Improved identification and enrolment into care of HIV-exposed and -infected infants and children following a community health worker intervention in Lilongwe,Malawi

Background

Early identification and entry into care is critical to reducing morbidity and mortality in children with HIV. The objective of this report is to describe the impact of the Tingathe programme, which utilizes community health workers (CHWs) to improve identification and enrolment into care of HIV-exposed and -infected infants and children.

Methods

Three programme phases are described. During the first phase, Mentorship Only (MO) (March 2007–February 2008) on-site clinical mentorship on paediatric HIV care was provided. In the second phase, Tingathe-Basic (March 2008–February 2009), CHWs provided HIV testing and counselling to improve case finding of HIV-exposed and -infected children. In the final phase, Tingathe-PMTCT (prevention of mother-to-child transmission) (March 2009–February 2011), CHWs were also assigned to HIV-positive pregnant women to improve mother-infant retention in care. We reviewed routinely collected programme data from HIV testing registers, patient mastercards and clinic attendance registers from March 2005 to March 2011.

Results

During MO, 42 children (38 HIV-infected and 4 HIV-exposed) were active in care. During Tingathe-Basic, 238 HIV-infected children (HIC) were newly enrolled, a six-fold increase in rate of enrolment from 3.2 to 19.8 per month. The number of HIV-exposed infants (HEI) increased from 4 to 118. During Tingathe-PMTCT, 526 HIC were newly enrolled over 24 months, at a rate of 21.9 patients per month. There was also a seven-fold increase in the average number of exposed infants enrolled per month (9.5–70 patients per month), resulting in 1667 enrolled with a younger median age at enrolment (5.2 vs. 2.5 months; p<0.001).During the Tingathe-Basic and Tingathe-PMTCT periods, CHWs conducted 44,388 rapid HIV tests, 7658 (17.3%) in children aged 18 months to 15 years; 351 (4.6%) tested HIV-positive. Over this time, 1781 HEI were enrolled, with 102 (5.7%) found HIV-infected by positive PCR. Additional HIC entered care through various mechanisms (including positive linkage by CHWs and transfer-ins) such that by February 2011, a total of 866 HIC were receiving care, a 23-fold increase from 2008.

Conclusions

A multipronged approach utilizing CHWs to conduct HIV testing, link HIC into care and provide support to PMTCT mothers can dramatically improve the identification and enrolment into care of HIV-exposed and -infected children.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity

Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated translocation of GLUT4 from its intracellular compartment to the plasma membrane is regulated by small guanosine triphosphate hydrolases (GTPases) and is essential for the maintenance of normal glucose homeostasis. Here we show that the p75 neurotrophin receptor (p75(NTR)) is a regulator of glucose uptake and insulin resistance. p75(NTR) knockout mice show increased insulin sensitivity on normal chow diet, independent of changes in body weight. Euglycemic-hyperinsulinemic clamp studies demonstrate that deletion of the p75(NTR) gene increases the insulin-stimulated glucose disposal rate and suppression of hepatic glucose production. Genetic depletion or shRNA knockdown of p75(NTR) in adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4 translocation. Conversely, overexpression of p75(NTR) in adipocytes decreases insulin-stimulated glucose transport. In adipocytes, p75(NTR) forms a complex with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5 and Rab31 directly interact with p75(NTR) primarily via helix 4 of the p75(NTR) death domain. Adipocytes from p75(NTR) knockout mice show increased Rab5 and decreased Rab31 activities, and dominant negative Rab5 rescues the increase in glucose uptake seen in p75(NTR) knockout adipocytes. Our results identify p75(NTR) as a unique player in glucose metabolism and suggest that signaling from p75(NTR) to Rab5 family GTPases may represent a unique therapeutic target for insulin resistance and diabetes.     

Role of the vein of marshall in atrial fibrillation recurrences after catheter ablation: therapeutic effect of ethanol infusion

Vein of Marshall Ethanol in Recurrent AF. Introduction: Atrial fibrillation (AF) or flutter can recur after pulmonary vein (PV) antral isolation (PVAI). The vein of Marshall (VOM) has been linked to the genesis of AF. We hypothesized that the VOM may play a role in AF recurrences and that VOM ethanol infusion may have therapeutic value in this setting. Methods and Results: Sixty-one patients with recurrent AF or flutter after PVAI were studied. The VOM was successfully cannulated in 54; VOM and PV electrograms were recorded, and differential PV-VOM pacing was performed. VOM signals were present in all patients; however, VOM triggers of AF could not be demonstrated. VOM tachycardia was present in 1 patient. Left inferior (LIPV) and left superior (LSPV) reconnection was present in 32 and 30 patients, respectively. Differential pacing in VOM and LIPV showed VOM-mediated LIPV reconnection in 5/32 patients. In others, VOM and PV connected indirectly via left atrial tissues. Up to four 1 cc infusions of 98% ethanol were delivered in the VOM. Regardless of the reconnection pattern, ethanol infusion eliminated LIPV and LSPV reconnection in 23/32 and 13/30 patients, respectively. Ethanol terminated VOM and LIPV tachycardias in 2 patients. There were no acute procedural complications. Conclusions: VOM signals are consistently present in recurrent AF. VOM may rarely play a role in PV reconnection. However, VOM ethanol infusion can be useful in patients with recurrent AF after PVAI, assisting in achieving redisconnection of reconnected left PVs.