional Cox regression was used to estimate the hazard ratio (HR) for incident CVD for daily compositions of movement behaviours characterized by 10 (20 or 30) minutes greater duration in one movement behaviour accompanied by decrease in another behaviour, while keeping the third behaviour constant, compared to reference composition. Analyses were adjusted for sociodemographic, lifestyle, cardiometabolic risk factors and multimorbidity index.ResultsOf the 3319 participants, 299 had an incident CVD over a mean (SD) follow-up of 6.2 (1.3) years. Compared to daily movement behaviour composition with MVPA at recommended 21 min per day (150 min/week), composition with additional 10 min of MVPA and 10 min less SB was associated with smaller risk reduction – 8% (HR, 0.92; 95% CI, 0.87–0.99) – than the 14% increase in risk associated with a composition of similarly reduced time in MVPA and more time in SB (HR, 1.14; 95% CI, 1.02–1.27). For a given MVPA duration, the CVD risk did not differ as a function of LIPA and SB durations.ConclusionsAmong older adults, an increase in MVPA duration at the expense of time in either SB or LIPA was found associated with lower incidence of CVD. This study lends support to public health guidelines encouraging increase in MVPA or at least maintain MVPA at current duration.

The effect of a dexmedetomidine infusion on delirium in the ICU

• A clinically small reduction in delirium risk was found with sedation utilizing dexmedetomidine. • There was no effect on short-term mortality among ICU patients sedated with dexmedetomidine. • Shorter duration of mechanical ventilation and ICU stay with dexmedetomidine infusion. • Dexmedetomidine infusion had a higher incidence of hypotension and bradycardia.

Plasma long-chain omega-3 fatty acid status and risk of recurrent early spontaneous preterm birth: a prospective observational study.

A 2018 Cochrane review found that omega-3 supplementation in pregnancy was associated with a risk reduction of early preterm birth of 0.58; prompting calls for universal supplementation. Recent analysis suggests the benefit may be confined to women with a low baseline omega-3 fatty acid status. However, the contemporary omega-3 fatty acid status of pregnant women in the UK is largely unknown. This is particularly pertinent for women with a previous preterm birth, in whom a small relative risk reduction would have a larger reduction of absolute risk. This study aimed to assess the omega-3 fatty acid status of a UK pregnant population and determine the association between the long-chain omega-3 fatty acids and recurrent spontaneous early preterm birth. A total of 283 high-risk women with previous early preterm birth were recruited to the prospective observational study in Liverpool, UK. Additionally, 96 pregnant women with previous term births and birth ≥39+0 weeks in the index pregnancy provided a low-risk population sample. Within the high-risk group we assessed the odds ratio of recurrent early preterm birth compared with birth at ≥37+0 weeks of gestation according to plasma eicosapentaenoic acid plus docosahexaenoic acid (EPA+DHA) at 15-22weeks of gestation. Our participants had low EPA+DHA; 62% (143/229) of women with previous preterm birth and 69% (68/96) of the population sample had levels within the lowest two quintiles of a previously published pregnancy cohort. We found no association between long-chain omega-3 status and recurrent early preterm birth (n=51). The crude odds ratio of a recurrent event was 0.91 (95% CI 0.38-2.15, p=0.83) for women in the lowest, compared with the highest three quintiles of EPA+DHA. In the majority of our participants, levels of long-chain omega-3 were low; within the range that may benefit from supplementation. However, levels showed no association with risk of recurrent early spontaneous preterm birth. This could be because our population levels were too low to show benefit in being omega-3 "replete"; or else omega-3 levels may be of lesser importance in recurrent early preterm birth.

Update Alert 5: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings.

LettersApril 2021Update Alert 5: Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community SettingsFREERoger Chou, MD, Tracy Dana, MLS, Rebecca Jungbauer, DrPH, and Chandler Weeks, MPHRoger Chou, MDPacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, OregonSearch for more papers by this author, Tracy Dana, MLSPacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, OregonSearch for more papers by this author, Rebecca Jungbauer, DrPHPacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, OregonSearch for more papers by this author, and Chandler Weeks, MPHPacific Northwest Evidence-based Practice Center and Oregon Health & Science University, Portland, OregonSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L21-0116 SectionsSupplemental MaterialAboutVisual AbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail This is the fifth update alert for a living rapid review on the use of masks for prevention of respiratory virus infections, including SARS-CoV-2, in health care and community settings (1). The first 3 updates were monthly, and the interval was switched to bimonthly for subsequent updates. Update searches were done from 3 December 2020 to 2 February 2021, using the same search strategies as the original review. The update searches identified 613 citations. Two studies (2, 3) on the use of masks and the prevention of SARS-CoV-2 were added for this update: 1 study (2) was done in a community setting, and the other (3) was done in a health care setting (Supplement Tables 1 to 3).On the basis of evidence from 1 randomized controlled trial (4) and 2 observational studies (5, 6), the strength of evidence for mask use versus nonuse for the prevention of SARS-CoV-2 in community settings was previously assessed as low for a small reduction in risk for infection with any mask use (Supplement Table 4). One new cross-sectional study done in Vermont reported an imprecise estimate for the association between wearing a mask (type unspecified) outside of a work environment or not wearing a mask and SARS-CoV-2 infection risk (odds ratio, 2.35 [95% CI, 0.67 to 8.25]) (Supplement Table 3) (2). Mask use was not included in multivariable models; in addition, the study had methodological limitations, including potential selection and recall bias and low participation and SARS-CoV-2 testing rates among eligible participants. Therefore, the strength of evidence for any mask use versus nonuse in community settings remains low (Supplement Table 4). Other strength-of-evidence ratings related to mask use in community settings were unchanged because of no new evidence.The evidence on various comparisons of mask use in health care settings and risk for SARS-CoV-2 infection was previously assessed as insufficient on the basis of 5 observational studies with methodological limitations (Supplement Table 4) (7–11). One new study done in 500 U.S. hospital workers in a high-prevalence area (SARS-CoV-2 seropositivity, 27%) was added for this update (3). In this study, only 2 hospital workers reported no mask use. Although the study evaluated N95 use only, surgical mask use only, or N95 and surgical mask use, analyses were of limited usefulness because the comparison group was any other mask use, including other types of masks or nonuse (for example, N95 only was compared with the combination of surgical mask only, N95 and surgical mask, or no mask use). In addition, estimates were imprecise, except for N95 and surgical mask use (odds ratio, 0.63 [CI, 0.41 to 1.0]). The comparison of N95 only versus surgical mask only favored the N95, but the difference was not statistically significant (odds ratio, 0.60 [CI, 0.31 to 1.15]). The study had methodological limitations, including no adjustment for confounders and potential recall and selection bias. On the basis of these limitations and because of inconsistent results across studies, evidence for N95 versus surgical mask use and other comparisons involving mask use and risk for SARS-CoV-2 infection in health care settings remains insufficient (Supplement Table 4).No new studies evaluated the effects of mask use and risk for SARS-CoV-1 infection, Middle East respiratory syndrome–CoV infection, or influenza or influenza-like illness. As with prior updates, there were no new studies on the effectiveness and safety of mask reuse or extended use.

Early Discharge After Total Hip and Knee Arthroplasty—An Observational Cohort Study Evaluating Safety in 330,000 Patients

BackgroundThere has been considerable interest in recent years for early discharge after arthroplasty. We endeavored to evaluate the safety of same-day discharge given the rapid uptake of this practice approach. MethodsThis is a retrospective observational cohort study of the American College of Surgeons National Surgical Quality Improvement Program registry database. We included patients who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA) between 2015 and 2018. We categorized length of stay (LOS) as same-day discharge (LOS = 0 days), accelerated discharge (LOS = 1 day), and routine discharge (LOS = 2-3 days). For each LOS cohort, we determined the incidence of major complications within 30 days (surgical site infection [SSI], reoperation, readmission, deep vein thrombosis [DVT], and PE) and evaluated risk using multivariate logistic regression analysis if incidence was >1%. Patients undergoing THA and TKA were evaluated independently. ResultsThe final study cohort consisted of 333,212 patients, including 124,150 who underwent THA (37%) and 209,062 who had TKA (63%). In the THA same-day discharge cohort, the incidence of superficial SSI (0.2%), deep/organ space SSI (0.3%), DVT (0.2%), and PE (0.2%) was low. The risk of reoperation was comparable to routine discharge (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.61-1.09; P = .17) and readmission rate was significantly lower (OR, 0.60; 95% CI, 0.48-0.76; P < .001). The risk of reoperation and readmission was also lower in the accelerated discharge cohort compared to routine discharge. In the TKA same-day discharge cohort, the risk of superficial SSI (0.3%), deep/organ space SSI (0.3%), reoperation (0.8%), DVT (0.4%), and PE (0.5%) was low. The risk of readmission after same-day discharge was comparable to routine discharge (OR, 0.85; 95% CI, 0.71-1.01; P = .07). In the accelerated discharge cohort, there was a small reduction in readmission risk (OR, 0.87; 95% CI, 0.81-0.93; P < .001). ConclusionThis large, observational, real-world study suggests that same-day and accelerated discharge management is safe clinical practice for patients undergoing total joint arthroplasty, yielding a similar risk of major acute 30-day complications. Further clinical trials evaluating long-term major outcomes, including patient-reported outcomes and experiences, would offer further and definitive insight into this practice approach.

Comparative Causal Analysis of the Effects of Long-Acting Muscarinic Antagonist Versus No Long-Acting Bronchodilator Use on Readmission or Mortality After Hospitalization for Chronic Obstructive Pulmonary Disease.

BackgroundRetrospective observational studies may provide real-world evidence about long-acting muscarinic receptor antagonist (LAMA) effectiveness in reducing mortality or COPD-related readmission risk after a COPD hospitalization. Causal inference and competing risk statistical procedures aid in managing confounding and competing outcome events that complicate retrospective analyses.ObjectiveTo compare COPD-related readmission and mortality risk among patients receiving a LAMA versus patients receiving no long-acting bronchodilator (“no LABD”) within 30 days post-discharge.MethodsThis retrospective observational analysis of patients (aged ≥ 40 years) hospitalized for COPD used claims data (years 2004–2012). Events occurring during the period from 31 days through 12 months post-discharge were compared. The hazard ratio (HR) for the combined outcome of COPD-related readmission or mortality was estimated using Cox regression. Confounding was addressed using inverse probability of treatment weighting (IPTW). The competing risk of non-COPD-related readmission was considered.Results10,405 COPD patients were included (LAMA = 751, no LABD = 9654). IPTW achieved a balanced sample (10,518 LAMA, 10,405 no LABD). Unweighted HR (LAMA vs no LABD) for COPD-related readmission or death, adjusted for age, sex, comorbidities, and baseline utilization, was 1.00 [95% confidence interval (CI) 0.84, 1.20]. Weighted (IPTW) adjusted HR was 0.94 (95% CI 0.88, 1.00). Unweighted and weighted HRs further adjusted for competing risk were 0.97 (95% CI 0.82, 1.16) and 0.91 (0.86, 0.98), respectively.ConclusionsBias by indication and comorbidities make the measurement of retrospective COPD treatment effectiveness difficult. Using IPTW and additionally considering the competing event risk, LAMA use was associated with a small reduction in risk for COPD-related readmission or death over the period from 31 days to 12 months post-discharge.Electronic supplementary materialThe online version of this article (10.1007/s40801-019-00171-w) contains supplementary material, which is available to authorized users.

Red and Processed Meat Consumption and Risk for All-Cause Mortality and Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Cohort Studies.

Dietary guidelines generally recommend limiting intake of red and processed meat. However, the quality of evidence implicating red and processed meat in adverse health outcomes remains unclear. To evaluate the association between red and processed meat consumption and all-cause mortality, cardiometabolic outcomes, quality of life, and satisfaction with diet among adults. EMBASE (Elsevier), Cochrane Central Register of Controlled Trials (Wiley), Web of Science (Clarivate Analytics), CINAHL (EBSCO), and ProQuest from inception until July 2018 and MEDLINE from inception until April 2019, without language restrictions, as well as bibliographies of relevant articles. Cohort studies with at least 1000 participants that reported an association between unprocessed red or processed meat intake and outcomes of interest. Teams of 2 reviewers independently extracted data and assessed risk of bias. One investigator assessed certainty of evidence, and the senior investigator confirmed the assessments. Of 61 articles reporting on 55 cohorts with more than 4 million participants, none addressed quality of life or satisfaction with diet. Low-certainty evidence was found that a reduction in unprocessed red meat intake of 3 servings per week is associated with a very small reduction in risk for cardiovascular mortality, stroke, myocardial infarction (MI), and type 2 diabetes. Likewise, low-certainty evidence was found that a reduction in processed meat intake of 3 servings per week is associated with a very small decrease in risk for all-cause mortality, cardiovascular mortality, stroke, MI, and type 2 diabetes. Inadequate adjustment for known confounders, residual confounding due to observational design, and recall bias associated with dietary measurement. The magnitude of association between red and processed meat consumption and all-cause mortality and adverse cardiometabolic outcomes is very small, and the evidence is of low certainty. None. (PROSPERO: CRD42017074074).

Optimal Consumption and Investment Problem Incorporating Housing and Life Insurance Decisions: The Continuous Time Case

AbstractThis study considers the optimal consumption‐investment‐insurance problem incorporating housing decisions of a household when interest rates and labor income are stochastic. Under the complete market assumption, we derive the closed‐form solution of the optimal insurance demand, portfolio choice, and housing consumption. We calibrate the model using data from the financial market of Taiwan. We find that the insurer's pricing strategy has a significant impact on the household's consumption pattern. Specifically, additional loading in insurance premium allows the life‐cycle model to produce hump‐shaped consumptions of both perishable goods and housing. Loading also creates an unfair background risk to households. However, we only find a small portfolio risk reduction, because households optimally choose a large coverage to mitigate the mortality exposure. This suggests empirical background risk studies overestimate the risk reduction when insurance is available.