Evidence of genetic variability of human immunodeficiency virus type 1 in plasma and cervicovaginal lavage in ethiopian women seeking care for sexually transmitted infections

Most human immunodeficiency virus type 1 (HIV-1) transmission in developing countries occurs through heterosexual intercourse or during birth from mother to child. It is critical to characterize the virus of the genital tract variants as a target for the development of an HIV-1 vaccine and microbicidal therapies. We compared the C2V3 env domain genetic diversity of HIV-1 in female genital secretions and in plasma from Ethiopian women seeking care for sexually transmitted infections (STIs). Sequences within an individual differed between the plasma and cervicovaginal lavage (CLV) compartments with nucleotide and amino acid median difference values of 8.3 and 4.8%, respectively. Sequence diversity in CVL was greater than in plasma. And the V3 loop positive charge was often more elevated in CVL. These are markers of the differential evolution of the viruses in CVL and peripheral blood indicating that limited evolution at the site of contact is not the limiting factor determining the preferential transmission of macrophage tropic viruses.     

Frequency-modulated electromagnetic neural stimulation (FREMS) as a treatment for symptomatic diabetic neuropathy: results from a double-blind, randomised, multicentre, long-term, placebo-controlled clinical trial

Aims/hypothesis

The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus.

Methods

This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18–75 years with diabetes for ≥1 year, HbA_1c <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients’ date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment.

Results

Patients (n?=?110) with symptomatic neuropathy were randomised to FREMS (n?=?54) or placebo (n?=?56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means?±?SE]: 0.74?±?0.71 vs 0.06?±?1.38 m/s; tibial: 2.08?±?0.84 vs 0.61?±?0.43 m/s; and sural: 0.80?±?1.08 vs ?0.91?±?1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study.

Conclusions/interpretation

FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV.

Trial registration

ClinicalTrials.gov NCT01628627

Funding

The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell’Emilia, Italy).     

Perceived control over ejaculation is central to treatment benefit in men with premature ejaculation: results from phase III trials with dapoxetine

OBJECTIVES

To assess the utility of perceived control over ejaculation (‘control’) in the evaluation of treatment benefit in men with premature ejaculation (PE), and to compare effects associated with a two‐category or greater increase in this variable between men receiving dapoxetine and placebo.

PATIENTS AND METHODS

This subanalysis used combined data from all treatment groups in an integrated analysis of two identically designed, 12‐week, double‐blind, randomized, placebo‐controlled trials of dapoxetine. Men (2614) met the Diagnostic and Statistical Manual of Mental Disorders (fourth edition, text revision) criteria for PE, had a stopwatch‐measured intravaginal ejaculatory latency time (IELT) of ≤2 min in ≥75% of events in a 2‐week baseline period, and self‐reported moderate or severe PE. Men received placebo or dapoxetine 30 or 60 mg, 1–3 h before intercourse. The stopwatch‐measured IELT was recorded for each episode; the patient‐reported global impression of change (PGI; 7‐point scale, ‘much worse’ to ‘much better’), control and satisfaction with sexual intercourse (5‐point scales, ‘very poor’ to ‘very good’) were assessed monthly. The utility of a two‐category or greater increase in control was evaluated by examining the relationship of this variable with IELT and satisfaction with sexual intercourse.

RESULTS

Of 2341 men with baseline and endpoint assessments, 96.8% reported ‘very poor’ or ‘poor’ control at baseline, and 748 (32%) reported a two‐category or greater increase in control after treatment. More than 95% of those men rated their PE as ‘slightly better’, ‘better’, or ‘much better’ on the PGI; 67.1% gave ratings of ‘better’ or ‘much better.’ They also had greater improvements in IELT than men with less than a two‐category increase in control, with a mean (sd ) change from baseline of 3.7 (4.3) vs 0.77 (1.8) min, respectively, and a greater percentage reported good or very good satisfaction with sexual intercourse than men with less than a two‐category increase in control (74% vs 19%, respectively). Nausea, headache and upper respiratory tract infection were the most common adverse events reported by men with a two‐category or greater increase in control (15.8%, 7.4% and 6.6%, respectively) and those without (8.5%, 5.5% and 6.5%, respectively). The proportions of men with a two‐category or greater increase in control with dapoxetine 30 and 60 mg were 36.3% and 44.5%, respectively (vs 15% with placebo).

CONCLUSIONS

A two‐category or greater increase in control (5‐point scale) is useful for assessing the treatment benefit in men with PE; it corresponds with improvements in the man’s perception of his condition, substantially greater prolongation of IELT, and higher levels of satisfaction with sexual intercourse.     

Relationship between autonomic neuropathy and hypertension—are we underestimating the problem?

Background Cardiac autonomic neuropathy (CAN) is associated with significant morbidity and mortality in diabetes and the risk is even greater in those with hypertension. Aims The aim of our study was to investigate the relationship between CAN and 24‐h blood pressure profile in normoalbuminuric patients with Type 2 diabetes mellitus. Methods Seventy patients with Type 2 diabetes (31 without CAN, 39 with CAN), who had no history of hypertension, and 29 healthy volunteers underwent five standard cardiovascular reflex tests to assess autonomic function and 24‐h ambulatory blood pressure monitoring. Results Twenty‐four‐hour mean systolic blood pressure, blood pressure load and hyperbaric impact values were significantly higher in diabetic patients with CAN compared with control subjects and diabetic patients without CAN (P < 0.05). In spite of normal clinic blood pressures, 54% of diabetic subjects with CAN and 29% without CAN were hypertensive (systolic blood pressure load > 20%, P < 0.05). In the diabetes group as a whole, Valsalva ratio, postural systolic blood pressure changes and diastolic blood pressure responses during sustained handgrip correlated significantly and negatively with 24‐h mean systolic blood pressure (P < 0.01, P < 0.001, P < 0.05) and blood pressure load (P < 0.05, P < 0.001, P < 0.05). Conclusions Cardiovascular autonomic neuropathy is independently associated with hypertension in normoalbuminuric Type 2 diabetic patients with no history of hypertension. Relying on clinic blood pressures in subjects with CAN could lead to a failure to diagnose hypertension in over half of cases. All normotensive patients with CAN should be screened for hypertension using ambulatory blood pressure monitoring in order to institute early aggressive interventions to improve their long‐term outlook.     

Immunization (EPI) in Ethiopia: acceptance, coverage, and sustainability

Ethiopia has been engaged in expanding immunization services against the six childhood diseases since 1980. According to plans set at the beginning of the program, the country should have achieved universal child immunization by now. However, the child immunization coverage has never reached the level that is desired to curtail disease transmission and to reduce the morbidity burden associated with the target diseases. This study used the potential of social science research methods in understanding social, cultural, political and economic factors that influence the efficiency and effectiveness of immunization programs in the Ethiopian context. A better understanding of these factors is believed to improve the quality and sustainability of immunization programs. This research focused on relevant issues at micro- and macro-levels. The study basically utilized qualitative research methods involving multiple data collection tools and information sources. Factors related to acceptors, immunization service providers and organization of health services that influence the successful implementation and sustainability of the immunization program in the Ethiopian context are identified and discussed. Strengthening efforts to improve technical capacity of service providers, increasing social mobilization activities, instituting quality assurance schemes and improving management of resources (human, finance and material) are among the major recommendations.     

Combining risk factors and demographic surveillance: potentials of WHO STEPS and INDEPTH methodologies for assessing epidemiological transition

AIMS: Demographic surveillance systems (DSSs) create platforms to monitor population dynamics. This paper discusses the potential of combining the WHO STEPwise approach to Surveillance (STEPS) within ongoing DSSs, to assess changes in non-communicable disease (NCD) risk factors. METHODS: Three DSSs in Ethiopia, Vietnam, and Indonesia have collected NCD risk factors using WHO STEPS, focusing on self-reported lifestyle risk factors (Step 1) and measurement of blood pressure and anthropometric parameters (Step 2). RESULTS: DSSs provide sampling frames for NCD risk factor surveillance, which reveals the distribution of risk factors and their dynamics at the population level. The WHO STEPS approach with its add-on modules is feasible and adaptable in DSS settings. Available mortality data in the DSSs enable mortality assessment by cause of death using verbal autopsy, which is relevant in estimating the impact of NCDs. DSSs as well as risk factor surveillance data may potentially be a lever for hypothesis-driven research to address specific a priori hypotheses or research questions. CONCLUSION: Combining DSSs with the WHO STEPS approach can potentially address basic epidemiological questions on NCDs, which can be used as a powerful advocacy tool in public health decision-making for NCD prevention.     

Screening of some medicinal plants of Ethiopia for their anti-microbial properties and chemical profiles

In the indigenous health care delivery system of Ethiopia, numerous plant species are used to treat diseases of infectious origin. Regardless of the number of species, if any of such claims could be verified scientifically, the potential significance for the improvement of the health care services would be substantial. The objective of this study was, therefore, to determine the presence of anti-microbial activity in the crude extracts of some of the commonly used medicinal plants as well as to identify the class of compounds in the plants that were subjected to such screening. Thus, the crude methanol, petroleum ether and aqueous extracts of 67 plant species were subjected to preliminary screening against 10 strains of bacterial species and 6 fungal strains using the agar dilution method. A sample concentration of 250-2000 microg/ml and 500-4000 microg/ml were used for the bacterial and fungal pathogens, respectively. The results indicated that 44 different plant species exhibited activity against one or more of the bacteria while one species, viz., Albizzia gummifera showed activity against all the 10 bacteria at different gradient of dilution. Twenty three species inhibited or retarded growth of one or more organisms at dilution as low as 250 microg/ml. Extracts of same plants species were also tested against six different fungal pathogenic agents of which eight species showed growth inhibition against one or more of the organisms. Trichila emetica and Dovyalis abyssinica, which inhibited growth of four and five fungal strains at 100 microg/ml concentration, respectively, were the most promising plants. Chemical screening conducted on the extracts of all the plants showed the presence of several secondary metabolites, mainly, polyphenols, alkaloids, tannins sterols/terpenes, saponins and glycosides. The plants containing more of these metabolites demonstrated stronger anti-microbial properties stressing the need for further investigations using fractionated extracts and purified chemical components.     

Phase I dose-finding study of weekly single-agent patupilone in patients with advanced solid tumors.

PURPOSE: To evaluate the safety and maximum-tolerated dose (MTD) of weekly patupilone, a natural epothilone B, in patients with advanced solid tumors. PATIENTS AND METHODS: Patients were treated with patupilone (0.3 to 3.6 mg/m2) for 6 weeks on/3 weeks off or 3 weeks on/1 week off. Dose-limiting toxicities (DLTs), MTD, and pharmacokinetics were determined for each schedule of administration. RESULTS: Ninety-one patients were enrolled. The most common tumor types included ovarian, breast, and colon cancers. Doses of patupilone less than 2.5 mg/m2 using either the 6 weeks on/3 weeks off or the 3 weeks on/1 week off schedule were tolerated well. At higher doses, DLTs were observed using both dosing schedules, with diarrhea the most common DLT. The MTD for both treatment schedules was 2.5 mg/m2. After a short infusion, patupilone blood concentrations declined in a multiphasic manner with a terminal half-life of 4 days. Drug clearance was nonrenal and was not related to body-surface area. Over the dose range evaluated, systemic drug exposure was approximately dose proportional. Three patients achieved a partial response, and 31 patients had stable disease. Two patients experiencing a partial response had received prior taxane therapy. CONCLUSION: Patupilone is well tolerated when administered at a dose of 2.5 mg/m2, using either a 6 weeks on/3 weeks off or a 3 weeks on/1 week off schedule. In contrast with murine studies, patupilone has a relatively prolonged terminal half-life in humans. The partial responses in patients previously treated with taxanes is consistent with promising preclinical results.