Nevirapine- and efavirenz-associated hepatotoxicity under programmatic conditions in Kenya and Mozambique

To describe the frequency, risk factors, and clinical signs and symptoms associated with hepatotoxicity (HT) in patients on nevirapine- or efavirenz-based antiretroviral therapy (ART), we conducted a retrospective cohort analysis of patients attending the ART clinic in Kibera, Kenya, from April 2003 to December 2006 and in Mavalane, Mozambique, from December 2002 to March 2007. Data were collected on 5832 HIV-positive individuals who had initiated nevirapine- or efavirenz-based ART. Median baseline CD4+ count was 125 cells/μL (interquartile range [IQR] 55-196). Over a median follow-up time of 426 (IQR 147-693) days, 124 (2.4%) patients developed HT. Forty-one (54.7%) of 75 patients with grade 3 HT compared with 21 (80.8%) of 26 with grade 4 had associated clinical signs or symptoms (P = 0.018). Four (5.7%) of 124 patients with HT died in the first six months compared with 271 (5.3%) of 5159 patients who did not develop HT (P = 0.315). The proportion of patients developing HT was low and HT was not associated with increased mortality. Clinical signs and symptoms identified 50% of grade 3 HT and most cases of grade 4 HT. This suggests that in settings where alanine aminotransferase measurement is not feasible, nevirapine- and efavirenz-based ART may be given safely without laboratory monitoring.     

Relationship among reproductive variables,sucrose taste reactivity and feeding behavior in humans

Magnitude-estimation of sucrose pleasantness and sweetness, and feeding behavior, were investigated in female and male college students. The subjects were individually tested five times over a five-week period. Female test intervals were scheduled to include the menses, pre-ovulatory, and luteal phases of the menstrual cycle. The data were analyzed by gender, length of menses, and phase of the menstrual cycle. The results of these analyses were consistent for both the sucrose taste reactivity tests and feeding tests. Male and long-menses females exhibited similar response patterns; and their pattern was significantly different from that of the short-menses females. The mean log pleasantness ratings of the males and long-menses females were significantly smaller than those of the short-menses females. Furthermore, both long-menses females and males behaved similarly in a time-limited surreptitious feeding test. They consumed significantly more food than did short-menses females. Phase of the menstrual cycle did not alter pleasantness response patterns, but there was one phase effect in the feeding tests. Luteal phase intake of short-menses females was elevated relative to that of the menses phase. These findings demonstrate that reproductive variables participate in the control of human regulatory behaviors.     

IL‐33 delivery induces serous cavity macrophage proliferation independent of interleukin‐4 receptor alpha

IL‐33 plays an important role in the initiation of type‐2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL‐33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL‐4 and IL‐13 signaling to IL‐4Rα. IL‐4 and IL‐13 also induce macrophage proliferation but IL‐33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL‐33 induced IL‐4Rα‐dependent alternative macrophage activation in the serous cavities. IL‐33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL‐4Rα signaling. In a filarial nematode infection model in which IL‐4Rα‐dependent alternative activation and proliferation in the pleural cavity is well described, IL‐33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL‐33 responses, we observed that both IL‐4Rα and IL‐33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL‐33R and IL‐4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.     

Alpha+ -thalassaemia and malaria in Melanesia: epidemiological perspectives

In 1948 Haldane first proposed that the high frequencies of thalassaemias in malaria-endemic regions were due to natural selection by malaria. Some of the highest frequencies of alpha+ -thalassaemia are found in the Pacific region of Melanesia. Consequently, Melanesia has provided a unique opportunity for an extensive study of the association between alpha+ -thalassaemia and malaria. Here we review the emergence of alpha+ -thalassaemia in this region and the research that has been carried out, both from the historical perspective and the most recent developments, which may give insight into the selection of alpha+ -thalassaemia by malaria.     

The prevalence of postoperative pain in a cross-sectional group of patients after day-case surgery in a university hospital

OBJECTIVES: Although a great variety of surgical procedures are performed on an ambulatory basis, little is known about postoperative pain experience at home after ambulatory surgery. This study was performed to assess the prevalence and course of postoperative pain in the early postoperative period after ambulatory surgery. METHODS: Over a period of 4 months, 648 patients who underwent day-case surgery were included in our study. Data were collected with interviews and questionnaires. Pain intensity was measured using a visual analog scale (VAS) during 4 days after surgery. Side effects of anesthesia and analgesia techniques were also recorded. RESULTS: On the day of the operation, 26% of the patients had moderate to severe pain (defined as mean VAS >40 mm). Mean VAS-scores were greater than 40 mm in 21% on postoperative day (POD) 1, in 13% on POD 2, in 10% on POD 3, and in 9% on POD 4. Operations of nose and pharynx, abdominal operations, plastic surgery of the breasts, and orthopedic operations were the most painful procedures during the first 48 hours. DISCUSSION: This study showed that an important number of patients still experience moderate to severe pain in the postoperative period after day-case surgery even after a 4-day period. Furthermore, the type of operation should be considered when planning postoperative analgesia for ambulatory surgery.     

Perceptions of hyperbaric oxygen therapy among podiatrists practicing in high‐risk foot clinics

Foot ulceration is a devastating and costly consequence of diabetes. Hyperbaric oxygen therapy is recognised as an adjunctive therapy to treat diabetes‐related foot ulceration, yet uptake is low. Semi‐structured interviews were conducted with 16 podiatrists who manage patients with foot ulcers related to diabetes to explore their perceptions of, and the barriers/facilitators to, referral for hyperbaric oxygen. Podiatrists cited logistical issues such as location of facilities as well as poor communication pathways, lack of delegation and lack of follow up when patients presented for hyperbaric treatment. In general, podiatrists had an understanding of the premise of hyperbaric oxygen therapy and evidence to support its use but could only provide very limited citations of key papers and guidelines to support their position. Podiatrists stated that they felt a patient was lost from their care when referred for hyperbaric oxygen and that aftercare might not be adequate. Improved referral and delegation pathways for patients presenting for hyperbaric oxygen, as well as the provision of easily accessible evidence to support this therapy, could help to increase podiatrists’ confidence in deciding whether or not to recommend their patients for hyperbaric oxygen therapy.     

Sustainability of a community-based anti-retroviral care delivery model – a qualitative research study in Tete,Mozambique

Introduction

To overcome patients’ reported barriers to accessing anti-retroviral therapy (ART), a community-based delivery model was piloted in Tete, Mozambique. Community ART Groups (CAGs) of maximum six patients stable on ART offered cost- and time-saving benefits and mutual psychosocial support, which resulted in better adherence and retention outcomes. To date, Médecins Sans Frontières has coordinated and supported these community-driven activities.

Methods

To better understand the sustainability of the CAG model, we developed a conceptual framework on sustainability of community-based programmes. This was used to explore the data retrieved from 16 focus group discussions and 24 in-depth interviews with different stakeholder groups involved in the CAG model and to identify factors influencing the sustainability of the CAG model.

Results

We report the findings according to the framework''s five components. (1) The CAG model was designed to overcome patients’ barriers to ART and was built on a concept of self-management and patient empowerment to reach effective results. (2) Despite the progressive Ministry of Health (MoH) involvement, the daily management of the model is still strongly dependent on external resources, especially the need for a regulatory cadre to form and monitor the groups. These additional resources are in contrast to the limited MoH resources available. (3) The model is strongly embedded in the community, with patients taking a more active role in their own healthcare and that of their peers. They are considered as partners in healthcare, which implies a new healthcare approach. (4) There is a growing enabling environment with political will and general acceptance to support the CAG model. (5) However, contextual factors, such as poverty, illiteracy and the weak health system, influence the community-based model and need to be addressed.

Conclusions

The community embeddedness of the model, together with patient empowerment, high acceptability and progressive MoH involvement strongly favour the future sustainability of the CAG model. The high dependency on external resources for the model''s daily management, however, can potentially jeopardize its sustainability. Further reflections are required on possible solutions to solve these challenges, especially in terms of human resources.