Lower early mortality rates among patients receiving antiretroviral treatment at clinics offering cotrimoxazole prophylaxis in Malawi

OBJECTIVE: To determine whether Malawi antiretroviral treatment (ART) clinics providing cotrimoxazole (CTX) prophylaxis had lower early mortality rates compared with clinics not providing CTX. METHODS: Retrospective cohort study of eleven ART clinics in Malawi that were or were not providing CTX. Medical record abstraction was performed for all patients (N = 1295) initiating ART between July 1 and December 15, 2005. At 5 ART sites, CTX was given to patients dosed at 960 mg daily or 480 mg twice a day (according to national guidelines). RESULTS: When all defaults (patients lost to follow-up for >90 days) were excluded from the analysis, the 6-month mortality rate was 10.7% in patients receiving ART at CTX clinics compared with 18.0% in those not at CTX clinics (6-month mortality risk reduction = 40.7%; P = 0.0013). Kaplan-Meier survival curves for patients receiving CTX and patients not receiving CTX were significantly different; survival differences were apparent as early as 40 to 45 days after initiation of ART. CONCLUSIONS: Patients receiving ART in Malawi at clinics offering CTX prophylaxis had significantly reduced mortality during the first 6 months of ART. This additional intervention may have the potential to improve the lives of patients on ART, because CTX is readily available and relatively inexpensive and can, in principle, be easily introduced into ART delivery programs.     

Support workers in maternity services

Reductions in doctors' hours and length of training and reconfigurations of obstetric and neonatal services in the UK have led to practitioners taking on new clinical roles. The need to free midwives' time for their extending clinical roles has led to greater use of support workers. These workers are increasingly assisting with clinical as well as clerical and administrative tasks but their training and responsibilities are variable. A recent scoping study of these workers in NHS Trusts in England, discussed here by its authors, reveals that managers welcome the support workers' contribution to maternity care, for example through breast-feeding support in the community, helping to provide continuity of care and one-to-one care in labour, attending at home births, assisting in obstetric theatres and running antenatal and postnatal groups. However, a national framework is needed to ensure governance, Research is also needed into the impact of support workers on outcomes for mothers and babies, the cost-effectiveness of the role, and the experience of mothers.     

Overexpression of the human VPAC2 receptor in the suprachiasmatic nucleus alters the circadian phenotype of mice

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to a superfamily of structurally related peptide hormones that includes glucagon, glucagon-like peptides, secretin, and growth hormone-releasing hormone. Microinjection of VIP or PACAP into the rodent suprachiasmatic nucleus (SCN) phase shifts the circadian pacemaker and VIP antagonists, and antisense oligodeoxynucleotides have been shown to disrupt circadian function. VIP and PACAP have equal potency as agonists of the VPAC(2) receptor (VPAC(2)R), which is expressed abundantly in the SCN, in a circadian manner. To determine whether manipulating the level of expression of the VPAC(2)R can influence the control of the circadian clock, we have created transgenic mice overexpressing the human VPAC(2)R gene from a yeast artificial chromosome (YAC) construct. The YAC was modified by a strategy using homologous recombination to introduce (i) the HA epitope tag sequence (from influenza virus hemagglutinin) at the carboxyl terminus of the VPAC(2)R protein, (ii) the lacZ reporter gene, and (iii) a conditional centromere, enabling YAC DNA to be amplified in culture in the presence of galactose. High levels of lacZ expression were detected in the SCN, habenula, pancreas, and testis of the transgenic mice, with lower levels in the olfactory bulb and various hypothalamic areas. Transgenic mice resynchronized more quickly than wild-type controls to an advance of 8 h in the light-dark (LD) cycle and exhibited a significantly shorter circadian period in constant darkness (DD). These data suggest that the VPAC(2)R can influence the rhythmicity and photic entrainment of the circadian clock.     

Comparative effectiveness of mechanically and electrically powered negative pressure wound therapy devices: A multicenter randomized controlled trial

This study was designed to compare the ultraportable mechanically powered Smart Negative Pressure (SNaP) Wound Care System (Spiracur, Sunnyvale, CA) with the electrically powered Vacuum‐Assisted Closure (VAC) Therapy System (Kinetic Concepts, Inc. [KCI], San Antonio, TX) in a multicenter, comparative efficacy, noninferiority‐powered, randomized controlled trial. We enrolled 132 people with noninfected, nonischemic, nonplantar lower extremity diabetic and venous wounds. Each subject was randomly assigned (1:1) to treatment with either system in conjunction with appropriate off‐loading and compression therapy. The trial evaluated treatment for up to 16 weeks or complete wound closure (defined as complete reepithelialization without drainage). Primary end point analysis of wound size reduction found that SNaP‐treated subjects demonstrated noninferiority to the VAC‐treated subjects at 4, 8, 12, and 16 weeks (p = 0.0030, 0.0130, 0.0051, and 0.0044, respectively). Kaplan–Meier analysis showed no significant difference in complete wound closure between SNaP‐ and VAC‐treated subjects at all time points. Device related adverse events and complications such as infection were also similar between treatment groups. These data support similar wound healing outcomes between the SNaP system and the VAC system in the population studied.     

Renal cell carcinoma with metastases to the gallbladder: four cases from the National Cancer Institute (NCI) and review of the literature

ObjectiveWe evaluate presentation and outcome of patients with metastatic RCC to the gallbladder from our institution and published literature.MethodsPatients with a history of gallbladder metastasis from RCC were selected from our institution's prospective database. A systematic PubMed search was performed to identify articles describing patients with metastatic RCC to the gallbladder. The final cohort included 33 patients: 4 from our institution and 29 from 28 previously published cases. Survival analysis was conducted using log-rank Kaplan-Meier analysis.ResultsMedian patient age was 63 years and the majority of patients were male. Most patients were asymptomatic and diagnosed with gallbladder metastasis on imaging performed for surveillance or staging. The median time to gallbladder metastasis following nephrectomy was 4 years. Metastasis to the gallbladder occurred both synchronously (33%) and metachronously (67%). Of the patients with available histology, all had clear cell RCC (n = 28). Of all patients, 13 (39%) had metastasis only to the gallbladder, while 20 (61%) had additional sites of metastasis. The most common sites of additional metastasis were contralateral kidney (30%), pancreas (21%), lung (18%), adrenal (18%), and lymph nodes (9%). All patients underwent cholecystectomy. At a median follow up time of 1.5 years after cholecystectomy, 54% of patients had no evidence of disease, 14% were alive with metastasis, 23% had died from metastatic RCC, and 9% died from causes unrelated to their cancer.ConclusionGallbladder metastasis from RCC is a rare event that may occur synchronously or metachronously with most patients being asymptomatic. Clear cell carcinoma appears to be the primary pathology associated with gallbladder metastasis. High rates of bilateral RCC and pancreatic metastasis suggest novel associations in patients with RCC and gallbladder metastasis.     

Impact of pathological tumour characteristics in patients with sarcomatoid renal cell carcinoma

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Sarcomatoid renal cell carcinoma can occur in the setting of all histological subtypes of kidney cancer. These tumours are very aggressive and many patients present with disseminated disease. Long‐term survival is poor and the durable responses to systemic therapy are infrequent. Our large cohort analyses the influence of pathological tumour characteristics in determining prognosis for patients with sarcomatoid renal cell carcinoma undergoing surgical resection. This series helps define the prognostic influence of histological subtype, type of sarcomatoid morphology, the percentage necrosis and sarcomatoid features, and the presence of microvascular invasion.

OBJECTIVES

• ? To examine the influence of pathological tumour characteristics on survival to aid prognostication and clinical trial design.
• ? Patients with sarcomatoid renal cell carcinoma (sRCC) are known to have poor prognosis and response to systemic therapy.

PATIENTS AND METHODS

• ? A single‐centre database was reviewed to identify all patients with sRCC.
• ? Clinical variables and pathological information, including histology, necrosis, percentage of sarcomatoid features (PSF) and microvascular invasion (MVI), were recorded and correlated to outcome.

RESULTS

• ? Analyses of 104 patients with sRCC found that the median (range) size of tumours was 9.5 cm (2.5–30), 65% of patients had areas of clear cell histology, and 69.2% had metastatic disease at presentation.
• ? The PSF did not influence tumour size, stage, necrosis, MVI, nodes or metastasis.
• ? A total of 85 patients (81.7%) died during the follow‐up period with a median (95% confidence interval [CI]) survival of 5.9 months (4.7–8.9).
• ? In the overall cohort, Eastern Cooperative Group performance status (ECOGPS), tumour size and metastatic disease were independent predictors of poor survival. MVI, PSF and percentage necrosis were strongly associated with outcome but were not independent predictors of outcome.
• ? A multivariate risk model was established that incorporated six covariates (tumour size, MVI, ECOGPS, PSF, necrosis, and metastatic disease) to produce a predictive tool.

CONCLUSIONS

• ? Both patients with localized and metastatic sRCC have very poor survival outcomes.
• ? Pathological features MVI, PSF and necrosis are important predictors of survival and could be used in a prognostic model while grade and histology do not influence prognosis.
• ? A prognostic model, if validated, could aid in patient counselling and/or clinical trial design.

     

Ikoma lyssavirus, highly divergent novel lyssavirus in an African civet

Evidence in support of a novel lyssavirus was obtained from brain samples of an African civet in Tanzania. Results of phylogenetic analysis of nucleoprotein gene sequences from representative Lyssavirus species and this novel lyssavirus provided strong empirical evidence that this is a new lyssavirus species, designated Ikoma lyssavirus.