Effectiveness of BNT162b2 COVID-19 primary series vaccination in children aged 5-17 years in the United States: a cohort study.

BACKGROUND: COVID-19 vaccines are authorized for use in children in the United States; real-world assessment of vaccine effectiveness in children is needed. This study's objective was to estimate the effectiveness of receiving a complete primary series of monovalent BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in US children. METHODS: This cohort study identified children aged 5-17 years vaccinated with BNT162b2 matched with unvaccinated children. Participants and BNT162b2 vaccinations were identified in Optum and CVS Health insurance administrative claims databases linked with Immunization Information System (IIS) COVID-19 vaccination records from 16 US jurisdictions between December 11, 2020, and May 31, 2022 (end date varied by database and IIS). Vaccinated children were followed from their first BNT162b2 dose and matched to unvaccinated children on calendar date, US county of residence, and demographic and clinical factors. Censoring occurred if vaccinated children failed to receive a timely dose 2 or if unvaccinated children received any dose. Two COVID-19 outcome definitions were evaluated: COVID-19 diagnosis in any medical setting and COVID-19 diagnosis in hospitals/emergency departments (EDs). Propensity score-weighted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with Cox proportional hazards models, and vaccine effectiveness (VE) was estimated as 1 minus HR. VE was estimated overall, within age subgroups, and within variant-specific eras. Sensitivity, negative control, and quantitative bias analyses evaluated various potential biases. RESULTS: There were 453,655 eligible vaccinated children one-to-one matched to unvaccinated comparators (mean age 12 years; 50% female). COVID-19 hospitalizations/ED visits were rare in children, regardless of vaccination status (Optum, 41.2 per 10,000 person-years; CVS Health, 44.1 per 10,000 person-years). Overall, vaccination was associated with reduced incidence of any medically diagnosed COVID-19 (meta-analyzed VE = 38% [95% CI, 36-40%]) and hospital/ED-diagnosed COVID-19 (meta-analyzed VE = 61% [95% CI, 56-65%]). VE estimates were lowest among children 5-11 years and during the Omicron-variant era. CONCLUSIONS: Receipt of a complete BNT162b2 vaccine primary series was associated with overall reduced medically diagnosed COVID-19 and hospital/ED-diagnosed COVID-19 in children; observed VE estimates differed by age group and variant era. REGISTRATION: The study protocol was publicly posted on the BEST Initiative website ( https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf ).

Effectiveness of monovalent COVID-19 booster/additional vaccine doses in the United States.

Background: Monovalent booster/additional doses of COVID-19 vaccines were first authorized in August 2021 in the United States. We evaluated the real-world effectiveness of receipt of a monovalent booster/additional dose of COVID-19 vaccine compared with receiving a primary vaccine series without a booster/additional dose. Methods: Cohorts of individuals receiving a COVID-19 booster/additional dose after receipt of a complete primary vaccine series were identified in 2 administrative insurance claims databases (Optum, CVS Health) supplemented with state immunization information system data between August 2021 and March 2022. Individuals with a complete primary series but without a booster/additional dose were one-to-one matched to boosted individuals on calendar date, geography, and clinical factors. COVID-19 diagnoses were identified in any medical setting, or specifically in hospitals/emergency departments (EDs). Propensity score-weighted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models; vaccine effectiveness (VE) was estimated as 1 minus the HR by vaccine brand overall and within subgroups of variant-specific eras, immunocompromised status, and homologous/heterologous booster status. Results: Across both data sources, we identified 752,165 matched pairs for BNT162b2, 410,501 for mRNA-1273, and 11,398 for JNJ-7836735. For any medically diagnosed COVID-19, meta-analyzed VE estimates for BNT162b2, mRNA-1273, and JNJ-7836735, respectively, were: BNT162b2, 54% (95% CI, 53%-56%); mRNA-1273, 58% (95% CI, 56%-59%); JNJ-7836735, 34% (95% CI, 23%-44%). For hospital/ED-diagnosed COVID-19, VE estimates ranged from 70% to 76%. VE was generally lower during the Omicron era than the Delta era and for immunocompromised individuals. There was little difference observed by homologous or heterologous booster status. Conclusion: The original, monovalent booster/additional doses were reasonably effective in real-world use among the populations for which they were indicated during the study period. Additional studies may be informative in the future as new variants emerge and new vaccines become available.Registration: The study protocol was publicly posted on the BEST Initiative website (https://bestinitiative.org/wp-content/uploads/2022/03/C19-VX-Effectiveness-Protocol_2022_508.pdf).

Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

BACKGROUND: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.) are needed to contextualize reports following COVID-19 vaccination. METHODS: We estimated annual and monthly IRs of overall TTS, common site TTS, and unusual site TTS for adults aged 18-64 years in Carelon Research and MarketScan commercial claims (2017-Oct 2020), CVS Health and Optum commercial claims (2019-Oct 2020), and adults aged ≥ 65 years using CMS Medicare claims (2019-Oct 2020); IRs were stratified by age, sex, and race/ethnicity (CMS Medicare). RESULTS: Across data sources, annual IRs for overall TTS were similar between Jan-Dec 2019 and Jan-Oct 2020. Rates were higher in Medicare (IRs: 370.72 and 365.63 per 100,000 person-years for 2019 and 2020, respectively) than commercial data sources (MarketScan IRs: 24.21 and 24.06 per 100,000 person-years; Optum IRs: 32.60 and 31.29 per 100,000 person-years; Carelon Research IRs: 24.46 and 26.16 per 100,000 person-years; CVS Health IRs: 30.31 and 30.25 per 100,000 person-years). Across years and databases, common site TTS IRs increased with age and were higher among males. Among adults aged ≥ 65 years, the common site TTS IR was highest among non-Hispanic black adults. Annual unusual site TTS IRs ranged between 2.02 and 3.04 (commercial) and 12.49 (Medicare) per 100,000 person-years for Jan-Dec 2019; IRs ranged between 1.53 and 2.67 (commercial) and 11.57 (Medicare) per 100,000 person-years for Jan-Oct 2020. Unusual site TTS IRs were higher in males and increased with age in commercial data sources; among adults aged ≥ 65 years, IRs decreased with age and were highest among non-Hispanic American Indian/Alaska native adults. CONCLUSION: TTS IRs were generally similar across years, higher for males, and increased with age. These rates may contribute to surveillance of post-vaccination TTS.

Are Exercise Interventions in Clinical Trials for Chronic Low Back Pain Dosed Appropriately to Meet the World Health Organization's Physical Activity Guidelines?

OBJECTIVE: This study aimed to estimate the proportion of exercise interventions tested in clinical trials of people with chronic low back pain (CLBP) that meet the World Health Organization's (WHO) physical activity guidelines. METHODS: A secondary analysis of the 2021 Cochrane review of exercise therapy for CLBP was performed. Data from each study were extracted by 1 reviewer and were checked by a second reviewer. Data extracted related to the frequency, duration and intensity of each exercise intervention, and the proportion of exercise interventions that met the WHO's physical activity guidelines (aerobic, muscle strengthening, or both) were determined. RESULTS: The 249 included trials comprised 426 exercise interventions. Few interventions reported an exercise type and dose consistent with the WHO guidelines (aerobic: 1.6%, muscle strengthening: 5.6%, both: 1.6%). Poor reporting of exercise intensity limited our ability to determine whether interventions met the guidelines. CONCLUSION: Few interventions tested in clinical trials for people with CLBP prescribe an exercise type and dose consistent with the WHO guidelines. Therefore, they do not appear sufficiently dosed to achieve broader health outcomes. Future trials should investigate the effect of WHO guideline-recommended exercise interventions on patient-reported outcomes (pain and disability) as well as health-related outcomes in people with CLBP. IMPACT: This exploratory analysis showed the lack of exercise interventions in the CLBP literature that meet the WHO's physical activity guidelines. With people in chronic pain groups, such as people with CLBP, being at higher risk for noncommunicable disease, it appears this is a key consideration for exercise practitioners when designing interventions for people with CLBP.

Systematic Review Procedures for the World Health Organization (WHO) Evidence Syntheses on Benefits and Harms of Structured and Standardized Education/Advice, Structured Exercise Programs, Transcutaneous Electrical Nerve Stimulation (TENS), and Needling Therapies for the Management of Chronic Low Back Pain in Adults.

As commissioned by the WHO, we updated and expanded the scope of four systematic reviews to inform its (in development) clinical practice guideline for the management of CPLBP in adults, including older adults. Methodological details and results of each review are described in the respective articles in this series. In the last article of this series, we discuss methodological considerations, clinical implications and recommendations for future research.

Systematic Review to Inform a World Health Organization (WHO) Clinical Practice Guideline: Benefits and Harms of Structured Exercise Programs for Chronic Primary Low Back Pain in Adults.

PURPOSE: Evaluate benefits and harms of structured exercise programs for chronic primary low back pain (CPLBP) in adults to inform a World Health Organization (WHO) standard clinical guideline. METHODS: We searched for randomized controlled trials (RCTs) in electronic databases (inception to 17 May 2022). Eligible RCTs targeted structured exercise programs compared to placebo/sham, usual care, or no intervention (including comparison interventions where the attributable effect of exercise could be isolated). We extracted outcomes, appraised risk of bias, conducted meta-analyses where appropriate, and assessed certainty of evidence using GRADE. RESULTS: We screened 2503 records (after initial screening through Cochrane RCT Classifier and Cochrane Crowd) and 398 full text RCTs. Thirteen RCTs rated with overall low or unclear risk of bias were synthesized. Assessing individual exercise types (predominantly very low certainty evidence), pain reduction was associated with aerobic exercise and Pilates vs. no intervention, and motor control exercise vs. sham. Improved function was associated with mixed exercise vs. usual care, and Pilates vs. no intervention. Temporary increased minor pain was associated with mixed exercise vs. no intervention, and yoga vs. usual care. Little to no difference was found for other comparisons and outcomes. When pooling exercise types, exercise vs. no intervention probably reduces pain in adults (8 RCTs, SMD = - 0.33, 95% CI - 0.58 to - 0.08) and functional limitations in adults and older adults (8 RCTs, SMD = - 0.31, 95% CI - 0.57 to - 0.05) (moderate certainty evidence). CONCLUSIONS: With moderate certainty, structured exercise programs probably reduce pain and functional limitations in adults and older people with CPLBP.

Improving Rehabilitation Research to Optimize Care and Outcomes for People with Chronic Primary Low Back Pain: Methodological and Reporting Recommendations from a WHO Systematic Review Series.

Chronic primary low back pain (CPLBP) is a prevalent and disabling condition that often requires rehabilitation interventions to improve function and alleviate pain. This paper aims to advance future research, including systematic reviews and randomized controlled trials (RCTs), on CPLBP management. We provide methodological and reporting recommendations derived from our conducted systematic reviews, offering practical guidance for conducting robust research on the effectiveness of rehabilitation interventions for CPLBP. Our systematic reviews contributed to the development of a WHO clinical guideline for CPLBP. Based on our experience, we have identified methodological issues and recommendations, which are compiled in a comprehensive table and discussed systematically within established frameworks for reporting and critically appraising RCTs. In conclusion, embracing the complexity of CPLBP involves recognizing its multifactorial nature and diverse contexts and planning for varying treatment responses. By embracing this complexity and emphasizing methodological rigor, research in the field can be improved, potentially leading to better care and outcomes for individuals with CPLBP.

Bias in the measurement of the outcome is associated with effect sizes in randomized clinical trials on exercise therapy for chronic low back pain: a meta-epidemiological study.

OBJECTIVES: To explore the relationships between the risk of bias and treatment effect estimates for exercise therapy interventions on pain intensity and physical functioning outcomes in randomized controlled trials (RCTs) involving patients with chronic low back pain. STUDY DESIGN AND SETTING: A cross-sectional meta-epidemiological study of the 230 RCTs (31,674 participants) in the 2021 'Exercise therapy for chronic low back pain' Cochrane Review were included. Study design characteristics, sample size, prospective trial registration, flowchart information, interventions, and comparisons were extracted. Independent pairs of reviewers assessed the risk of bias using the Cochrane Risk of Bias 2 tool. RESULTS: The metaregression included 220 (pain intensity) and 203 (physical functioning) effect sizes. Unadjusted and adjusted metaregression models showed no significant associations between the bias domains and pain intensity effect sizes. Only domain 'bias in the measurement of the outcome' was significantly associated with physical functioning (standardized mean difference: -0.40, 95% confidence interval: -0.77 to -0.02) when adjusted for flowchart reported (yes/no), prospective trial registration, sample size, and comparator type. CONCLUSION: The risk of bias in the measurement of the outcome could lead to slight overestimates of the effect size for physical functioning. Clinicians should consider this when they read and assess RCT results in this field. We encourage metaresearchers to replicate our findings using a consistent approach for evaluating the risk of bias (i.e., the RoB 2 tool) in other musculoskeletal conditions and interventions to investigate their generalizability.

Cervical High-Grade Squamous Intraepithelial Lesion Burden and Standard of Care Treatment Effectiveness and Safety in the United States, 2008-2018: The EACH-WOMAN Project.

OBJECTIVE: Management of cervical high-grade squamous intraepithelial lesions (HSILs), the immediate precursor of cervical cancer, consists largely of surgical treatment for women at higher risk for progression to cancer. The authors' objective was to describe the occurrence of cervical HSIL in the United States and various outcomes for women who received surgical treatment. METHODS: From a US commercial health insurer, a cohort of adult women with cervical HSIL diagnoses receiving surgical treatment within 3 months of diagnosis between January 2008 and September 2018 was identified. This cohort was followed for several outcomes, including cervical HSIL recurrence, human papillomavirus clearance, preterm birth, infection, and bleeding. RESULTS: The incidence rate of cervical HSIL declined from 2.34 (95% CI = 2.30-2.39) cases per 1,000 person-years in 2008 to 1.39 (95% CI = 1.35-1.43) cases per 1,000 person-years in 2014, remaining near that level through 2018. Among 65,527 women with cervical HSIL, 47,067 (72%) received surgical treatment within 3 months of diagnosis. Among the women receiving surgical treatment, cervical HSIL recurred in 6% of surgically treated women, whereas 45% of surgically treated women underwent subsequent virological testing that indicated human papillomavirus clearance. Preterm birth was observed in 5.9% by 5 years follow-up and bleeding and infection each at 2.2% by 7 days follow-up. CONCLUSIONS: From 2008 through 2018, the incidence of diagnosed cervical HSIL decreased for several years before stabilizing. Surgical treatment of HSIL may be beneficial in removing the precancerous lesion, but cervical HSIL may recur, and the surgery is associated with complications including preterm birth, infection, and bleeding.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

BACKGROUND: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety. METHODS: We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020. RESULTS: The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell's palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019. CONCLUSION: AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Trends in COVID-19 patient characteristics in a large electronic health record database in the United States: A cohort study.

BACKGROUND: Electronic health record (EHR) databases provide an opportunity to facilitate characterization and trends in patients with COVID-19. METHODS: Patients with COVID-19 were identified based on an ICD-10 diagnosis code for COVID-19 (U07.1) and/or a positive SARS-CoV-2 viral lab result from January 2020 to November 2020. Patients were characterized in terms of demographics, healthcare utilization, clinical comorbidities, therapies, laboratory results, and procedures/care received, including critical care, intubation/ventilation, and occurrence of death were described, overall and by month. RESULTS: There were 393,773 patients with COVID-19 and 56,996 with a COVID-19 associated hospitalization. A greater percentage of patients hospitalized with COVID-19 relative to all COVID-19 cases were older, male, African American, and lived in the Northeast and South. The most common comorbidities before admission/infection date were hypertension (40.8%), diabetes (29.5%), and obesity (23.8%), and the most common diagnoses during hospitalization were pneumonia (59.6%), acute respiratory failure (44.8%), and dyspnea (28.0%). A total of 85.7% of patients hospitalized with COVID-19 had CRP values > 10 mg/L, 75.5% had fibrinogen values > 400 mg/dL, and 76.8% had D-dimer values > 250 ng/mL. Median values for platelets, CRP, lactate dehydrogenase, D-dimer, and fibrinogen tended to decrease from January-March to November. The use of chloroquine/hydroxychloroquine during hospitalization peaked by March (71.2%) and was used rarely by May (5.1%) and less than 1% afterwards, while the use of remdesivir had increased by May (10.0%) followed by dexamethasone by June (27.7%). All-cause mortality was 3.2% overall and 15.0% among those hospitalized; 21.0% received critical care and 16.0% received intubation/ventilation/ECMO. CONCLUSIONS: This study characterizes US patients with COVID-19 and their management during hospitalization over the first eleven months of this disease pandemic.

Risk of myocarditis and pericarditis after the COVID-19 mRNA vaccination in the USA: a cohort study in claims databases.

BACKGROUND: Several passive surveillance systems reported increased risks of myocarditis or pericarditis, or both, after COVID-19 mRNA vaccination, especially in young men. We used active surveillance from large health-care databases to quantify and enable the direct comparison of the risk of myocarditis or pericarditis, or both, after mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) vaccinations. METHODS: We conducted a retrospective cohort study, examining the primary outcome of myocarditis or pericarditis, or both, identified using the International Classification of Diseases diagnosis codes, occurring 1-7 days post-vaccination, evaluated in COVID-19 mRNA vaccinees aged 18-64 years using health plan claims databases in the USA. Observed (O) incidence rates were compared with expected (E) incidence rates estimated from historical cohorts by each database. We used multivariate Poisson regression to estimate the adjusted incidence rates, specific to each brand of vaccine, and incidence rate ratios (IRRs) comparing mRNA-1273 and BNT162b2. We used meta-analyses to pool the adjusted incidence rates and IRRs across databases. FINDINGS: A total of 411 myocarditis or pericarditis, or both, events were observed among 15 148 369 people aged 18-64 years who received 16 912 716 doses of BNT162b2 and 10 631 554 doses of mRNA-1273. Among men aged 18-25 years, the pooled incidence rate was highest after the second dose, at 1·71 (95% CI 1·31 to 2·23) per 100 000 person-days for BNT162b2 and 2·17 (1·55 to 3·04) per 100 000 person-days for mRNA-1273. The pooled IRR in the head-to-head comparison of the two mRNA vaccines was 1·43 (95% CI 0·88 to 2·34), with an excess risk of 27·80 per million doses (-21·88 to 77·48) in mRNA-1273 recipients compared with BNT162b2. INTERPRETATION: An increased risk of myocarditis or pericarditis was observed after COVID-19 mRNA vaccination and was highest in men aged 18-25 years after a second dose of the vaccine. However, the incidence was rare. These results do not indicate a statistically significant risk difference between mRNA-1273 and BNT162b2, but it should not be ruled out that a difference might exist. Our study results, along with the benefit-risk profile, continue to support vaccination using either of the two mRNA vaccines. FUNDING: US Food and Drug Administration.

Predictors of critical care, mechanical ventilation, and mortality among hospitalized patients with COVID-19 in an electronic health record database.

BACKGROUND: There are limited data on risk factors for serious outcomes and death from COVID-19 among patients representative of the U.S. POPULATION: The objective of this study was to determine risk factors for critical care, ventilation, and death among hospitalized patients with COVID-19. METHODS: This was a cohort study using data from Optum's longitudinal COVID-19 electronic health record database derived from a network of healthcare provider organizations across the US. The study included patients with confirmed COVID-19 (presence of ICD-10-CM code U07.1 and/or positive SARS-CoV-2 test) between January 2020 and November 2020. Patient characteristics and clinical variables at start of hospitalization were evaluated for their association with subsequent serious outcomes (critical care, mechanical ventilation, and death) using odds ratios (OR) and 95% confidence intervals (CI) from logistic regression, adjusted for demographic variables. RESULTS: Among 56,996 hospitalized COVID-19 patients (49.5% male and 72.4% ≥ 50 years), 11,967 received critical care, 9136 received mechanical ventilation, and 8526 died. The median duration of hospitalization was 6 days (IQR: 4, 11), and this was longer among patients that experienced an outcome: 11 days (IQR: 6, 19) for critical care, 15 days (IQR: 8, 24) for mechanical ventilation, and 10 days (IQR: 5, 17) for death. Dyspnea and hypoxemia were the most prevalent symptoms and both were associated with serious outcomes in adjusted models. Additionally, temperature, C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, and oxygen saturation measured during hospitalization were predictors of serious outcomes as were several in-hospital diagnoses. The strongest associations were observed for acute respiratory failure (critical care: OR, 6.30; 95% CI, 5.99-6.63; ventilation: OR, 8.55; 95% CI, 8.02-9.11; death: OR, 3.36; 95% CI, 3.17-3.55) and sepsis (critical care: OR, 4.59; 95% CI, 4.39-4.81; ventilation: OR, 5.26; 95% CI, 5.00-5.53; death: OR, 4.14; 95% CI, 3.92-4.38). Treatment with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers during hospitalization were inversely associated with death (OR, 0.57; 95% CI, 0.54-0.61). CONCLUSIONS: We identified several clinical characteristics associated with receipt of critical care, mechanical ventilation, and death among COVID-19 patients. Future studies into the mechanisms that lead to severe COVID-19 disease are warranted.

Low Back Pain in a Nova Scotian Emergency Department: Prevalence and Patient Characteristics in the Older Adult Patient Population.

Low back pain is a major cause of disability in older adults, and results in many emergency department visits each year. Characteristics of the older back pain population are largely unknown. We conducted a retrospective study to examine the prevalence and patient characteristics for older (≥ 65 years of age) and younger (16-64 years of age) adults presenting with back pain. Study objectives were to describe the characteristics of older adults with back pain presenting to an emergency department and to identify age-group-based differences in management. Older adults were most commonly diagnosed with non-specific low back pain (49%). For older adults with this diagnosis, the length of stay was 2.1 times longer (p < 0.001), and odds of being admitted to the hospital were 5.1 times higher (p < 0.001) than for younger adults. Patterns of management are different for younger and older adults with low back pain; this information can be used to direct future resource planning.

Incidence of VTE in Patients With OSA: A Cohort Study.

BACKGROUND: Previous studies suggesting that OSA may be an independent risk factor for VTE have been limited by reliance on administrative data and lack of adjustment for clinical variables, including obesity. RESEARCH QUESTION: Does OSA confer an independent risk of incident VTE among a large clinical cohort referred for sleep-disordered breathing evaluation? STUDY DESIGN AND METHODS: We analyzed the clinical outcomes of 31,309 patients undergoing overnight polysomnography within a large hospital system. We evaluated the association of OSA severity with incident VTE, using Cox proportional hazards modeling accounting for age, sex, BMI, and common comorbid conditions. RESULTS: Patients were of mean age 50.4 years, and 50.1% were female. There were 1,791 VTE events identified over a mean follow-up of 5.3 years. In age- and sex-adjusted analyses, each 10-event/h increase in the apnea-hypopnea index was associated with a 4% increase in incident VTE risk (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). After adjusting for BMI, this association disappeared (HR, 1.01; 95% CI, 0.99-1.03). In contrast, nocturnal hypoxemia had an independent association with incident VTE. Patients with > 50% sleep time spent with oxyhemoglobin saturation < 90% are at 48% increased VTE risk compared with those without nocturnal hypoxemia (HR, 1.48; 95% CI, 1.16-1.69). INTERPRETATION: In this large cohort, we found that patients with more severe OSA as measured by the apnea-hypopnea index are more likely to have incident VTE. Adjusted analyses suggest that this association is explained on the basis of confounding by obesity. However, severe nocturnal hypoxemia may be a mechanism by which OSA heightens VTE risk.

Some types of exercise are more effective than others in people with chronic low back pain: a network meta-analysis.

QUESTION: What are the effects of specific types of exercise treatments on pain intensity and functional limitation outcomes for adults with chronic low back pain? DESIGN: Systematic review with network meta-analysis of randomised controlled trials. PARTICIPANTS: Adults with non-specific low back pain for ≥ 12 weeks. INTERVENTION: Exercise treatments prescribed or planned by a health professional that involved conducting specific activities, postures and/or movements with a goal to improve low back pain outcomes. OUTCOME MEASURES: Pain intensity (eg, visual analogue scale or numerical rating scale) and back-related functional limitations (eg, Roland Morris Disability Questionnaire or Oswestry Disability Index), each standardised to range from 0 to 100. RESULTS: This review included 217 randomised controlled trials with 20,969 participants and 507 treatment groups. Most exercise types were more effective than minimal treatment for pain and functional limitation outcomes. Network meta-analysis results were compatible with moderate to clinically important treatment effects for Pilates, McKenzie therapy, and functional restoration (pain only) and flexibility exercises (function only) compared with minimal treatment, other effective treatments and other exercise types. The estimated mean differences for these exercise types compared with minimal treatment ranged from -15 to -19 for pain and from -10 to -12 for functional limitation. CONCLUSION: This review found evidence that Pilates, McKenzie therapy and functional restoration were more effective than other types of exercise treatment for reducing pain intensity and functional limitations. Nevertheless, people with chronic low back pain should be encouraged to perform the exercise that they enjoy to promote adherence. REGISTRATION: DOI:10.1002/14651858.CD009790.

Exercise therapy for chronic low back pain.

BACKGROUND: Low back pain has been the leading cause of disability globally for at least the past three decades and results in enormous direct healthcare and lost productivity costs. OBJECTIVES: The primary objective of this systematic review is to assess the impact of exercise treatment on pain and functional limitations in adults with chronic non-specific low back pain compared to no treatment, usual care, placebo and other conservative treatments. SEARCH METHODS: We searched CENTRAL (which includes the Cochrane Back and Neck trials register), MEDLINE, Embase, CINAHL, PsycINFO, PEDro, SPORTDiscus, and trials registries (ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform), and conducted citation searching of relevant systematic reviews to identify additional studies. The review includes data for trials identified in searches up to 27 April 2018. All eligible trials have been identified through searches to 7 December 2020, but have not yet been extracted; these trials will be integrated in the next update. SELECTION CRITERIA: We included randomised controlled trials that assessed exercise treatment compared to no treatment, usual care, placebo or other conservative treatment on the outcomes of pain or functional limitations for a population of adult participants with chronic non-specific low back pain of more than 12 weeks' duration. DATA COLLECTION AND ANALYSIS: Two authors screened and assessed studies independently, with consensus. We extracted outcome data using electronic databases; pain and functional limitations outcomes were re-scaled to 0 to 100 points for meta-analyses where 0 is no pain or functional limitations. We assessed risk of bias using the Cochrane risk of bias (RoB) tool and used GRADE to evaluate the overall certainty of the evidence. When required, we contacted study authors to obtain missing data. To interpret meta-analysis results, we considered a 15-point difference in pain and a 10-point difference in functional limitations outcomes to be clinically important for the primary comparison of exercise versus no treatment, usual care or placebo. MAIN RESULTS: We included 249 trials of exercise treatment, including studies conducted in Europe (122 studies), Asia (38 studies), North America (33 studies), and the Middle East (24 studies). Sixty-one per cent of studies (151 trials) examined the effectiveness of two or more different types of exercise treatment, and 57% (142 trials) compared exercise treatment to a non-exercise comparison treatment. Study participants had a mean age of 43.7 years and, on average, 59% of study populations were female. Most of the trials were judged to be at risk of bias, including 79% at risk of performance bias due to difficulty blinding exercise treatments. We found moderate-certainty evidence that exercise treatment is more effective for treatment of chronic low back pain compared to no treatment, usual care or placebo comparisons for pain outcomes at earliest follow-up (MD -15.2, 95% CI -18.3 to -12.2), a clinically important difference. Certainty of evidence was downgraded mainly due to heterogeneity. For the same comparison, there was moderate-certainty evidence for functional limitations outcomes (MD -6.8 (95% CI -8.3 to -5.3); this finding did not meet our prespecified threshold for minimal clinically important difference. Certainty of evidence was downgraded mainly due to some evidence of publication bias.  Compared to all other investigated conservative treatments, exercise treatment was found to have improved pain (MD -9.1, 95% CI -12.6 to -5.6) and functional limitations outcomes (MD -4.1, 95% CI -6.0 to -2.2). These effects did not meet our prespecified threshold for clinically important difference. Subgroup analysis of pain outcomes suggested that exercise treatment is probably more effective than education alone (MD -12.2, 95% CI -19.4 to -5.0) or non-exercise physical therapy (MD -10.4, 95% CI -15.2 to -5.6), but with no differences observed for manual therapy (MD 1.0, 95% CI -3.1 to 5.1). In studies that reported adverse effects (86 studies), one or more adverse effects were reported in 37 of 112 exercise groups (33%) and 12 of 42 comparison groups (29%). Twelve included studies reported measuring adverse effects in a systematic way, with a median of 0.14 (IQR 0.01 to 0.57) per participant in the exercise groups (mostly minor harms, e.g. muscle soreness), and 0.12 (IQR 0.02 to 0.32) in comparison groups. AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that exercise is probably effective for treatment of chronic low back pain compared to no treatment, usual care or placebo for pain. The observed treatment effect for the exercise compared to no treatment, usual care or placebo comparisons is small for functional limitations, not meeting our threshold for minimal clinically important difference. We also found exercise to have improved pain (low-certainty evidence) and functional limitations outcomes (moderate-certainty evidence) compared to other conservative treatments; however, these effects were small and not clinically important when considering all comparisons together. Subgroup analysis suggested that exercise treatment is probably more effective than advice or education alone, or electrotherapy, but with no differences observed for manual therapy treatments.

Are Emergency Medicine Provider Characteristics Associated With Diagnostic Imaging for Low Back Pain?

Background Low back pain (LBP) is one of the most common reasons for presentation to the emergency department (ED). LBP is most commonly non-specific or mechanical in nature yet can be debilitating. Diagnostic imaging (DI) is commonly ordered contrary to guideline recommendations for patients with LBP. This study seeks to determine if physician characteristics are associated with ordering of DI for patients with non-specific or mechanical LBP in the ED. These characteristics include physician sex, age, experience level, location of residency training, and full-time status. Methodology We included all patients presenting to the ED of a Canadian tertiary care center with a diagnosis of non-specific or mechanical LBP between January 2015 and June 2018. We tracked the use of DI for physicians caring for patients presenting to the ED over this period. Simple and multivariable logistic regression analyses were performed, controlling for patient characteristics, to identify provider characteristics that were independently associated with DI use. Results Internationally trained physicians were less likely to order diagnostic radiographs than Canadian trained physicians (odds ratio [OR], 0.625; 95% confidence interval [CI], 0.48-0.95), while middle-aged physicians ordered more computed tomography scans (OR, 6.34; 95% CI, 1.52-26.52) compared to younger physicians; there was no significant difference between younger and older physicians. Conclusions Few physician characteristics were associated with any DI ordering for non-specific or mechanical LBP. The likelihood of receiving DI for non-specific or mechanical LBP may be more strongly related to unmeasured patient characteristics, settings, or logistical factors.

Search methods for prognostic factor systematic reviews: a methodologic investigation.

OBJECTIVE: This study retroactively investigated the search used in a 2019 review by Hayden et al., one of the first systematic reviews of prognostic factors that was published in the Cochrane Library. The review was designed to address recognized weaknesses in reviews of prognosis by using multiple supplementary search methods in addition to traditional electronic database searching. METHODS: The authors used four approaches to comprehensively assess aspects of systematic review literature searching for prognostic factor studies: (1) comparison of search recall of broad versus focused electronic search strategies, (2) linking of search methods of origin for eligible studies, (3) analysis of impact of supplementary search methods on meta-analysis conclusions, and (4) analysis of prognosis filter performance. RESULTS: The review's focused electronic search strategy resulted in a 91% reduction in recall, compared to a broader version. Had the team relied on the focused search strategy without using supplementary search methods, they would have missed 23 of 58 eligible studies that were indexed in MEDLINE; additionally, the number of included studies in 2 of the review's primary outcome meta-analyses would have changed. Using a broader strategy without supplementary searches would still have missed 5 studies. The prognosis filter used in the review demonstrated the highest sensitivity of any of the filters tested. CONCLUSIONS: Our study results support recommendations for supplementary search methods made by prominent systematic review methodologists. Leaving out any supplemental search methods would have resulted in missed studies, and these omissions would not have been prevented by using a broader search strategy or any of the other prognosis filters tested.

Prolonged opioid use among opioid-naive individuals after prescription for nonspecific low back pain in the emergency department.

ABSTRACT: Low back pain is a leading cause of disability globally. It is a common reason for presentation to the emergency department where opioids are commonly prescribed. This is a retrospective cohort study of opioid-naive adults with low back pain presenting to 1 of 4 emergency departments in Nova Scotia. We use routinely collected administrative clinical and drug-use data (July 2010-November 2017) to investigate the prevalence of prolonged opioid use and associated individual and prescription characteristics. In total, 23,559 eligible individuals presented with nonspecific low back pain, with 84.4% being opioid-naive. Our study population included 4023 opioid-naive individuals who filled a new opioid prescription within 7 days after their index emergency department visit (24.4%). The prevalence of prolonged opioid use after a new opioid prescription for low back pain (filling an opioid prescription 8-90 days after the emergency department visit and filling a subsequent prescription ±30 days of 6 months) was 4.6% (185 individuals). Older age and female sex were associated with clinically important increased odds of prolonged opioid use. First prescription average >90 morphine milligram equivalents/day (odds ratio 1.6, 95% confidence interval 1.0-2.6) and greater than 7-day supply (1.9, 1.1-3.1) were associated with prolonged opioid use in adjusted models. We found evidence of declining opioid prescriptions over the study period, but that 24.3% of first opioid prescriptions in 2016 would not have aligned with current guideline recommendations. Our study provides evidence to support a cautious approach to prescribing in opioid-naive populations.