Diffuse White Matter Signal Abnormalities on Magnetic Resonance Imaging Are Associated With Human Immunodeficiency Virus Type 1 Viral Escape in the Central Nervous System Among Patients With Neurological Symptoms.

Background: Human immunodeficiency virus type 1 (HIV-1) can replicate independently in extravascular compartments such as the central nervous system, resulting in either cerebrospinal fluid (CSF) discordance (viral load [VL] in CSF 0.5 log10 copies HIV-1 RNA greater than plasma VL) or escape (detection of HIV VL >50 copies/mL in CSF in patients with suppressed plasma VL <50 copies/mL). Both discordance and escape may be associated with neurological symptoms. We explored risk factors for CSF discordance and escape in patients presenting with diverse neurological problems. Methods: HIV-infected adult patients undergoing diagnostic lumbar puncture (LP) at a single center between 2011 and 2015 were included in the analysis. Clinical and neuroimaging variables associated with CSF discordance/escape were identified using multivariate logistic regression. Results: One hundred forty-six patients with a median age of 45.3 (interquartile range [IQR], 39.6-51.5) years underwent 163 LPs. Median CD4 count was 430 (IQR, 190-620) cells/µL. Twenty-four (14.7%) LPs in 22 patients showed CSF discordance, of which 10 (6.1%) LPs in 9 patients represented CSF escape. In multivariate analysis, both CSF discordance and escape were associated with diffuse white matter signal abnormalities (DWMSAs) on cranial magnetic resonance imaging (adjusted odds ratio, 10.3 [95% confidence interval {CI}, 2.3-45.0], P = .007 and 56.9 [95% CI, 4.0-882.8], P = .01, respectively). All 7 patients with CSF escape (10 LPs) had been diagnosed with HIV >7 years prior to LP, and 6 of 6 patients with resistance data had documented evidence of drug-resistant virus in plasma. Conclusions: Among patients presenting with diverse neurological problems, CSF discordance or escape was observed in 15%, with treatment-experienced patients dominating the escape group. DWMSAs in HIV-infected individuals presenting with neurological problems should raise suspicion of possible CSF discordance/escape.

How we did the Question Time Forum (QTF).

BACKGROUND: We piloted a new method of feedback to supplement online surveys and student representation. METHODS: The face-to-face feedback session enabled all Year 5 students to ask questions directly to a faculty panel, regarding their curriculum. Questions were gathered in advance so the panel could review and prepare appropriate responses. "Ask the audience" questions were also included. EVALUATION: The panel and a convenience sample of 25 students (attenders and non-attenders) were interviewed. All interviews were recorded, transcribed and themed using long table technique. QTF was also evaluated on-the-day by using "Ask the Audience" questions. RESULTS: Sixty-three Year 5 students attended (from a cohort of 337), of whom 96% felt it was a useful addition to current methods of feedback and 93% would attend again. Students felt QTF was "brilliant" and a "triumph in transparency" while the faculty hailed the "novel" event and "honest discussion". CONCLUSION: QTF was well-received by students and faculty. Both encouraged repetition of the event, thought to enhance the transparency of decisions about the running of the course and promote more in-depth dialogue between staff and students.

Cross-sectional study of unexplained white matter lesions in HIV positive individuals undergoing brain magnetic resonance imaging.

White matter (WM) abnormalities are frequently seen on brain MRI of HIV positive (HIV+) patients. We aimed to determine the prevalence of unexplained WM abnormalities and their associations with HIV disease and cardiovascular risk factors. We conducted a retrospective, cross-sectional study of brain MRI of HIV+ patients conducted between 2004 and 2009 at our center. Clinical and laboratory data were compiled, and images were independently reviewed for WM lesions. Images were obtained from 254 patients: 70% male, 53% white, 40% black, mean age 42 years, median current CD4 count 240 cells/mm(3), and 41% not taking antiretroviral therapy (ART). Hyperintense WM lesions were present in 161 patients (63.4%): 89 scans (35.0%) showed diffuse WM signal abnormality (DWMSA), 61 (24.0%) were consistent with small vessel disease (SVD, graded by Fazekas' scale), and 37 (14.6%) showed large asymmetrical focal WM lesions. SVD changes were associated with age and cardiovascular risk factors, and while cerebral SVD may be related to HIV infection, the MRI findings were not associated with HIV-related factors. The only risk factor for DWMSA was black race, and no correlation with cardiovascular risk factors, CD4 count, or clinical presentation was identified. DWMSA are therefore of uncertain neurological significance in HIV+ patients and could represent more than one clinicopathological entity.

How we implemented team-based learning for postgraduate doctors.

BACKGROUND: Team-based learning (TBL) has been shown to improve knowledge, teamwork and interactivity in medical school settings. There are fewer reports of its use with postgraduate doctors. We report on our experience of using TBL with residents. WHAT WE DID: We converted a didactic module of lectures into a TBL module for 44 psychiatry residents. This involved training faculty, orientating residents, writing TBL materials, delivering and evaluating the module. On the basis of the positive evaluations we aim to introduce more TBL. CONCLUSIONS: TBL can be successfully introduced into a residency training programme. Tips for implementation include: involve a TBL expert and provide experiential training for faculty; hold an orientation session for residents; and provide individual and team incentives to reinforce pre-class preparation and promote engagement with TBL. Avoid underestimating the effort involved in converting lecture-based teaching into TBL and do not assign excessive pre-session assignments.

Discovery and validation of urinary biomarkers for detection of renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is often accompanied by non-specific symptoms. The increase of incidentally discovered small renal masses also presents a diagnostic dilemma. This study investigates whether RCC-specific peptides with diagnostic potential can be detected in urine and whether a combination of such peptides could form a urinary screening tool. MATERIALS AND METHODS: For the discovery of RCC-specific biomarkers, we have employed CE-MS to analyze urine samples from patients with RCC (N=40) compared to non-diseased controls (N=68). RESULTS AND DISCUSSION: 86 peptides were found to be specifically associated to RCC, of which sequence could be obtained for 40. A classifier based on these peptides was evaluated in an independent set of 76 samples, resulting in 80% sensitivity and 87% specificity. The specificity of the marker panel was further validated in a historical dataset of 1077 samples including age-matched controls (N=218), patients with related cancer types and renal diseases (N=859). In silico protease prediction based on the cleavage sites of differentially excreted peptides, suggested modified activity of certain proteases including cathepsins, ADAMTS and kallikreins some of which were previously found to be associated to RCC. CONCLUSIONS: RCC can be detected with high accuracy based on specific urinary peptides. BIOLOGICAL SIGNIFICANCE: Clear cell renal cell carcinoma (RCC) has the highest incidence among the renal malignancies, often presenting non-specific or no symptoms at all. Moreover, with no diagnostic marker being available so far, almost 30% of the patients are diagnosed with metastatic disease and 30-40% of the patients initially diagnosed with localized tumor relapse. These facts introduce the clinical need of early diagnosis. This study is focused on the investigation of a marker model based on urinary peptides, as a tool for the detection of RCC in selected patients at risk. Upon evaluation of the marker model in an independent blinded set of 76 samples, 80% sensitivity and 87% specificity were reported. An additional dataset of 1077 samples was subsequently employed for further evaluation of the specificity of the classifier.

HIV and the brain: from AIDS to old age.

The field of HIV medicine has changed rapidly in the last two decades since effective and tolerable antiretroviral treatment became available. As a result, although classical opportunistic infections of the brain have become less common, clinicians need to be aware of a wider range of acute and chronic complications of HIV and its treatment. In this article, we summarise major opportunistic infections, immune reconstitution inflammatory syndrome, HIV-associated neurocognitive disorders, and cerebrovascular disease in HIV positive patients. We also emphasise the preventability and reversibility of most of the central nervous system complications of HIV, and hence the importance of early diagnosis of HIV and involvement of clinicians with special expertise in HIV medicine.

Team-based learning for psychiatry residents: a mixed methods study.

BACKGROUND: Team-based learning (TBL) is an effective teaching method for medical students. It improves knowledge acquisition and has benefits regarding learner engagement and teamwork skills. In medical education it is predominately used with undergraduates but has potential benefits for training clinicians. The aims of this study were to examine the impact of TBL in a sample of psychiatrists in terms of classroom engagement, attitudes towards teamwork, learner views and experiences of TBL. METHODS: Forty-four psychiatry residents participated in an Addictions Psychiatry TBL module. Mixed-methods were used for evaluation. Self-rated measures of classroom engagement (Classroom Engagement Survey, CES) were compared with conventional lectures, and attitudes regarding the value of teams (Value of Teams Scale, VTS) were compared before and after the module. Independent t-tests were used to compare 'lecture' CES scores with TBL CES scores and pre and post scores for the VTS. Feedback questionnaires were completed. Interviews were conducted with a subset of residents and transcripts analysed using thematic analysis. RESULTS: Twenty-eight residents completed post-course measures (response rate 63.6%). Seven participants volunteered for qualitative interviews-one from each team. There was a significant difference in the mean CES score lectures compared to TBL (p < 0.001) but no difference was found in mean VTS score pre and post for either subscale (p = 0.519; p = 0.809). All items on the feedback questionnaire were positively rated except two regarding session preparation. The qualitative analysis generated seven themes under four domains: 'Learning in teams', 'Impact on the individual learner', 'Relationship with the teacher' and 'Efficiency and effectiveness of the learning process'. CONCLUSIONS: In this group of residents, TBL significantly improved learner-rated classroom engagement and seemed to promote interactivity between learners. TBL was generally well-received, although required learners to prepare for class which was difficult for some. TBL did not change these clinicians' views about teamwork.

Acceptability and feasibility of universal offer of rapid point of care testing for HIV in an acute admissions unit: results of the RAPID project.

BACKGROUND: UK guidance recommend all acute medical admissions be offered an HIV test. Our aim was to determine whether a dedicated staff member using a multimedia tool, a model found to be effective in the USA, is an acceptable, feasible, and cost-effective model when translated to a UK setting. DESIGN: Between 14(th) Jan to 12(th) May 2010, a Health advisor (HA) approached 19-65 year olds at a central London acute medical admissions unit (AAU) and offered a rapid HIV point of care test (POCT) with the aid of an educational video. Patients with negative results had the option to watch a post-test video providing risk-reduction information. For reactive results the HA arranged a confirmatory test, and ensured linkage into HIV specialist care. Feasibility and acceptability were assessed through surveys and uptake rates. Costs per case of HIV identified were established. RESULTS: Of the 606 eligible people admitted during the pilot period, 324 (53.5%) could not be approached or testing was deemed inappropriate. In total 23.0% of eligible admissions had an HIV POCT. Of the patients who watched the video and had not recently tested for HIV, 93.6% (131/140) agreed to an HIV test; four further patients had an HIV test but did not watch the video. Three tests (2.2%, 3/135) were reactive and all were confirmed HIV positive on laboratory testing. 97.5% felt HIV testing in this setting was appropriate, and 90.1% liked receiving the information via video. The cost per patient of the intervention was £21. DISCUSSION: Universal POCT HIV testing in an acute medical setting, facilitated by an educational video and dedicated staff appears to be acceptable, feasible, effective, and low cost. These findings support the recommendation of HIV testing all admissions to AAU in high prevalence settings, although with the model used a significant proportion remained untested.

A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy.

BACKGROUND: Long-term antiretroviral therapy, while dramatically reducing HIV-related morbidity and mortality, is associated with metabolic and morphological changes. Peripheral fat loss, lipoatrophy, appears most associated with prolonged therapy with thymidine nucleoside analogues. METHODS: A randomized, open-label, comparative study of switching from a thymidine nucleoside analogue to either tenofovir disoproxil fumarate (DF) or abacavir in 105 individuals on successful antiretroviral therapy with clinically evident moderate to severe lipoatrophy. RESULTS: Individuals were randomized to tenofovir DF (52) or abacavir (53). The switch was well tolerated and the majority of patients completed 48 weeks of study. One individual in the tenofovir DF group and three in the abacavir group discontinued due to drug-related adverse events. Both groups similarly maintained virological control. Limb fat mass increased similarly in both groups: mean increases by week 48 of 329 and 483 g in tenofovir DF and abacavir groups, respectively [mean 95% confidence interval for difference, -154.3 (range -492.8 to 184.3)]. This change from baseline was statistically significant in both groups (tenofovir DF, P = 0.01; abacavir, P = 0.0001). Mean total cholesterol, low density lipoprotein cholesterol and triglycerides improved modestly with switching to tenofovir DF but were unchanged with abacavir. The changes in these parameters were significantly greater in the tenofovir DF arm relative to abacavir. CONCLUSIONS: Switching from a thymidine nucleoside analogue to either tenofovir DF or abacavir leads to significant improvement in limb fat mass over 48 weeks. Tenofovir DF may have modest advantages over abacavir for changes in lipids. Peripheral lipoatrophy, when clinically apparent, resolves slowly following treatment switching.

Septic shock and multi-organ failure in HIV infection-'sepsis tuberculosa gravissima'.

A profoundly immunosuppressed HIV-infected man developed sepsis syndrome with multi-organ failure. A septic screen failed to identify a bacterial or fungal cause and despite empirical treatment for these pathogens the patient remained unwell. Investigations revealed disseminated tuberculosis. With specific anti-tuberculosis therapy the patient rapidly recovered. Although most cases of sepsis syndrome in HIV-infected patients are due to bacteria, tuberculosis should be added to the differential diagnosis of this presentation.