Influenza-Associated Outcomes and Healthcare Utilization by Race and Ethnicity in the USA: a Retrospective Cohort Study Using the National Inpatient Sample Database.

BACKGROUND: The influenza virus continues to be a public health concern every season. We aimed to evaluate influenza-associated outcomes and healthcare utilization by race and ethnicity. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample across 2019 and 2020. Influenza pneumonia was selected as the principal diagnosis. Outcomes included mortality, use of respiratory support ventilation, length of stay, and total hospitalization charge. Regression models were adjusted for age, gender, Charlson Comorbidity Index, hospitals' region, bed size, teaching status, insurance status, and median income. RESULTS: We identified 73,098 individuals hospitalized with influenza pneumonia; 39,807 and 33,291 were admitted in 2019 and 2020, respectively. The sample included 49,829 (68%) White, 11,356 (15.5%) Black, 7526 (10%) Hispanic, 1860 (2.5%) Asian/Pacific, and 617 (0.84%) Native American patients. In-hospital mortality rates and respiratory support (non-invasive ventilation and invasive mechanical ventilation) in 2019 and 2020 were not significantly different across all the races. In 2019 and 2020, the adjusted odds ratios of in-patient mortality were not significantly different. Asians had higher odds of receiving NIV in 2019 but not in 2020 compared to White patients (adjusted odds ratio (aOR) 1.67, p value 0.04). The adjusted odds ratios for receiving IMV were not significantly different between the races in 2019 and 2020. CONCLUSIONS: This study contributes valuable insight into influenza-associated outcomes and healthcare utilization patterns among diverse racial and ethnic groups. Disparities in healthcare utilization were observed among younger (< 65 years) individuals of Black and Hispanic ethnicity.

Fatal Occupational Asthma in Cannabis Production - Massachusetts, 2022.

Multiple respiratory hazards have been identified in the cannabis cultivation and production industry, in which occupational asthma and work-related exacerbation of preexisting asthma have been reported. An employee working in a Massachusetts cannabis cultivation and processing facility experienced progressively worsening work-associated respiratory symptoms, which culminated in a fatal asthma attack in January 2022. This report represents findings of an Occupational Safety and Health Administration inspection, which included a worksite exposure assessment, coworker and next-of-kin interviews, medical record reviews, and collaboration with the Massachusetts Department of Public Health. Respiratory tract or skin symptoms were reported by four of 10 coworkers with similar job duties. Prevention is best achieved through a multifaceted approach, including controlling asthmagen exposures, such as cannabis dust, providing worker training, and conducting medical monitoring for occupational allergy. Evaluation of workers with new-onset or worsening asthma is essential, along with prompt diagnosis and medical management, which might include cessation of work and workers' compensation when relation to work exposures is identified. It is important to recognize that work in cannabis production is potentially causative.

Who is getting boosted? Disparities in COVID-19 vaccine booster uptake among health care workers.

COVID-19 vaccination remains one of the most effective tools to reduce the risk of SARS-CoV-2 infection. Unfortunately, vaccine hesitancy has limited primary vaccination and booster uptake among the general population and HCWs. To gain a better understanding of factors associated with booster vaccine uptake, we analyzed COVID-19 vaccine booster rates among HCWs and identified risk factors associated with nonacceptance. Of the 62,387 HCWs included in our analysis, the overall booster uptake rate was 64.8%. Older age, Non-Hispanic White racial group, early initial vaccine uptake and longer duration of employment were associated with higher booster uptake. Significant differences were observed between different job categories. This persistence of vaccine hesitancy and disparities in COVID-19 booster uptake among HCWs, almost 2 years after the rollout of the COVID-19 vaccination, call for further efforts to increase vaccine confidence among HCWs and the general population in light of the continued need for further COVID-19 protection.

Diagnostic accuracy of the physical examination in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for GRACE-3.

BACKGROUND: History and physical examination are key features to narrow the differential diagnosis of central versus peripheral causes in patients presenting with acute vertigo. We conducted a systematic review and meta-analysis of the diagnostic test accuracy of physical examination findings. METHODS: This study involved a patient-intervention-control-outcome (PICO) question: (P) adult ED patients with vertigo/dizziness; (I) presence/absence of specific physical examination findings; and (O) central (ischemic stroke, hemorrhage, others) versus peripheral etiology. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was assessed. RESULTS: From 6309 titles, 460 articles were retrieved, and 43 met the inclusion criteria: general neurologic examination-five studies, 869 patients, pooled sensitivity 46.8% (95% confidence interval [CI] 32.3%-61.9%, moderate certainty) and specificity 92.8% (95% CI 75.7%-98.1%, low certainty); limb weakness/hemiparesis-four studies, 893 patients, sensitivity 11.4% (95% CI 5.1%-23.6%, high) and specificity 98.5% (95% CI 97.1%-99.2%, high); truncal/gait ataxia-10 studies, 1810 patients (increasing severity of truncal ataxia had an increasing sensitivity for central etiology, sensitivity 69.7% [43.3%-87.9%, low] and specificity 83.7% [95% CI 52.1%-96.0%, low]); dysmetria signs-four studies, 1135 patients, sensitivity 24.6% (95% CI 15.6%-36.5%, high) and specificity 97.8% (94.4%-99.2%, high); head impulse test (HIT)-17 studies, 1366 patients, sensitivity 76.8% (64.4%-85.8%, low) and specificity 89.1% (95% CI 75.8%-95.6%, moderate); spontaneous nystagmus-six studies, 621 patients, sensitivity 52.3% (29.8%-74.0%, moderate) and specificity 42.0% (95% CI 15.5%-74.1%, moderate); nystagmus type-16 studies, 1366 patients (bidirectional, vertical, direction changing, or pure torsional nystagmus are consistent with a central cause of vertigo, sensitivity 50.7% [95% CI 41.1%-60.2%, moderate] and specificity 98.5% [95% CI 91.7%-99.7%, moderate]); test of skew-15 studies, 1150 patients (skew deviation is abnormal and consistent with central etiology, sensitivity was 23.7% [95% CI 15%-35.4%, moderate] and specificity 97.6% [95% CI 96%-98.6%, moderate]); HINTS (head impulse, nystagmus, test of skew)-14 studies, 1781 patients, sensitivity 92.9% (95% CI 79.1%-97.9%, high) and specificity 83.4% (95% CI 69.6%-91.7%, moderate); and HINTS+ (HINTS with hearing component)-five studies, 342 patients, sensitivity 99.0% (95% CI 73.6%-100%, high) and specificity 84.8% (95% CI 70.1%-93.0%, high). CONCLUSIONS: Most neurologic examination findings have low sensitivity and high specificity for a central cause in patients with acute vertigo or dizziness. In acute vestibular syndrome (monophasic, continuous, persistent dizziness), HINTS and HINTS+ have high sensitivity when performed by trained clinicians.

Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department.

BACKGROUND: Patients presenting to the emergency department (ED) with acute vertigo or dizziness represent a diagnostic challenge. Neuroimaging has variable indications and yield. We aimed to conduct a systematic review and meta-analysis of the diagnostic test accuracy of neuroimaging for patients presenting with acute vertigo or dizziness. METHODS: An electronic search was designed following patient-intervention-control-outcome (PICO) question-(P) adult patients with acute vertigo or dizziness presenting to the ED; (I) neuroimaging including computed tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI), magnetic resonance angiography (MRA), and ultrasound (US); (C) MRI/clinical criterion standard; and (O) central causes (stroke, hemorrhage, tumor, others) versus peripheral causes of symptoms. Articles were assessed in duplicate. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) was used to assess certainty of evidence in pooled estimates. RESULTS: We included studies that reported diagnostic test accuracy. From 6309 titles, 460 articles were retrieved, and 12 were included: noncontrast CT scan-six studies, 771 patients, pooled sensitivity 28.5% (95% confidence interval [CI] 14.4%-48.5%, moderate certainty) and specificity 98.9% (95% CI 93.4%-99.8%, moderate certainty); MRI-five studies, 943 patients, sensitivity 79.8% (95% CI 71.4%-86.2%, high certainty) and specificity 98.8% (95% CI 96.2%-100%, high certainty); CTA-one study, 153 patients, sensitivity 14.3% (95% CI 1.8%-42.8%) and specificity 97.7% (95% CI 93.8%-99.6%), CT had higher sensitivity than CTA (21.4% and 14.3%) for central etiology; MRA-one study, 24 patients, sensitivity 60.0% (95% CI 26.2%-87.8%) and specificity 92.9% (95% CI 66.1%-99.8%); US-three studies, 258 patients, sensitivity ranged from 30% to 53.6%, specificity from 94.9% to 100%. CONCLUSIONS: Noncontrast CT has very low sensitivity and MRI will miss approximately one in five patients with stroke if imaging is obtained early after symptom onset. The evidence does not support neuroimaging as the only tool for ruling out stroke and other central causes in patients with acute dizziness or vertigo presenting to the ED.

Coworkers are more likely than patients to transmit SARS-CoV-2 infection to healthcare personnel.

OBJECTIVES: To compare the impact of occupational exposures to SARS-CoV-2 positive patients and SARS-CoV-2 positive coworkers, by comparing the frequency of occupational exposure incidents and the rate of healthcare personnel (HCP) who developed a positive PCR test for SARS-COV-2 after occupational exposure to the two different types of infectious individuals. METHODS: A retrospective analysis of all confirmed higher risk occupational exposure incidents that occurred in HCP from 20 March 2020 to 31 December 2020 at a large multisite US academic medical centre. Comparisons between groups for source type were performed using unpaired Student's t-test for continuous variables and the χ2 test for categorical variables, regression analysis was conducted to assess the associations between source type and risk of positive COVID-19 test after occupational exposure. RESULTS: In total, 2253 confirmed medium or high-risk occupational exposures occurred during the study period. 57% were exposures from coworker sources. Each source individual exposed a mean of 2.6 (95% CI 2.3 to 2.9) HCP; during postexposure surveillance, 4.5% of exposed HCP tested positive within 14 days. A coworker source on average exposed 2.2 (95% CI 2.01 to 2.4) other HCP and infected 0.14 (95% CI 0.1 to 0.17) HCP, while patient sources exposed a mean of 3.4 (95% CI 2.6 to 4.2) HCP but only infected 0.07 (95% CI 0.04 to 0.11) HCP. The multivariate analysis demonstrated that exposure to a coworker source carried a higher risk of testing positive compared with exposure to a patient source (OR 3.22; 95% CI 1.72 to 6.04). CONCLUSION: Occupational exposures to coworker sources were not only more frequent but also associated with triple the risk of developing COVID-19 infection, compared with exposures to patient sources.

Disparities in COVID-19 vaccine uptake among health care workers.

BACKGROUND: COVID-19 vaccine uptake by healthcare workers (HCWs) is critical to protect HCWs, the patients they care for, and the healthcare infrastructure. Our study aims to examine the actual COVID-19 vaccination rate among HCWs and identify risk factors associated with vaccine nonacceptance. STUDY DESIGN AND METHODS: A retrospective analysis of COVID-19 vaccinations for HCWs at a large multi-site US academic medical center from 12/18/2020 through 05/04/2021. Comparisons between groups were performed using unpaired student t-test for continuous variables and the chi-square test for categorical variables. A logistic regression analysis was used to assess the associations between vaccine uptake and risk factor(s). RESULTS: Of the 65,270 HCWs included in our analysis, the overall vaccination rate was 78.6%. Male gender, older age, White and Asian race, and direct patient care were associated with higher vaccination rates (P <.0001). Significant differences were observed between different job categories. Physicians and advanced practice staff, and healthcare professionals were more likely to be vaccinated than nurses and support staff. CONCLUSIONS: Our data demonstrated higher initial vaccination rates among HCWs than the general population national average during the study period. We observed significant disparities among different high-risk HCWs groups, especially among different job categories, black HCWs and younger HCWs despite their high risk of contracting the infection. Interventions to address lower vaccination rate and vaccine hesitancy should be built with these disparities and differences in mind to create more targeted interventions.

Occupational exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and risk of infection among healthcare personnel.

OBJECTIVE: To assess the rate and factors associated with healthcare personnel (HCP) testing positive for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) after an occupational exposure. DESIGN: Retrospective cohort study. SETTING: Academic medical center with sites in Minnesota, Wisconsin, Arizona, and Florida. PARTICIPANTS: HCP with a high or medium risk occupational exposure to a patient or other HCP with SARS-CoV-2. METHODS: We reviewed the records of HCP with significant occupational exposures from March 20, 2020, through December 31, 2020. We then performed regression analysis to assess the impact of demographic and occupational variables to assess their impact on the likelihood of testing positive for SARS-CoV-2. RESULTS: In total, 2,253 confirmed occupational exposures occurred during the study period. Employees were the source for 57.1% of exposures. Overall, 101 HCP (4.5%) tested positive in the postexposure period. Of these, 80 had employee sources of exposure and 21 had patient sources of exposure. The postexposure infection rate was 6.2% when employees were the source, compared to 2.2% with patient sources. In a multivariate analysis, occupational exposure from an employee source had a higher risk of testing positive compared to a patient source (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.72-6.04). Sex, age, high-risk exposure, and HCP role were not associated with an increased risk of testing positive. CONCLUSIONS: The risk of acquiring coronavirus disease 2019 (COVID-19) following a significant occupational exposure has remained relatively low, even in the prevaccination era. Exposure to an infectious coworker carries a higher risk than exposure to a patient. Continued vigilance and precautions remain necessary in healthcare settings.

Association Between SARS-CoV-2 Cycle Threshold Values and Clinical Outcomes in Patients With COVID-19: A Systematic Review and Meta-analysis.

Cycle threshold (CT) values are correlated with the amount of viral nucleic acid in a sample and may be obtained from some qualitative real-time polymerase chain reaction tests used for diagnosis of most patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, CT values cannot be directly compared across assays, and they must be interpreted with caution as they are influenced by sample type, timing of sample collection, and assay design. Presently, the correlation between CT values and clinical outcomes is not well understood. We conducted a systematic review and meta-analysis of published studies through April 19, 2021, that reported an association between CT values and hospitalization, disease severity, and mortality in patients ≥18 years old with SARS-CoV-2. A meta-analysis of 7 studies showed no significant difference in mean CT values between hospitalized and nonhospitalized patients. Among hospitalized patients, those with CT values <25 had a high risk of more severe disease and mortality than patients with CT values >30 (odds ratio [OR], 2.31; 95% CI, 1.70 to 3.13; and OR, 2.95; 95% CI, 2.19 to 3.96; respectively). The odds of increased disease severity and mortality were less pronounced in patients with CT values of 25-30 compared with >30.

Is Unplanned PICU Readmission a Proper Quality Indicator? A Systematic Review and Meta-analysis.

CONTEXT: Unplanned PICU readmissions within 48 hours of discharge (to home or a different hospital setting) are considered a quality metric of critical care. OBJECTIVE: We sought to determine identifiable risk factors associated with early unplanned PICU readmissions. DATA SOURCES: A comprehensive search of Medline, Embase, the Cochrane Database of Systematic Reviews, and Scopus was conducted from each database's inception to July 16, 2018. STUDY SELECTION: Observational studies of early unplanned PICU readmissions (<48 hours) in children (<18 years of age) published in any language were included. DATA EXTRACTION: Two reviewers selected and appraised studies independently and abstracted data. A meta-analysis was performed by using the random-effects model. RESULTS: We included 11 observational studies in which 128 974 children (mean age: 5 years) were evaluated. The presence of complex chronic diseases (odds ratio 2.42; 95% confidence interval 1.06 to 5.55; I 2 79.90%) and moderate to severe disability (odds ratio 2.85; 95% confidence interval 2.40 to 3.40; I 2 11.20%) had the highest odds of early unplanned PICU readmission. Other significant risk factors included an unplanned index admission, initial admission to a general medical ward, spring season, respiratory diagnoses, and longer initial PICU stay. Readmission was less likely after trauma- and surgery-related index admissions, after direct admission from home, or during the summer season. Modifiable risk factors, such as evening or weekend discharge, revealed no statistically significant association. Included studies were retrospective, which limited our ability to account for all potential confounders and establish causality. CONCLUSIONS: Many risk factors for early unplanned PICU readmission are not modifiable, which brings into question the usefulness of this quality measure.

A Meta-analysis to Guide the Enhancement of CBT for Childhood Anxiety: Exposure Over Anxiety Management.

Cognitive behavior therapy (CBT) is the most empirically supported therapy for childhood anxiety disorders (CADs) but has not reliably outperformed other credible interventions. The current study used meta-analysis to examine the frequency with which the most common treatment components are included in outcome studies and the relation of these components to symptom improvement. Seventy-five studies were identified that included youth with an anxiety disorder treated with CBT or a comparison condition. The protocols for the 111 CBT conditions generally consisted of 12, 1-h sessions delivered to the child with minimal parent inclusion. A greater amount of in-session exposure was related to significantly larger effect sizes between CBT and waitlist control across reporters (- 0.12 to - 0.15; P's < .05) and from pre- to post-treatment for child report (- .06; P < .01). Compared to treatments that omitted relaxation, treatments that included relaxation strategies were associated with significantly smaller pre- to post-treatment effect sizes across reporters (0.38 to 0.80; P's < .05). The current study suggests that CBT protocols for CADs that emphasize in-session exposure and do not include relaxation have the potential to improve the efficacy and effectiveness of therapy. Dismantling studies directly testing these hypotheses are needed.

Efficacy of Pharmacological Therapies for the Prevention of Fractures in Postmenopausal Women: A Network Meta-Analysis.

BACKGROUND: Osteoporosis and osteopenia are associated with increased fracture incidence in postmenopausal women. We aimed to determine the comparative effectiveness of various available pharmacological therapies. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science, and Scopus for randomized controlled trials that enrolled postmenopausal women with primary osteoporosis and evaluated the risk of hip, vertebral, or nonvertebral fractures. A network meta-analysis was conducted using the multivariate random effects method. RESULTS: We included 107 trials (193,987 postmenopausal women; mean age, 66 years; 55% white; median follow-up, 28 months). A significant reduction in hip fractures was observed with romosozumab, alendronate, zoledronate, risedronate, denosumab, estrogen with progesterone, and calcium in combination with vitamin D. A significant reduction in nonvertebral fractures was observed with abaloparatide, romosozumab, denosumab, teriparatide, alendronate, risedronate, zoledronate, lasofoxifene, tibolone, estrogen with progesterone, and vitamin D. A significant reduction in vertebral fractures was observed with abaloparatide, teriparatide, parathyroid hormone 1-84, romosozumab, strontium ranelate, denosumab, zoledronate, risedronate, alendronate, ibandronate, raloxifene, bazedoxifene, lasofoxifene, estrogen with progesterone, tibolone, and calcitonin. Teriparatide, abaloparatide, denosumab, and romosozumab were associated with the highest relative risk reductions, whereas ibandronate and selective estrogen receptor modulators had lower efficacy. The evidence for the treatment of fractures with vitamin D and calcium remains limited despite numerous large trials. CONCLUSIONS: This network meta-analysis provides comparative effective estimates for the various available treatments to reduce the risk of fragility fractures in postmenopausal women.

A Systematic Review for Variables to Be Collected in a Transplant Database for Improving Risk Prediction.

BACKGROUND: This systematic review was commissioned to identify new variables associated with transplant outcomes that are not currently collected by the Organ Procurement and Transplantation Network (OPTN). METHODS: We identified 81 unique studies including 1 193 410 patients with median follow-up of 36 months posttransplant, reporting 108 unique risk factors. RESULTS: Most risk factors (104) were recipient related; few (4) were donor related. Most risk factors were judged to be practical and feasible to routinely collect. Relative association measures were small to moderate for most risk factors (ranging between 1.0 and 2.0). The strongest relative association measure for a heart transplant outcome with a risk factor was 8.6 (recipient with the previous Fontan operation), for a kidney transplant 2.8 (sickle cell nephropathy as primary cause of end-stage renal disease), for a liver transplant 14.3 (recipient serum ferritin >500 µg/L), and for a lung transplant 6.3 (Burkholderia cepacia complex infection for 1 y or less). OPTN may consider some of these 108 variables for future collection to enhance transplant research and clinical care. CONCLUSIONS: Evidence-based approaches can be used to determine variables collected in databases and registries. Several candidate variables have been identified for OPTN.

Death and Postoperative Complications After Hip Fracture Repair: Dialysis Effect.

INTRODUCTION: It is unknown whether patients receiving dialysis have a higher morbidity and mortality risk after hip fracture repair conferred by their kidney failure or by the high comorbidity burden often present. METHODS: We examined associations of dialysis dependency with postoperative complications, death, and readmission in a matched cohort study of U.S. patients undergoing hip fracture repair, from January 2010 to December 2013, in the American College of Surgeons National Surgical Quality Improvement Program. Matching included sex, age, race, diabetes mellitus, operation year, primary surgery type, and anesthesia technique. RESULTS: Among 22,621 patients, 377 dialysis-dependent patients were matched to 1508 nondialysis patients. Median age was 78 years (interquartile range = 68-85) years, 56% were men, 70% were white, 43% had diabetes, and 47% underwent fracture fixation under mostly (80%) general anesthesia. Dialysis-dependent patients had higher physical status classification, had more heart failure and hypoalbuminemia, and were less often smokers. After adjustment, a greater risk of prolonged postoperative stays beyond 7 days (odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.09-1.89), higher in-hospital mortality (OR = 3.13, CI = 1.72-5.7), and 30-day death (OR = 2.29, CI = 1.51-3.48) but not 30-day readmission (P = 0.09) was observed with dialysis dependency. Adjusted analyses in the original cohort (n = 22,621) were similar: the dialysis group had greater risk of prolonged postoperative stay (OR = 1.77, CI = 1.42-2.21), in-hospital mortality (OR = 2.65, CI = 1.74-4.05), and 30-day death (OR = 2.03, CI = 1.48-2.80) and 30-day readmission (OR = 1.62, CI = 1.66-2.26). CONCLUSION: Dialysis dependency is associated with an increased risk of death and postoperative complications after hip fracture repair. These findings have implications for case-mix adjustment and quality metrics.

Testosterone therapy and venous thromboembolism: A systematic review and meta-analysis.

BACKGROUND: Testosterone prescribing for men has dramatically increased, and there have been concerns about inappropriate use and adverse events. While regulatory bodies have warned about increased risk of venous thromboembolism (VTE), published clinical data supporting an increased risk for VTE are limited. OBJECTIVE: To conduct a systematic review of studies examining the association between testosterone therapy in men and VTE. METHODS: Comprehensive searches of multiple databases were performed from inception through October 3rd, 2018. Randomized control trials (RCTs) and observational studies examining the association between exogenous testosterone (any route) and VTE. Study selection and data extraction were performed by two independent investigators. Random-effect model meta-analyses were used to estimate pooled odds ratios (OR) and 95% confidence intervals (CIs). Heterogeneity among studies was evaluated using the I2 statistic. Risk of bias was assessed using the Cochrane and Newcastle-Ottawa tools. RESULTS: Six RCTs (n = 2236) and 5 observational studies (n = 1,249,640) were included. Five RCTs were performed in men with documented hypogonadism. The observational studies included: 2 case-control studies, 2 retrospective cohorts, and 1 retrospective cohort with a nested case-control study. There was no evidence of a statistically significant association between VTE and testosterone (OR 1.41, 95%CI 0.96-2.07). Heterogeneity was high (I-squared = 84.4%). The association remained nonsignificant when the analysis was stratified by study design: RCTs (2.05, 95% CI 0.78-5.39); cohort (1.06, 95% CI 0.85-1.33); and case-control (1.34, 95% CI 0.78-2.28). The overall risk of bias was moderate. CONCLUSIONS: The current evidence is of low certainty but does not support an association between testosterone use and VTE in men.

Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies.

BACKGROUND: Several pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology. OBJECTIVE: We conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations. STUDY SELECTION: Multiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model. FINDINGS: 30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD -0.90 (95% CI -1.58 to -0.22)) and improving quality of life scores assessed by the St George's Respiratory Questionnaire (WMD -6.07 (95% CI -10.7 to -1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy. CONCLUSIONS: Moderate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.

Treatment Effect in Earlier Trials of Patients With Chronic Medical Conditions: A Meta-Epidemiologic Study.

OBJECTIVE: To determine whether the early trials in chronic medical conditions demonstrate an effect size that is larger than that in subsequent trials. METHODS: We identified randomized controlled trials (RCTs) evaluating a drug or device in patients with chronic medical conditions through meta-analyses (MAs) published between January 1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact factor. We estimated the prevalence of having the largest effect size or heterogeneity in the first 2 published trials. We evaluated the association of the exaggerated early effect with several a priori hypothesized explanatory variables. RESULTS: We included 70 MAs that had included a total of 930 trials (average of 13 [range, 5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity in the first 2 trials) was 37%. These early trials had an effect size that was on average 2.67 times larger than the overall pooled effect size (ratio of relative effects, 2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly associated with trial size; number of events; length of follow-up; intervention duration; number of study sites; inpatient versus outpatient setting; funding source; stopping a trial early; adequacy of random sequence generation, allocation concealment, or blinding; loss to follow-up or the test for publication bias. CONCLUSION: Trials evaluating treatments of chronic medical conditions published early in the chain of evidence commonly demonstrate an exaggerated treatment effect compared with subsequent trials. At the present time, this phenomenon remains unpredictable. Considering the increasing morbidity and mortality of chronic medical conditions, decision makers should act on early evidence with caution.

Readability of Online Health Information: A Meta-Narrative Systematic Review.

Online health information should meet the reading level for the general public (set at sixth-grade level). Readability is a key requirement for information to be helpful and improve quality of care. The authors conducted a systematic review to evaluate the readability of online health information in the United States and Canada. Out of 3743 references, the authors included 157 cross-sectional studies evaluating 7891 websites using 13 readability scales. The mean readability grade level across websites ranged from grade 10 to 15 based on the different scales. Stratification by specialty, health condition, and type of organization producing information revealed the same findings. In conclusion, online health information in the United States and Canada has a readability level that is inappropriate for general public use. Poor readability can lead to misinformation and may have a detrimental effect on health. Efforts are needed to improve readability and the content of online health information.

Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: A systematic review and meta-analysis.

Hepatocellular carcinoma (HCC) is a complex disease most commonly arising in the background of chronic liver disease. In the past two decades, there has been a significant increase in our understanding of both the clinical and molecular heterogeneity of HCC. There has been a robust increase in clinical trial activity in patients with poor prognostic factors, such as macrovascular invasion and extrahepatic spread (EHS). We aimed to synthesize the evidence for the treatment of patients with advanced HCC based on these baseline characteristics, including patients with both Child-Pugh (CP) scores of A and B. A comprehensive search of several databases from each database inception to February 15, 2016 any language was conducted. We included 14 studies (three randomized controlled studies [RCTs] and 11 observational studies). We included studies that compared sorafenib, transarterial bland embolization/transarterial chemoembolization, yttrium-90/radiation therapy, ablation (or combination), and no therapy. Two RCTs comparing sorafenib to best supportive care demonstrated a consistent improvement in overall survival (OS) for patients with advanced HCC and metastatic vascular invasion (MVI) and/or EHS and CP A liver disease (hazard ratio, 0.66 [95% confidence interval, 0.51-0.87]; I2 = 0%). Several observational studies evaluated locoregional therapies alone or in combination with other treatments and were limited by very-low-quality of evidence. This was true for both patients with EHS and MVI. CONCLUSION: In patients with advanced HCC and CP A liver function, sorafenib is the only treatment that has been shown to improve OS in randomized studies. High-quality data supporting the use of other treatment modalities in this setting, or in the setting of patients with less compensated (CP B) liver disease, are lacking. (Hepatology 2018;67:422-435).