E-values are a recently introduced approach to evaluate confounding in observational studies. We aimed to empirically assess the current use of E-values in published literature.
We conducted a ...systematic literature search for all publications, published up till the end of 2018, which cited at least one of two inceptive E-value papers and presented E-values for original data. For these case publications we identified control publications, matched by journal and issue, where the authors had not calculated E-values.
In total, 87 papers presented 516 E-values. Of the 87 papers, 14 concluded that residual confounding likely threatens at least some of the main conclusions. Seven of these 14 named potential uncontrolled confounders. 19 of 87 papers related E-value magnitudes to expected strengths of field-specific confounders. The median E-value was 1.88, 1.82, and 2.02 for the 43, 348, and 125 E-values where confounding was felt likely to affect the results, unlikely to affect the results, or not commented upon, respectively. The 69 case-control publication pairs dealt with effect sizes of similar magnitude. Of 69 control publications, 52 did not comment on unmeasured confounding and 44/69 case publications concluded that confounding was unlikely to affect study conclusions.
Few papers using E-values conclude that confounding threatens their results, and their E-values overlap in magnitude with those of papers acknowledging susceptibility to confounding. Facile automation in calculating E-values may compound the already poor handling of confounding. E-values should not be a substitute for careful consideration of potential sources of unmeasured confounding. If used, they should be interpreted in the context of expected confounding in specific fields.
To compare the effect of exercise regimens and medications on systolic blood pressure (SBP).
Medline (via PubMed) and the Cochrane Library.
Randomised controlled trials (RCTs) of ...angiotensin-converting enzyme inhibitors (ACE-I), angiotensin-2 receptor blockers (ARBs), β-blockers, calcium channel blockers (CCBs) and diuretics were identified from existing Cochrane reviews. A previously published meta-analysis of exercise interventions was updated to identify recent RCTs that tested the SBP-lowering effects of endurance, dynamic resistance, isometric resistance, and combined endurance and resistance exercise interventions (up to September 2018).
Random-effects network meta-analysis.
Difference in mean change from baseline SBP between comparator treatments (change from baseline in one group minus that in the other group) and its 95% credible interval (95% CrI), measured in mmHg.
We included a total of 391 RCTs, 197 of which evaluated exercise interventions (10 461 participants) and 194 evaluated antihypertensive medications (29 281 participants). No RCTs compared directly exercise against medications. While all medication trials included hypertensive populations, only 56 exercise trials included hypertensive participants (≥140 mmHg), corresponding to 3508 individuals. In a 10% random sample, risk of bias was higher in exercise RCTs, primarily due to lack of blinding and incomplete outcome data. In analyses that combined all populations, antihypertensive medications achieved higher reductions in baseline SBP compared with exercise interventions (mean difference -3.96 mmHg, 95% CrI -5.02 to -2.91). Compared with control, all types of exercise (including combination of endurance and resistance) and all classes of antihypertensive medications were effective in lowering baseline SBP. Among hypertensive populations, there were no detectable differences in the SBP-lowering effects of ACE-I, ARB, β-blocker and diuretic medications when compared with endurance or dynamic resistance exercise. There was no detectable inconsistency between direct and indirect comparisons. Although there was evidence of small-study effects, this affected both medication and exercise trials.
The effect of exercise interventions on SBP remains under-studied, especially among hypertensive populations. Our findings confirm modest but consistent reductions in SBP in many studied exercise interventions across all populations but individuals receiving medications generally achieved greater reductions than those following structured exercise regimens. Assuming equally reliable estimates, the SBP-lowering effect of exercise among hypertensive populations appears similar to that of commonly used antihypertensive medications. Generalisability of these findings to real-world clinical settings should be further evaluated.
Background Risk assessment is the cornerstone for atherosclerotic cardiovascular disease ( ASCVD ) treatment decisions. The Pooled Cohort Equations ( PCE ) have not been validated in disaggregated ...Asian or Hispanic populations, who have heterogeneous cardiovascular risk and outcomes. Methods and Results We used electronic health record data from adults aged 40 to 79 years from a community-based, outpatient healthcare system in northern California between January 1, 2006 and December 31, 2015, without ASCVD and not on statins. We examined the calibration and discrimination of the PCE and recalibrated the equations for disaggregated race/ethnic subgroups. The cohort included 231 622 adults with a mean age of 53.1 (SD 9.7) years and 54.3% women. There were 56 130 Asian (Chinese, Asian Indian, Filipino, Japanese, Vietnamese, and other Asian) and 19 760 Hispanic (Mexican, Puerto Rican, and other Hispanic) patients. There were 2703 events (332 and 189 in Asian and Hispanic patients, respectively) during an average of 3.9 (SD 1.5) years of follow-up. The PCE overestimated risk for NHW s, African Americans, Asians, and Hispanics by 20% to 60%. The extent of overestimation of ASCVD risk varied by disaggregated racial/ethnic subgroups, with a predicted-to-observed ratio of ASCVD events ranging from 1.1 for Puerto Rican patients to 1.9 for Chinese patients. The PCE had adequate discrimination, although it varied significantly by race/ethnic subgroups (C-indices 0.66-0.83). Recalibration of the PCE did not significantly improve its performance. Conclusions Using electronic health record data from a large, real-world population, we found that the PCE generally overestimated ASCVD risk, with marked heterogeneity by disaggregated Asian and Hispanic subgroups.
Lipid-lowering therapy (LLT) reduces cardiovascular (CV) events, but data are conflicting on all-cause mortality, especially among older adults. Though LLT does not induce cancer, some randomized ...clinical trials (RCTs) found a pattern of increased cancer death under LLT. Our objective was to assess a possible shift from CV to cancer death in LLT trials (i.e. an increase in cancer and decrease in CV death) and to investigate potential subgroups at risk.
We performed a systematic review and meta-analysis. We retrieved RCTs from MEDLINE, Embase, and Cochrane Central until 08/2023. We extracted the number of CV and cancer deaths in the treatment vs. in the control arm, calculated the relative risk (RR) by dividing the risk of death in the treatment over the risk of death in the control group and then pooled them using random-effect meta-analysis. We performed subgroup analyses on primary and secondary prevention, and according to different age cut-offs.
We included 27 trials with 188'259 participants (23 statin; 4 ezetimibe trials). The trials reported 4056 cancer deaths, 2061 under LLT and 1995 in control groups. Overall, there was no increased risk of cancer mortality (RR 1.03, 95% confidence interval 0.97-1.10), with no difference between primary and secondary prevention. In the subgroup analyses for RCTs with ≥15% of participants aged ≥75 years, the RR of cancer death was 1.11 (1.00-1.23), while the RR for CV death was 0.96 (0.91-1.01). For RCTs with a mean age ≥ 70 years, the RR for cancer death was 1.21 (0.99-1.47).
LLT does not lead to a shift from CV to cancer death. However, there might be a possible shift with a pattern of increased cancer deaths in trials with more older adults, particularly ≥75 years. Individual participant data from LLT trials should be made public to allow further investigations.
CRD42021271658.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Several trials and meta-analyses found a benefit of adjunct corticosteroids for community-acquired pneumonia with respect to short-term outcome, but there is uncertainty about longer-term health ...effects. Herein, we evaluated clinical outcomes at long term in patients participating in the STEP trial (Corticosteroid Treatment for Community-Acquired Pneumonia).
This predefined secondary analysis investigated 180-day outcomes in 785 adult patients hospitalized with community-acquired pneumonia included in STEP, a randomised, placebo-controlled, double-blind trial. The primary endpoint was time to death from any cause at 180 days verified by telephone interview. Additional secondary endpoints included pneumonia-related death, readmission, recurrent pneumonia, secondary infections, new hypertension, and new insulin dependence.
From the originally included 785 patients, 727 were available for intention-to-treat analysis at day 180. There was no difference between groups with respect to time to death from any cause (HR for corticosteroid use 1.15, 95% CI 0.68 to 1.95, p = 0.601). Compared to placebo, corticosteroid-treated patients had significantly higher risks for recurrent pneumonia (OR 2.57, 95% CI 1.29 to 5.12, p = 0.007), secondary infections (OR 1.94, 95% CI 1.25 to 3.03, p = 0.003) and new insulin dependence (OR 8.73, 95% CI 1.10 to 69.62, p = 0.041). There was no difference regarding pneumonia-related death, readmission and new hypertension.
In patients with community-acquired pneumonia, corticosteroid use was associated with an increased risk for recurrent pneumonia, secondary infections and new insulin dependence at 180 days. Currently, it is uncertain whether these long-term adverse effects outweigh the short-term effects of corticosteroids in moderate CAP.
This trial was registered with ClinicalTrials. gov, number NCT00973154 before the recruitment of the first patient. First posted: September 9, 2009. Last update posted: April 21, 2015.
Trueperella pyogenes (T. pyogenes) is a bacterium that colonizes the skin and mucosal surfaces of various domestic and wild animals. It rarely leads to infections in humans, with only a few ...descriptions available in the literature. T. pyogenes is a rare causative organism of infectious endocarditis in humans and descriptions are mainly restricted to case reports. In our review of the literature, we found that both an impaired immune system and contact with farm animals might be risk factors. Growth of T. pyogenes in blood cultures is unlikely to be missed during routine analysis, as it shows marked beta-hemolysis on blood agar culture plates, which generally leads to further characterization of the bacteria. Susceptibility to penicillin, ceftriaxone, and macrolides seems to be retained and the reported mortality in the few patients with T. pyogenes endocarditis is high.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction/Aims
Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic ...factors that may support treatment decisions.
Methods
We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow‐up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure.
Results
Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio HR 0.42, 95% confidence interval CI 0.23–0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27–0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6‐minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin‐converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function.
Discussion
Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE‐inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction.
Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are ...excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.
Subclinical hypothyroidism, which is defined as elevated thyroid-stimulating hormone (TSH) levels with free thyroxine concentrations within the reference range, is a common disorder that increases ...with age and affects up to 18% of the elderly, with a higher prevalence in women compared to men. Prospective data have shown an increased risk of coronary heart disease events, heart failure, and cardiovascular mortality among affected adults. Conflicting results have been found on the association between subclinical hypothyroidism and cognitive impairment, depression and the risk of fractures. Management strategies including screening and treatment of subclinical hypothyroidism are still controversial, while the ongoing European randomised controlled trial "TRUST" targets to solve these uncertainties. This narrative review aims to assess current evidence on the clinical aspects, as well as screening and treatment recommendations in adults with subclinical hypothyroidism.
Subclinical hypothyroidism has been associated with heart failure, but only small trials assessed whether treatment with levothyroxine has an impact on cardiac function.
In a randomized, ...double-blind, placebo-controlled, trial nested within the TRUST trial, Swiss participants ages ≥65 years with subclinical hypothyroidism (thyroid-stimulating hormone TSH 4.60-19.99 mIU/L; free thyroxine level within reference range) were randomized to levothyroxine (starting dose of 50 µg daily) to achieve TSH normalization or placebo. The primary outcomes were the left ventricular ejection fraction for systolic function and the ratio between mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e′ ratio) for diastolic function. Secondary outcomes included e′ lateral/septal, left atrial volume index, and systolic pulmonary artery pressure.
A total of 185 participants (mean age 74.1 years, 47% women) underwent echocardiography at the end of the trial. After a median treatment duration of 18.4 months, the mean TSH decreased from 6.35 mIU/L to 3.55 mIU/L with levothyroxine (n = 96), and it remained elevated at 5.29 mIU/L with placebo (n = 89). The adjusted between-group difference was not significant for the mean left ventricular ejection fraction (62.7% vs 62.5%, difference = 0.4%, 95% confidence interval −1.8% to 2.5%, P = 0.72) and the E/e′ ratio (10.6 vs 10.1, difference 0.4, 95% confidence interval −0.7 to 1.4, P = 0.47). No differences were found for the secondary diastolic function parameters or for interaction according to sex, baseline TSH, preexisting heart failure, and treatment duration (P value >0.05).
Systolic and diastolic heart function did not differ after treatment with levothyroxine compared with placebo in older adults with mild subclinical hypothyroidism.
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