Impact of Prior Tuberculosis Treatment With New/Companion Drugs on Clinical Outcomes in Patients Receiving Concomitant Bedaquiline and Delamanid for Multidrug- and Rifampicin-Resistant Tuberculosis.

BACKGROUND: There are scarce data on the clinical outcomes of persons retreated with new/companion anti-tuberculosis (TB) drugs for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB). We sought to evaluate the efficacy and safety of bedaquiline and delamanid containing regimens among patients with and without prior exposure to the new/companion drugs (bedaquiline, delamanid, linezolid, clofazimine, and fluoroquinolones). METHODS: We conducted a retrospective cohort study among patients with pulmonary MDR/RR-TB in Georgia who received bedaquiline and delamanid combination as a part of a salvage regimen from November 2017 to December 2020 in a programmatic setting. RESULTS: Among 106 persons with a median age of 39.5 years, 44 (41.5%) were previously treated with new/companion TB drugs. Patients with prior exposure to new/companion drugs had higher rates of baseline resistance compared to those without exposure to new/companion TB drugs (bedaquiline 15.2% vs 1.8%, linezolid 22.2% vs 16.7%). Sputum culture conversion rates among patients exposed and not exposed to new/companion drugs were 65.9% vs 98.0%, respectively (P < .001). Among patients with and without prior new/companion TB drug use, favorable outcome rates were 41.0% and 82.3%, respectively (P < .001). Treatment adherence in 32 (30.2%) patients was ≤80%. Five of 21 patients (23.8%) who had a baseline and repeat susceptibility test had acquired bedaquiline resistance. QTC/F prolongation (>500 ms) was rare (2.8%). CONCLUSIONS: Prior exposure to new/companion TB drugs was associated with poor clinical outcomes and acquired drug resistance. Tailoring the TB regimen to each patient's drug susceptibility test results and burden of disease and enhancing adherence support may improve outcomes.

Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study.

BACKGROUND: MRT5005, a codon-optimized CFTR mRNA, delivered by aerosol in lipid nanoparticles, was designed as a genotype-agnostic treatment for CF lung disease. METHODS: This was a randomized, double-blind, placebo-controlled Phase 1/2 study performed in the US. Adults with 2 severe class I and/or II CFTR mutations and baseline ppFEV1 values between 50 and 90% were randomized 3:1 (MRT5005: placebo). Six dose levels of MRT5005 (4, 8, 12, 16, 20, and 24 mg) or placebo (0.9% Sodium Chloride) were administered by nebulization. The single ascending dose cohort was treated over a range from 8 to 24 mg; the multiple ascending dose cohort received five weekly doses (range 8-20 mg); and the daily dosing cohort received five daily doses (4 mg). RESULTS: A total of 42 subjects were assigned to MRT5005 [31] or placebo [11]. A total of 14 febrile reactions were observed in 10 MRT5005-treated participants, which were mild [3] or moderate [11] in severity; two subjects discontinued related to these events. Additionally, two MRT5005-treated patients experienced hypersensitivity reactions, which were managed conservatively. The most common treatment emergent adverse events were cough and headache. No consistent effects on FEV1 were noted. CONCLUSIONS: MRT5005 was generally safe and well tolerated through 28 days of follow-up after the last dose, though febrile and hypersensitivity reactions were noted. The majority of these reactions resolved within 1-2 days with supportive care allowing continued treatment with MRT5005 and careful monitoring. In this small first-in-human study, FEV1 remained stable after treatment, but no beneficial effects on FEV1 were observed.

Factors associated with receiving CF care and use of telehealth in 2020 among persons with Cystic Fibrosis in the United States.

BACKGROUND: The COVID-19 pandemic resulted in the use of telehealth to deliver the cystic fibrosis (CF) care model, which recommends routine follow-up for monitoring of nutritional status, bacterial culture surveillance, pulmonary function testing, and screening for CF-related complications such as diabetes or osteoporosis. METHODS: The objective of this study was to use Cystic Fibrosis Foundation Patient Registry (CFFPR) data to quantify the extent to which persons with CF received the recommended components of the care model in 2019 versus 2020. A risk factor analysis was implemented to identify patient characteristics associated with attaining the recommended CF care and use of any telehealth using multivariable logistic regression. RESULTS: A total of 28,132 CFFPR participants were included in the study. The proportion of individuals meeting the recommendations for CF care was lower in 2020 for every indicator, and lower in adults compared to children. In adults, demographic, socioeconomic and CF-related disease covariates were significantly associated with both achieving an aggregate level of care and use of telehealth. In the pediatric population, minority race/ethnicity and markers of lower socioeconomic status were associated with a lower odds of telehealth use. In all analyses, having received the recommended level of care in 2019 was associated with a higher odds of both reported telehealth use and achieving the recommended elements of the CF care model in 2020. CONCLUSION: Fewer participants met recommendations for care in 2020 despite widespread use of telehealth, and use of telehealth did not equate to adherence to all aspects of CF care.

Urethral duplication as cause of incontinence in a 5-years-old female: Surgical approach.

INTRODUCTION: Duplication of the urethra is a rare congenital anomaly in females which, if left unidentified, might cause refractory urinary incontinence. This video demonstrates its identification and treatment. PATIENT & METHODS: A 5-year-old female was referred for primary refractory diurnal incontinence without any dry moment since birth. Initial clinical examination showed permanent urine leakage from an opening cranial to the clitoris. Ultrasound did not show any bladder or kidney abnormalities. A diagnostic cystoscopy under anesthesia revealed an accessory meatus located cranially to the orthotopic meatus and to the clitoris. RESULTS: Lying in dorsal decubitus under general anesthesia, catheters were inserted in respectively the orthotopic and accessory meatus. The accessory meatus and urethra were dissected away into the bladder dome from a circumferential skin incision. Defects were closed and bladder drainage per urethram was left in situ for 10 days. P ostoperative recovery was uncomplicated. Complete resolution of the incontinence was immediately achieved at catheter removal. Daytime and night-time continence are observed with 3 years follow-up. CONCLUSION: Urethral duplication is a rare finding in females but should be excluded during the workup of primary incontinence. In girls with isolated urethral duplication, resection of the accessory urethra is the best surgical option.

Linezolid use for drug-resistant tuberculosis in Georgia: a retrospective cohort study.

SETTING: Data on the long-term use of linezolid (LZD) in the treatment of drug-resistant pulmonary tuberculosis (DR-PTB) are limited.OBJECTIVE: To assess safety, tolerability and efficacy of LZD-containing regimens for the treatment of DR-PTB in the country of Georgia.DESIGN: A retrospective study was conducted among DR-PTB patients receiving LZD 600 mg/day as part of newly implemented regimens (bedaquiline or delamanid, repurposed and second-line drugs) from July 2014 to October 2015 in programmatic conditions and following WHO recommendations.RESULTS: One hundred mostly male (82%) patients with a median age of 33 years received LZD. Most patients (77%) had previously been treated for TB; 57% had extensively drug-resistant TB. The median duration of LZD use was 503 days (interquartile range 355-616). LZD-associated adverse events occurred in 12 patients, leading to discontinuation in 4 (2 each due to peripheral neuropathy and cytopenias), and dose reduction to 300 mg/day in 6 cases (4 due to peripheral neuropathy and 2 for cytopenias). Almost all patients (95%) achieved culture conversion and 79% had a successful treatment outcomes.CONCLUSION: Treatment regimens including lengthy LZD use showed fairly good safety and tolerability and were associated with high rates of culture conversion and favorable outcomes.

Evaluation of a comprehensive diabetic foot ulcer care quality model.

AIMS: Diabetes-related amputations are typically preceded by a diabetic foot ulcer (DFU) but models to assess the quality of care are lacking. We investigated a model to measure inpatient and outpatient quality. METHODS: Cohort study among adults hospitalized with a DFU to a safety-net hospital during 2016. We measured adherence to DFU-related quality metrics based on guidelines during and 12 months following hospitalization. Inpatient metrics included ankle-brachial index measurement during or 6 months prior to hospitalization, receiving diabetes education and a wound offloading device prior to discharge. Outpatient metrics included wound care ≤30 days of discharge, in addition to hemoglobin A1c (HbA1c) ≤8%, tobacco cessation, and retention in care (≥2 clinic visits ≥90 days apart) 12 months following discharge. RESULTS: 323 patients were included. Regarding inpatient metrics, 8% had an ankle brachial index measurement, 37% received diabetes education, and 20% received offloading prior to discharge. Regarding outpatient metrics, 33% received wound care ≤30 days of discharge. Twelve months following discharge, 34% achieved a HbA1c ≤8%, 13% quit tobacco, and 52% were retained in care. Twelve-month amputation-free survival was 71%. CONCLUSIONS: Our model demonstrated large gaps in DFU guideline-adherent care. Implementing measures to close these gaps could prevent amputations.

The Cedar Project: exploring determinants of psychological distress among young Indigenous people who use drugs in three Canadian cities.

BACKGROUND: Mental health and wellbeing, including addressing impacts of historical trauma and substance use among young people, has been identified as a key priority by Indigenous communities and leaders across Canada and globally. Yet, research to understand mental health among young Indigenous people who have used drugs is limited. AIMS: To examine longitudinal risk and strengths-based factors associated with psychological distress among young Indigenous people who use drugs. METHOD: The Cedar Project is an ongoing cohort study involving young Indigenous people who use drugs in Vancouver, Prince George, and Chase, British Columbia, Canada. This study included participants who completed the Symptom Checklist-90-Revised, returned for follow-up between 2010 and 2012, and completed the Childhood Trauma Questionnaire. Adjusted linear mixed-effects models estimated effects of study variables on changes in area T-scores of psychological distress. RESULTS: Of 202 eligible participants, 53% were women and the mean age was 28 years. Among men, childhood maltreatment (emotional abuse, physical abuse, sexual abuse, physical neglect), any drug use, blackouts from drinking, and sex work were associated with increased distress. Among women, childhood maltreatment (emotional abuse, physical abuse, physical neglect), blackouts from drinking, and sexual assault were associated with increased distress, while having attempted to quit using drugs was associated with reduced distress. Marginal associations were observed between speaking their traditional language and living by traditional culture with lower distress among men. CONCLUSION: Culturally safe mental wellness interventions are urgently needed to address childhood trauma and harmful coping strategies that exacerbate distress among young Indigenous people who use drugs.

Demographic and HIV-specific characteristics of participants enrolled in the INSIGHT Strategic Timing of AntiRetroviral Treatment (START) trial.

OBJECTIVES: The risks and benefits of initiating antiretroviral treatment (ART) at high CD4 cell counts have not been reliably quantified. The Strategic Timing of AntiRetroviral Treatment (START) study is a randomized international clinical trial that compares immediate with deferred initiation of ART for HIV-positive individuals with CD4 cell counts above 500 cells/µL. We describe the demographics, HIV-specific characteristics and medical history of this cohort. METHODS: Data collected at baseline include demographics, HIV-specific laboratory values, prior medical diagnoses and concomitant medications. Baseline characteristics were compared by geographical region, gender and age. RESULTS: START enrolled 4685 HIV-positive participants from 215 sites in 35 countries. The median age is 36 years [interquartile range (IQR) 29-44 years], 27% are female, and 45% self-identify as white, 30% as black, 14% as Latino/Hispanic, 8% as Asian and 3% as other. The route of HIV acquisition is reported as men who have sex with men in 55% of participants, heterosexual sex in 38%, injecting drug use in 1% and other/unknown in 5%. Median time since HIV diagnosis is 1.0 year (IQR 0.4-3.0 years) and the median CD4 cell count and HIV RNA values at study entry are 651 cells/µL (IQR 584-765 cells/µL) and 12,754 HIV RNA copies/mL (IQR 3014-43,607 copies/mL), respectively. CONCLUSIONS: START has enrolled a diverse group of ART-naïve individuals with high CD4 cell counts who are comparable to the HIV-positive population from the regions in which they were enrolled. The information collected with this robust study design will provide a database with which to evaluate the risks and benefits of early ART use for many important outcomes.

Acoustic interactions between inversion symmetric and asymmetric two-level systems.

Amorphous solids, as well as many disordered lattices, display remarkable universality in their low temperature acoustic properties. This universality is attributed to the attenuation of phonons by tunneling two-level systems (TLSs), facilitated by the interaction of the TLSs with the phonon field. TLS-phonon interaction also mediates effective TLS-TLS interactions, which dictates the existence of a glassy phase and its low energy properties. Here we consider KBr:CN, the archetypal disordered lattice showing universality. We calculate numerically, using conjugate gradients method, the effective TLS-TLS interactions for inversion symmetric (CN flips) and asymmetric (CN rotations) TLSs, in the absence and presence of disorder, in two and three dimensions. The observed dependence of the magnitude and spatial power law of the interaction on TLS symmetry, and its change with disorder, characterizes TLS-TLS interactions in disordered lattices in both extreme and moderate dilutions. Our results are in good agreement with the two-TLS model, recently introduced to explain long-standing questions regarding the quantitative universality of phonon attenuation and the energy scale of ≈ 1-3 K below which universality is observed.

ASXL1 and DNMT3A mutation in a cytogenetically normal B3 thymoma.

The molecular drivers of thymoma are poorly understood. Outside of the identification of rarely occurring epidermal growth factor receptor and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog mutations via candidate gene sequencing, mutations in common cancer genes have yet to be observed. Only a single thymoma genome sequence has been previously reported, with no mutations in known cancer genes identified. Thus, we attempted to identify somatic driver mutations in a cytogenetically normal thymoma. A stage IVB type B3 thymoma from a 47-year-old male of Asian descent with no history of myasthenia gravis or other autoimmune condition was genomically evaluated. Exome sequencing and low-pass whole-genome sequencing was performed to identify somatic point mutations, copy number changes and structural variants. Mutations in known tumor suppressors DNMT3A (p.G728D) and ASXL1 (p.E657fs), consistent with mutations of known consequence in acute myeloid leukemia, were identified. Contrary to a previous report, this finding suggests the genetic etiology of thymomas may not be fundamentally distinct from other tumor types. Rather, these findings suggest that further sequencing of cytogenetically normal thymoma samples should reveal the specific molecular drivers of thymoma.

Antiviral efficacy of entecavir in nucleos(t)ide-naïve patients of Black/African descent with chronic hepatitis B.

This single-arm, open-label, descriptive study assessed the efficacy and safety of entecavir (ETV) in nucleos(t)ide-naïve Black/African American patients with chronic hepatitis B (CHB), a patient population underrepresented in ETV registration trials. Forty patients with HBeAg(+) or HBeAg(-) compensated CHB of self-described Black/African American race received ETV 0.5 mg daily for 52 weeks; 37 patients completed 52 weeks of treatment. At Week 48, 29/40 (72.5%, noncompleter = failure) patients achieved the primary endpoint of HBV DNA <50 IU/mL. Rates for HBeAg loss (11/22; 50%) and HBeAg seroconversion (9/22; 41%) were high, possibly due to the high HBV genotype A prevalence (70%). No patient experienced virological breakthrough. Samples for resistance testing were available in 6/8 patients with HBV DNA >50 IU/mL at Week 48 or last on-treatment visit. No ETV resistance was detected. The safety profile of ETV was consistent with that observed in ETV registration trials. This study shows that in Black/African American patients with CHB, ETV was well tolerated and demonstrated comparable antiviral efficacy to that observed in White and Asian patients in ETV Phase III studies.

Endocannabinoid receptor deficiency affects maternal care and alters the dam's hippocampal oxytocin receptor and brain-derived neurotrophic factor expression.

Maternal care is the newborn's first experience of social interaction, and this influences infant survival, development and social competences throughout life. We recently found that postpartum blocking of the endocannabinoid receptor-1 (CB1R) altered maternal behaviour. In the present study, maternal care was assessed by the time taken to retrieve pups, pups' ultrasonic vocalisations (USVs) and pup body weight, comparing CB1R deleted (CB1R KO) versus wild-type (WT) mice. After culling on postpartum day 8, hippocampal expression of oxytocin receptor (OXTR), brain-derived neurotrophic factor (BDNF) and stress-mediating factors were evaluated in CB1R KO and WT dams. Comparisons were also performed with nulliparous (NP) CB1R KO and WT mice. Compared to WT, CB1R KO dams were slower to retrieve their pups. Although the body weight of the KO pups did not differ from the weight of WT pups, they emitted fewer USVs. This impairment of the dam-pup relationship correlated with a significant reduction of OXTR mRNA and protein levels among CB1R KO dams compared to WT dams. Furthermore, WT dams exhibited elevated OXTR mRNA expression, as well as increased levels of mineralocorticoid and glucocorticoid receptors, compared to WT NP mice. By contrast, CB1R KO dams showed no such elevation of OXTR expression, alongside lower BDNF and mineralocorticoid receptors, as well as elevated corticotrophin-releasing hormone mRNA levels, when compared to CB1R KO NP. Thus, it appears that the disruption of endocannabinoid signalling by CB1R deletion alters expression of the OXTR, apparently leading to deleterious effects upon maternal behaviour.

Tuberculosis in HIV programmes in lower-income countries: practices and risk factors.

BACKGROUND: Tuberculosis (TB) is a common diagnosis in human immunodeficiency virus (HIV) infected patients on antiretroviral treatment (ART). OBJECTIVE: To describe TB-related practices in ART programmes in lower-income countries and identify risk factors for TB in the first year of ART. METHODS: Programme characteristics were assessed using standardised electronic questionnaire. Patient data from 2003 to 2008 were analysed and incidence rate ratios (IRRs) calculated using Poisson regression models. RESULTS: Fifteen ART programmes in 12 countries in Africa, South America and Asia were included. Chest X-ray, sputum microscopy and culture were available free of charge in respectively 13 (86.7%), 14 (93.3%) and eight (53.3%) programmes. Eight sites (53.3%) used directly observed treatment and five (33.3%) routinely administered isoniazid preventive treatment (IPT). A total of 19 413 patients aged ≥ 16 years contributed 13,227 person-years of follow-up; 1081 new TB events were diagnosed. Risk factors included CD4 cell count (>350 cells/µl vs. <25 cells/µl, adjusted IRR 0.46, 95%CI 0.33-0.64, P < 0.0001), sex (women vs. men, adjusted IRR 0.77, 95%CI 0.68-0.88, P = 0.0001) and use of IPT (IRR 0.24, 95%CI 0.19-0.31, P < 0.0001). CONCLUSIONS: Diagnostic capacity and practices vary widely across ART programmes. IPT prevented TB, but was used in few programmes. More efforts are needed to reduce the burden of TB in HIV co-infected patients in lower income countries.

Prioritising prevention strategies for patients in antiretroviral treatment programmes in resource-limited settings.

Expanded access to antiretroviral therapy (ART) offers opportunities to strengthen HIV prevention in resource-limited settings. We invited 27 ART programmes from urban settings in Africa, Asia and South America to participate in a survey, with the aim to examine what preventive services had been integrated in ART programmes. Twenty-two programmes participated; eight (36%) from South Africa, two from Brazil, two from Zambia and one each from Argentina, India, Thailand, Botswana, Ivory Coast, Malawi, Morocco, Uganda and Zimbabwe and one occupational programme of a brewery company included five countries (Nigeria, Republic of Congo, Democratic Republic of Congo, Rwanda and Burundi). Twenty-one sites (96%) provided health education and social support, and 18 (82%) provided HIV testing and counselling. All sites encouraged disclosure of HIV infection to spouses and partners, but only 11 (50%) had a protocol for partner notification. Twenty-one sites (96%) supplied male condoms, seven (32%) female condoms and 20 (91%) provided prophylactic ART for the prevention of mother-to child transmission. Seven sites (33%) regularly screened for sexually transmitted infections (STI). Twelve sites (55%) were involved in activities aimed at women or adolescents, and 10 sites (46%) in activities aimed at serodiscordant couples. Stigma and discrimination, gender roles and funding constraints were perceived as the main obstacles to effective prevention in ART programmes. We conclude that preventive services in ART programmes in lower income countries focus on health education and the provision of social support and male condoms. Strategies that might be equally or more important in this setting, including partner notification, prompt diagnosis and treatment of STI and reduction of stigma in the community, have not been implemented widely.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil.

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73%), 55 (11%), and 76 (16%) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25%) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

Effectiveness of highly active antiretroviral therapy using non-brand name drugs in Brazil

In Brazil, HIV-infected individuals receive drugs (including non-brand name drugs which comprise locally produced generics and drugs that have not been tested in bioequivalence trials) free of charge from the government. The objective of the present study was to evaluate the effectiveness of highly active antiretroviral therapy (HAART) in Rio de Janeiro, Brazil, where non-brand drugs are widely used. For this purpose, we estimated the proportion of subjects with virologic failure (plasma HIV viral load greater than 400 copies/mL at 6 months after initiation of treatment). This was a retrospective cohort study of drug-naive HIV-infected subjects who initiated HAART. Subjects were included in the analysis if they were 18 years of age or older, were treatment naive, started HAART with a minimum of 3 drugs, and had available information on blood plasma HIV-1 viral load after 6 months on therapy. All subjects used antiretrovirals in dosing regimens recommended by the Brazilian National Advisory Committee for Antiretroviral Therapy. Chart reviews were conducted in three settings: at two public health outpatient units, at one clinical trial unit and at one private office. No comparisons of the effectiveness of non-brand name with the effectiveness of brand name drugs were made. We present results for 485 patients; of these, 354 (73 percent), 55 (11 percent), and 76 (16 percent) were seen at the public health outpatient units, private office, and clinical trial unit, respectively. Virologic failure was observed in 119 (25 percent) of the subjects. This study demonstrates the effectiveness of HAART in a setting where non-brand name drugs are widely used.

HIV and ethnicity in Canada: is the HIV risk-taking behaviour of young foreign-born MSM similar to Canadian born MSM?

There is a dearth of information on the HIV risk-taking behaviour of foreign-born men who have sex with men (MSM) in Canada. This study focused on identifying sexual risk behaviour among MSM who immigrated to Canada and compared them to MSM who were born in Canada. Baseline data from the Omega Cohort in Montreal and the Vanguard Project in Vancouver were combined to form four ethnicity/race analytical categories (n = 1,148): White born in Canada (WBIC), White born outside of Canada, non-White born in Canada (NBIC) and non-White born outside of Canada (NBOC). Psychological, demographic and sexual behaviour characteristics of the groups were similar except: NBOC were more likely to be unemployed, less likely to be tattooed, had fewer bisexual experiences and less likely worried of insufficient funds. WBOC were more likely to report unprotected sex with seropositives and more likely to have had unprotected sex while travelling. NBIC were more likely to have ever sold sex and to have had body piercing. WBOC are at high risk of acquiring as well as transmitting HIV. It is important to consider place of birth in addition to ethnicity when developing programmes to prevent the transmission of HIV.

Clinical trial to compare tinnitus masking and tinnitus retraining therapy.

CONCLUSION: Both tinnitus masking (TM) and tinnitus retraining therapy (TRT) can be effective therapies for amelioration of tinnitus. TM may be more effective for patients in the short term, but with continued treatment TRT may produce the greatest effects. OBJECTIVES: Although TM and TRT have been used for many years, research has not documented definitively the efficacy of these methods. The present study was a controlled clinical trial to prospectively evaluate the clinical efficacy of these two methods for US military veterans with severe tinnitus. SUBJECTS AND METHODS: Over 800 veterans were screened to ensure that enrolled patients had tinnitus of sufficient severity to justify 18 months of individualized treatment. Qualifying patients (n=123) were placed quasi-randomly (alternating placement) into treatment with either TM or TRT. Treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated primarily using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index). RESULTS: Findings are presented from the three written questionnaires with respect to three categories of patients: describing tinnitus as a 'moderate,' 'big,' and 'very big' problem at baseline. Based on effect sizes, both groups showed considerable improvement overall. In general, TM effects remained fairly constant over time while TRT effects improved incrementally. For the patients with a 'moderate' and 'big' problem, TM provided the greatest benefit at 3 and 6 months; benefit to these TRT patients was slightly greater at 12 months, and much greater at 18 months. For patients with a 'very big' problem, TM provided the greatest benefit at 3 months. For these latter patients, results were about the same between groups at 6 months, and improvement for TRT was much greater at 12 months, with further gains at 18 months.

Inadequacies in antiretroviral therapy use among Aboriginal and other Canadian populations.

We undertook this study to provide a profile of Aboriginal people initiating antiretroviral therapy and their response to treatment. Aboriginal peoples were identified through self-report. Baseline socio-demographics and risk factors were compared between Aboriginal and non-Aboriginal participants as were baseline factors associated with two consecutive plasma viral load measures below 500 copies/ml using contingency table analysis. Multivariate survival analysis of the prognostic factors associated with time to two consecutive plasma viral load measures below 500 copies/ml among eligible participants was undertaken to characterize response to antiretroviral therapy. There were 892 participants with available data for this analysis, of those 146 (16%) self-identified as Aboriginal. Aboriginal participants were more likely to be female (p < or = 0.001), have lower baseline plasma viral loads (p = 0.010), be co-infected with HCV (p < 0.001), live in unstable housing (p < or = 0.001), and report an income of >10K CDN (p < or = 0.001) per annum. Aboriginal people were less likely to report men who have sex with men (p < or = 0.001) and more likely to report injection drug use (p < or = 0.001) as a risk factor for HIV infection. Aboriginal participants were more likely to receive double versus triple combination antiretroviral therapy (p = 0.002), be less adherent in the first year on therapy (p = 0.001) and to have a physician less experienced with treating HIV (p < or = 0.001). When these factors were controlled for, Aboriginal people treated with triple combination therapy were as likely to respond and suppress their viral load below 500 copies. In the era of HAART, our results indicate that Aboriginal people living with HIV/AIDS were less likely to receive optimal therapy. However, when Aboriginals did receive triple drug therapy they suppressed just as well as non-Aboriginals.

Drastic elevations in mortality among female injection drug users in a Canadian setting.

The health and social conditions of women living in Vancouver's Downtown Eastside has recently been the focus of substantial international attention. Since few studies have examined rates and correlates of death among addicted women in Canada, we have characterized patterns of mortality among female injection drug users (IDUs) in Vancouver. The Vancouver Injection Drug Users Study (VIDUS) is a prospective open cohort study of IDUs. The analyses presented here, were restricted to women enrolled between May 1996 and May 2002 and who were aged 14 years or older. We estimated cumulative mortality rates using Kaplan-Meier methods and Cox regression was used to calculate univariate and adjusted relative hazards. Between May 1996 and May 2002, 520 female IDUs have been recruited from the Vancouver area among whom 68 died during the study period. Elevated rates of mortality were observed among those who reported, baseline sex-trade involvement, those with HIV-infection at baseline, and those who lived in unstable housing at baseline (all log-rank: p<0.05). In adjusted analyses, HIV infection (RH = 3.09 [95% CI: 1.86-5.11]; p<0.001), unstable housing (RH = 1.74 [95% CI: 1.10-2.86]; p=0.029) and sex-trade involvement (RH = 1.82 [95% CI: 0.95-3.45]; p=0.071) were associated with the time to death. When the number of observed deaths was compared to the number of expected deaths based on the general female population of British Columbia using indirect standardization, the rate of death among female IDUs was elevated by a factor of 47.3 (95% CI: 36.1-58.5). In Vancouver, female IDUs have rates of mortality almost 50 times that of the province's female population. Our findings are consistent with a growing number of reports from other settings internationally, and demonstrate the need for an appropriate evidence-based strategy to address the health and social needs of addicted women.