Smoked drug use in patients with TB is associated with higher bacterial burden.

BACKGROUND: Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy.METHODS: Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation.RESULTS: People who smoked drugs (PWSD) comprised 54.8% (n = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10-1.97; P = 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22-4.34; P = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62-1.87; P = 0.799) was not associated with increased cavitation.CONCLUSIONS: PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.

Mandrax use, sexual risk, and opportunities for pre-exposure prophylaxis among out-of-school adolescent girls and young women in Cape Town, South Africa.

BACKGROUND: In South Africa (SA), adolescent girls and young women (AGYW) aged 15 - 24 years account for nearly 25% of all new HIV infections in the country. The intersection of substance use and sexual risk continues to drive the HIV epidemic among AGYW. For example, methaqualone, also known as Mandrax, has sedative effects that may affect women's ability to negotiate condom use during sex, refuse sex without a condom, or consent to sex, thereby increasing their risk for HIV. Consequently, it is critical to understand how Mandrax use affects HIV risk among AGYW and to assess awareness of and willingness to use biomedical HIV prevention methods, such as pre-exposure prophylaxis (PrEP), among AGYW who use Mandrax. OBJECTIVES: To examine the role of Mandrax use in sexual behaviours and investigate the extent to which AGYW who use Mandrax are aware of and willing to initiate PrEP. METHODS: Data for this report were derived from baseline and 6-month follow-up data provided by 500 AGYW participating in a cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. AGYW who self-identified as black African or coloured, reported using substances, reported condomless sex in the past 3 months, and had discontinued school early were recruited from 24 community clusters across Cape Town, SA. Following consent/assent, participants provided biological specimens to test for recent drug use (including Mandrax) and completed the self-report questionnaire. RESULTS: Logistic regression analysis revealed that the AGYW who had a positive test result for Mandrax use were less likely to use a condom with their main partner (p=0.01), and almost three times more likely to use alcohol and/or other drugs before or during their last act of sexual intercourse (p<0.001), compared with the AGYW who had a negative Mandrax test result. Mandrax use was not significantly related to PrEP awareness (p>0.10) or willingness to use PrEP (p>0.10), but 70% of AGYW who used Mandrax were willing to initiate PrEP. CONCLUSION: The study findings highlight how Mandrax use may contribute to HIV risk among SA AGYW. Key decision-makers should consider incorporating substance use prevention efforts into existing HIV reduction programmes and equip youth-friendly clinics with the resources to identify AGYW who use Mandrax and offer them PrEP.

Substance use and depressive and anxiety symptoms among out-of-school adolescent girls and young women in Cape Town, South Africa.

BACKGROUND: There is a high prevalence of substance use among youth in South Africa (SA), and adolescent girls and young women (AGYW) experience high rates of depression and anxiety. Substance use behaviours and mental health are associated with other public health problems among AGYW such as HIV and unintended pregnancy. Therefore, understanding the relationship between substance use and mental health is imperative to improve AGYW's health. OBJECTIVES: To examine the association between heavy drinking, marijuana, methamphetamine and methaqualone (Mandrax) use and depressive and anxiety symptoms among AGYW aged 16 - 19 years who have dropped out of school in Cape Town, SA. METHODS: Data for this report come from the baseline data of 500 participants of an ongoing cluster-randomised trial assessing the efficacy of a young woman-focused intervention to reduce substance use and HIV risk. After AGYW consented/assented to participate, they completed a urine drug screen and a baseline questionnaire. RESULTS: Logistic and negative binomial regressions, controlling for clustering at the neighbourhood level, revealed that frequency of depressive symptoms was significantly and positively related to a positive drug screen for Mandrax (ß=0.07; p=0.03). All other associations between the frequency of depressive symptoms and substance use were not statistically significant (ps>0.05). The associations between frequency of anxiety symptoms and substance use were not statistically significant (ps>0.05). CONCLUSIONS: Our findings highlight the need to address substance use, especially Mandrax use and its associated risk, and depression in an integrated, youth-friendly setting.

Reducing substance use and risky sexual behaviour among drug users in Durban, South Africa: Assessing the impact of community-level risk-reduction interventions.

Alcohol and other drug (AOD) use is increasingly recognised as having a direct and indirect effect on the transmission of human immunodeficiency virus (HIV). However, there is evidence to suggest that drug- and sex-related HIV risk-reduction interventions targeted at drug users within drug treatment centres or via community outreach efforts can lead to positive health outcomes. This study aimed to test whether a community-level intervention aimed at AOD users has an impact on risky AOD use and sexual risk behaviour. In 2007, in collaboration with a local non-governmental organisation (NGO) in Durban, an initiative was begun to implement a number of harm reduction strategies for injection and non-injection drug users. The NGO recruited peer outreach workers who received intensive initial training, which was followed by six-monthly monitoring and evaluation of their performance. Participants had to be 16 years of age or older, and self-reported alcohol and/or drug users. Peer outreach workers completed a face-to-face baseline questionnaire with participants which recorded risk behaviours and a risk-reduction plan was developed with participants which consisted of reducing injection (if applicable) and non-injection drug use and sex-related risks. Other components of the intervention included distribution of condoms, risk-reduction counselling, expanded access to HIV Testing Services, HIV/sexually transmitted infection care and treatment, and referrals to substance abuse treatment and social services. At follow-up, the baseline questionnaire was completed again and participants were also asked the frequency of reducing identified risk behaviours. Baseline information was collected from 138 drug users recruited into the study through community-based outreach, and who were subsequently followed up between 2010 and 2012. No injection drug users were reached. The data presented here are for first contact (baseline) and the final follow-up contact with the participants. There were no decreases in drug use practices such as use of cannabis, heroin, cocaine and Ecstasy after the intervention with drug users; however, there was a significant reduction in alcohol use following the intervention. While there was a substantial increase in the proportion of participants using drugs daily as opposed to more often, the reduction in the frequency of drug use was not statistically significant. Following the intervention, drug users had significantly fewer sexual partners, but there were no significant differences following the intervention with regard to frequency of sex or use of condoms. Substance use in general and during sex was, however, decreased. While the findings were mixed, the study shows that it is possible to provide HIV risk-reduction services to a population of substance users who are less likely to receive services through community outreach, and provide risk-reduction information, condoms and condom demonstration and other services. More intensive interventions might be needed to have a substantial impact on substance use and substance use-related HIV risk behaviours.

Medicines containing codeine: perspectives of medical professionals in the Republic of Ireland.

AIMS: The aim of the study was to examine prescribing professional's perceptions on prescribed and OTC medicines, containing codeine in the Republic of Ireland. A secondary aim was to examine perceptions on codeine dependence, screening and treatment. METHODS: A cross-sectional study of a nationally representative group of prescribing professionals was conducted using a questionnaire containing a number of open and closed ended items. Data were analysed using SPSS version 21 and content analysis techniques. RESULTS: 398 medical professionals participated in the study giving a response rate of 18%. 77% of respondents agreed to routinely review patient prescribed codeine. 59% of respondents routinely asked patients about their use of OTC medicines and 50% documented use of OTC codeine in their patients' medical notes. 93% indicated concern about the potential to purchase codeine from multiple sources. 88% implied that patients did not fully understand the risks of taking OTC medicine containing codeine. Only 21% of respondents were confident in identifying codeine dependence without being informed by the patient and 11.4% agreed to have suitable screening methods in practice. 76% indicated that they would like more instruction on prescribing addictive medicines. CONCLUSION: Policy should examine the need for greater public health awareness on codeine use and should examine the role of OTC and internet sales in the development of dependence. Further consideration should be given to training and support for those who prescribe addictive medicines in practice.

Coercion in the treatment of anorexia nervosa: clinical, ethical and legal implications.

Because of its high mortality and treatment resistence, clinicians sometimes invoke the law in aid of retaining their most acutely ill-patients in treatment or re-feeding programs. Depending on the jurisdiction, various laws, including mental health and adult guardianship laws, have been invoked to achieve this objective (Carney, Tait, Saunders, Touyz & Beumont, 2003). Until recently, little was known about the therapeutic impact of coercion on patients (Saunders, 2001, Carney & Saunders 2003), or the relative advantages of different avenues of coercion (Carney, Saunders, Tait, Touyz & Ingvarson 2004). Most obscure of all, however, has been our understanding of the factors influencing clinical decisions within specialist anorexia treatment units regarding which in-patients will be selected for coerced treatment. This paper reports legal and ethical implications of findings from analysis of data gathered from a major Australian specialist anorexia treatment facility over nearly 5 years.

Zebrafish colourless encodes sox10 and specifies non-ectomesenchymal neural crest fates.

Waardenburg-Shah syndrome combines the reduced enteric nervous system characteristic of Hirschsprung's disease with reduced pigment cell number, although the cell biological basis of the disease is unclear. We have analysed a zebrafish Waardenburg-Shah syndrome model. We show that the colourless gene encodes a sox10 homologue, identify sox10 lesions in mutant alleles and rescue the mutant phenotype by ectopic sox10 expression. Using iontophoretic labelling of neural crest cells, we demonstrate that colourless mutant neural crest cells form ectomesenchymal fates. By contrast, neural crest cells which in wild types form non-ectomesenchymal fates generally fail to migrate and do not overtly differentiate. These cells die by apoptosis between 35 and 45 hours post fertilisation. We provide evidence that melanophore defects in colourless mutants can be largely explained by disruption of nacre/mitf expression. We propose that all defects of affected crest derivatives are consistent with a primary role for colourless/sox10 in specification of non-ectomesenchymal crest derivatives. This suggests a novel mechanism for the aetiology of Waardenburg-Shah syndrome in which affected neural crest derivatives fail to be generated from the neural crest.

Electrophysiological estimate of human cortical magnification.

OBJECTIVE: The cortical magnification factor characterizes the area of human primary visual cortex activated by a stimulus as a function of angular distance from an observer's line of sight. This study estimates human cortical magnification using an electrophysiological method with excellent temporal resolution: visual evoked potential (VEP) dipole source localization. METHODS: For each of 60 independently modulated checkerboard patches within the central 18 deg of the visual field, location, orientation, magnitude, and time-course of the dipole current source that best described the VEP distribution across a multi-electrode array was obtained. At numerous eccentricities, cortical magnification was determined using two different techniques: (1) the distance between each pair of adjacent stimulus patches was matched to the corresponding distance between adjacent cortical sources; and (2) the area of each stimulus patch was matched to the magnitude of the corresponding cortical source (which was assumed to be proportional to cortical area). RESULTS: The estimates of human cortical magnification using our electrophysiological method were similar to previous estimates from psychophysics, cortical stimulation, and functional magnetic resonance imaging. CONCLUSIONS: The concordance of results provided by these disparate technologies, with differing spatial and temporal limitations, supports their combination in studying the spatio-temporal dynamics of human brain function.

Frequent attenders in general practice: a retrospective 20-year follow-up study.

We describe a 20-year retrospective study of 58 patients with a cross-matched control group in one practice, who initially attended more than 12 times in 1975. The study establishes that frequent attendance is not consistent; the majority of high-attending patients in general practice revert over a short period of time to a normal consulting pattern. Diseases, rather than patients, appear to dictate high consulting rates. Consistent high attendance is largely owing to multiple pathology.

The prevalence of bacteriuria in older institutionalized patients.

We set out to determine the prevalence of bacteriuria in elderly patients institutionalised in 10 homes in Northumberland. Single mid-stream urine (MSU) specimens were collected from 161 asymptomatic patients aged 64-101 years. Thirty-four (21%) samples had > 100 white blood cells (WBC/microliter) on microscopy as well as a significant bacteriuria of > 10(8) bacteria/l, being suggestive of a true urinary tract infection. A total of 115(71%) samples had < 100 WBC. Seventy-five (46%) samples could be described as 'contaminated' or 'infection unlikely' but of these only 31 (19.2% of all samples) were reported as 'contaminated' by the laboratory. This study confirms previous work in America to indicate the high level of bacteriuria in institutionalised elderly patients as well as the very high number (46%) who may show bacteriuria but no rise in the number of WBC suggesting contamination only. Nurses and GPs must be very cautious in interpreting MSU results from such patients.

Setting up a pain management programme. The Ayrshire experience.

A controlled trial of an outpatient cognitive behavioural pain management programme for sufferers of non-cancer chronic pain is described. A multidisciplinary team set up a programme of ten half day sessions for groups of ten to fourteen patients aiming to improve activity levels and control over pain; to reduce maladaptive pain behaviours and drug intake; to mitigate negative mood; to modify unhelpful beliefs and to maintain treatment gains by operant and cognitive methods. Self report questionnaires were employed before and six weeks, six months and one year after the programme. Fifty-eight patients entered the study group and 39 patients completed the programme and initial follow up with further attrition in long term follow up. There were no changes in the waiting list control group of twelve subjects but the study group made significant short and long term improvements in pain severity, activity levels, mood, coping and experienced fewer catastrophizing thoughts.

Unmasking the mechanisms for Vernier acuity: evidence for a template model for Vernier acuity.

The goal of this study was to evaluate the mechanisms underlying Vernier acuity, over a range of spatial scales using narrow-band Vernier stimuli and oblique masking. Specifically, the test stimuli consisted of a pair of vertical ribbons of horizontal cosine grating with a vertical Vernier offset between the ribbons. These stimuli have two important advantages for studying Vernier acuity: (1) they are relatively well localized in vertical spatial frequency, and (2) they are localized in their horizontal extent (width). We measured the orientation, spatial frequency and width tuning of Vernier acuity over a wide range of ribbon spatial frequencies, using a simultaneous oblique masking paradigm. Our masking results suggest that the mechanisms underlying Vernier acuity are tuned to the orientation, spatial frequency and width of the ribbon stimuli. The peak of the bimodal orientation tuning function varies systematically with the spatial frequency of the ribbon. The peak of the spatial frequency tuning function varies systematically with both the ribbon spatial frequency, and the ribbon width (i.e. the grating length). A 'template' model, in which the 'mechanism' is a windowed version of the stimulus is able to account for many features of the data, including results which cannot be easily accounted for by standard multi-scale filter models. Specifically, the template model can account for: (i) the bimodal orientation tuning function, (ii) the systematic variation in the peak of the orientation and spatial frequency tuning functions with spatial frequency, and (iii) the systematic effect of ribbon width on spatial frequency tuning.

Using multi-stimulus VEP source localization to obtain a retinotopic map of human primary visual cortex.

OBJECTIVE: The goal of this study was to acquire a detailed spatial and temporal map of primary visual cortex using a novel VEP stimulus and analysis technique. METHODS: A multi-stimulus array spanning the central 18 degrees of the visual field was used where each of 60 checkerboard stimulus 'patches' was simultaneously modulated with an independent binary m-sequence (Sutter, 1992). VEPs corresponding to each patch were recorded from 3 subjects using a dense posterior electrode array. For each stimulus patch, single dipole source localization was conducted to determine the location, magnitude, and time-function of the underlying neural activation. To reduce ambiguity in the solution, a common time-function was assumed for stimulus patches at the same visual eccentricity (defining an annulus). The analysis was conducted independently for each annulus composed of 4-12 patches. RESULTS: The loci of the dipole solutions followed a smooth retinotopic pattern across annuli consistent with the classical organization of primary visual cortex. Specifically, each dipole was found contralateral to the corresponding stimulus patch and field inversion was observed for all subjects. CONCLUSIONS: Using this technique, the most detailed spatial and temporal retinotopic map of primary visual cortex to date has been obtained.

Optimal spatial localization is limited by contrast sensitivity.

Bisection is one of several spatial localization tasks that achieve hyperacuity performance levels. We find that optimal bisection thresholds, and hyperacuity tasks in general, are no better than might be expected from simple contrast detection and discrimination performance. The three-line bisection task can be described in terms of the test-pedestal paradigm where the test pattern is a horizontal dipole and the pedestal is a horizontal three-line pattern with equal spacing between the lines. When the dipole test is added to the center line, the line shifts up or down, depending on the test polarity. For low contrast pedestal lines at the optimal separation, the bisection threshold falls between the observer's own dipole contrast detection threshold and the bottom of the dipole contrast discrimination dipper function. At higher pedestal strengths performance degrades with a slope of about 0.5-0.7, similar to that found in contrast discrimination tasks. Therefore, bisection performance is compatible with expectations based on contrast discrimination data. At large pedestal line separations (> 10 min) bisection thresholds in min are about 1/60 the separation and relatively independent of pedestal strength. These findings are consistent with the idea that two processes are involved in limiting bisection performance; the first limit is based on contrast sensitivity of the system and the second limit to performance is based on a local sign or position tag processing. Finally, when bisection is compared with Vernier acuity and blur resolution tasks, where the test is also a dipole, bisection performance falls roughly midway, better than Vernier acuity but worse than blur resolution.