Insulin Resistance is Associated with Higher Plasma Viral Load Among HIV-Positive Adults Receiving Longer-Term (1 Year) Combination Antiretroviral Therapy (ART).

Background: As HIV-positive persons survive longer due to the success of combination antiretroviral therapy (ART) in decreasing mortality, the burden of non-communicable diseases including diabetes mellitus (DM) is anticipated to rise. HIV is characterized by systemic inflammations, markers of which decrease quickly following ART initiation, but typically do not completely normalize. Inflammation may be accompanied by insulin resistance (IR), and both are implicated in the pathogenesis of DM in HIV-positive individuals. Sub-Saharan Africa accounts for almost two-thirds of the global HIV burden but there are few reports of IR, DM and HIV in this region. We assessed the relationship between IR and viral suppression among HIV-positive adults in the Zambian national ART program. Methods: We conducted a cross-sectional survey evaluating HIV-positive adults that had received first line ART (usually TDF/FTC/EFV) for 12 months (± 3 months). Twenty clinics were sampled systematically based on the random starting-point, sampling interval and cumulative population size. Eligible patients had plasma viral load (VL), fasting insulin, and glucose performed. Insulin resistance was determined using Homeostatic model assessment (HOMA). We determined proportions for each outcome using linearized standard error 95% confidence intervals and summary estimates. Viral suppression was defined according to the detection threshold of<20 copies/mL and treatment failure was defined as VL>1,000 copies/mL. Results: Of 473 patients enrolled, 46.8% were male and 53.2% were female. 142 (30%) [95% CI: 0.26-0.34] had IR. Among those with IR, 55 (38.7%) were male whereas 87 (61.3%) were female (p value=0.104). 19% of individuals with IR had treatment failure compared to 5.7% without IR (p value<0.0001). 427 (90.3%) participants had treatment success (VL<1,000 copies/mL), and this was associated with a lower likelihood of IR (odds ratio (OR)=0.26 [0.14, 0.48], p value<0.0001). In addition, a significantly lower proportion of patients with IR were virologically suppressed at one-year compared to individuals without IR, 58% [0.54-0.70] versus 70% [0.65-0.75], respectively (p value=0.042). Conclusion: In Zambian adults on ART for a year, the development of insulin resistance was strongly associated with suboptimal HIV outcomes, specifically non-viral suppression and treatment failure. Further investigations are warranted to determine if this positive association between IR and VL is causally related, and if so in which direction.

Modelling adverse treatment outcomes of HIV-infected adolescents attending public-sector HIV clinics in Lusaka.

BACKGROUND: In resource-limited setting, there is scarce evidence comparing antiretroviral therapy (ART) outcomes among HIV-infected adolescents to that of other age groups. METHODS AND STUDY DESIGN: We analysed data from 25 ART facilities in Lusaka District, comparing treatment-naïve ART-eligible young adolescents (10-14 years), older adolescents (15-19) and young adults (20-24 years) initiating first-line ART to those aged 24 years or older. The adjusted relative risk (RR) of failure to achieve an adequate CD4 response (defined as failure to increase CD4 count by ≥ 50 cells/mm3 at 6 months or by ≥ 100 cells/mm3) at 6 or 12 months after ART initiation was modelled using log-binomial regression. The effect of age group on mortality and loss to follow-up (LTFUP; ≥60 days since scheduled visit date) was estimated using adjusted Cox proportional hazards models, respectively. This was a routine retrospective design using program data. RESULTS: Of the 94,023 patients initiating ART from May 2004 to February 2011, 1303 (1.4%) were young adolescents, 1440 (1.5%) were older adolescents and 5825 (6.2%) were young adults. 85,455 (90.9%) were 24 years or older at the time of ART initiation. Compared with adults, both young adolescents (RR: 0.88, 95% confidence interval [CI]: 0.76-1.01 at 6 months and RR: 0.80, 95% CI: 0.69-0.93 at 12 months) and older adolescents (RR: 0.82, 95% CI: 0.71-0.95 at 6 months) were less likely to achieve adequate CD4 response. No evidence of a difference in mortality risk was observed among older adolescents (hazard ratio [HR] 1.20, 95% CI: 0.93-1.56) compared with adults; however, there was a reduced risk of mortality in young adolescents compared with adults (HR: 0.61, 95% CI: 0.40-0.92). Young adolescents were less likely to be LTFUP following ART initiation (HR: 0.74, 95% CI: 0.59-0.92), while older adolescents and young adults were reported to be more likely to drop out of care (HR: 1.54 95% CI: 1.33-1.78; HR: 1.51 95% CI: 1.40-1.63 respectively). CONCLUSION: Older adolescents and young adults had poorer ART treatment outcomes, including failure to achieve adequate CD4 recovery and failure to remain in long-term care, when compared with adults. Interventions are necessary to help increase outcomes and retention in care.

Bonding in women with postnatal anaemia: a pilot case control study looking at postnatal bonding in women who have been diagnosed with anaemia at a University Hospital in the East of England.

PURPOSE: Anaemia is common postpartum; however, the effect of anaemia on mother-infant bonding is presently unknown. This case controlled study was designed to evaluate the effects of anaemia on mother and baby bonding in the first month following delivery. METHODS: 945 consecutive postpartum women who gave birth at home or in the obstetric unit at a university hospital in the East of England were identified from the hospital computer records. Blood counts had been performed on 279 of these women within 48 h of delivery, entirely at the discretion of the clinical team. The women with available blood count data were sent a self-reporting questionnaire which included a validated postpartum bonding questionnaire (PBQ). Data were collected from the 115 (41%) responses and analysed for the evidence of an effect of anaemia on bonding. RESULTS: 57 (50%) of women responding to the questionnaire were anaemic (haemoglobin < 10 g/dL). There was no evidence of a difference between maternal, age, parity, mode of delivery, gestational age, baby weight or baby age at the time of completing questionnaire between the anaemic and non-anaemic groups. Moreover, there was no evidence of a difference in maternal perception of mother-infant bonding between the anaemic and non-anaemic groups. CONCLUSION: Our study suggested no evidence of an association between postnatal anaemia and the mother's ability to bond with the baby; however a small but significant effect may still exist which we were not able to detect due to a possible lack of power, hence we suggest, further larger studies to be conducted.

Age, co-morbidity and poor mobility: no evidence of predicting in-patient death and acute hospital length of stay in the oldest old.

BACKGROUND: The oldest old (aged over 90 years) are the fastest growing section of the UK population. Limited data exist regarding the effect of age, location, co-morbidity and physical performance status on outcome of acute illness in this age group. METHODS: We performed a prospective study in people aged ≥ 90 years using hospital audit data in three hospitals in England and Scotland. We examined the characteristics of those admitted over three consecutive calendar months and calculated risk ratios of death and prolonged length of acute hospital stay (>7 days). RESULTS: A total of 419 patients were included in this study (68% female, median age 93 years). There were similarities in presentation and diagnoses, but patients in Scotland (n = 164) were more likely to be admitted from sheltered housing or nursing homes than those in England (n = 255). Patients in England were significantly less likely to be able to mobilize < 10 m (41 vs. 34%, P < 0.001) but had lower prevalence of hypertension (40 vs. 55%, P = 0.02), ischaemic heart disease (30% vs. 45%, P = 0.02) and fewer prescribed medications (median 2 vs. 3, P < 0.001). Mortality was similar for the England and Scotland centres (P = 0.98). Previously recognized risk factors for death following hospital admission and length of stay e.g. older age, higher number of co-morbidities and poor mobility were not predictive in this study. CONCLUSION: The 'oldest old' should not be considered as a homogenous group and findings from single-centre studies involving this age group may not be generalizable. We found no conclusive evidence that patient-related factors predict outcome in this age group in acute medical admission settings.

Autoimmune disease as a risk factor for globus pharyngeus: a cross-sectional epidemiological study.

OBJECTIVE: To assess the prevalence and severity of globus-type symptoms in individuals who have a prior diagnosis of autoimmune disease. DESIGN: Cross-sectional questionnaire. PARTICIPANTS AND SETTING: One hundred and nine patients with autoimmune disease (rheumatoid arthritis, seronegative spondarthritis, connective tissue disease, systemic vasculitis) and 41 patients with non-autoimmune disease (osteoarthritis/osteoporosis) attending a rheumatology tertiary referral clinic at Norfolk & Norwich University Hospitals NHS Foundation Trust. The results from this study were compared to previous published figures in patients with globus pharyngeus (n = 105) and normal population (n = 174). MAIN OUTCOME MEASURES: Glasgow Edinburgh Throat Scale questionnaire; Reflux Symptom Index; Anxiety/Depression Scale. RESULTS: Patients with autoimmune disease demonstrate a significantly higher prevalence for 5/10 symptoms on the Glasgow Edinburgh Throat scale score when compared to the non-autoimmune control group (P ≤ 0.01). This significant difference increases to 9/10 symptoms when compared to published results for the normal population (P = 0.01). No significant difference was found when comparing the autoimmune and non-autoimmune control group reflux symptom index (P = 0.64) or anxiety depression scale (P = 0.71). CONCLUSION: Patients with autoimmune disease have a significantly increased prevalence of globus symptoms when compared to the healthy population. A further prospective study is required to decipher the effect of pharmacotherapy as a possible causative factor.

Predicting the risk of endometrial cancer in postmenopausal women presenting with vaginal bleeding: the Norwich DEFAB risk assessment tool.

BACKGROUND: This study aimed to show the longitudinal use of routinely collected clinical data from history and ultrasound evaluation of the endometrium in developing an algorithm to predict the risk of endometrial carcinoma for postmenopausal women presenting with vaginal bleeding. METHODS: This prospective study collected data from 3047 women presenting with postmenopausal bleeding. Data regarding the presence of risk factors for endometrial cancer was collected and univariate and multivariate analyses were performed. RESULTS: Age distribution ranged from 35 to 97 years with a median of 59 years. A total of 149 women (5% of total) were diagnosed with endometrial carcinoma. Women in the endometrial cancer group were significantly more likely to be older, have higher BMI, recurrent episodes of bleeding, diabetes, hypertension, or a previous history of breast cancer. An investigator best model selection approach was used to select the best predictors of cancer, and using logistic regression analysis we created a model, 'Norwich DEFAB', which is a clinical prediction rule for endometrial cancer. The calculated Norwich DEFAB score can vary from a value of 0 to 9. A Norwich DEFAB value equal to or greater than 3 has a positive predictive value (PPV) of 7.78% and negative predictive value (NPV) of 98.2%, whereas a score equal to or greater than 5 has a PPV of 11.9% and NPV of 97.8%. CONCLUSION: The combination of clinical information with our investigation tool for women with postmenopausal vaginal bleeding allows the clinician to calculate a predicted risk of endometrial malignancy and prioritise subsequent clinical investigations.

One-stage versus two-stage bilateral unicompartmental knee replacement: a comparison of immediate post-operative complications.

We retrospectively studied the major complications occurring after one- and two-stage bilateral unicompartmental knee replacements (UKR). Between 1999 and 2008, 911 patients underwent 1150 UKRs through a minimally invasive approach in our unit. Of these, 159 patients (318 UKRs) had one-stage and 80 patients (160 UKRs) had two-stage bilateral UKRs. The bilateral UKR groups were comparable in age and American Society of Anaesthesiology grade, but more women were in the two-stage group (p = 0.019). Mechanical thromboprophylaxis was used in all cases. Major complications were recorded as death, pulmonary embolus, proximal deep-vein thrombosis and adverse cardiac events within 30 days of surgery. No statistical differences between the groups were found regarding the operating surgeon, the tourniquet time or minor complications except for distal deep-vein thrombosis. The anaesthetic times were longer for the two-stage group (p = 0.0001). Major complications were seen in 13 patients (8.2%) with one-stage operations but none were encountered in the two-stage group (p = 0.005). Distal deep-vein thrombosis was more frequent in the two-stage group (p = 0.036). Because of the significantly higher risk of major complications associated with one-stage bilateral UKR we advocate caution before undertaking such a procedure.

Influenza vaccine uptake among staff in care homes in Nottinghamshire: a random cluster sample survey.

OBJECTIVES: To establish uptake of influenza vaccine amongst care home clinical staff in Greater Nottingham, and to investigate what could be done to improve vaccine uptake in this group. STUDY DESIGN: Postal questionnaire surveys were used. In the first instance, a total sample survey was used. In the second instance, a sample of care home staff was surveyed, randomized at the care home level. METHODS: A postal questionnaire completed by care home matrons was used to obtain a preliminary estimate of staff vaccine uptake. Individual staff questionnaires were then used to validate this finding, and measure attitudes, beliefs and behaviours associated with vaccination. RESULTS: Vaccine uptake among those working in care homes with nursing was found to be low. Vaccine uptake was higher in homes with a policy recommending vaccination of staff. Most respondents who had received vaccination reported that they had done so because of an existing medical condition, rather than because of being a healthcare worker. A statistically significant relationship (P=0.02) was found between individuals' reported beliefs on how well they could resist influenza and their vaccination status. CONCLUSIONS: All care homes for the elderly should have a vaccination policy which recommends staff vaccination. Educational campaigns, vaccination in the workplace and free provision of the influenza vaccine may help to improve vaccine uptake in this group.

Performance of CURB-65 and CURB-age in community-acquired pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) is common and associated with significant mortality. In this study, we validated a newly proposed severity assessment rule for CAP, CURB-age, and also compared with to the currently recommended criteria in UK, CURB-65. METHODS: We conducted a prospective study in three hospitals in Norfolk and Suffolk, UK. One hundred and ninety patients were included and followed up for 6 weeks. RESULTS: Of 190 patients, 100 were men (53%). The age range was 18-101 years (median 76 years). Sixty-five (34%) had severe pneumonia by CURB-65 and 54 (28%) had severe pneumonia by CURB-age. There were 54 deaths during follow-up. There were 32 deaths (50%) in severe and 22 deaths (18%) in non-severe group by CURB-65. There were 27 deaths each in both the groups by CURB-age (50% of severe cases and 20% of non-severe cases). For CURB-65, sensitivity, specificity, and positive and negative predictive values were 59.3% (45.0-72.4), 75.7% (67.6-82.7), 49.2% (36.6-61.9) and 82.4% (74.6-88.6), respectively. For CURB-age, the respective values were 50.0% (31.1-63.9), 80.1% (72.4-86.5), 50.0% (36.1-63.9) and 80.1% (72.4-86.5). Exclusion of patients aged < 65 years did not alter the results. CONCLUSIONS: Despite better specificity in correctly identifying 6-week mortality for CAP, CURB-age appears to be less sensitive than CURB-65. Our findings further assure the usefulness of CURB-65 for predicting mortality in CAP.

Testosterone selectively increases primary follicles in ovarian cortex grafted onto embryonic chick membranes: relevance to polycystic ovaries.

Histological studies have demonstrated that polycystic ovaries (PCO) contain increased numbers of preantral follicles with a specific increase in primary follicles. Polycystic ovary syndrome is associated with hyperandrogenism and pre- and postnatal androgenization of primates increases the pool of growing follicles producing changes resembling PCO. In vitro studies could test the hypothesis that androgens alter early folliculogenesis, but conventional culture techniques for small follicles are generally unsuitable in non-rodent species. Our objective was to develop and use a method to investigate the effects of testosterone on early folliculogenesis. We adapted an in ovo technique in which lamb cortical ovarian fragments were grafted onto the chorioallantoic membrane of fertilised chick eggs. Optimal experimental conditions for vascularisation and survival of tissue were determined and the model then used to investigate the effects of testosterone on follicle growth. Eggs were inoculated with testosterone at the time of implantation of the ovarian tissue, which was retrieved 5 days later. Tissue was sectioned and follicles staged and counted. There was no wholesale initiation of primordial follicle growth over the 5-day in ovo culture. Importantly, the proportion of primordial, primary and secondary follicles remained similar to those in unimplanted tissue. Testosterone increased the number of primary follicles by 50% compared with controls, an effect that was largely due to a reduction in atresia. In conclusion, incubation of ovarian cortex with testosterone reproduces the changes in early folliculogenesis reported in histological studies of PCO.