Study Type – Symptom prevalence (prospective cohort)
Level of Evidence 1b OBJECTIVE To evaluate patient‐reported reasons for discontinuing antimuscarinic prescription medications for overactive bladder (OAB). PATIENTS AND METHODS A phase 1 screening survey was sent to a representative sample of 260 000 households in the USA to identify patients using antimuscarinic agents for OAB. A detailed phase‐2 follow‐up survey was sent to 6577 respondents with one or more antimuscarinic prescriptions for OAB in the 12 months before the phase 1 survey. The follow‐up survey included questions about demographics, clinical characteristics, antimuscarinic use, beliefs about OAB, treatment expectations, OAB symptom bother, and pre‐coded reasons for discontinuation. Patients who reported discontinuing one or more OAB medication during the 12 months before phase 2 were grouped by reason, using latent class analysis (LCA); the Lo‐Mendell‐Rubin likelihood statistical test was used to determine the number of classes. Conditional probabilities of reasons for discontinuation were calculated for each class. Multivariable logistic regression was used to assess the influence of demographic and clinical characteristics on class assignment. RESULTS In all, 162 906 (63%) and 5392 (82%) useable responses were returned in phases 1 and 2, respectively; the demographics were similar in respondents and nonrespondents in both phases. In all, 1322 phase 2 respondents (24.5%) reported discontinuing one or more antimuscarinic drugs during the 12 months before phase 2. LCA identified two classes (Lo‐Mendell‐Rubin statistic, P = 0.01) based on reasons for discontinuation. Most respondents (89%) reported discontinuing OAB medication primarily due to unmet treatment expectations and/or tolerability; many respondents in this class switched to a new antimuscarinic agent. A smaller group (11%) indicated a general aversion to taking medication. Age, sex, race, income, and history of incontinence were not predictive of class assignment. CONCLUSIONS Expectations about treatment efficacy and side‐effects are the most important considerations in discontinuing OAB medications for most patients. Interventions to promote realistic expectations about treatment efficacy and side‐effects might enhance adherence.

IntroductionAs atrial fibrillation (AF) is often asymptomatic, it may remain undiagnosed until or even after development of complications, such as stroke. Consequently the observed prevalence of AF may underestimate total disease burden.MethodsTo estimate the prevalence of undiagnosed AF in the United States, we performed a retrospective cohort modeling study in working age (18–64) and elderly (≥65) people using commercial and Medicare administrative claims databases. We identified patients in years 2004–2010 with incident AF following an ischemic stroke. Using a back-calculation methodology, we estimated the prevalence of undiagnosed AF as the ratio of the number of post-stroke AF patients and the CHADS2-specific stroke probability for each patient, adjusting for age and gender composition based on United States census data.ResultsThe estimated prevalence of AF (diagnosed and undiagnosed) was 3,873,900 (95%CI: 3,675,200–4,702,600) elderly and 1,457,100 (95%CI: 1,218,500–1,695,800) working age adults, representing 10.0% and 0.92% of the respective populations. Of these, 698,900 were undiagnosed: 535,400 (95%CI: 331,900–804,400) elderly and 163,500 (95%CI: 17,700–400,000) working age adults, representing 1.3% and 0.09% of the respective populations. Among all undiagnosed cases, 77% had a CHADS2 score ≥1, and 56% had CHADS2 score ≥2.ConclusionsUsing a back-calculation approach, we estimate that the total AF prevalence in 2009 was 5.3 million of which 0.7 million (13.1% of AF cases) were undiagnosed. Over half of the modeled population with undiagnosed AF was at moderate to high risk of stroke.

Among the DOACs in the study, only apixaban is associated with a significantly lower risk of stroke/SE and major bleeding and lower related medical costs compared to warfarin.

Human immunodeficiency virus (HIV) vaccines have the potential to improve antiretroviral drug treatment by inducing cytotoxic killing of HIV-infected cells. Prophylactic vaccines utilize new antigens to initiate immunity; however, in HIV-infected individuals the load of viral antigen is not the limiting factor for the restoration of immune responses. Here we describe a novel immunization strategy with DermaVir that improves viral antigen presentation using dendritic cells (DC). DermaVir contains a distinctive plasmid DNA expressing all HIV proteins except integrase to induce immune responses with broad specificity. The DNA is formulated to a mannosilated particle to target antigen-presenting cells and to protect the DNA from intracellular degradation. After topical application, DermaVir-transduced cells migrate from the skin to the draining lymph node and interdigitate as DermaVir-expressing, antigen-presenting DC. We compared the immunogenicity of topical and ex vivo DC-based DermaVir vaccinations in naive rhesus macaques. Both vaccinations induced simian immunodeficiency virus-specific CD4 helper and CD8 memory T cells detected by an in vivo skin test and an in vitro intracellular cytokine-based assay. Topical DermaVir vaccination represents an improvement upon existing ex vivo DC-based immunization technologies and may provide a new therapeutic option for HIV-infected patients.

The results indicate the feasibility of therapeutic immunization even in immune compromised hosts, and suggest that DermaVir can complement antiretroviral drugs to sustain suppression of HIV-1 replication.