Andrew Anglemyer

The Accessibility of Firearms and Risk for Suicide and Homicide Victimization Among Household Members: A Systematic Review and Meta-analysis

Firearms cause an estimated 31000 deaths annually in the United States (1). Data from the 16-state National Violent Death Reporting System indicate that 51.8% of deaths from suicide in 2009 (n= 9949) were firearm-related; among homicide victims (n= 4057), 66.5% were firearm-related. Most suicides (76.4%) occurred in the victims homes. Homicides also frequently occurred in the home, with 45.5% of male victims and 74.0% of female victims killed at home (2). Firearm ownership is more prevalent in the United States than in any other country; approximately 35% to 39% of households have firearms (3, 4), and 22% of persons report owning firearms. The annual rate of suicide by firearms (6.3 suicides per 100000 residents) is higher in the United States than in any other country with reported data, and the annual rate of firearm-related homicide in the United States (7.1 homicides per 100000 residents) is the highest among high-income countries (4). Results from ecological studies suggest that state restrictions on firearm ownership are associated with decreases in firearm-related suicides and homicides (5). Specific characteristics about storage and types of firearms seem to increase suicide risk. Firearms that are stored loaded or unlocked are more likely to be used than those that are unloaded or locked (6, 7), and adolescent suicide victims often use an unlocked firearm in the home (8). The apparent increased risk for suicide associated with firearms in the home is not unique to persons with a history of mental illness (7) and may be more of an indicator of the ease of impulsive suicide. Impulsiveness may be a catalyst in using a firearm to commit suicide and may also play a role in firearm-related homicide. Researchers have estimated higher odds of homicide victimization among women than men (9, 10). Because most homicide victims know their perpetrators (9), this finding may indicate an impulsive reaction to domestic disputes. To our knowledge, this is the first systematic review and meta-analysis to estimate the association between firearm accessibility and suicide or homicide victimization. Supplement. Original Version (PDF) Methods We used Cochrane Collaboration methods (11) throughout the review process. Data Sources and Searches We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and Web of Science without date, geographic, or language limitations. We also examined bibliographies of included articles to identify additional references. In addition, we searched the gray literature for papers related to firearms and suicide or homicide. The Appendix and Appendix Table 1 (both available at www.annals.org) present details of our search strategy and screening process. Appendix Table 1. Search Strategy Study Selection Study Design Study designs eligible for inclusion in our review were randomized, controlled trials; nonrandomized, controlled trials; pre- or postintervention evaluations; and observational studies (for example, cohort or casecontrol studies) if a comparator was available. Because we were concerned with the individual effects of firearm accessibility, we included only studies with individual-level data and excluded those with population-level data (for example, ecological studies). Types of Participants Participants were not restricted by age, sex, or country of residence. Types of Exposures Studies needed to assess whether firearms were available for all participants. In addition, included studies needed to assess outcomes between participants with and without access to firearms. Specifically, studies needed to compare firearm ownership or availability (that is, accessibility) with no firearm ownership or availability (that is, no accessibility) or provide adequate data to estimate the effect that firearms had on selected harms outcomes. Firearm accessibility could be defined as self- or proxy-reported or assumed from other types of exposure data (for example, firearm purchase records). Types of Outcome Measures The primary outcomes of interest were suicide or homicide victimization (that is, being a victim of homicide rather than a perpetrator). Data Extraction and Quality Assessment Two authors independently extracted relevant data into a standardized, prepiloted data extraction form. Assessment of Risk of Bias Two authors independently assessed the risk of bias for each study by using the NewcastleOttawa Scale (12, 13). We resolved disagreements by discussion or by involving the third author to adjudicate (Table 1 and Appendix Table 2). Table 1. Summary of Critical Appraisal of Included Studies Using the NewcastleOttawa Scale for Assessing the Quality of Observational Studies* Appendix Table 2. Detailed Risk of Bias Results Using the NewcastleOttawa Scale for Assessing Quality for Observational Studies Data Synthesis and Analysis When necessary, we calculated the odds ratio (OR) and 95% CI for dichotomous outcomes, although published adjusted estimates were preferentially used if provided in the report. We pooled data across studies and estimated summary effect sizes by using fixed- and random-effects models. The choice of model was determined by the significance of the maximum likelihood estimate of the heterogeneity parameter ( 2) (14). If the estimate of 2 did not significantly differ from 0, the fixed-effects model was used (14). We present 2 estimates of heterogeneitythe I 2 statistic and the coefficient. Estimates of the former are interpreted as the percentage of variability in effect estimates due to heterogeneity rather than chance, whereas the latter can be interpreted as the clinical heterogeneity as determined by the estimated SD of underlying effects across studies. Unlike the I 2 statistic, the coefficient does not change with the number of patients included in the studies in a meta-analysis (15). We used R, version 3.0.0 (R Foundation for Statistical Computing, Vienna, Austria), for statistical analyses. The coefficient was measured on the log OR scale. This review is registered in PROSPERO (CRD42013004469). Results Search Results The database searches yielded 6902 references (Figure 1). We removed 2929 duplicates and an additional 2881 clearly irrelevant references. We then identified 2382 records through gray-literature searches. We closely reviewed 3474 titles and abstracts. After this screening, we selected 70 articles for full-text review. We identified an additional 4 studies by cross-referencing bibliographies (1619). Overall, 16 observational studies met our inclusion criteria. The Appendix shows the disposition of studies excluded after full-text review. Figure 1. Summary of evidence search and selection. Fourteen of the included studies estimated the odds of suicide in the context of firearm accessibility (68, 10, 1625), and 6 studies estimated the odds of homicide victimization in this context (9, 10, 2224, 48). Four studies reported both outcomes (10, 2224). Study Characteristics Demographic Characteristics Persons who completed suicide (mean, 75% [range, 70% to 85%]) (68, 10, 1621, 23) and homicide victims (mean, 79% [range, 63% to 92%]) (9, 10, 23, 48) were more commonly men. Most persons who completed suicide were white (range, 78% to 98%) (6, 8, 10, 1619, 21, 23, 26), whereas most homicide victims were non-Hispanic black or another race (range, 47% to 88%) (9, 10, 23, 48). Four (28.6%) of the 14 suicide studies were among adolescents only (6, 8, 16, 17), and 10 (71.4%) were among adults only (7, 10, 1825). All studies of outcomes of homicide victimization were among adults only (9, 10, 2224, 48). Firearm Access Among 11 U.S. casecontrol studies using survey data, proportions of firearm access ranged from 62.7% to 75.4% among case patients and from 26.4% to 50.8% among controls participants. One non-U.S. study (20) used survey data to estimate the proportion of case patients (23.9%) and control participants (18.5%) with firearm access, and another non-U.S. study (25) assumed firearm access from military duty and estimated the proportion of case patients (41%) and control participants (17%) with access. Among U.S.-based studies with reported data, the proportion of completed suicides using a firearm ranged from 47% to 73% (6, 7, 10, 16, 17, 2124); 3 studies did not report adequate data (8, 18, 19). One nonU.S.-based study of civilians reported that 13% of suicides were completed using a firearm (20), whereas another non-U.S. study of military personnel reported that 52% of suicides were completed using a firearm (25). The proportion of homicides using a firearm ranged from 50% to 76% (13, 15, 2729). Studies of Suicide Eleven of 14 studies (78.6%) interviewed proxies to determine firearm accessibility among decedents or control participants (68, 10, 1621, 23), whereas 3 studies (21.4%) used firearm purchase records or military duty to determine accessibility among decedents or control participants (22, 24, 25) (Table 2). Twelve studies (85.7%) defined suicide as self-inflicted, intentional death by any means (6, 7, 10, 1623, 25), whereas 2 studies (14.3%) defined suicide as injury related only to firearms or firearm- or violence-related injury (8, 24). All suicides were reported consecutively or identified using death certificates. In casecontrol studies, various types of control participants were identified, such as inpatients who attempted suicide (14.3%) (16, 17), community or school control participants (42.9%) (68, 18, 20, 21), decedents from causes other than suicide (28.6%) (18, 19, 24, 25), participants in a national health survey (7.1%) (10), or living HMO-based control participants (7.1%) (22). Table 2. Characteristics of Included Studies of Suicide and Homicide Victimization Studies of Homicide Victimization Three of 6 studies (50.0%) interviewed proxies to determine firearm accessibility in the home of decedents or control participants (Table 1) (9, 10, 23). Two studies (33.0%) used firearm purchase records to determine firearm acc

Predicting treatment failure in adults and children on antiretroviral therapy: a systematic review of the performance characteristics of the 2010 WHO immunologic and clinical criteria for virologic failure.

Objective:We systematically reviewed the performance of 2010 WHO immunologic and clinical criteria for predicting virologic failure in HIV-infected patients on antiretroviral therapy (ART). Design:Systematic review. Methods:We used Cochrane Collaboration methods. We calculated unweighted sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of immunologic and clinical criteria for predicting virologic failure. Results:We identified 18 studies. Sixteen assessed immunologic criteria in adults; 12 defined virologic failure as a plasma viral load of more than 50 to more than 1000 copies/ml in adults, three as viral load at least 5000 copies/ml, and two as viral load more than 10 000 copies/ml; the sensitivity ranged from 16.8 to 54.9%, specificity from 82.9 to 95.5%, PPV from 15.0 to 38.8%, and NPV from 90.9 to 98.6%. Seven studies assessed clinical criteria to predict viral load of more than 50 to more than 1000 copies/ml; the sensitivity was 11.0%, specificity 90.5%, PPV 44.9%, and NPV 90.2%. Seven studies assessed clinical or immunologic criteria defining virologic failure as viral load of more than 50 to more than1000 copies/ml; their sensitivity was 26.6%, specificity 85.9%, PPV 49.4%, and NPV 91.1%. Four studies assessed immunologic criteria in children; three defined virologic failure as viral load at least 5000 copies/ml and one as viral load at least 400 copies/ml. The sensitivity ranged from 4.5 to 6.3%, specificity from 97.7 to 99.3%, PPV from 20.0 to 54.9%, and NPV from 85.5 to 91.8%. Conclusion:The 2010 WHO clinical and immunologic criteria are insensitive and have low PPV for predicting virologic failure. These data support the strong recommendation 2013 treatment guidelines that viral load testing be used to monitor for, diagnose, and confirm ART failure.

Antiretroviral Therapy for Prevention of HIV Transmission in HIV-Discordant Couples

CLINICAL QUESTION Does treating the HIV-infected partner in a serodiscordant couple reduce the risk of HIV transmission to the uninfected partner? BOTTOM LINE Compared with serodiscordant couples without treatment, couples in which the infected partner is treated with antiretroviral therapy have a lower risk of HIV transmission.

Improving code team performance and survival outcomes: implementation of pediatric resuscitation team training.

Objective:To determine whether implementation of Composite Resuscitation Team Training is associated with improvement in survival to discharge and code team performance after pediatric in-hospital cardiopulmonary arrest. Design, Setting, and Subjects:We conducted a prospective observational study with historical controls at a 302-bed, quaternary care, academic children’s hospital. Inpatients who experienced cardiopulmonary arrest between January 1, 2006, and December 31, 2009, were included in the control group (123 patients experienced 183 cardiopulmonary arrests) and between July 1, 2010, and June 30, 2011, were included in the intervention group (46 patients experienced 65 cardiopulmonary arrests). Intervention:Code team members were introduced to Composite Resuscitation Team Training and continued training throughout the intervention period (January 1, 2010–June 30, 2011). Training was integrated via in situ code blue simulations (n = 16). Simulations were videotaped and participants were debriefed for education and process improvement. Primary outcome was survival to discharge after cardiopulmonary arrest. Secondary outcome measures were 1) change in neurologic morbidity from admission to discharge, measured by Pediatric Cerebral Performance Category, and 2) code team adherence to resuscitation Standard Operating Performance variables. Measurements and Main Results:The intervention group was more likely to survive than the control group (60.9% vs 40.3%) (unadjusted odds ratio, 2.3 [95% CI, 1.15–4.60]) and had no significant change in neurologic morbidity (mean change in Pediatric Cerebral Performance Category 0.11 vs 0.27; p = 0.37). Code teams exposed to Composite Resuscitation Team Training were more likely than control group to adhere to resuscitation Standard Operating Performance (35.9% vs 20.8%) (unadjusted odds ratio, 2.14 [95% CI, 1.15–3.99]). After adjusting for adherence to Standard Operating Performance, survival remained improved in the intervention period (odds ratio, 2.13 [95% CI, 1.06–4.36]). Conclusion:With implementation of Composite Resuscitation Team Training, survival to discharge after pediatric cardiopulmonary arrest improved, as did code team performance. Demonstration of improved survival after adjusting for code team adherence to resuscitation standards suggests that this may be a valuable resuscitation training program. Further studies are needed to determine causality and generalizability.

Early initiation of antiretroviral therapy in HIV-infected adults and adolescents: a systematic review

Objectives:The objective of this review was to update evidence on when to initiate antiretroviral therapy (ART) to inform revision of the 2013 WHO guidelines for ART in low and middle-income countries. Design:A systematic review and meta-analysis. Methods:We comprehensively searchescohorts. Outcomes were mortality, clinical progression, virologic failure, immunologic recover, and severe adverse events. We pooled data across studies and estimated summary effect sizes. We graded the quality of evidence from the literature for each outcome. Results:We identified 24 studies; 3 were RCTs. Studies found reduced risk of mortality [1 RCT: hazard ratio 0.77, 95% confidence interval (CI) 0.34–1.76; 13 cohorts: relative risk (RR) 0.66, 95% CI 0.55–0.79], progression to AIDS or death (2 RCTs: RR 0.48, 95% CI 0.26–0.91; 9 cohorts: RR 0.70, 95% CI 0.40–1.24) and diagnosis of a non-AIDS-defining illness (1 RCT: RR 0.14, 95% CI 0.03–0.64; 1 cohort: RR 0.47, 95% CI 0.23–0.98), and an increased risk of grade 3/4 laboratory abnormalities in patients initiating ART at at least 350 cells/&mgr;l (1 RCT: RR 1.49, 95% CI 1.25–1.77). The quality of evidence was low or very low for clinical outcomes due to few events and imprecision, and high for adverse events. Conclusions:Our findings contributed to the evidence base for the revised 2013 WHO guidelines on ART, which recommend initiating ART at CD4+ T-cell counts of 350–500 cells/&mgr;l, but not above 500 cells/&mgr;l compared to initiating it later when CD4+ T-cell counts fall below 350 cells/&mgr;l.

A Double-Blinded, Randomized, Placebo-Controlled Clinical Trial of Aminophylline to Prevent Acute Kidney Injury in Children Following Congenital Heart Surgery With Cardiopulmonary Bypass.

Objectives: Acute kidney injury occurs commonly in children following congenital cardiac surgery with cardiopulmonary bypass and has been associated with increased morbidity and mortality. Aminophylline, a methylxanthine nonselective adenosine receptor antagonist, has been effective in the management of acute kidney injury in certain populations. This study sought to determine whether postoperative administration of aminophylline attenuates acute kidney injury in children undergoing congenital cardiac surgery with cardiopulmonary bypass. Design: Single-center, double-blinded, placebo-controlled, randomized clinical trial. Setting: Tertiary center, pediatric cardiovascular ICU. Patients: A total of 144 children after congenital heart surgery with cardiopulmonary bypass. Interventions: Seventy-two patients were randomized to receive aminophylline and 72 patients received placebo. Study drug was administered every 6 hours for 72 hours. Measurements and Main Results: The primary outcome variable was the development of any acute kidney injury, defined by the serum creatinine criteria of the Kidney Diseases: Improving Global Outcomes. Secondary outcomes included the development of severe acute kidney injury, time between cardiovascular ICU admission and first successful extubation, percent fluid overload, total fluid balance, urine output, bioelectrical impedance, and serum neutrophil gelatinase–associated lipocalin. The unadjusted rate and severity of acute kidney injury were not different between groups; 43 of 72 (60%) of the treatment group and 36 of 72 (50%) of the placebo group developed acute kidney injury (p = 0.32). Stage 2/3 acute kidney injury occurred in 23 of 72 (32%) of the treatment group and 15 of 72 (21%) of the placebo group (p = 0.18). Secondary outcome measures also demonstrated no significant difference between treatment and placebo groups. Aminophylline administration was safe; no deaths occurred in either group, and rates of adverse events were similar (14% in the treatment group vs 18% in the placebo group; p = 0.30). Conclusions: In this placebo-controlled randomized clinical trial, we found no effect of aminophylline to prevent acute kidney injury in children recovering from cardiac surgery performed with cardiopulmonary bypass. Future study of preoperative aminophylline administration to prevent acute kidney injury may be warranted.

Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.

Objective: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU. Design: Single-center retrospective cohort study. Setting: Pediatric cardiovascular ICU, university-affiliated children’s hospital. Patients: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload. Interventions: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload. Measurements and Main Results: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (–0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m2 (+3.66 mL/min/1.73 m2/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration. Conclusions: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.

Nonindustry-sponsored preclinical studies on statins yield greater efficacy estimates than industry-sponsored studies: a meta-analysis.

This study by Lisa Bero and colleagues uses published preclinical statin research to show that nonindustry-funded animal studies yield more efficacious drug results than do industry-funded ones.

Radiographic evaluation of the tegmen in patients with superior semicircular canal dehiscence.

Objective To determine a radiographic association between superior semicircular canal dehiscence (SSCD) and tegmen dehiscence (TD). Study Design Retrospective case-control series. Setting Tertiary referral center. Patients Patients seen between 2003 and 2010 with radiographic SSCD were compared with cochlear implant recipient controls. Intervention The tegmen and superior semicircular canal were evaluated on computed tomographic temporal bone scans. Main Outcome Measure If detected, the widest point of the SSCD was measured. The tegmen was graded on a 5-point scale. After analysis, a radiographic TD was defined as any single area of absent tegmen greater than 5 mm, multiple areas of absent tegmen, or evidence of meningocele. Age, sex, and body mass index were also noted. Results Thirty-eight patients with SSCD and 41 cochlear implant controls were identified. Seventy-six percent (29/38) of patients with unilateral or bilateral SSCD had a radiographic TD on at least 1 side compared with 22% (9/41) of the comparison group. Ninety-four percent (7/18) of patients with bilateral SSCD had a TD on at least 1 side. Patients with SSCD had a 10.2 times (p < 0.001) higher odds of having radiographic TD in either ear compared to the controls. Among patients with any SSCD, for every millimeter increase in the width of dehiscence, the relative risk for any TD increased more than 2-fold (odds ratio, 2.5; p = 0.019). Age, sex, and a body mass index greater than 30 did not confound the association between SSCD and TD. Conclusion There is a strong radiologic association between SSCD and TD, suggesting a similar etiologic process. The tegmen should be carefully evaluated in patients with SSCD. We have also proposed a new system for radiographically grading the integrity of the tegmen.

Epidemiology, outcomes and predictors of recovery in childhood encephalitis: A hospital-based study

Background: Pediatric encephalitis is a devastating diagnosis with little guidance regarding prognostic indicators early in the hospitalization. Methods: This is a retrospective cohort study of patients with encephalitis referred to the California Encephalitis Project from Children’s Hospital & Research Center Oakland from 1998 to 2010. Demographic, clinical, laboratory and neuroimaging data were collected by California Encephalitis Project and chart review. Outcomes were classified into “recovery” or “incomplete recovery” and evaluated at discharge and other times (7–10 days postadmission, 3 and 12 months postdischarge). Using logistic regression, predictors associated with recovery were identified. Results: Of 190 patients with outcomes available at discharge, 128 patients (67.4%) recovered, whereas 62 (32.6%) had an incomplete recovery, including 13 deaths (6.8%). Variables predictive of outcomes at discharge in the bivariate and multivariable analyses included Asian/Pacific Islander race, neuroimaging results and Glasgow Coma Score. Asian/Pacific Islander patients were less likely to recover than patients of other races (adjusted odds ratio = 0.43, P = 0.046). Patients with normal neuroimaging studies were more likely to recover than patients with abnormal neuroimaging (adjusted odds ratio = 2.54, P = 0.008). Patients with Glasgow Coma Score ≥7 were more likely to recover than patients with Glasgow Coma Score <7 (adjusted odds ratio = 5.82, P < 0.001). In a multivariable analysis, similar statistically significant findings were noted at all other analyzed times. Results were similar using a different population for validation, however, due to the small number of Asian/Pacific Islander patients; this finding could not be validated. Conclusions: This study is unique in identification of race/ethnicity as an independent predictor of pediatric encephalitis outcomes. Additional variables may be useful ancillary tools in determining prognosis.