Marijuana Use, Respiratory Symptoms, and Pulmonary Function: A Systematic Review and Meta-analysis: Annals of Internal Medicine: Vol 169, No 2

Background: The health effects of smoking marijuana are not well-understood. Purpose: To examine the association between marijuana use and respiratory symptoms, pulmonary function, and obstructive lung disease among adolescents and adults. Data Sources: PubMed, Embase, PsycINFO, MEDLINE, and the Cochrane Library from 1 January 1973 to 30 April 2018. Study Selection: Observational and interventional studies published in English that reported pulmonary outcomes of adolescents and adults who used marijuana. Data Extraction: Four reviewers independently extracted study characteristics and assessed risk of bias. Three reviewers assessed strength of evidence. Studies of similar design with low or moderate risk of bias and sufficient data were pooled. Data Synthesis: Twenty-two studies were included. A pooled analysis of 2 prospective studies showed that marijuana use was associated with an increased risk for cough (risk ratio [RR], 2.04 [95% CI, 1.02 to 4.06]) and sputum production (RR, 3.84 [CI, 1.62 to 9.07]). Pooled analysis of cross-sectional studies (1 low and 3 moderate risk of bias) showed that marijuana use was associated with cough (RR, 4.37 [CI, 1.71 to 11.19]), sputum production (RR, 3.40 [CI, 1.99 to 5.79]), wheezing (RR, 2.83 [CI, 1.89 to 4.23]), and dyspnea (RR, 1.56 [CI, 1.33 to 1.83]). Data on pulmonary function and obstructive lung disease were insufficient. Limitation: Few studies were at low risk of bias, marijuana exposure was limited in the population studied, cohorts were young overall, assessment of marijuana exposure was not uniform, and study designs varied. Conclusion: Low-strength evidence suggests that smoking marijuana is associated with cough, sputum production, and wheezing. Evidence on the association between marijuana use and obstructive lung disease and pulmonary function is insufficient. Primary Funding Source: None. (PROSPERO: CRD42017059224)

On-Demand Sildenafil as a Treatment for Raynaud Phenomenon: A Series of n-of-1 Trials: Annals of Internal Medicine: Vol 169, No 10

Background: Treatment of Raynaud phenomenon (RP) with phosphodiesterase-5 inhibitors has shown moderate efficacy. Adverse effects decrease the risk–benefit profile of these drugs, and patients may not be willing to receive long-term treatment. On-demand single doses before or during exposure to cold may be a good alternative. Objective: To assess the efficacy and safety of on-demand sildenafil in RP. Design: Series of randomized, double-blind, n-of-1 trials. (ClinicalTrials.gov: NCT02050360) Setting: Outpatients at a French university hospital. Participants: Patients with primary or secondary RP. Intervention: Each trial consisted of a multiple crossover study in a single patient. Repeated blocks of 3 periods of on-demand treatment were evaluated: 1 week of placebo, 1 week of sildenafil at 40 mg per dose, and 1 week of sildenafil at 80 mg per dose, with a maximum of 2 doses daily. Measurements: Raynaud Condition Score (RCS) and frequency and daily duration of attacks. Skin blood flow in response to cooling also was assessed with laser speckle contrast imaging. Mixed-effects models were used and parameters were estimated in a Bayesian framework to determine individual and aggregated efficacy. Results: 38 patients completed 2 to 5 treatment blocks. On the basis of aggregated data, the probability that sildenafil at 40 mg or 80 mg was more effective than placebo was greater than 90% for all outcomes (except for RCS with sildenafil, 80 mg). However, the aggregated effect size was not clinically relevant. Yet, substantial heterogeneity in sildenafil's efficacy was observed among participants, with clinically relevant efficacy in some patients. Limitation: The response to sildenafil was substantially heterogeneous among patients. Conclusion: Despite a high probability that sildenafil is superior to placebo, substantial heterogeneity was observed in patient response and aggregated results did not show that on-demand sildenafil has clinically relevant efficacy. In this context, the use of n-of-1 trials may be an original and relevant approach in RP. Primary Funding Source: GIRCI (Groupement Interrégional de Recherche Clinique et d'Innovation) Auvergne Rhône-Alpes (academic funding) and Pfizer.

National Institutes of Health Pathways to Prevention Workshop: Methods for Evaluating Natural Experiments in Obesity

On 5 and 6 December 2017, the National Institutes of Health (NIH) convened the Pathways to Prevention Workshop: Methods for Evaluating Natural Experiments in Obesity to identify the status of methods for assessing natural experiments to reduce obesity, areas in which these methods could be improved, and research needs for advancing the field. This article considers findings from a systematic evidence review on methods for evaluating natural experiments in obesity, workshop presentations by experts and stakeholders, and public comment. Research gaps are identified, and recommendations related to 4 key issues are provided. Recommendations on population-based data sources and data integration include maximizing use and sharing of existing surveillance and research databases and ensuring significant effort to integrate and link databases. Recommendations on measurement include use of standardized and validated measures of obesity-related outcomes and exposures, systematic measurement of co-benefits and unintended consequences, and expanded use of validated technologies for measurement. Study design recommendations include improving guidance, documentation, and communication about methods used; increasing use of designs that minimize bias in natural experiments; and more carefully selecting control groups. Cross-cutting recommendations target activities that the NIH and other funders might undertake to improve the rigor of natural experiments in obesity, including training and collaboration on modeling and causal inference, promoting the importance of community engagement in the conduct of natural experiments, ensuring maintenance of relevant surveillance systems, and supporting extended follow-up assessments for exemplar natural experiments. To combat the significant public health threat posed by obesity, researchers should continue to take advantage of natural experiments. The recommendations in this report aim to strengthen evidence from such studies.

Clinicians' Perspectives on Providing Emergency-Only Hemodialysis to Undocumented Immigrants: A Qualitative Study: Annals of Internal Medicine: Vol 169, No 2

Background: In the United States, nearly half of undocumented immigrants with end-stage kidney disease receive hemodialysis only when they are evaluated in an emergency department and are found to have life-threatening renal failure (“emergency-only hemodialysis” [EOHD]). These patients experience psychosocial distress and much higher mortality than patients receiving regularly scheduled hemodialysis, but little is known about how providing EOHD affects the clinicians involved. Objective: To understand clinicians' experiences providing EOHD. Design: Qualitative study using semistructured interviews. Setting: A safety-net hospital in Denver, Colorado, and a safety-net system in Houston, Texas. Participants: Fifty interdisciplinary clinicians experienced in providing EOHD. Measurements: Interviews were analyzed using thematic analysis. Outcomes included themes and subthemes. Results: Four themes and 13 subthemes (in parentheses) were identified: 1) drivers of professional burnout (emotional exhaustion from witnessing needless suffering and high mortality, jeopardizing patient trust, detaching from patients, perceived lack of control over EOHD criteria, and physical exhaustion from overextending to bridge care), 2) moral distress from propagating injustice (altered care based on nonmedical factors, focus on volume at the expense of quality, and need to game the system), 3) confusing and perverse financial incentives (wasting resources, confusing financial incentives, and concerns about sustainability), and 4) inspiration toward advocacy (deriving inspiration from patients and strengthened altruism). Limitation: Whether the findings apply to other settings is unknown, and social desirability response bias might have reduced reporting of negative perceptions and experiences. Conclusion: Clinicians in safety-net settings who provide EOHD to undocumented patients describe experiencing moral distress and being driven toward professional burnout. The burden of EOHD on clinicians should inform discussions of systemic approaches to support provision of adequate care based on medical need. Primary Funding Source: Robert Wood Johnson Foundation and Doris Duke Charitable Foundation.

Should This Patient Receive Prophylactic Medication to Prevent Delirium?: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 168, No 7

In 2015, the American Geriatrics Society released recommendations for prevention and management of postoperative delirium, based on a systematic literature review and evaluation of nonpharmacologic and pharmacologic approaches by an expert panel. The guidelines recommend an interdisciplinary focus on nonpharmacologic measures (reorientation, medication management, early mobility, nutrition, and gastointestinal motility) for prevention and consideration of this strategy for acute management. They also recommend optimizing nonopioid medication as a means to manage pain and avoiding benzodiazepines other than to treat substance withdrawal. The authors concluded that evidence to recommend antipsychotics for prevention of delirium is insufficient but that these drugs may be considered for short-term treatment in the setting of imminent harm to the patient or caregivers or severe distress due to agitation. Patients should be given the lowest possible dose for the shortest duration when other nonpharmacologic measures have failed. In this Beyond the Guidelines, a psychiatrist and a geriatrician debate whether Mr. W, a 79-year-old man at high risk for postoperative delirium, should receive prophylactic antipsychotics with his next surgery. They review risk factors, appropriate evaluation, and potential benefits and harms of the various medications often used in this setting.

Determined Action Needed on Social Determinants

Methods for Evaluating Natural Experiments in Obesity: A Systematic Review: Annals of Internal Medicine: Vol 168, No 11

Background: Given the obesity pandemic, rigorous methodological approaches, including natural experiments, are needed. Purpose: To identify studies that report effects of programs, policies, or built environment changes on obesity prevention and control and to describe their methods. Data Sources: PubMed, CINAHL, PsycINFO, and EconLit (January 2000 to August 2017). Study Selection: Natural experiments and experimental studies evaluating a program, policy, or built environment change in U.S. or non-U.S. populations by using measures of obesity or obesity-related health behaviors. Data Extraction: 2 reviewers serially extracted data on study design, population characteristics, data sources and linkages, measures, and analytic methods and independently evaluated risk of bias. Data Synthesis: 294 studies (188 U.S., 106 non-U.S.) were identified, including 156 natural experiments (53%), 118 experimental studies (40%), and 20 (7%) with unclear study design. Studies used 106 (71 U.S., 35 non-U.S.) data systems; 37% of the U.S. data systems were linked to another data source. For outcomes, 112 studies reported childhood weight and 32 adult weight; 152 had physical activity and 148 had dietary measures. For analysis, natural experiments most commonly used cross-sectional comparisons of exposed and unexposed groups (n = 55 [35%]). Most natural experiments had a high risk of bias, and 63% had weak handling of withdrawals and dropouts. Limitation: Outcomes restricted to obesity measures and health behaviors; inconsistent or unclear descriptions of natural experiment designs; and imperfect methods for assessing risk of bias in natural experiments. Conclusion: Many methodologically diverse natural experiments and experimental studies were identified that reported effects of U.S. and non-U.S. programs, policies, or built environment changes on obesity prevention and control. The findings reinforce the need for methodological and analytic advances that would strengthen evaluations of obesity prevention and control initiatives. Primary Funding Source: National Institutes of Health, Office of Disease Prevention, and Agency for Healthcare Research and Quality. (PROSPERO: CRD42017055750)

A Physician's Place in the #MeToo Movement

New Strategies Are Needed to Stop Overdose Fatalities: The Case for Supervised Injection Facilities

A Novel Strategy for Increasing Access to Treatment for Hepatitis C Virus Infection for Medicaid Beneficiaries