Does One Size Fit All? Drug Resistance and Standard Treatments: Results of Six Tuberculosis Programmes in Former Soviet Countries.

SETTING: After the collapse of the Soviet Union, countries in the region faced a dramatic increase in tuberculosis cases and the emergence of drug resistance. OBJECTIVE: To discuss the relevance of the DOTS strategy in settings with a high prevalence of drug resistance. DESIGN: Retrospective analysis of one-year treatment outcomes of short-course chemotherapy (SCC) and results of drug susceptibility testing (DST) surveys of six programmes located in the former Soviet Union: Kemerovo prison, Russia; Abkhasia, Georgia; Nagorno-Karabagh, Azerbaijan; Karakalpakstan, Uzbekistan; Dashoguz Velayat, Turkmenistan; and South Kazakhstan Oblast, Kazakhstan. Results are reported for new and previously treated smear-positive patients. RESULTS: Treatment outcomes of 3090 patients and DST results of 1383 patients were collected. Treatment success rates ranged between 87% and 61%, in Nagorno-Karabagh and Kemerovo, respectively, and failure rates between 7% and 23%. Any drug resistance ranged between 66% and 31% in the same programmes. MDR rates ranged between 28% in Karakalpakstan and Kemerovo prison and 4% in Nagorno-Karabagh. CONCLUSION: These results show the limits of SCC in settings with a high prevalence of drug resistance. They demonstrate that adapting treatment according to resistance patterns, access to reliable culture, DST and good quality second-line drugs are necessary

Coping with stigma and discrimination: evidence from mental health service users in England

Mental health stigma and discrimination are significant problems. Common coping orientations include: concealing mental health problems, challenging others and educating others. We describe the use of common stigma coping orientations and explain variations within a sample of English mental health service users. Cross-sectional survey data were collected as part of the Viewpoint survey of mental health service users’ experiences of discrimination (n = 3005). Linear regression analyses were carried out to identify factors associated with the three stigma coping orientations. The most common coping orientation was to conceal mental health problems (73%), which was strongly associated with anticipated discrimination. Only 51% ever challenged others because of discriminating behaviour, this being related to experienced discrimination, but also to higher confidence to tackle stigma. Although stigma coping orientations vary by context, individuals often choose to conceal problems, which is associated with greater anticipated and experienced discrimination and less confidence to challenge stigma. The direction of this association requires further investigation

Physical Aspects of Axonemal Beating and Swimming

We discuss a two-dimensional model for the dynamics of axonemal deformations driven by internally generated forces of molecular motors. Our model consists of an elastic filament pair connected by active elements. We derive the dynamic equations for this system in presence of internal forces. In the limit of small deformations, a perturbative approach allows us to calculate filament shapes and the tension profile. We demonstrate that periodic filament motion can be generated via a self-organization of elastic filaments and molecular motors. Oscillatory motion and the propagation of bending waves can occur for an initially non-moving state via an instability termed Hopf bifurcation. Close to this instability, the behavior of the system is shown to be independent of microscopic details of the axoneme and the force-generating mechanism. The oscillation frequency however does depend on properties of the molecular motors. We calculate the oscillation frequency at the bifurcation point and show that a large frequency range is accessible by varying the axonemal length between 1 and 50$\mu$m. We calculate the velocity of swimming of a flagellum and discuss the effects of boundary conditions and externally applied forces on the axonemal oscillations.Comment: 14 pages, 8 figures, REVTE

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis.

SETTING: Civilian population of the Republic of Azerbaijan. OBJECTIVES: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. DESIGN: National cross-sectional survey conducted in 2012-2013. RESULTS: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6-39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1-4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1-7.4). CONCLUSION: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance

Multidrug-Resistant Tuberculosis Treatment Outcomes in Karakalpakstan, Uzbekistan: Treatment Complexity and XDR-TB among Treatment Failures

BACKGROUND: A pilot programme to treat multidrug-resistant TB (MDR-TB) was implemented in Karakalpakstan, Uzbekistan in 2003. This region has particularly high levels of MDR-TB, with 13% and 40% among new and previously treated cases, respectively. METHODOLOGY: This study describes the treatment process and outcomes for the first cohort of patients enrolled in the programme, between October 2003 and January 2005. Confirmed MDR-TB cases were treated with an individualised, second-line drug regimen based on drug susceptibility test results, while suspected MDR-TB cases were treated with a standardised regimen pending susceptibility results. PRINCIPAL FINDINGS: Of 108 MDR-TB patients, 87 were started on treatment during the study period. Of these, 33 (38%) were infected with strains resistant to at least one second-line drug at baseline, but none had initial ofloxacin resistance. Treatment was successful for 54 (62%) patients, with 13 (15%) dying during treatment, 12 (14%) defaulting and 8 (8%) failing treatment. Poor clinical condition and baseline second-line resistance contributed to treatment failure or death. Treatment regimens were changed in 71 (82%) patients due to severe adverse events or drug resistance. Adverse events were most commonly attributed to cycloserine, ethionamide and p-aminosalicylic acid. Extensively drug resistant TB (XDR-TB) was found among 4 of the 6 patients who failed treatment and were still alive in November 2006. CONCLUSIONS: While acceptable treatment success was achieved, the complexity of treatment and the development of XDR-TB among treatment failures are important issues to be addressed when considering scaling up MDR-TB treatment

HCN Channels Are Not Required for Mechanotransduction in Sensory Hair Cells of the Mouse Inner Ear

The molecular composition of the hair cell transduction channel has not been identified. Here we explore the novel hypothesis that hair cell transduction channels include HCN subunits. The HCN family of ion channels includes four members, HCN1-4. They were orginally identified as the molecular correlates of the hyperpolarization-activated, cyclic nucleotide gated ion channels that carry currents known as If, IQ or Ih. However, based on recent evidence it has been suggested that HCN subunits may also be components of the elusive hair cell transduction channel. To investigate this hypothesis we examined expression of mRNA that encodes HCN1-4 in sensory epithelia of the mouse inner ear, immunolocalization of HCN subunits 1, 2 and 4, uptake of the transduction channel permeable dye, FM1-43 and electrophysiological measurement of mechanotransduction current. Dye uptake and transduction current were assayed in cochlear and vestibular hair cells of wildtype mice exposed to HCN channel blockers or a dominant-negative form of HCN2 that contained a pore mutation and in mutant mice that lacked HCN1, HCN2 or both. We found robust expression of HCNs 1, 2 and 4 but little evidence that localized HCN subunits in hair bundles, the site of mechanotransduction. Although high concentrations of the HCN antagonist, ZD7288, blocked 50–70% of the transduction current, we found no reduction of transduction current in either cochlear or vestibular hair cells of HCN1- or HCN2- deficient mice relative to wild-type mice. Furthermore, mice that lacked both HCN1 and HCN2 also had normal transduction currents. Lastly, we found that mice exposed to the dominant-negative mutant form of HCN2 had normal transduction currents as well. Taken together, the evidence suggests that HCN subunits are not required for mechanotransduction in hair cells of the mouse inner ear

Toward a multi-level strategy to reduce stigma in global mental health: overview protocol of the Indigo Partnership to develop and test interventions in low- and middle-income countries

There is increasing attention to the impacts of stigma and discrimination related to mental health on quality of life and access to and quality of healthcare. Effective strategies for stigma reduction exist, but most evidence comes from high-income settings. Recent reviews of stigma research have identified gaps in the field, including limited cultural and contextual adaptation of interventions, a lack of contextual psychometric information on evaluation tools, and, most notably, a lack of multi-level strategies for stigma reduction. The Indigo Partnership research programme will address these knowledge gaps through a multi-country, multi-site collaboration for anti-stigma interventions in low- and middle-income countries (LMICs) (China, Ethiopia, India, Nepal, and Tunisia). The Indigo Partnership aims to: (1) carry out research to strengthen the understanding of mechanisms of stigma processes and reduce stigma and discrimination against people with mental health conditions in LMICs; and (2) establish a strong collaborative research consortium through the conduct of this programme. Specifically, the Indigo Partnership involves developing and pilot testing anti-stigma interventions at the community, primary care, and mental health specialist care levels, with a systematic approach to cultural and contextual adaptation across the sites. This work also involves transcultural translation and adaptation of stigma and discrimination measurement tools. The Indigo Partnership operates with the key principle of partnering with people with lived experience of mental health conditions for the development and implementation of the pilot interventions, as well as capacity building and cross-site learning to actively develop a more globally representative and equitable mental health research community. This work is envisioned to have a long-lasting impact, both in terms of the capacity building provided to participating institutions and researchers, and the foundation it provides for future research to extend the evidence base of what works to reduce and ultimately end stigma and discrimination in mental health

Mental health literacy of depression: gender differences and attitudinal antecedents in a representative British sample

Background Poor mental health literacy and negative attitudes toward individuals with mental health disorders may impede optimal help-seeking for symptoms of mental ill-health. The present study examined the ability to recognize cases of depression as a function of respondent and target gender, as well as individual psychological differences in attitudes toward persons with depression. Methods In a representative British general population survey, the ability to correctly recognize vignettes of depression was assessed among 1,218 adults. Respondents also rated the vignettes along a number of attitudinal dimensions and completed measures of attitudes toward seeking psychological help, psychiatric skepticism, and anti-scientific attitudes. Results There were significant differences in the ability to correctly identify cases of depression as a function of respondent and target gender. Respondents were more likely to indicate that a male vignette did not suffer from a mental health disorder compared to a female vignette, and women were more likely than men to indicate that the male vignette suffered from a mental health disorder. Attitudes toward persons with depression were associated with attitudes toward seeking psychological help, psychiatric skepticism, and anti-scientific attitudes. Conclusion Initiatives that consider the impact of gender stereotypes as well as individual differences may enhance mental health literacy, which in turn is associated with improved help-seeking behaviors for symptoms of mental ill-health