Booked and unbooked mothers delivering at Harare Maternity Hospital Zimbabwe: a comparison of maternal characteristics and foetal outcome

A journal article comparing maternal characteristics and foetal outcomes of mothers (booked and un-booked) delivering at Harare Maternity Hospital in Zimbabwe.This study was prompted by the poor maternal and foetal outcome at Harare Maternity Hospital, Zimbabwe, in unbooked mothers compared to women who had booked for antenatal care. Comparison was made of 195 recently delivered unbooked mothers with 196 booked mothers. Unbooked mothers were significantly more likely to be younger, of lower piuity, be single, have lower socio-economic status, live in or migrate from rural areas, be uneducated and have an unwanted pregnancy. Their infants were significantly more likely to preterm and/or of low birth weight and had a higher perinatal mortality. The major reasons cited by the women for not booking were lack of money and delivery occurring before the intended time of booking. Discussion focuses on how to improve outcome in unbooked mothers

Complications and Functional Results of Surgery for Locally Advanced Prostate Cancer

The role of surgery in clinical stage T3 prostate cancer (cT3 PCa) is still subject to debate. We reviewed the records of 139 consecutive patients who underwent a radical prostatectomy (RP) for cT3 PCa with a mean follow-up of 8 years. All data related to surgical and perioperative complications were collected. Continence and erectile function were assessed at 12 months postoperatively and long-term oncologic outcomes were analyzed. Rectal injury and injury of the obturator nerve occurred both in 0.7% of cases. No serious in-hospital complications were noted and no reintervention was needed. Lymphatic leakage was noted in 2.2% of patients and 1.4% experienced prolonged drainage of urine. In 7.2%, wound-related problems occurred. Anastomotic stricture occurred in 2.9%. These complication rates were not different compared to surgical series of RP in localized PCa. At 12 months, complete continence was 87.8% and erectile function had fully recovered in 6% and 10% of patients who underwent a non-nerve sparing or unilateral nerve-sparing procedure, respectively. 10-year estimated biochemical PFS, clinical PFS, CSS and OS were 51.8%, 85.6%, 94.6% and 85.9%, respectively. In cT3 PCa, RP is technically feasible with morbidity comparable to RP in clinically localized PCa. Long-term oncologic control was excellent

Prospect Farm and the Middle and Later Stone Age Occupation of Mt. Eburru (Central Rift, Kenya) in an East African Context

Located within the Nakuru-Naivasha basin on the northern slope of Mt. Eburru, the open-air site of Prospect Farm (Central Rift, Kenya) is one of the few East African sites that have yielded a stratigraphic sequence containing archaeological levels dating from the late Middle Pleistocene to the Holocene. Excavations at the site by Barbara Whitehead Anthony and Glynn Isaac in 1963–1964 exposed Pastoral Neolithic (Stone Bowl culture) and Later Stone Age (LSA; Kenya Capsian) levels overlying four Middle Stone Age (MSA) levels attributed to the Prospect Industry, a local expression of the Kenya Stillbay. This paper integrates the information currently available for the site and discusses its relevance in a wider East African context. Furthermore, it presents the results of a density survey completed in 2014, mapping the spatial distribution of artifacts along the northern slope of Mt. Eburru and providing data on the landscape setting of the site. The survey identified marked differences in the distribution of diagnostic MSA vs. LSA artifacts: whereas MSA finds cluster at two particular mid-altitude locations (2,102–2,108 m and 2,138–2,140 m a.s.l.) corresponding to the position of Anthony’s Localities I and II, LSA finds tend to show a much broader spatial distribution including both higher and lower altitudes

Current and future diagnostic and treatment strategies for patients with invasive lobular breast cancer.

BACKGROUND: Invasive lobular breast cancer (ILC) is the second most common type of breast cancer after invasive breast cancer of no special type (NST), representing up to 15% of all breast cancers. DESIGN: Latest data on ILC are presented, focusing on diagnosis, molecular make-up according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT) guidelines, treatment in the early and metastatic setting and ILC-focused clinical trials. RESULTS: At the imaging level, magnetic resonance imaging-based and novel positron emission tomography/computed tomography-based techniques can overcome the limitations of currently used imaging techniques for diagnosing ILC. At the pathology level, E-cadherin immunohistochemistry could help improving inter-pathologist agreement. The majority of patients with ILC do not seem to benefit as much from (neo-)adjuvant chemotherapy as patients with NST, although chemotherapy might be required in a subset of high-risk patients. No differences in treatment efficacy are seen for anti-human epidermal growth factor receptor 2 (HER2) therapies in the adjuvant setting and cyclin-dependent kinases 4 and 6 inhibitors in the metastatic setting. The clinical utility of the commercially available prognostic gene expression-based tests is unclear for patients with ILC. Several ESCAT alterations differ in frequency between ILC and NST. Germline BRCA1 and PALB2 alterations are less frequent in patients with ILC, while germline CDH1 (gene coding for E-cadherin) alterations are more frequent in patients with ILC. Somatic HER2 mutations are more frequent in ILC, especially in metastases (15% ILC versus 5% NST). A high tumour mutational burden, relevant for immune checkpoint inhibition, is more frequent in ILC metastases (16%) than in NST metastases (5%). Tumours with somatic inactivating CDH1 mutations may be vulnerable for treatment with ROS1 inhibitors, a concept currently investigated in early and metastatic ILC. CONCLUSION: ILC is a unique malignancy based on its pathological and biological features leading to differences in diagnosis as well as in treatment response, resistance and targets as compared to NST

Challenges in physician supply planning: the case of Belgium

<p>Abstract</p> <p>Introduction</p> <p>Planning human resources for health (HRH) is a complex process for policy-makers and, as a result, many countries worldwide swing from surplus to shortage. In-depth case studies can help appraising the challenges encountered and the solutions implemented. This paper has two objectives: to identify the key challenges in HRH planning in Belgium and to formulate recommendations for an effective HRH planning, on the basis of the Belgian case study and lessons drawn from an international benchmarking.</p> <p>Case description</p> <p>In Belgium, a numerus clausus set up in 1997 and effective in 2004, aims to limit the total number of physicians working in the curative sector. The assumption of a positive relationship between physician densities and health care utilization was a major argument in favor of medical supply restrictions. This new regulation did not improve recurrent challenges such as specialty imbalances, with uncovered needs particularly among general practitioners, and geographical maldistribution. New difficulties also emerged. In particular, limiting national training of HRH turned out to be ineffective within the open European workforce market. The lack of integration of policies affecting HRH was noteworthy. We described in the paper what strategies were developed to address those challenges in Belgium and in neighboring countries.</p> <p>Discussion and evaluation</p> <p>Planning the medical workforce involves determining the numbers, mix, and distribution of health providers that will be required at some identified future point in time. To succeed in their task, health policy planners have to take a broader perspective on the healthcare system. Focusing on numbers is too restrictive and adopting innovative policies learned from benchmarking without integration and coordination is unfruitful. Evolving towards a strategic planning is essential to control the effects of the complex factors impacting on human resources. This evolution requires an effective monitoring of all key factors affecting supply and demand, a dynamic approach, and a system-level perspective, considering all healthcare professionals, and integrating manpower planning with workforce development.</p> <p>Conclusion</p> <p>To engage in an evidence-based action, policy-makers need a global manpower picture, from their own country and abroad, as well as reliable and comparable manpower databases allowing proper analysis and planning of the workforce.</p

Human immunodeficiency virus: 25 years of diagnostic and therapeutic strategies and their impact on hepatitis B and C virus

The human immunodeficiency virus (HIV) had spread unrecognized in the human population as sexually transmitted disease and was finally identified by its disease AIDS in 1981. Even after the isolation of the causative agent in 1983, the burden and death rate of AIDS accelerated worldwide especially in young people despite the confection of new drugs capable to inhibit virus replication since 1997. However, at least in industrialised countries, this trend could be reversed by the introduction of combination therapy strategies. The design of new drugs is on going; besides the inhibition of the three enzymes of HIV for replication and maturation (reverse transcriptase, integrase and protease), further drugs inhibits fusion of viral and cellular membranes and virus maturation. On the other hand, viral diagnostics had been considerably improved since the emergence of HIV. There was a need to identify infected people correctly, to follow up the course of immune reconstitution of patients by measuring viral load and CD4 cells, and to analyse drug escape mutations leading to drug resistance. Both the development of drugs and the refined diagnostics have been transferred to the treatment of patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV). This progress is not completed; there are beneficial aspects in the response of the scientific community to the HIV burden for the management of other viral diseases. These aspects are described in this contribution. Further aspects as handling a stigmatising disease, education of self-responsiveness within sexual relationships, and ways for confection of a protective vaccine are not covered

Safety and efficacy of a dapivirine vaginal ring for HIV prevention in women

BACKGROUND The incidence of human immunodeficiency virus (HIV) infection remains high among women in sub-Saharan Africa. We evaluated the safety and efficacy of extended use of a vaginal ring containing dapivirine for the prevention of HIV infection in 1959 healthy, sexually active women, 18 to 45 years of age, from seven communities in South Africa and Uganda. METHODS In this randomized, double-blind, placebo-controlled, phase 3 trial, we randomly assigned participants in a 2:1 ratio to receive vaginal rings containing either 25 mg of dapivirine or placebo. Participants inserted the rings themselves every 4 weeks for up to 24 months. The primary efficacy end point was the rate of HIV type 1 (HIV-1) seroconversion. RESULTS A total of 77 participants in the dapivirine group underwent HIV-1 seroconversion during 1888 person-years of follow-up (4.1 seroconversions per 100 person-years), as compared with 56 in the placebo group who underwent HIV-1 seroconversion during 917 person-years of follow-up (6.1 seroconversions per 100 person-years). The incidence of HIV-1 infection was 31% lower in the dapivirine group than in the placebo group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.99; P = 0.04). There was no significant difference in efficacy of the dapivirine ring among women older than 21 years of age (hazard ratio for infection, 0.63; 95% CI, 0.41 to 0.97) and those 21 years of age or younger (hazard ratio, 0.85; 95% CI, 0.45 to 1.60; P = 0.43 for treatment-by-age interaction). Among participants with HIV-1 infection, nonnucleoside reverse-transcriptase inhibitor resistance mutations were detected in 14 of 77 participants in the dapivirine group (18.2%) and in 9 of 56 (16.1%) in the placebo group. Serious adverse events occurred more often in the dapivirine group (in 38 participants [2.9%]) than in the placebo group (in 6 [0.9%]). However, no clear pattern was identified. CONCLUSIONS Among women in sub-Saharan Africa, the dapivirine ring was not associated with any safety concerns and was associated with a rate of acquisition of HIV-1 infection that was lower than the rate with placebo.Supported by the International Partnership for Microbicides (a not-for-profit product-development partnership), which receives support from the Bill and Melinda Gates Foundation, Irish Aid, the Ministry of Foreign Affairs of Denmark, the Ministry of Foreign Affairs of the Netherlands, the Norwegian Agency for Development Cooperation, the U.K. Department for International Development, the American people through the U.S. Agency for International Development, and the President’s Emergency Plan for AIDS Relief.http://www.nejm.org2017-06-01am2017Family Medicin

Calcium and copper transport ATPases: analogies and diversities in transduction and signaling mechanisms

The calcium transport ATPase and the copper transport ATPase are members of the P-ATPase family and retain an analogous catalytic mechanism for ATP utilization, including intermediate phosphoryl transfer to a conserved aspartyl residue, vectorial displacement of bound cation, and final hydrolytic cleavage of Pi. Both ATPases undergo protein conformational changes concomitant with catalytic events. Yet, the two ATPases are prototypes of different features with regard to transduction and signaling mechanisms. The calcium ATPase resides stably on membranes delimiting cellular compartments, acquires free Ca2+ with high affinity on one side of the membrane, and releases the bound Ca2+ on the other side of the membrane to yield a high free Ca2+ gradient. These features are a basic requirement for cellular Ca2+ signaling mechanisms. On the other hand, the copper ATPase acquires copper through exchange with donor proteins, and undergoes intracellular trafficking to deliver copper to acceptor proteins. In addition to the cation transport site and the conserved aspartate undergoing catalytic phosphorylation, the copper ATPase has copper binding regulatory sites on a unique N-terminal protein extension, and has also serine residues undergoing kinase assisted phosphorylation. These additional features are involved in the mechanism of copper ATPase intracellular trafficking which is required to deliver copper to plasma membranes for extrusion, and to the trans-Golgi network for incorporation into metalloproteins. Isoform specific glyocosylation contributes to stabilization of ATP7A copper ATPase in plasma membranes