Cannabis Use in Pregnancy and Neonatal Outcomes: A Systematic Review and Meta-Analysis.

Objective: To determine whether prenatal cannabis use alone increases the likelihood of fetal and neonatal morbidity and mortality. Study Design: We searched bibliographic databases, such as PubMed, Embase, Scopus, Cochrane reviews, PsycInfo, MEDLINE, Clinicaltrials.gov, and Google Scholar from inception through February 14, 2022. Cohort or case-control studies with prespecified fetal or neonatal outcomes in pregnancies with prenatal cannabis use. Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small-for-gestational-age (SGA), birthweight (grams), and perinatal mortality. Two independent reviewers screened studies. Studies were extracted by one reviewer and confirmed by a second using a predefined template. Risk of bias assessment of studies, using the Newcastle-Ottawa Quality Assessment Scale, and Grading of Recommendations Assessment, Development, and Evaluation for evaluating the certainty of evidence for select outcomes were performed by two independent reviewers with disagreements resolved by a third. Random effects meta-analyses were conducted, using adjusted and unadjusted effect estimates, to compare groups according to prenatal exposure to cannabis use status. Results: Fifty-three studies were included. Except for birthweight, unadjusted and adjusted meta-analyses had similar results. We found very-low- to low-certainty evidence that cannabis use during pregnancy was significantly associated with greater odds of PTB (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.19 to 1.69; I2, 93%; p=0.0001), SGA (aOR, 1.76; 95% CI, 1.52 to 2.05; I2, 86%; p<0.0001), and perinatal mortality (aOR, 1.5; 95% CI, 1.39 to 1.62; I2, 0%; p<0.0001), but not significantly different for birthweight (mean difference, -40.69 g; 95% CI, -124.22 to 42.83; I2, 85%; p=0.29). Because of substantial heterogeneity, we also conducted a narrative synthesis and found comparable results to meta-analyses. Conclusion: Prenatal cannabis use was associated with greater odds of PTB, SGA, and perinatal mortality even after accounting for prenatal tobacco use. However, our confidence in these findings is limited. Limitations of most existing studies was the failure to not include timing or quantity of cannabis use. This review can help guide health care providers with counseling, management, and addressing the limited existing safety data. Protocol Registration: PROSPERO CRD42020172343.

Lung cancer diagnosis and mortality beyond 15 years since quit in individuals with a 20+ pack-year history: A systematic review.

Current US lung cancer screening recommendations limit eligibility to adults with a pack-year (PY) history of ≥20 years and the first 15 years since quit (YSQ). The authors conducted a systematic review to better understand lung cancer incidence, risk and mortality among otherwise eligible individuals in this population beyond 15 YSQ. The PubMed and Scopus databases were searched through February 14, 2023, and relevant articles were searched by hand. Included studies examined the relationship between adults with both a ≥20-PY history and ≥15 YSQ and lung cancer diagnosis, mortality, and screening ineligibility. One investigator abstracted data and a second confirmed. Two investigators independently assessed study quality and certainty of evidence (COE) and resolved discordance through consensus. From 2636 titles, 22 studies in 26 articles were included. Three studies provided low COE of elevated lung cancer incidence beyond 15 YSQ, as compared with people who never smoked, and six studies provided moderate COE that the risk of a lung cancer diagnosis after 15 YSQ declines gradually, but with no clinically significant difference just before and after 15 YSQ. Studies examining lung cancer-related disparities suggest that outcomes after 15 YSQ were similar between African American/Black and White participants; increasing YSQ would expand eligibility for African American/Black individuals, but for a significantly larger proportion of White individuals. The authors observed that the risk of lung cancer not only persists beyond 15 YSQ but that, compared with individuals who never smoked, the risk may remain significantly elevated for 2 or 3 decades. Future research of nationally representative samples with consistent reporting across studies is needed, as are better data from which to examine the effects on health disparities across different populations.

Factors Associated with Health Inequalities in Infectious Disease Pandemics Predating COVID-19 in the United States: A Systematic Review.

Objective: Previous pandemics may offer evidence on mediating factors that contributed to disparities in infection and poor outcomes, which could inform the effort to mitigate potential unequal outcomes during the current COVID-19 pandemic. This systematic review sought to examine those factors. Methods: We searched MEDLINE, PsycINFO, and Cochrane to May 2020. We included studies examining health disparities in adult U.S. populations during infectious disease epidemics or pandemics. Two investigators screened abstracts and full text. We assessed study quality using the Newcastle/Ottawa Scale or the Critical Appraisal Skills Programme Checklist for Qualitative Studies. Results: Sixteen articles were included, of which 14 focused on health disparities during the 2009 H1N1 influenza pandemic. Studies showed that disparities during the H1N1 pandemic were more related to differential exposure to the virus than to susceptibility or access to care. Overall, pandemic-related disparities emanate primarily from inequalities in social conditions that place racial and ethnic minorities and low socioeconomic status populations at greater risk of exposure and infection, rather than individual-level factors such as health behaviors and comorbidities. Conclusions: Policy- and systems-level interventions should acknowledge and address these social determinants of heightened risk, and future research should evaluate the effects of such interventions to avoid further exacerbation of health inequities during the current and future pandemics.

Disparities in H1N1 Vaccination Rates: a Systematic Review and Evidence Synthesis to Inform COVID-19 Vaccination Efforts.

BACKGROUND: Data suggest that there were disparities in H1N1 vaccine uptake, and these may inform COVID-19 vaccination efforts. We conducted a systematic review to evaluate disparities in H1N1 vaccine uptake, factors contributing to disparities, and interventions to reduce them. METHODS: We searched English-language articles in MEDLINE ALL, PsycINFO, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials from database inception through May 8, 2020. Observational studies examining H1N1 vaccine uptake by race/ethnicity, socioeconomic status, rurality, and disability status in US settings were included. Two reviewers independently assessed study eligibility. Single-reviewer data abstraction was confirmed by a second reviewer. We conducted independent dual quality assessment, and collective strength of evidence assessment. RESULTS: We included 21 studies. African American/Black, Latino, and low-socioeconomic status participants had disproportionately lower H1N1 vaccination rates (low- to moderate-strength evidence). However, Latinos were more likely than Whites to intend to be vaccinated, and African American/Blacks and participants with lower-socioeconomic status were just as likely to intend to be vaccinated as their White and higher-socioeconomic status counterparts (low-strength evidence). Vaccine uptake for other groups has been insufficiently studied. Factors potentially contributing to disparities in vaccine uptake included barriers to vaccine access, inadequate information, and concerns about vaccine safety and efficacy. Studies were largely cross-sectional. Many of the studies are a decade old and were conducted in the context of a different pandemic. The categorization of racial and ethnic groups was not consistent across studies and not all groups were well-studied. DISCUSSION: Efforts to avoid disparities in COVID-19 vaccination uptake should prioritize vaccine accessibility and convenience in African American/Black, Latino, and low-SES communities; engage trusted stakeholders to share vaccine information; and address concerns about vaccine safety and efficacy. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. PROTOCOL REGISTRATION: PROSPERO CRD42020187078.

Biological measures and diagnostic tools for Gulf War Illness - A systematic review.

AIMS: Gulf War Illness (GWI) is a chronic multisymptom illness with debated etiology and pathophysiology. This systematic review catalogues studies of validated biological tests for diagnosing GWI and of associations between biological measures and GWI for their promise as biomarkers. MAIN METHODS: We searched multiple sources through February 2020 for studies of diagnostic tests of GWI and of associations between biological measures and GWI. We abstracted data on study design, demographics, and outcomes. We assessed the risk of bias of included studies. KEY FINDINGS: We did not identify any studies validating tests of biomarkers that distinguish cases of GWI from non-cases. We included the best-fitting studies, 32 completed and 24 ongoing or unpublished studies, of associations between GWI and biological measures. The less well-fitting studies (n = 77) were included in a Supplementary Table. Most studies were of the central nervous and immune systems and indicated a significant association of the biological measure with GWI case status. Biological measures were heterogeneous across studies. SIGNIFICANCE: Our review indicates that there are no existing validated biological tests to determine GWI case status. Many studies have assessed the potential association between a variety of biological measures and GWI, the majority of which pertain to the immune and central nervous systems. More importantly, while most studies indicated a significant association between biological measures and GWI case status, the biological measures across studies were extremely heterogeneous. Due to the heterogeneity, the focus of the review is to map out what has been examined, rather than synthesize information.

A qualitative study of VHA clinicians' knowledge and perspectives on cannabis for medical purposes.

BACKGROUND: The legalization of cannabis is expanding across the USA, and its use has increased significantly, including among Veterans. Although the Veterans Health Administration (VHA) abides by the classification of cannabis as a Schedule I substance, it recently recommended that clinicians discuss cannabis with their patients. Little is known about VHA clinicians' perspectives on and knowledge of cannabis. OBJECTIVE: We sought to better understand clinicians' attitudes, beliefs, knowledge and communication with patients regarding cannabis. METHODS: We conducted semi-structured phone interviews with 14 VHA clinicians. Interviews were audio-recorded, transcribed verbatim and analysed using qualitative thematic analysis. RESULTS: VA clinicians described ambivalence towards cannabis for therapeutic purposes and identified several factors that inhibit conversations about cannabis use with their patients including discomfort with the lack of product standardization; lack of research examining the effectiveness and risks of cannabis use; unfamiliarity with pharmacology, formulations, and dosing of cannabis; and uncertainty regarding VHA policy. Clinicians had differing views on cannabis in the context of the opioid crisis. CONCLUSIONS: VA clinicians face challenges in navigating the topic of medical cannabis. Educational materials about cannabis products, dose and harms would be helpful to clinicians.

Our research study examines Veterans Health Administration clinicians' attitudes, beliefs, knowledge and communication with patients about cannabis (marijuana) use. We conducted phone interviews with 14 VHA clinicians in order to describe their experiences of talking to their patients about cannabis. Interviews were audio-recorded, transcribed and analysed to identify themes. We describe both common and unique experiences. Our findings suggest that VA clinicians have feelings of uncertainty towards cannabis use for medical purposes and described several reasons that prevent conversations about cannabis use with their patients, including discomfort with the lack of product regulation; lack of research examining the effect cannabis has on the body; unfamiliarity with the different cannabis products that are available; and uncertainty about VHA policy. VA clinicians have diverse views of cannabis in relation to the opioid epidemic.

Preventing Unequal Health Outcomes in COVID-19: A Systematic Review of Past Interventions.

Background: We sought to identify interventions that reduced disparities in health outcomes in infectious disease outbreaks or natural disasters in the United States to understand whether these interventions could reduce health disparities in the current COVID-19 pandemic. Methods: We searched MEDLINE and other databases to May 2020 to find studies that examined interventions to mitigate health inequalities in previous infectious disease pandemics or disasters. We assessed study quality using the Newcastle-Ottawa Scale and the Critical Appraisal Skills Program (CASP) Checklist for Qualitative Studies. Results: We included 14 articles (12 studies) and 5 Centers for Disease Control (CDC) stakeholder meeting articles on pandemic influenza preparedness in marginalized populations. Studies called for intervention and engagement before pandemic or disaster onset. Several studies included interventions that could be adapted to COVID-19, including harnessing technology to reach disadvantaged populations, partnering with trusted community liaisons to deliver important messaging around disease mitigation, and using culturally specific communication methods and messages to best reach marginalized groups. Discussion: To our knowledge this is the first systematic review to examine interventions to mitigate health inequities during an infectious disease pandemic. However, given that we identified very few disparities-focused infectious disease intervention studies, we also included studies from the disaster response literature, which may not be as generalizable to the current context of COVID-19. Overall, community outreach and tailored communication are essential in disease mitigation. More research is needed to evaluate systemic interventions that target the distal determinants of poor health outcomes among marginalized populations during pandemics and natural disasters.

The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic Review.

Adults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment-related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. SSRIs were the most studied type of drug and the evidence was largely insufficient. We found moderate SOE that long-term, high-dose vitamin D3 is ineffective for reducing depression severity. Cognitive behavioral therapy is more effective than (undefined) psychotherapy and placebo for depression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed. Systematic Review registry name and registration number: PROSPERO, CRD42020140227.

Racial and Ethnic Disparities in COVID-19-Related Infections, Hospitalizations, and Deaths : A Systematic Review.

BACKGROUND: Data suggest that the effects of coronavirus disease 2019 (COVID-19) differ among U.S. racial/ethnic groups. PURPOSE: To evaluate racial/ethnic disparities in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and COVID-19 outcomes, factors contributing to disparities, and interventions to reduce them. DATA SOURCES: English-language articles in MEDLINE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus, searched from inception through 31 August 2020. Gray literature sources were searched through 2 November 2020. STUDY SELECTION: Observational studies examining SARS-CoV-2 infections, hospitalizations, or deaths by race/ethnicity in U.S. settings. DATA EXTRACTION: Single-reviewer abstraction confirmed by a second reviewer; independent dual-reviewer assessment of quality and strength of evidence. DATA SYNTHESIS: 37 mostly fair-quality cohort and cross-sectional studies, 15 mostly good-quality ecological studies, and data from the Centers for Disease Control and Prevention and APM Research Lab were included. African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection, hospitalization, and COVID-19-related mortality compared with non-Hispanic White populations, but not higher case-fatality rates (mostly reported as in-hospital mortality) (moderate- to high-strength evidence). Asian populations experience similar outcomes to non-Hispanic White populations (low-strength evidence). Outcomes for other racial/ethnic groups have been insufficiently studied. Health care access and exposure factors may underlie the observed disparities more than susceptibility due to comorbid conditions (low-strength evidence). LIMITATIONS: Selection bias, missing race/ethnicity data, and incomplete outcome assessments in cohort and cross-sectional studies must be considered. In addition, adjustment for key demographic covariates was lacking in ecological studies. CONCLUSION: African American/Black and Hispanic populations experience disproportionately higher rates of SARS-CoV-2 infection and COVID-19-related mortality but similar rates of case fatality. Differences in health care access and exposure risk may be driving higher infection and mortality rates. PRIMARY FUNDING SOURCE: Department of Veterans Affairs, Veterans Health Administration, Health Services Research & Development. (PROSPERO: CRD42020187078).

A Systematic Review of Therapeutic Interventions and Management Strategies for Gulf War Illness.

INTRODUCTION: After the 1990 to 1991 conflict in the Persian Gulf, many Gulf War Veterans began reporting numerous unexplained symptoms including, but not limited to, systemic pain, fatigue, flu-like symptoms, and difficulty with memory/concentration. These symptom clusters are now referred to as Gulf War Illness (GWI). Although the etiology of GWI is still debated, as many as 250,000 former service members have been continually suffering from GWI since 1991, making the need for treatment urgent. A broad variety of treatments have been considered for GWI, but there has not been a broad and comprehensive assessment of what is known and not known about GWI treatment. We conducted a systematic review to catalogue the types of treatments that have been examined for GWI, to evaluate the effectiveness and harms of these interventions, and to identify promising and ongoing areas of future GWI treatment research. MATERIALS AND METHODS: We searched electronic databases, trial registries, and reference lists through September 2019 for randomized controlled trial and nonrandomized controlled trial and cohort studies directly comparing interventions for Veterans with GWI to each other, placebo, or usual care. We abstracted data on study design, demographics, interventions, and outcomes. Two reviewers independently assessed studies for inclusion, quality, and strength of evidence (SOE) using prespecified criteria. We resolved discordant ratings by discussion and consensus. RESULTS: We identified 12 randomized controlled trials, each of which examined a different intervention for GWI. We found moderate SOE that cognitive behavioral therapy and exercise, separately and in combination, were associated with improvements in several GWI symptom domains. There was low SOE of benefit from two mindfulness-based interventions and continuous positive airway pressure (CPAP). Mindfulness-based stress reduction improved pain, cognitive functioning, fatigue, depression, and posttraumatic stress disorder (PTSD), whereas mind-body bridging improved fatigue, depression, posttraumatic stress disorder, and sleep, although pain and other outcomes did not improve. Continuous positive airway pressure improved overall physical health, pain, cognitive functioning, fatigue, mental health, and sleep quality in a small study of Veterans with sleep-disordered breathing and GWI. We found moderate SOE that doxycycline is ineffective for GWI in mycoplasma DNA-positive Veterans and increases the risk of adverse events compared with placebo. We also found 33 ongoing, single-arm pilot, or unpublished studies examining a variety of interventions. CONCLUSION: Cognitive behavioral therapy (moderate SOE), exercise (moderate SOE), and mindfulness-based interventions (low SOE) may be effective in improving several symptom domains in patients with GWI. Doxycycline was ineffective and associated with harms (moderate SOE). Larger, more rigorous studies are needed to confirm the benefits found in completed trials. A wide array of treatments are being assessed in ongoing trials. A sufficient evidence base will need to be developed to guide clinicians about which treatments are most likely to be effective in clinical practice and which treatments should be avoided.

Depression Screening Tools for Patients with Kidney Failure: A Systematic Review.

BACKGROUND AND OBJECTIVES: Patients with kidney failure experience depression at rates higher than the general population. Despite the Centers for Medicare and Medicaid Services' ESRD Quality Incentive Program requirements for routine depression screening for patients with kidney failure, no clear guidance exists. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: For this systematic review, we searched MEDLINE, PsycINFO, and other databases from inception to June 2020. Two investigators screened all abstracts and full text. We included studies assessing patients with kidney failure and compared a tool to a clinical interview or another validated tool (e.g., Beck Depression Inventory II). We abstracted data related to sensitivity and specificity, positive and negative predictive value, and the area under the curve. We evaluated the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2. RESULTS: A total of 16 studies evaluated the performance characteristics of depression assessment tools for patients with kidney failure. The Beck Depression Inventory II was by far the best studied. A wide range of thresholds were reported. Shorter tools in the public domain such as the Patient Health Questionnaire 9 and Geriatric Depression Scale 15 (adults over 60) performed well but were not well studied. Short tools such as the Beck Depression Inventory-Fast Screen may be a good option for an initial screen. CONCLUSIONS: There is limited research evaluating the diagnostic accuracy of most screening tools for depression in patients with kidney failure, and existing studies may not be generalizable to US populations. Studies suffer from limitations related to methodology quality and/or reporting. Future research should target widely used, free tools such as the Patient Health Questionnaire 2 and the Patient Health Questionnaire 9. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Systematic Review Registration: PROSPERO CRD42020140227.

Pharmacotherapy for the Treatment of Cannabis Use Disorder: A Systematic Review.

Background: Cannabis use disorder (CUD) is a growing concern, and evidence-based data are needed to inform treatment options. Purpose: To review the benefits and risks of pharmacotherapies for the treatment of CUD. Data Sources: MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, and clinical trial registries from inception through September 2019. Study Selection: Pharmacotherapy trials of adults or adolescents with CUD that targeted cannabis abstinence or reduction, treatment retention, withdrawal symptoms, and other outcomes. Data Extraction: Data were abstracted by 1 investigator and confirmed by a second. Study quality was dually assessed, and strength of evidence (SOE) was determined by consensus according to standard criteria. Data Synthesis: Across 26 trials, the evidence was largely insufficient. Low-strength evidence was found that selective serotonin reuptake inhibitors (SSRIs) do not reduce cannabis use or improve treatment retention. Low- to moderate-strength evidence was found that buspirone does not improve outcomes and that cannabinoids do not increase abstinence rates (moderate SOE), reduce cannabis use (low SOE), or increase treatment retention (low SOE). Across all drug studies, no consistent evidence of increased harm was found. Limitations: Few methodologically rigorous trials have been done. Existing trials are hampered by small sample sizes, high attrition rates, and heterogeneity of concurrent interventions and outcomes assessment. Conclusion: Although data on pharmacologic interventions for CUD are scarce, evidence exists that several drug classes, including cannabinoids and SSRIs, are ineffective. Because of increasing access to and use of cannabis in the general population, along with a high prevalence of CUD among current cannabis users, an urgent need exists for more research to identify effective pharmacologic treatments. Primary Funding Source: U.S. Department of Veterans Affairs. (PROSPERO: CRD42018108064).