Hepatitis C among vulnerable populations: A seroprevalence study of homeless, people who inject drugs and prisoners in London.

Injecting drugs substantially increases the risk of hepatitis C virus (HCV) infection and is common in the homeless and prisoners. Capturing accurate data on disease prevalence within these groups is challenging but is essential to inform strategies to reduce HCV transmission. The aim of this study was to estimate the prevalence of HCV in these populations. We conducted a cross-sectional study between May 2011 and June 2013 in London and, using convenience sampling, recruited participants from hostels for the homeless, drug treatment services and a prison. A questionnaire was administered and blood samples were tested for hepatitis C. We recruited 491 individuals who were homeless (40.7%), 205 drug users (17%) and 511 prisoners (42.3%). Eight per cent of patients (98/1207, 95% CI: 6.7%-9.8%) had active HCV infection and 3% (38/1207, 95% CI: 2.3%-4.3%) past HCV infection. Overall, one quarter (51/205) of people recruited in drug treatment services, 13% (65/491) of people from homeless residential sites and 4% (20/511) prisoners in this study were anti-HCV positive. Seventy-seven of the 136 (56.6%, 95% CI: 47.9%-65%) of HCV infected participants identified had a history of all three risk factors (homelessness, imprisonment and drug use), 27.3% (95% CI: 20.1%-35.6%) had 2 overlapping risk factors, and 15.4% (95% CI: 10.6%-23.7%) one risk factor. Drug treatment services, prisons and homelessness services provide good opportunities for identifying hepatitis C-infected individuals. Effective models need to be developed to ensure case identification in these settings that can lead to an effective treatment and an efficient HCV prevention.

Tuberculosis control in big cities and urban risk groups in the European Union: a consensus statement.

In low-incidence countries in the European Union (EU), tuberculosis (TB) is concentrated in big cities, especially among certain urban high-risk groups including immigrants from TB high-incidence countries, homeless people, and those with a history of drug and alcohol misuse. Elimination of TB in European big cities requires control measures focused on multiple layers of the urban population. The particular complexities of major EU metropolises, for example high population density and social structure, create specific opportunities for transmission, but also enable targeted TB control interventions, not efficient in the general population, to be effective or cost effective. Lessons can be learnt from across the EU and this consensus statement on TB control in big cities and urban risk groups was prepared by a working group representing various EU big cities, brought together on the initiative of the European Centre for Disease Prevention and Control. The consensus statement describes general and specific social, educational, operational, organisational, legal and monitoring TB control interventions in EU big cities, as well as providing recommendations for big city TB control, based upon a conceptual TB transmission and control model.

Outcomes of a residential respite service for homeless people with tuberculosis in London, UK: a cross-sectional study.

BACKGROUND: Many countries are seeking to eliminate tuberculosis (TB), but incidence remains high in socially excluded groups such as people experiencing homelessness. There is limited research into the effectiveness of residential respite services (RRS), which provide accomodation and social and clinical support for homeless people with active TB. METHODS: We used a register of all cases of TB diagnosed in London between 1 January 2010 and 3 October 2019 to compare characteristics and outcomes of patients treated in an RRS with patients receiving standard care. The primary outcome was successful treatment completion. We used logistic regression to compare likelihood of completing treatment, and simulation to estimate the absolute change in treatment completion resulting from this service. RESULTS: A total of 78 homeless patients finished an episode of TB treatment at the RRS. Patients treated in the RRS were more likely than patients treated in standard care to have clinical and social risk factors including drug resistance, history of homelessness, drug or alcohol use, and need for directly observed therapy. After adjusting for these factors, patients treated in the RRS had 2.97 times the odds of completing treatment (95% CI = 1.44-6.96). Treatment ended in failure for 8/78 patients treated in the RRS (10%, 95% CI = 5%-20%). We estimated that in the absence of the RRS, treatment would have ended in failure for 17/78 patients (95% CI = 11-25). CONCLUSION: The residential respite service for homeless TB patients with complex social needs was associated with better treatment outcomes.

Clinical standards for drug-susceptible pulmonary TB.

BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.

HIV prevalence and testing practices among tuberculosis cases in London: a missed opportunity for HIV diagnosis?

BACKGROUND: Universal testing for HIV in patients with tuberculosis (TB) has been advocated for over a decade. The aim of this study was to describe the prevalence and testing practices of HIV in TB centres in London. METHODS: A cohort study was undertaken of all patients with TB in Greater London in 2003-4 (n = 1941). Logistic regression was used to assess factors affecting being offered and accepting testing and having a positive HIV result. RESULTS: The overall known prevalence of HIV was 9.9% (193/1941). In those with a test result (including those diagnosed previously) it was 25.6%. Overall, 50.8% of patients aged > or =20 years without previous testing were offered HIV testing and, of these, 73% accepted. In multivariable analysis, factors associated with being HIV positive were age 20-49 years, black ethnicity and being born overseas. Those with smear-negative disease and with a poor understanding of English were significantly less likely to be offered HIV testing. Factors associated with refusal of an offered test were female gender or age >49 years. HIV status was not associated with smear status, drug resistance or death, but was associated with CNS disease (OR 1.8, 95% CI 1.0 to 3.0, p = 0.003). CONCLUSIONS: Nearly half the patients with TB in London in 2003-4 were not offered HIV testing. In those offered testing, uptake was high. Patients in higher risk groups were more likely to be offered testing but, even within the highest risk groups, testing was not universally offered. This represents a missed opportunity for diagnosing HIV in patients with TB in London.

High prevalence of albuminuria amongst people who inject drugs: A cross-sectional study.

Albuminuria is a key biomarker for cardiovascular disease and chronic kidney disease. Our study aimed to describe the prevalence of albuminuria amongst people who inject drugs in London and to test any potential associations with demographic characteristics, past diagnoses, and drug preparation and administration practices. We carried out a cross-sectional survey amongst people who use drugs in London. The main outcome measure was any albuminuria including both microalbuminuria and macroalbuminuria. Three-hundred and sixteen samples were tested by local laboratory services. Our study initially employed point-of-care testing methods but this resulted in a high number of false positives. Our findings suggest the prevalence of albuminuria amongst PWID is twice that of the general population at 19% (95%CI 15.3-24.0%). Risk factors associated with albuminuria were HIV (aOR 4.11 [95% CI 1.37-12.38]); followed by overuse of acidifier for dissolving brown heroin prior to injection (aOR 2.10 [95% CI 1.04-4.22]). Albuminuria is high amongst people who inject drugs compared to the general population suggesting the presence of increased cardiovascular and renal pathologies. This is the first study to demonstrate an association with acidifier overuse. Dehydration may be common amongst this population and may affect the diagnostic accuracy of point-of-care testing for albuminuria.

Active case finding and treatment adherence in risk groups in the tuberculosis pre-elimination era.

Vulnerable populations, including homeless persons, high-risk drug and alcohol users, prison inmates and other marginalised populations, contribute a disproportionate burden of tuberculosis (TB) cases in low-incidence settings. Drivers of this disease burden include an increased risk of both TB transmission in congregate settings, and progression from infection to active disease. Late diagnosis and poor treatment completion further propagate the epidemic and fuel the acquisition of drug resistance. These groups are therefore a major priority for TB control programmes in low-incidence settings. Targeted strategies include active case finding (ACF) initiatives and interventions to improve treatment completion, both of which should be tailored to local populations. ACF usually deploys mobile X-ray unit screening, which allows sensitive, high-throughput screening with immediate availability of results. Such initiatives have been found to be effective and cost-effective, and associated with reductions in proxy measures of transmission in hard-to-reach groups. The addition of point-of-care molecular diagnostics and automated X-ray readers may further streamline the screening pathway. There is little evidence to support interventions to improve adherence among these risk groups. Such approaches include enhanced case management and directly observed treatment, while video-observed therapy (currently under evaluation) appears to be a promising tool for the future. Integrating outreach services to include both case detection and case-management interventions that share a resource infrastructure may allow cost-effectiveness to be maximised. Integrating screening and treatment for other diseases that are prevalent among targeted risk groups into TB outreach interventions may further improve cost-effectiveness. This article reviews the existing literature, and highlights priorities for further research.

Accuracy of an automated system for tuberculosis detection on chest radiographs in high-risk screening.

SETTING: Tuberculosis (TB) screening programmes can be optimised by reducing the number of chest radiographs (CXRs) requiring interpretation by human experts. OBJECTIVE: To evaluate the performance of computerised detection software in triaging CXRs in a high-throughput digital mobile TB screening programme. DESIGN: A retrospective evaluation of the software was performed on a database of 38 961 postero-anterior CXRs from unique individuals seen between 2005 and 2010, 87 of whom were diagnosed with TB. The software generated a TB likelihood score for each CXR. This score was compared with a reference standard for notified active pulmonary TB using receiver operating characteristic (ROC) curve and localisation ROC (LROC) curve analyses. RESULTS: On ROC curve analysis, software specificity was 55.71% (95%CI 55.21-56.20) and negative predictive value was 99.98% (95%CI 99.95-99.99), at a sensitivity of 95%. The area under the ROC curve was 0.90 (95%CI 0.86-0.93). Results of the LROC curve analysis were similar. CONCLUSION: The software could identify more than half of the normal images in a TB screening setting while maintaining high sensitivity, and may therefore be used for triage.

Evaluation of Weight Change During Carboplatin Therapy in Dogs With Appendicular Osteosarcoma.

BACKGROUND: The prevalence of cancer cachexia in veterinary medicine has not been studied widely, and as of yet, no definitive diagnostic criteria effectively assess this syndrome in veterinary patients. OBJECTIVES: (1) To determine the patterns of weight change in dogs with appendicular osteosarcoma treated with amputation and single-agent carboplatin during the course of adjuvant chemotherapy; and (2) to determine whether postoperative weight change is a negative prognostic indicator for survival time in dogs with osteosarcoma. ANIMALS: Eighty-eight dogs diagnosed with appendicular osteosarcoma. Animals were accrued from 3 veterinary teaching hospitals. METHODS: Retrospective, multi-institutional study. Dogs diagnosed with appendicular osteosarcoma and treated with limb amputation followed by a minimum of 4 doses of single-agent carboplatin were included. Data analyzed in each patient included signalment, tumor site, preoperative serum alkaline phosphatase activity (ALP), and body weight (kg) at each carboplatin treatment. RESULTS: A slight increase in weight occurred over the course of chemotherapy, but this change was not statistically significant. Weight change did not have a significant effect on survival. Institution, patient sex, and serum ALP activity did not have a significant effect on survival. CONCLUSIONS AND CLINICAL IMPORTANCE: Weight change was not a prognostic factor in these dogs, and weight loss alone may not be a suitable method of determining cancer cachexia in dogs with appendicular osteosarcoma.

Epidemiology and response to the growing problem of tuberculosis in London.

As in other countries with low tuberculosis incidence, tuberculosis in England and Wales tends to be concentrated in some subgroups of the population, and is mainly a problem in large cities. In 2003, almost half of all tuberculosis cases reported in England and Wales were from London, where the incidence was almost five times higher than in the rest of England and Wales. While the highest proportion of cases occur in foreign born patients, evidence from a large outbreak of drug resistant tuberculosis points to ongoing active transmission among marginalised groups including homeless people, hard drug users, and prisoners. Increasing rates of disease and levels of drug resistance, combined with a concentration of disease in hard-to-reach risk groups now present a major challenge to tuberculosis control in the city. To respond to the changing epidemiology observed in recent years, treatment and control services are being reconfigured, surveillance has been improved with the implementation of the London TB register, and the utility of mobile digital x ray screening for at risk populations such as homeless people and prisoners is being evaluated. However, tuberculosis in London is not yet under control and more needs to be done. Services must adapt to the needs of those groups now most affected. This will require continued improvements to surveillance and monitoring, combined with improved access to care, better case detection, rapid diagnosis and active social support for people undergoing treatment.

Dihydrotestosterone and estrogen regulation of rat brain androgen-receptor immunoreactivity.

Androgen-receptor upregulation that occurs with androgenic-anabolic steroid (AAS) administration may be mediated by AAS metabolites, dihydrotestosterone (DHT), and estrogen. Castrated and intact male rats received 14 s.c. daily injections of AAS (2 mg/kg testosterone cypionate, 2 mg/kg nandrolone decanoate, and 1 mg/kg boldenone undecylenate in sesame oil vehicle), DHT (5 mg/kg dihydrotestosterone), EB (5 mg/kg estradiol benzoate), or sesame oil vehicle. Approximately 18-24 h after the fourteenth injection, brain tissues were removed and processed immunocytochemically using the PG-21 androgen-receptor antibody. As reported before, castration eliminated AR-ir (androgen-receptor immunoreactivity) and AAS upregulated AR-ir in the ventromedial hypothalamus (VMHVL), medial amygdala (MePV), and medial preoptic area (MPOM). When compared to AAS, DHT fully upregulated AR-ir in the VM VL and MPOM and partially upregulated AR-ir in the MePV. EB treatment partially upregulated AR-ir in the VMHVL and MePV, but not in the MPOM of castrated rats. Because AR-ir in the MPOM was consistently upregulated by DHT or AAS, and not EB, androgen-receptor availability in this region may be mediated specifically via androgen receptors.

Depression, realism, and the overconfidence effect: are the sadder wiser when predicting future actions and events?

Do depressed individuals make more realistic judgments than their nondepressed peers in real world settings? Depressed and nondepressed Ss in 2 studies were asked to make predictions about future actions and outcomes that might occur in their personal academic and social worlds. Both groups of Ss displayed overconfidence, that is, they overestimated the likelihood that their predictions would prove to be accurate. Of key importance, depressed Ss were less accurate in their predictions, and thus more overconfident, than their nondepressed counterparts. These differences arose because depressed Ss (a) were more likely to predict the occurrence of low base-rate events and (b) were less likely to be correct when they made optimistic predictions (i.e., stated that positive events would occur or that aversive outcomes would not). Discussion focuses on implications of these findings for the depressive realism hypothesis.

Self-serving prototypes of social categories.

Why and when do people disagree on their conceptions or prototypes of social categories? In 6 studies, it was revealed that such differences tend to be self-serving. Ss tended to endorse self-descriptive attributes as central to their prototypes of desirable social concepts and emphasize features that were not self-descriptive in their conceptions of undesirable categories. Such disagreements were constrained to attributes potentially central to the domain in question and did not occur for clearly peripheral features. Self-serving differences in prototype structure were exhibited in social information processing tasks and led to disagreements in judgments of others. Potential mechanisms underlying the development of these egocentric cognitive structures and their implications for self-serving judgments of ability are discussed.

The effects of psychiatric disorders on the probability and timing of first marriage.

While studies of psychopathology have begun to consider social consequences of psychiatric disorders during the past decade, marriage has received little attention, despite evidence that it influences life quality. The present paper examines the effects of clinically significant psychiatric disorders on the probability and timing of first marriage and whether the relationships between psychiatric disorders and marriage differ by type of disorder, gender, and birth cohort. Psychiatric disorders are found to have substantial effects on entry into first marriage. These effects are the same for men and women across all cohorts. Individual psychiatric disorders have similar effects on entry into first marriage. Psychiatric disorders are positively associated with early first marriage, which is strongly related to adverse consequences, and negatively associated with on-time and late first marriage, which are related to benefits such as financial security and social support. These results highlight the importance of early interventions for psychiatric disorders-if not for the purposes of primary prevention, then for the purposes of preventing the cumulation of adversities that occur secondarily through early marriage.

Tuberculosis peer educators: personal experiences of working with socially excluded communities in London.

SETTING: Peer education is a relatively unexplored intervention for tuberculosis (TB) control, particularly among socially excluded communities. In London, peer educators are used to raise awareness of TB and promote uptake of radiological screening among people using homeless and/or drug and alcohol treatment services. OBJECTIVE: To understand the motivation and personal impact of being a peer educator on people with experience of anti-tuberculosis treatment, homelessness and addiction. DESIGN: In-depth semi-structured interviews with peer educators were recorded and transcribed, and then analysed using a grounded theory approach to identify themes. Reflexivity and thick description were used to support transparency of findings. RESULTS: Becoming a peer educator supports individuals in making sense of past experiences and renewing their sense of self. The role places value on personal experience and the communication approach this supports. The project environment is an important motivator, providing the peer with structure, social support and respect. CONCLUSION: Being a peer educator with experience of homelessness and addiction can be beneficial and empowering and help long-term recovery. Peers are an underused resource for strengthening TB control among socially excluded populations. There is a need for further research into the contribution of peers to TB control, including analyses of economic effectiveness.

Active case finding for pulmonary tuberculosis using mobile digital chest radiography: an observational study.

BACKGROUND: Mobile digital chest radiography (CXR) is used routinely to screen for pulmonary tuberculosis (PTB) in London among homeless populations, persons accessing drug treatment services and prisoners. OBJECTIVE: 1) To establish the sensitivity and specificity of mobile digital CXR, and 2) to test the hypothesis that actively identified cases have reduced odds of sputum smear positivity vs. those presenting passively to health care services from the same populations. METHODS: Sensitivity and specificity were calculated using a gold standard comparator of culture-confirmed cases of PTB reported to the national surveillance system within 90 days of screening. Logistic regression was used to determine whether actively detected cases had reduced odds of smear positivity compared to passively detected cases after adjustment for confounding. RESULTS: The intervention had a sensitivity of 81.8% (95%CI 64.5-93.0) and a specificity of 99.2% (95%CI 99.1-99.3). After adjusting for confounding, there was evidence that cases identified through screening were less likely to be smear-positive than passively identified cases (OR 0.34, 95%CI 0.14-0.85; likelihood ratio test P = 0.022). CONCLUSION: Digital CXR achieves a high level of sensitivity and specificity in an operational setting; targeted mobile radiographic screening can reduce the risk of onward transmission by identifying cases before they become infectious.

Record-linkage and capture-recapture analysis to estimate the incidence and completeness of reporting of tuberculosis in England 1999-2002.

In 1999 the Enhanced Tuberculosis Surveillance (ETS) system was introduced in the United Kingdom to strengthen surveillance of tuberculosis (TB). The aim of this study was to assess the use of record-linkage and capture-recapture methodology for estimating the completeness of TB reporting in England between 1999 and 2002. Due to the size of the TB data sources sophisticated record-linkage software was required and the proportion of false-positive cases among unlinked hospital-derived TB records was estimated through a population mixture model. This study showed that record-linkage of TB data sources and cross-validation with additional TB-related datasets improved data quality as well as case ascertainment. Since the introduction of ETS observed completeness of notification in England has increased and the results were consistent with expected levels of under-notification. Completeness of notification estimated by a log-linear capture-recapture model was highly inconsistent with prior estimates and the validity of this methodology was further examined.

Estimating infectious diseases incidence: validity of capture-recapture analysis and truncated models for incomplete count data.

Capture-recapture analysis has been used to evaluate infectious disease surveillance. Violation of the underlying assumptions can jeopardize the validity of the capture-recapture estimates and a tool is needed for cross-validation. We re-examined 19 datasets of log-linear model capture-recapture studies on infectious disease incidence using three truncated models for incomplete count data as alternative population estimators. The truncated models yield comparable estimates to independent log-linear capture-recapture models and to parsimonious log-linear models when the number of patients is limited, or the ratio between patients registered once and twice is between 0.5 and 1.5. Compared to saturated log-linear models the truncated models produce considerably lower and often more plausible estimates. We conclude that for estimating infectious disease incidence independent and parsimonious three-source log-linear capture-recapture models are preferable but truncated models can be used as a heuristic tool to identify possible failure in log-linear models, especially when saturated log-linear models are selected.