HIV multidisciplinary teams work: support services improve access to and retention in HIV primary care

The multidisciplinary team model of HIV care evolved out of necessity due to the diverse characteristics and needs of people living with HIV disease. Though it is now accepted as the international standard of care, it represents a significant departure from methods of care for other infectious diseases, and debate continues regarding the effectiveness of its interventions. The debate has been largely uninformed by data; for example, little is known about the relationship between ancillary support services and primary care outcomes. We hypothesized that support services increase access to and retention in HIV primary care in an inner city public hospital clinic. We conducted a retrospective analysis of clinical data sets on 2,647 patients at the CORE Center, Chicago from 1997-1998 to investigate the relationship between four support services-case management (CM), transportation (TRANS), mental health (MH) and chemical dependency (CD)-and access to and retention in HIV primary care. We found that patients who received each of these services were significantly more likely to receive any care, regular care and had more visits than patients with no service, and retention increased by 15-18%. Female gender, younger age, self-pay status and IDU predicted less regular care. Need for all services was substantial and significantly greater in women. Outcomes improved to the greatest extent among patients who needed and received each service. We conclude that support services significantly increased access to and retention in HIV primary care. Our findings validate the multidisciplinary team model of HIV care, and suggest that health services that are tailored to the express needs of patients lead to better care and improved health outcomes. Further testing of changes in health care delivery to meet the rapidly changing needs of people living with HIV disease and respond to the constantly changing practice of HIV medicine is urgently needed to maintain and extend the advances in HIV care outcomes of the past decade.     

Does blood pressure inevitably rise with age?: longitudinal evidence among forager-horticulturalists

The rise in blood pressure with age is a major risk factor for cardiovascular and renal disease, stroke, and type 2 diabetes mellitus. Age-related increases in blood pressure have been observed in almost every population, except among hunter-gatherers, farmers, and pastoralists. Here we tested for age-related increases in blood pressure among Tsimane forager-farmers. We also test whether lifestyle changes associated with modernization lead to higher blood pressure and a greater rate of age-related increase in blood pressure. We measured blood pressure longitudinally on 2248 adults age ≥ 20 years (n=6468 observations over 8 years). Prevalence of hypertension was 3.9% for women and 5.2% for men, although diagnosis of persistent hypertension based on multiple observations reduced prevalence to 2.9% for both sexes. Mixed-effects models revealed systolic, diastolic, and pulse blood pressure increases of 2.86 (P<0.001), 0.95 (P<0.001), and 1.95 mmHg (P<0.001) per decade for women and 0.91 (P<0.001), 0.93 (P<0.001), and -0.02 mmHg (P=0.93) for men, substantially lower than rates found elsewhere. Lifestyle factors, such as smoking and Spanish fluency, had minimal effect on mean blood pressure and no effect on age-related increases in blood pressure. Greater town proximity was associated with a lower age-related increase in pulse pressure. Effects of modernization were, therefore, deemed minimal among Tsimane, in light of their lean physique, active lifestyle, and protective diet.     

Predisposing germline mutations in high hyperdiploid acute lymphoblastic leukemia in children

High hyperdiploidy (HD) is the most common cytogenetic subtype of childhood acute lymphoblastic leukemia (ALL), and a higher incidence of HD has been reported in ALL patients with congenital cancer syndromes. We assessed the frequency of predisposing germline mutations in 57 HD‐ALL patients from the California Childhood Leukemia Study via targeted sequencing of cancer‐relevant genes. Three out of 57 patients (5.3%) harbored confirmed germline mutations that were likely causal, in NBN, ETV6, and FLT3, with an additional six patients (10.5%) harboring putative predisposing mutations that were rare in unselected individuals (<0.01% allele frequency in the Exome Aggregation Consortium, ExAC) and predicted functional (scaled CADD score ≥ 20) in known or potential ALL predisposition genes (SH2B3, CREBBP, PMS2, MLL, ABL1, and MYH9). Three additional patients carried rare and predicted damaging germline mutations in GAB2, a known activator of the ERK/MAPK and PI3K/AKT pathways and binding partner of PTPN11‐encoded SHP2. The frequency of rare and predicted functional germline GAB2 mutations was significantly higher in our patients (2.6%) than in ExAC (0.28%, P = 4.4 × 10^?3), an observation that was replicated in ALL patients from the TARGET project (P = .034). We cloned patient GAB2 mutations and expressed mutant proteins in HEK293 cells and found that frameshift mutation P621fs led to reduced SHP2 binding and ERK1/2 phosphorylation but significantly increased AKT phosphorylation, suggesting possible RAS‐independent leukemogenic effects. Our results support a significant contribution of rare, high penetrance germline mutations to HD‐ALL etiology, and pinpoint GAB2 as a putative novel ALL predisposition gene.     

Effect of Cardiac-Cycle-Synchronized Selective Vagal Stimulation on Heart Rate and Blood Pressure in Rats

Introduction

Activation of the baroreflex system through the selective vagal nerve stimulation (sVNS) may become a treatment option for therapy-resistant hypertension, which is a frequently observed problem in the antihypertensive therapy. In previous studies, we used continuous sVNS to lower blood pressure (BP) without major side effects in a rat model. As continuous stimulation is energy consuming and sVNS could be implemented in an antihypertensive stimulator, it was the aim of this study to investigate the efficacy of pulsatile, cardiac-cycle-synchronized sVNS (cssVNS) on the reduction of BP.

Methods

A multichannel cuff electrode was wrapped around the left vagal nerve in six male Wistar rats under Isoflurane anesthesia. BP was recorded in the left carotid artery. An electrocardiogram (ECG) was obtained via subcutaneous needle electrodes. The aortic depressor nerve fibers in the vagal nerve bundle were selectively stimulated with 18 parameter settings within a window of 15–30 ms after the R-peak in the ECG. The stimulation paradigm included every heartbeat, every second heart beat, and every third heart beat. BP and heart rate were initially recorded over 10 min.

Results

Using cssVNS, BP could be significantly reduced over 30 min and maintained at this level. While the highest BP reduction was seen during cssVNS at every heartbeat with minimal bradycardia, less—yet significant—BP reduction was seen during cssVNS at every second or third heartbeat without causing detectable bradycardia.

Conclusion

cssVNS can chronically reduce BP in rats avoiding measurable bradycardic side effects. This energy-efficient technique might allow the implementation of sVNS using an implantable device to permanently lower BP in patients.

Funding

The study was funded by Bundesministerium fur Bildung und Forschung/German Federal Ministry of Education and Research among the call “Individualisierte Medizintechnik” under the grant number FKZ 13GW0120B.