Community Health Work and Social Work Collaboration: Integration in Health Care and Public Health Settings: A Conceptual Framework.

Community health worker (CHW) and social worker (SW) collaboration is crucial to illness prevention and intervention, yet systems often engage the 2 workforces in silos and miss opportunities for cross-sector alignment. In 2021, a national workgroup of over 2 dozen CHWs, SWs, and public health experts convened to improve CHW/SW collaboration and integration across the United States. The workgroup developed a conceptual framework that describes structural, systemic, and organizational factors that influence CHW/SW collaboration. Best practices include standardized training, delineated roles and scopes of practice, clear workflows, regular communication, a shared system for documentation, and ongoing support or supervision.

Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Persistent hemolytic anemia and a lack of oral treatments are challenges for patients with paroxysmal nocturnal hemoglobinuria who have received anti-C5 therapy or have not received complement inhibitors. Iptacopan, a first-in-class oral factor B inhibitor, has been shown to improve hemoglobin levels in these patients. METHODS: In two phase 3 trials, we assessed iptacopan monotherapy over a 24-week period in patients with hemoglobin levels of less than 10 g per deciliter. In the first, anti-C5-treated patients were randomly assigned to switch to iptacopan or to continue anti-C5 therapy. In the second, single-group trial, patients who had not received complement inhibitors and who had lactate dehydrogenase (LDH) levels more than 1.5 times the upper limit of the normal range received iptacopan. The two primary end points in the first trial were an increase in the hemoglobin level of at least 2 g per deciliter from baseline and a hemoglobin level of at least 12 g per deciliter, each without red-cell transfusion; the primary end point for the second trial was an increase in hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. RESULTS: In the first trial, 51 of the 60 patients who received iptacopan had an increase in the hemoglobin level of at least 2 g per deciliter from baseline, and 42 had a hemoglobin level of at least 12 g per deciliter, each without transfusion; none of the 35 anti-C5-treated patients attained the end-point levels. In the second trial, 31 of 33 patients had an increase in the hemoglobin level of at least 2 g per deciliter from baseline without red-cell transfusion. In the first trial, 59 of the 62 patients who received iptacopan and 14 of the 35 anti-C5-treated patients did not require or receive transfusion; in the second trial, no patients required or received transfusion. Treatment with iptacopan increased hemoglobin levels, reduced fatigue, reduced reticulocyte and bilirubin levels, and resulted in mean LDH levels that were less than 1.5 times the upper limit of the normal range. Headache was the most frequent adverse event with iptacopan. CONCLUSIONS: Iptacopan treatment improved hematologic and clinical outcomes in anti-C5-treated patients with persistent anemia - in whom iptacopan showed superiority to anti-C5 therapy - and in patients who had not received complement inhibitors. (Funded by Novartis; APPLY-PNH ClinicalTrials.gov number, NCT04558918; APPOINT-PNH ClinicalTrials.gov number, NCT04820530.).

Addition of danicopan to ravulizumab or eculizumab in patients with paroxysmal nocturnal haemoglobinuria and clinically significant extravascular haemolysis (ALPHA): a double-blind, randomised, phase 3 trial.

BACKGROUND: Symptoms of anaemia due to clinically significant extravascular haemolysis can affect patients with paroxysmal nocturnal haemoglobinuria (PNH) treated with C5 inhibitors (ravulizumab or eculizumab). The aim of this study was to assess the efficacy and safety of danicopan (ALXN2040), an investigational, first-in-class, oral complement factor D inhibitor, as add-on therapy to ravulizumab or eculizumab in patients with PNH and clinically significant extravascular haemolysis. METHODS: ALPHA is an ongoing, international, phase 3, randomised, double-blind, placebo-controlled trial evaluating danicopan as add-on therapy to ravulizumab or eculizumab. Eligible patients were adults (age ≥18 years) with PNH and clinically significant extravascular haemolysis (haemoglobin ≤9·5 g/dL; absolute reticulocyte count ≥120 × 109/L) on ravulizumab or eculizumab for at least 6 months. Patients were randomly assigned (2:1) to danicopan or placebo added to ravulizumab or eculizumab for 12 weeks using an interactive response technology system. Randomisation was stratified based on transfusion history, haemoglobin, and patients enrolled from Japan. The initial oral danicopan dose was 150 mg three times a day; escalation to 200 mg three times a day was permitted based on clinical response. The infusion dose level of eculizumab (every 2 weeks) ranged from 900 mg to 1500 mg, and for ravulizumab (monthly or every 8 weeks) ranged from 3000 mg to 3600 mg. The primary endpoint was change in haemoglobin concentration from baseline to week 12. Here we present the protocol-prespecified interim analysis, planned when approximately 75% of participants were randomly assigned to treatment and completed or discontinued at 12 weeks. This trial is registered with ClinicalTrials.gov (NCT04469465). FINDINGS: Individuals were randomly assigned between Dec 16, 2020, and Aug 29, 2022. At data cutoff (June 28, 2022), 73 individuals were randomly assigned, received treatment, and were analysed for safety (danicopan, n=49; placebo, n=24). The protocol-prespecified interim efficacy analysis set included the first 63 participants (danicopan, n=42; placebo, n=21). At week 12, danicopan plus ravulizumab or eculizumab increased haemoglobin versus placebo plus ravulizumab or eculizumab (least squares mean [LSM] change from baseline: danicopan, 2·94 g/dL [95% CI 2·52 to 3·36]; placebo, 0·50 g/dL [-0·13 to 1·12]; LSM difference, 2·44 g/dL [1·69 to 3·20]; p<0·0001). Grade 3 adverse events in the danicopan group were increased alanine aminotransferase (two [4%] of 49 patients), leukopenia (one [2%]), neutropenia (two [4%]), cholecystitis (one [2%]), COVID-19 (one [2%]), increased aspartate aminotransferase (one [2%]), and increased blood pressure (one [2%]), and in the placebo group were anaemia (one [4%] of 24 patients), thrombocytopenia (one [4%]), and asthenia (one [4%]). The serious adverse events reported in the danicopan group were cholecystitis (one [2%] patient) and COVID-19 (one [2%]) and in the placebo group were anaemia and abdominal pain, both in one (4%) patient. There were no serious adverse events related to study drug or deaths reported in the study. INTERPRETATION: These primary efficacy and safety results show that danicopan as add-on treatment to ravulizumab or eculizumab significantly improved haemoglobin concentrations at week 12 with no new safety concerns, suggesting an improved benefit-risk profile in patients with PNH and clinically significant extravascular haemolysis. FUNDING: Alexion, AstraZeneca Rare Disease.

The indirect impact of the COVID-19 pandemic on people with type 2 diabetes mellitus and without COVID-19 infection: Systematic review and meta-analysis.

BACKGROUND: The effect directly from the coronavirus disease 2019 (COVID-19) infection on health and fatality has received considerable attention, particularly among people with type 2 diabetes mellitus (T2DM). However, evidence on the indirect impact of disrupted healthcare services during the pandemic on people with T2DM is limited. This systematic review aims to assess the indirect impact of the pandemic on the metabolic management of T2DM people without a history of COVID-19 infection. METHODS: PubMed, Web of Science, and Scopus were systematically searched for studies that compared diabetes-related health outcomes between pre-pandemic and during-pandemic periods in people with T2DM and without the COVID-19 infection and published from January 1, 2020, to July 13, 2022. A meta-analysis was performed to estimate the overall effect on the diabetes indicators, including hemoglobin A1c (HbA1c), lipid profiles, and weight control, with different effect models according to the heterogeneity. RESULTS: Eleven observational studies were included in the final review. No significant changes in HbA1c levels [weighted mean difference (WMD), 0.06 (95% CI -0.12 to 0.24)] and body weight index (BMI) [0.15 (95% CI -0.24 to 0.53)] between the pre-pandemic and during-pandemic were found in the meta-analysis. Four studies reported lipid indicators; most reported insignificant changes in low-density lipoprotein (LDL, n = 2) and high-density lipoprotein (HDL, n = 3); two studies reported an increase in total cholesterol and triglyceride. CONCLUSIONS: This review did not find significant changes in HbA1c and BMI among people with T2DM after data pooling, but a possible worsening in lipids parameters during the COVID-19 pandemic. There were limited data on long-term outcomes and healthcare utilization, which warrants further research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022360433.

Effects of electronic cigarettes and hookah (waterpipe) use on home air quality.

INTRODUCTION: A major site of secondhand smoke exposure for children and adults is the home. Few studies have evaluated the impact of e-cigarette or hookah use on home air quality, despite evidence finding toxic chemicals in secondhand e-cigarette aerosols and hookah smoke. We assessed the effect of e-cigarette and hookah use on home air quality and compared it with air quality in homes where cigarettes were smoked and where no smoking or e-cigarette use occurred. METHODS: Non-smoking homes and homes where e-cigarettes, hookah or cigarettes were used were recruited in the New York City area (n=57) from 2015 to 2019. Particulate matter with diameter less than 2.5 µm (PM2.5), black carbon and carbon monoxide (CO) were measured during a smoking or vaping session, both in a 'primary' smoking room and in an adjacent 'secondary' room where no smoking or vaping occurred. Log transformed data were compared with postanalysis of variance Tukey simultaneous tests. RESULTS: Use of hookah significantly increased PM2.5 levels compared with non-smoking homes, in both the primary and secondary rooms, while use of e-cigarettes increased PM2.5 levels only in primary rooms. Additionally, in-home use of hookah resulted in greater CO concentrations than the use of cigarettes in primary rooms. CONCLUSIONS: Use of e-cigarettes or hookah increases air pollution in homes. For hookah, increases in PM2.5 penetrated even into rooms adjacent to where smoking occurs. Extending smoke-free rules inside homes to include e-cigarette and hookah products is needed to protect household members and visitors from passive exposure to harmful aerosols and gases.

Characterizing the 'feel-good experience' in multiple sclerosis patients treated with natalizumab or other therapies.

Aim: Patients with relapsing-remitting multiple sclerosis (RRMS) treated with natalizumab have anecdotally reported a 'feel-good experience' (FGE). The authors characterized the FGE using survey data from patients with RRMS treated with natalizumab or other disease-modifying therapies (other-DMT). Methods: Questionnaire data from RRMS patients who use MyMSTeam, an online patient social network, were analyzed. Results: The survey included 347 patients (95 natalizumab; 252 other-DMT). More natalizumab than other-DMT patients self-reported having an FGE (62.1 vs 44.8%; p = 0.001) as well as other physical, emotional and cognitive benefits. Conclusion: This study demonstrates that physical, emotional and cognitive benefits were more commonly reported by patients treated with natalizumab than those treated with other disease-modifying therapies and helps characterize patient-reported factors associated with the FGE.

Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis.

BACKGROUND: The monoclonal antibody ublituximab enhances antibody-dependent cellular cytolysis and produces B-cell depletion. Ublituximab is being evaluated for the treatment of relapsing multiple sclerosis. METHODS: In two identical, phase 3, double-blind, double-dummy trials (ULTIMATE I and II), participants with relapsing multiple sclerosis were randomly assigned in a 1:1 ratio to receive intravenous ublituximab (150 mg on day 1, followed by 450 mg on day 15 and at weeks 24, 48, and 72) and oral placebo or oral teriflunomide (14 mg once daily) and intravenous placebo. The primary end point was the annualized relapse rate. Secondary end points included the number of gadolinium-enhancing lesions on magnetic resonance imaging (MRI) by 96 weeks and worsening of disability. RESULTS: A total of 549 participants were enrolled in the ULTIMATE I trial, and 545 were enrolled in the ULTIMATE II trial; the median follow-up was 95 weeks. In the ULTIMATE I trial, the annualized relapse rate was 0.08 with ublituximab and 0.19 with teriflunomide (rate ratio, 0.41; 95% confidence interval [CI], 0.27 to 0.62; P<0.001); in the ULTIMATE II trial, the annualized relapse rate was 0.09 and 0.18, respectively (rate ratio, 0.51; 95% CI, 0.33 to 0.78; P = 0.002). The mean number of gadolinium-enhancing lesions was 0.02 in the ublituximab group and 0.49 in the teriflunomide group (rate ratio, 0.03; 95% CI, 0.02 to 0.06; P<0.001) in the ULTIMATE I trial and 0.01 and 0.25, respectively (rate ratio, 0.04; 95% CI, 0.02 to 0.06; P<0.001), in the ULTIMATE II trial. In the pooled analysis of the two trials, 5.2% of the participants in the ublituximab group and 5.9% in the teriflunomide group had worsening of disability at 12 weeks (hazard ratio, 0.84; 95% CI, 0.50 to 1.41; P = 0.51). Infusion-related reactions occurred in 47.7% of the participants in the ublituximab group. Serious infections occurred in 5.0% in the ublituximab group and in 2.9% in the teriflunomide group. CONCLUSIONS: Among participants with relapsing multiple sclerosis, ublituximab resulted in lower annualized relapse rates and fewer brain lesions on MRI than teriflunomide over a period of 96 weeks but did not result in a significantly lower risk of worsening of disability. Ublituximab was associated with infusion-related reactions. (Funded by TG Therapeutics; ULTIMATE I and II ClinicalTrials.gov numbers, NCT03277261 and NCT03277248.).

Workforce Readiness Training: A Comprehensive Training Model That Equips Community Health Workers to Work at the Top of Their Practice and Profession.

Background: Recent reports have recognized that only 20 percent of health outcomes are attributed to clinical care. Environmental conditions, behaviors, and social determinants of health account for 80 percent of overall health outcomes. With shortages of clinical providers stressing an already burdened healthcare system, Community Health Workers (CHWs) can bridge healthcare gaps by addressing these nonmedical factors influencing health. This paper details how a comprehensive training model equips CHWs for workforce readiness so they can perform at the top of their practice and profession and deliver well-coordinated client/patient-centered care. Methods: Literature reviews and studies revealed that training CHWs alone is not sufficient for successful workforce readiness, rather CHW integration within the workforce is needed. Consequently, this comprehensive training model is developed for CHWs with varying skill levels and work settings, and supervisors to support organizational readiness and CHW integration efforts. A systematic training program development approach along with detailed implementation methods are presented. Continuing education sessions to support CHW practice and Organizational Readiness Training for supervisors, leadership and team members directly engaged with CHWs in the workplace are also discussed. CHWs were involved in all phases of the research, development, implementation, and actively serve in evaluations and curriculum review committees. Results: Components of the comprehensive training model are presented with an emphasis on the core CHW training. Two CHW training tracks are offered using three delivery modalities. Process measures with student learning objectives, outcome measures developed using the Kirkpatrick model to capture attitude, perceptions, knowledge acquisition, confidence, behavior, and overall experience, and impact stories by two CHWs are presented. Lessons learned from the implementation of the training program are discussed in three categories: Practice-driven curricula, student-centered training implementation, and adaptations in response to COVID-19 pandemic. Conclusion: This comprehensive training model recognizes that training CHWs in a robust training program is key as the demand for well-rounded CHWs increases. Furthermore, a comprehensive training program must include training for supervisors, leadership, and team members working directly with CHWs. Such efforts strengthen the CHW practice and profession to support the delivery of well-coordinated and holistic client/patient-centered care.

Natalizumab in Early Relapsing-Remitting Multiple Sclerosis: A 4-Year, Open-Label Study.

INTRODUCTION: STRIVE was a 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative (JCV-negative) relapsing-remitting multiple sclerosis (RRMS) patients with disease duration ≤ 3 years. The objective of STRIVE was to examine no evidence of disease activity (NEDA) status and predictors of NEDA in natalizumab-treated patients with early RRMS. METHODS: Proportions of patients with NEDA were evaluated along with baseline predictors of NEDA, annualized relapse rate, 24-week confirmed disability worsening (CDW), magnetic resonance imaging assessments (T2 and gadolinium-enhancing lesions), and serious adverse events. RESULTS: In years 1 and 2, 56.1% (95% confidence interval [CI] 48.7-63.4%) and 73.6% (95% CI 66.2-80.2%) of patients (intent-to-treat population [N = 222]), respectively, achieved NEDA. In years 3 and 4, 84.6% (95% CI 78.0-89.9%) and 91.9% (95% CI 86.4-95.8%) of patients, respectively, achieved Clinical NEDA (no relapses or 24-week CDW). Baseline predictors of NEDA in year 4 were Expanded Disability Status Scale score ≤ 2.0 (odds ratio [OR] = 3.85 [95% CI 1.54-9.63]; p = 0.004) and T2 lesion volume > 4 cc (OR = 0.39 [95% CI 0.15-0.98]; p = 0.046), with the latter also predicting Clinical NEDA in year 4 (OR = 0.21 [95% CI 0.05-0.92]; p = 0.038). The cumulative probability of CDW at year 4 was 19.3%. Serious adverse events were reported in 11.3% of patients. CONCLUSION: These results support the long-term safety and effectiveness of natalizumab. Baseline predictors of NEDA help to inform benefit-risk assessments of natalizumab treatment in JCV-negative patients with early RRMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01485003.

Stillbirth in Canada: anachronistic definition and registration processes impede public health surveillance and clinical care.

The archaic definition and registration processes for stillbirth currently prevalent in Canada impede both clinical care and public health. The situation is fraught because of definitional problems related to the inclusion of induced abortions at ≥20 weeks' gestation as stillbirths: widespread uptake of prenatal diagnosis and induced abortion for serious congenital anomalies has resulted in an artefactual temporal increase in stillbirth rates in Canada and placed the country in an unfavourable position in international (stillbirth) rankings. Other problems with the Canadian stillbirth definition and registration processes extend to the inclusion of fetal reductions (for multi-fetal pregnancy) as stillbirths, and the use of inconsistent viability criteria for reporting stillbirth. This paper reviews the history of stillbirth registration in Canada, provides a rationale for updating the definition of fetal death and recommends a new definition and improved processes for fetal death registration. The recommendations proposed are intended to serve as a starting point for reformulating issues related to stillbirth, with the hope that building a consensus regarding a definition and registration procedures will facilitate clinical care and public health.

RéSUMé: La définition et les méthodes d'enregistrement archaïques des mortinaissances qui prévalent actuellement au Canada entravent à la fois les soins cliniques et la santé publique. La situation est délicate à cause des problèmes de définition que pose l'inclusion des avortements provoqués à ≥ 20 semaines de gestation parmi les mortinaissances : le recours généralisé au diagnostic prénatal et les avortements provoqués en cas d'anomalies congénitales graves ont entraîné une augmentation temporelle artéfactuelle des taux de mortinatalité au Canada et placé le pays dans une position défavorable dans les classements internationaux (de la mortinatalité). Les autres problèmes dans la définition et les méthodes d'enregistrement canadiennes des mortinaissances sont l'inclusion de la réduction fœtale (pour les grossesses multifœtales) parmi les mortinaissances et l'emploi de critères de viabilité inconsistants pour déclarer les mortinaissances. Nous examinons ici l'histoire de l'enregistrement des mortinaissances au Canada, nous justifions une révision possible de la définition de la mort fœtale et nous recommandons une nouvelle définition et des méthodes d'enregistrement améliorées des morts fœtales. Les recommandations proposées se veulent un point de départ à une reformulation des questions liées à la mortinatalité, dans l'espoir que l'établissement d'un consensus sur une définition et sur les méthodes d'enregistrement facilitera les soins cliniques et la santé publique.

Nocturia and electrocardiographic abnormalities among patients at an inner-city cardiology clinic.

AIMS: Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. METHODS: Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. RESULTS: Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. CONCLUSIONS: Nocturia may be a risk marker for underlying structural cardiac abnormalities.

Dual Mobility Total Hip Arthroplasty Is Not Associated with a Greater Incidence of Groin Pain in Comparison with Conventional Total Hip Arthroplasty and Hip Resurfacing:A Retrospective Comparative Study.

BACKGROUND: Groin pain is a common long-term complication of total hip arthroplasty (THA). Femoral head size has been proposed as one of the primary causes. The implants used in dual mobility (DM) THA have large outer-bearing articulations, which could increase the risk of post-operative groin pain. Hip resurfacing (HR), too, has been shown to be associated with a risk of groin pain. QUESTIONS/PURPOSES: The goals of this study were to compare the incidence of groin pain at 1 year after hip arthroplasty in patients with different femoral head diameters and in patients undergoing conventional THA, DM THA, and HR. METHODS: After combing an institutional registry for all patients who had undergone THA or HR for primary hip osteoarthritis, we included 3193 patients in the analysis; 2008 underwent conventional THA, 416 underwent DM THA, and 769 underwent HR. We used logistic regression modeling to analyze the relation of groin pain at 1 year after surgery to patient demographics and clinical characteristics, including age, sex, body mass index (BMI), University of California at Los Angeles activity score at 1 year after surgery, bearing couple, and the ratio of acetabular diameter to femoral head diameter. We also measured cup inclination and anteversion in a subset of patients with and without groin pain at 1 year to assess whether pain could be related to implant position. RESULTS: Overall, 8.7% of patients reported groin pain at 1 year. Patients with groin pain were younger and had lower BMIs. There were increased odds of groin pain with a greater cup-to-head ratio, although DM implants, interestingly, were not significantly associated with groin pain; this may be attributable to so much of their movement taking place inside the implant. Subgroup analysis measuring cup inclination and anteversion showed no difference in cup position between patients with and without pain. CONCLUSION: In this population of hip arthroplasty patients, the incidence of groin pain 1 year after surgery did not differ among patients undergoing DM and conventional THA; DM THA in particular was not associated with a higher risk of groin pain, despite its comparatively larger femoral head sizes. HR, on the other hand, was associated with a higher risk of pain. Appropriate implant sizing and bearing couple choice may optimize the functional benefit of THA.

Accuracy of Blood Transfusion Records in a Population-based Perinatal Data Registry.

BACKGROUND: Blood transfusion is frequently used as an indicator of severe maternal morbidity during pregnancy. However, few studies have examined its validity in population perinatal databases. METHODS: We linked a perinatal database from British Columbia, Canada, with the province's Central Transfusion Registry for 2004-2015 deliveries. Using the Central Transfusion Registry records for red blood cell transfusion as the gold standard, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the perinatal database variable for red blood cell transfusion, overall and by transfusion risk factor status. We used multivariable logistic regression to examine whether outcome misclassification altered the odds ratios for different transfusion risk factors. RESULTS: Among 473,688 deliveries, 4,033 (8.5 per 1,000) had a red blood cell transfusion according to the Central Transfusion Registry. The sensitivity of the perinatal database transfusion variable was 72.3 [95% confidence interval (CI) = 72.2, 72.4]. Sensitivity differed according to the presence of many transfusion risk factors (e.g., 84.9% vs. 72.2% in deliveries with versus without uterine rupture). Odds ratios associated with some transfusion risk factors were exaggerated when the perinatal database transfusion variable was used to define the outcome instead of the Central Transfusion Registry variable, but 95% confidence intervals for these estimates overlapped. CONCLUSION: Blood transfusion was documented with reasonable sensitivity in this large population perinatal database. However, validity varied according to risk factor status. Our findings enable researchers to better account for outcome misclassification in studies of obstetrical transfusion risk factors.

Similarities Between Alcohol and Tobacco Advertising Exposure and Adolescent Use of Each of These Substances.

OBJECTIVE: Underage alcohol use is a major public health problem and substantial corporate money supports alcohol advertising across multiple venues. A diverse research literature demonstrates that adolescent exposure to such advertising is associated with drinking attitudes and behavior, but no scientific body has determined these associations to be causal. The objective of this study was to assess the association between alcohol advertising and teen drinking in the context of the "Analogy" criterion of the Bradford Hill criteria and consider a determination that the association between exposure to alcohol advertising and alcohol use is causal. METHOD: This study was a narrative review on the association between adolescent exposure to alcohol advertising and subsequent alcohol use in the context of domains utilized in the Surgeon General's 2012 Report, Preventing Tobacco Use Among Youth and Young Adults, which concluded, "Advertising and promotional activities by tobacco companies have been shown to cause the onset and continuation of smoking among adolescents and young adults." RESULTS: In every aspect compared (i.e., adolescent knowledge; attitudes toward; initiation of use; continuation of use; mediums of advertisement; the use of mascots, celebrities, and themes; and frequency and density of advertisements and retailers), the findings for both tobacco and alcohol and their association with exposure to advertising are analogous. CONCLUSIONS: Application of the Analogy criterion of the Bradford Hill criteria comparing alcohol and tobacco supports a judgment that the association between exposure to alcohol advertising and increased adolescent knowledge, attitudes toward, initiation, and continuation of alcohol use are causal in nature.

The 5-year Tysabri global observational program in safety (TYGRIS) study confirms the long-term safety profile of natalizumab treatment in multiple sclerosis.

BACKGROUND: Natalizumab is an effective treatment for multiple sclerosis (MS) and has a well-characterized safety profile, with more than 10 years of postmarketing experience. TYGRIS was a 5-year observational cohort study designed to obtain long-term safety data in natalizumab-treated MS patients. We examined the incidence and pattern of serious adverse events (SAEs) in this large postmarketing sample of natalizumab-treated patients. METHODS: Investigators reported SAEs in natalizumab-treated patients. Malignancy incidence rates were compared with rates in the general population using external databases. RESULTS: Of 6508 enrolled patients, 4938 (75.9%) completed the study. SAEs occurring in more than 0.5% of patients included urinary tract infection (n = 50; 0.8%), pneumonia (n = 46; 0.7%), progressive multifocal leukoencephalopathy (PML; n = 44; 0.7%), and immune reconstitution inflammatory syndrome (n = 44; 0.7%). Fifty-five patients (0.9%) experienced treatment-emergent serious opportunistic infections, 44 of which were PML. Two patients with PML died. The overall malignancy incidence rate was 449.0 per 100,000 patient-years (95% confidence interval [CI], 375.1-533.1). With few exceptions, incidence rates for individual malignancies had 95% CIs encompassing incidence rates in the general population. Hepatotoxic events occurred in 6 patients; 4 patients had evidence of alternative cause or confounders. Of 96 fatal events, investigators considered 81 unrelated or unlikely to be related to treatment and 5 related or possibly related; causality was not provided for 10. CONCLUSION: Data from this large, long-term study indicate that the nature, character, and frequency of SAEs in real-world settings are consistent with natalizumab's known safety profile. (Funded by Biogen; ClinicalTrials.gov identifiers: NCT00477113 and NCT00483847.).