Publications

Little information exists on the impact of integrating family planning (FP) services into HIV care and treatment on patients' familiarity with and attitudes toward FP. We conducted a cluster-randomized trial in 18 public HIV clinics with 12 randomized to integrated FP and HIV services and 6 to the standard referral-based system where patients are referred to an FP clinic. Serial cross-sectional surveys were done before (n = 488 women, 486 men) and after (n = 479 women, 481 men) the intervention to compare changes in familiarity with FP methods and attitudes toward FP between integrated and nonintegrated (NI) sites. We created an FP familiarity score based on the number of more effective FP methods patients could identify (score range: 0-6). Generalized estimating equations were used to control for clustering within sites. An increase in mean familiarity score between baseline (mean = 5.16) and post-intervention (mean = 5.46) occurred with an overall mean change of 0.26 (95% confidence intervals [CI] = 0.09, 0.45; p = 0.003) across all sites. At end line, there was no difference in increase of mean FP familiarity scores at intervention versus control sites (mean = 5.41 vs. 5.49, p = 0.94). We observed a relative decrease in the proportion of males agreeing that FP was "women's business" at integrated sites (baseline 42% to end line 30%; reduction of 12%) compared to males at NI sites (baseline 35% to end line 42%; increase of 7%; adjusted odds ration [aOR] = 0.43; 95% CI = 0.22, 0.85). Following FP-HIV integration, familiarity with FP methods increased but did not differ by study arm. Integration was associated with a decrease in negative attitudes toward FP among men.

BACKGROUND

Inpatient antiarrhythmic drug initiation for atrial fibrillation is mandated for dofetilide (DF) and is often performed for sotalol (SL), particularly if proarrhythmia risk factors are present. Whether low-risk patients can be identified to safely allow outpatient initiation is unknown.

METHODS

A single-center retrospective cohort study was performed on patients initiated with DF or SL. Risk factors for adverse events (AEs), defined as any arrhythmia or electrocardiogram change requiring dose reduction or cessation, were identified.

RESULTS

Of 329 patients, 227 (69%) received SL and 102 (31%) DF. The cohort had a mean age of 63 ± 13 years; 70% of patients were male and had a baseline QTc of 440 ± 37 ms. A total of 105 AEs occurred in 92 patients: QTc prolongation or ventricular tachyarrhythmia in 70 patients (67% of AEs), bradyarrhythmias in 35 patients (33% of AEs), with some experiencing both AE types. Ventricular arrhythmias were seen in 23 patients (7%) and torsades de pointes in one (0.3%). Total AE rates were similar between drugs (P = 0.09); however, DF patients had more QTc prolongation or ventricular arrhythmias (P = 0.001). In SL patients, there were no predictors for QTc prolongation or ventricular proarrhythmia. In DF patients, higher baseline QTc interval (odds ratio = 1.64/25 ms, P = 0.01) was an independent predictor of QTc prolongation or ventricular proarrhythmias. For patients without proarrhythmia risk factors, overall AE rate was 26%.

CONCLUSIONS

In conclusion, AEs are common during DF and SL initiation but rarely severe in hospitalized inpatients. Baseline QTc predicts AEs for DF patients only and AE are common even in "low-risk" patients. These results support in-hospital drug initiation for all DF and SL patients.

Chronic stress is well known to exacerbate pain. We tested the hypothesis that neonatal handling, which induces resilience to the negative impact of stress by increasing the quality and quantity of maternal care, attenuates the mechanical hyperalgesia produced by water-avoidance stress in the adult rat. Neonatal male rats underwent the handling protocol on postnatal days 2-9, weaned at 21 days and tested for muscle mechanical nociceptive threshold at postnatal days 50-75. Decrease in mechanical nociceptive threshold in skeletal muscle in adult rats, produced by exposure to water-avoidance stress, was significantly attenuated by neonatal handling. Neonatal handling also attenuated the mechanical hyperalgesia produced by intramuscular administration of the pronociceptive inflammatory mediator, prostaglandin E2 in rats exposed as adults to water-avoidance stress. Neonatal handling, which induces a smaller corticosterone response in adult rats exposed to a stressor as well as changes in central nervous system neurotransmitter systems, attenuates mechanical hyperalgesia produced by water-avoidance stress and enhanced prostaglandin hyperalgesia in adult animals.

PURPOSE

A male infant developed generalized rash, intestinal inflammation and severe infections including persistent cytomegalovirus. Family history was negative, T cell receptor excision circles were normal, and engraftment of maternal cells was absent. No defects were found in multiple genes associated with severe combined immunodeficiency. A 9/10 HLA matched unrelated hematopoietic cell transplant (HCT) led to mixed chimerism with clinical resolution. We sought an underlying cause for this patient's immune deficiency and dysregulation.

METHODS

Clinical and laboratory features were reviewed. Whole exome sequencing and analysis of genomic DNA from the patient, parents and 2 unaffected siblings was performed, revealing 2 MALT1 variants. With a host-specific HLA-C antibody, we assessed MALT1 expression and function in the patient's post-HCT autologous and donor lymphocytes. Wild type MALT1 cDNA was added to transformed autologous patient B cells to assess functional correction.

RESULTS

The patient had compound heterozygous DNA variants affecting exon 10 of MALT1 (isoform a, NM_006785.3), a maternally inherited splice acceptor c.1019-2A > G, and a de novo deletion of c.1059C leading to a frameshift and premature termination. Autologous lymphocytes failed to express MALT1 and lacked NF-κB signaling dependent upon the CARMA1, BCL-10 and MALT1 signalosome. Transduction with wild type MALT1 cDNA corrected the observed defects.

CONCLUSIONS

Our nonconsanguineous patient with early onset profound combined immunodeficiency and immune dysregulation due to compound heterozygous MALT1 mutations extends the clinical and immunologic phenotype reported in 2 prior families. Clinical cure was achieved with mixed chimerism after nonmyeloablative conditioning and HCT.