Increased targeted HIV testing and reduced undiagnosed HIV infections among gay and bisexual men.

OBJECTIVES: To evaluate the impact of government HIV strategies that aimed to increase HIV testing uptake and frequency among gay and bisexual men (GBM) in New South Wales (NSW), Australia. DESIGN: We analysed HIV testing data from existing passive and sentinel surveillance systems between 2010 and 2018. METHODS: Six indicators were measured: (1) state-wide total HIV laboratory tests; (2) number of GBM attending publicly-funded clinics; (3) 12-monthly testing uptake; (4) annual testing frequency; (5) HIV testing with a STI diagnosis; and (6) HIV positivity. Mathematical modelling was used to estimate (7) the proportion of men with undiagnosed HIV. Indicators were stratified by Australian vs. overseas-born. RESULTS: Overall, 43,560 GBM attended participating clinics (22,662 Australian-born, 20,834 overseas-born) from 2010-2018. Attendees increased from 5,186 in 2010 to 16,507 in 2018. There were increasing trends (p<0.001 for all) in testing uptake (83.9% to 95.1%); testing with a STI diagnosis (68.7% to 94.0%); annual HIV testing frequency (1.4 to 2.7); and a decreasing trend (p<0.01) in HIV positivity (1.7% to 0.9%).Increases in testing were similar in Australian-born and overseas-born GBM. However, there were decreasing trends in the estimated undiagnosed HIV proportion overall (9.5% to 7.7%) and in Australian-born GBM (7.1% to 2.8%), but an increasing trend in overseas-born GBM (15.3% to 16.9%) (p<0.001 for all).

Heller's myotomy and pneumatic dilatation in the treatment of achalasia: a population-based case-control study assessing long-term quality of life.

Long-term health-related quality-of-life (HRQL) outcomes have not been widely reported in the treatment of achalasia. The aims of this study were to examine long-term disease-specific and general HRQL in achalasia patients using a population-based case-control method, and to assess HRQL between treatment interventions. Manometrically diagnosed achalasia cases (n = 120) were identified and matched with controls (n = 115) using a population-based approach. Participants completed general (SF-12) and disease-specific (Achalasia Severity Questionnaire [ASQ]) HRQL questionnaires, as appropriate, in a structured interview. Mean composite scores for SF-12 (Mental Component Summary score [MCS-12] and Physical Component Summary score [PCS-12]) and ASQ were compared between cases and controls, or between intervention groups, using an independent t-test. Adjusted mean differences in HRQL scores were evaluated using a linear regression model. Achalasia cases were treated with a Heller's myotomy (n = 43), pneumatic dilatation (n = 44), or both modalities (n = 33). The median time from last treatment to HRQL assessment was 5.7 years (interquartile range 2.4-11.5). Comparing achalasia patients with controls, PCS-12 was significantly worse (40.9 vs. 44.2, P = 0.01), but MCS-12 was similar. However, both PCS-12 (39.9 vs. 44.2, P = 0.03) and MCS-12 (46.7 vs. 53.5, P = 0.004) were significantly impaired in those requiring dual treatment compared with controls. Overall however, there was no difference in adjusted HRQL between patients treated with Heller's myotomy, pneumatic dilatation or both treatment modalities. In summary, despite treatment achalasia patients have significantly worse long-term physical HRQL compared with population controls. No HRQL differences were observed between the treatment modalities to suggest a benefit of one treatment over another.

Quantification of tumour and circulating vascular endothelial growth factor (VEGF) in patients with oesophagogastric cancer: a long-term follow-up study.

Vascular endothelial growth factor (VEGF) is an angiogenic cytokine that regulates tumour angiogenesis. The prognostic significance of VEGF expression remains incompletely investigated for patients with oesophagogastric cancer. This study assesses the significance of tumour VEGF (T-VEGF) and circulating VEGF (C-VEGF) expression in a 10-year follow-up of patients with oesophagogastric cancer. Patients undergoing surgical resection were prospectively recruited between February 1999 and August 2000. Circulating VEGF, derived both from plasma (P-VEGF) and serum (S-VEGF), and T-VEGF were assessed using a commercial enzyme-linked immunosorbent assay (ELISA). As platelet count may contribute to C-VEGF, pre-operative platelet levels were also recorded to exclude a confounding effect. Patients were followed up over a 10-year period using the Northern Ireland Cancer Registry. Sixty-one patients were recruited (men=45) with a mean age of 65.7 years. The 10-year survival was 19.7% (n=12) with a median follow-up of 808 days (inter-quartile range [IQR]: 349.5-2358.5). Union for International Cancer Control (UICC) tumour staging was Stage I=9 (14.8%), Stage II=15 (24.6%), Stage III=33 (54.1%) and Stage IV=4 (6.6%). The only significant relationship between clinicopathological features and the study variables was for S-VEGF, which was elevated in patients with advanced T-stage (P = 0.05). Circulating VEGF did not correlate with platelet count. Although a trend towards decreased survival was observed for patients who had positive lymph nodes (P = 0.08) and advanced UICC stage (P = 0.09) on univariate analysis, only lymphovascular invasion significantly predicted poor prognosis in this cohort (P = 0.05). Therefore, ELISA quantification of circulatory or tumour VEGF does not appear to be a significant predictor of mortality in patients with oesophagogastric cancer.

Bone marrow micrometastases in esophageal carcinoma: a 10-year follow-up study.

Detection of bone marrow micrometastases (BMMs) in patients with esophageal carcinoma may indicate a metastatic phenotype. We assessed if the presence of BMMs had adverse prognostic significance in a 10-year follow-up study. Patients undergoing surgery for esophageal cancer were prospectively recruited between February 1999 and August 2000. Bone marrow aspirates were obtained from the iliac crest of patients under general anesthesia at the time of surgery. Immunocytochemical analysis using anticytokeratin antibodies CAM 5.2 and AE1/AE3 was undertaken to determine the presence of BMMs. Union International Contre le Cancer staging was recorded for all patients. Patient follow-up was completed over a 10-year period through analysis of the Northern Ireland Cancer Registry. Forty-two patients (male = 35) were included, with a mean age of 67.2 years (range 39-83). BMMs were detected in 19 patients (45.2%). International Contre le Cancer tumor staging was stage I = 6, stage II = 10, stage III = 24, and stage IV = 2. BMMs were associated with lymphovascular invasion (P= 0.02) and advanced T stage (P= 0.02). Overall, 10-year survival was 21.4% (n= 9), with a median follow-up of 877.5 days (interquartile range 391.5-2546.3). There was no statistically significant difference between the survival of patients with or without BMMs (1451.4 vs. 1431.6 days, P= 0.99). Univariate analysis demonstrated a trend toward decreased survival for patients with positive lymph nodes (P= 0.07), an increased T stage (P= 0.06), and lymphovascular invasion (P= 0.07). Multivariate analysis demonstrated that none of the variables were significant predictors of mortality. Although the presence of BMMs correlates with recognized adverse tumor characteristics in patients with esophageal cancer, micrometastases detected in the bone marrow at time of surgery does not influence long-term survival.

Self-expanding metal stent insertion for inoperable esophageal carcinoma in Belfast: an audit of outcomes and literature review.

Successful palliation of dysphagia in patients with inoperable esophageal carcinoma has a major effect on quality of life. Self-expanding metal stents (SEMS) are currently recommended for rapid symptomatic relief when life expectancy is less than 3 months. We assessed complication and reintervention rates along with survival outcomes in patients with inoperable esophageal carcinoma undergoing stent insertion. A retrospective audit was performed from April 2007 to June 2009 for all inoperable primary esophageal carcinoma patients who had an esophageal stent inserted for dysphagia. Case notes were reviewed for clinical, pathological, stent and complication details, while ICD-10 causes of death were obtained from the Department of Health and Social Services, Northern Ireland. Fifty-six stents were inserted into 53 patients (66.0% male, mean age of 70 years). Inoperability was defined by metastatic spread (n= 34, 64.2%), locally advanced disease (n= 7, 13.2%), and severe medical comorbidities (n= 12, 22.6%). The median time from diagnosis to stent insertion was 109 (interquartile range [IQR] 43-187) days. Fifty stents (94.3%) were successfully deployed, while three patients (5.7%) required an additional stent as the primary stent had not bridged the tumor (proximal deployment = 2, suboptimal stent length = 1). Post-SEMS dysphagia scores were significantly better than pre-SEMS scores (2.90 vs. 1.54, P < 0.001). There were 27 complications identified in 23 (43.4%) patients (major complications = 9, minor complications = 14). Twelve patients (22.6%) required additional endoscopic procedures. The 30-day mortality rate was 11.3% (n= 6). Only one patient (1.9%) remains alive with a cumulative median survival rate of 84 (IQR 38-156) days. Esophageal stent insertion in this group of patients still presents a clinical challenge, with complication and endoscopic reintervention rates of 43.4 and 22.6%, respectively. Our results are comparable with previously published series, and as a palliative modality stent insertion remains appropriate when expected survival is less than 3 months. A range of SEMS is currently available with broadly similar efficacy and safety profiles. Data regarding the newly available fully covered SEMS suggest that they should be avoided.

Male circumcision for HIV prevention in Papua New Guinea: a summary of research evidence and recommendations for public health following a national policy forum.

In 2005, a clinical trial in South Africa found that circumcision of young men could reduce their risk of acquiring HIV (human immunodeficiency virus) infection by over 60%. In the following year, two more trials in Africa confirmed this finding, leading the World Health Organization to recommend male circumcision as a public health strategy for HIV prevention in high-incidence countries. In order to inform public health policy in Papua New Guinea (PNG), two major research projects were initiated with the goals of investigating the status of penile cutting practices and assessing understandings, acceptability, feasibility and cost-effectiveness of male circumcision for HIV prevention. In addition, behavioural surveillance surveys systematically asked questions on penile cutting practices and an ethnographic literature review informed historical perspectives of penile cutting in PNG. Key findings from these research activities were presented at a National Policy Forum on Male Circumcision for HIV Prevention held in Port Moresby in November 2011. The Forum made three key recommendations: (1) the formation of a joint National Department of HealthlNational AIDS Council Secretariat Policy Committee on male circumcision; (2) the establishment of an integrated harm reduction program; and (3) that future policy on wide-scale roll-out of male circumcision for HIV prevention in PNG be informed by a combination of data from (a) male circumcision intervention pilot programs and (b) research on the potential protective effect of other forms of penile cutting.

Post-operative telephone review is cost-effective and acceptable to patients.

INTRODUCTION: Patients undergoing selective minor emergency and elective procedures are followed up by a nurse-led structured telephone review six weeks post-operatively in our hospital. Our study objectives were to review patients' satisfaction, assess cost-effectiveness and compare our practice with other surgical units in Northern Ireland (NI). PATIENTS AND METHODS: Completed telephone follow-up forms were reviewed retrospectively for a three-year period and cost savings calculated. Fifty patients were contacted prospectively by telephone using a questionnaire to assess satisfaction of this follow-up. A postal questionnaire was sent to 68 general and vascular surgeons in NI, assessing individual preferences for patient follow-up. RESULTS: A total of 1378 patients received a telephone review from September 2005 to September 2008. One thousand one hundred and seventy-seven (85.4%) were successfully contacted, while 201 (14.6%) did not respond despite multiple attempts. One hundred and forty-seven respondents (10.7%) required further outpatient follow-up, thereby saving 1231 outpatient reviews, equivalent to £41,509 per annum. Thirty-nine (78%) patients expected post-operative follow-up, with 29 (58%) expecting this in the outpatient department. However, all patients were satisfied with the nurse-led telephone review. Fifty-three (78%) consultants responded. Those who always, or occasionally, review patients post-operatively varies according to the operation performed, ranging from 2.2% appendicectomy patients to 40.0% for varicose vein surgery. CONCLUSION: Current practice in NI varies, but a significant proportion of patients are not routinely reviewed. This study confirmed that patients expect post-operative follow-up. A nurse-led telephone review service is acceptable to patients, cost-effective and reduces the number of unnecessary outpatient reviews.

Dynamical reconnection and stability constraints on cortical network architecture.

Stability under dynamical changes to network connectivity is invoked alongside previous criteria to constrain brain network architecture. A new hierarchical network is introduced that satisfies all these constraints, unlike more commonly studied regular, random, and small-world networks. It is shown that hierarchical networks can simultaneously have high clustering, short path lengths, and low wiring costs, while being robustly stable under large scale reconnection of substructures.

Mean-field modeling of the basal ganglia-thalamocortical system. II Dynamics of parkinsonian oscillations.

Neuronal correlates of Parkinson's disease (PD) include a shift to lower frequencies in the electroencephalogram (EEG) and enhanced synchronized oscillations at 3-7 and 7-30 Hz in the basal ganglia, thalamus, and cortex. This study describes the dynamics of a recent physiologically based mean-field model of the basal ganglia-thalamocortical system, and shows how it accounts for many key electrophysiological correlates of PD. Its detailed functional connectivity comprises partially segregated direct and indirect pathways through two populations of striatal neurons, a hyperdirect pathway involving a corticosubthalamic projection, thalamostriatal feedback, and local inhibition in striatum and external pallidum (GPe). In a companion paper, realistic steady-state firing rates were obtained for the healthy state, and after dopamine loss modeled by weaker direct and stronger indirect pathways, reduced intrapallidal inhibition, lower firing thresholds of the GPe and subthalamic nucleus (STN), a stronger projection from striatum to GPe, and weaker cortical interactions. Here it is shown that oscillations around 5 and 20 Hz can arise with a strong indirect pathway, which also causes increased synchronization throughout the basal ganglia. Furthermore, increased theta power with progressive nigrostriatal degeneration is correlated with reduced alpha power and peak frequency, in agreement with empirical results. Unlike the hyperdirect pathway, the indirect pathway sustains oscillations with phase relationships that coincide with those found experimentally. Alterations in the responses of basal ganglia to transient stimuli accord with experimental observations. Reduced cortical gains due to both nigrostriatal and mesocortical dopamine loss lead to slower changes in cortical activity and may be related to bradykinesia. Finally, increased EEG power found in some studies may be partly explained by a lower effective GPe firing threshold, reduced GPe-GPe inhibition, and/or weaker intracortical connections in parkinsonian patients. Strict separation of the direct and indirect pathways is not necessary to obtain these results.

Adherence to and invasion of tissue culture cells by Vibrio hollisae.

The adherence to and invasion of cultured epithelial cells by Vibrio hollisae were examined by quantitative studies and by light, fluorescent, and electron microscopy. Condensed actin was observed around clustered adherent and intracellular bacteria. Bacteria multiplied intracellularly. Inhibitor studies indicated that internalization occurred by an integrated pleiotropic process involving eukaryotic and prokaryotic protein syntheses, microfilaments, microtubules, and receptor-mediated endocytosis.

Bacterial succession within a biofilm in water supply lines of dental air-water syringes.

Biofilms have been implicated as reservoirs for bacterial contamination of water delivered by dental air-water syringes. A 6-month study was done of bacterial colonization and biofilm formation in plastic water supply lines connected to dental air-water syringes. Changes in biofilm flora were observed by both scanning electron microscopy and bacteriologic culture. By day 7, many rod- and spiral-shaped bacteria had colonized the ridged surface of the luminal wall of the tubing, as revealed by scanning electron microscopy. By day 30, individual microcolonies were embedded in extracellular polymeric material. By day 120, these microcolonies had begun to coalesce, and by day 180 the biofilm had developed into a multilayered, heterogeneous mixture of microcolonies. The mean aerobic plate counts of colony-forming units of planktonic and biofilm populations were, in log10 values, 5.9 +/- 0.54/mL and 4.2 +/- 0.82/cm2, respectively. Early colonizers were predominantly Pseudomonas spp., but included Pasteurella, Moraxella, Ochrobactrum, and Aeromonas spp. Flavobacterium and Acinetobacter spp. were observed later. Many of these organisms are opportunistic pathogens. These results demonstrate the longitudinal dynamics of biofilm formation.

Life changes and urinary norepinephrine in myocardial infarction.

The relationship between norepinephrine and stress caused by life changes was assessed using urinary norepinephrine levels and responses to a 57-item stress questionnaire interview obtained from 21 post-myocardial infarction and 27 healthy control male and female subjects. High correlations between norepinephrine and duration of present stress and duration and severity of life changes, and moderate correlations between norepinephrine and anxiety and depression were found among the post-infarction group. No significant correlations were found in the control group. Post-infarction subjects with elevated norepinephrine had significantly higher scores on duration of present stress and duration and severity of life changes than did post-infarction subjects with normal norepinephrine levels. Control subjects with normal and elevated norepinephrine did not differ significantly on any of the comparison variables. Standard risk factors failed to add significantly to the prediction of norepinephrine in either group. However, 68.3 percent of the variance in norepinephrine was accounted for by a single predictor, the duration of present stress.