Predictors of poor treatment outcomes in multidrug-resistant tuberculosis patients: a retrospective cohort study.

OBJECTIVES: We aimed to determine the characteristics, treatment outcomes and risk factors for poor treatment outcomes among multidrug-resistant (MDR) tuberculosis (TB) patients in Khyber Pakhtunkhwa province, Pakistan. METHODS: A retrospective cohort study including all patients with MDR-TB who sought care at the MDR-TB unit in Peshawar was conducted between January 2012 and April 2014. Patients were followed until an outcome of TB treatment was recorded as successful (cured or completed) or unsuccessful. Binary logistic regression was used to identify predictors of poor outcome, i.e. unsuccessful treatment outcomes. RESULTS: Overall, 535 patients were included. The proportion of female subjects was relatively higher (n = 300, 56.1%) than male subjects. The mean (standard deviation) age of patients was 30.37 (14.09) years. Of 535 patients for whom treatment outcomes were available, 402 (75.1%) were cured, 4 (0.7%) completed therapy, 34 (6.4%) had disease that failed to respond to therapy, 93 (17.4%) died and two (0.4%) defaulted; in total, 129 (24.1%) had an unsuccessful outcome. We found three significant predictors of unsuccessful treatment during multivariate logistic regression: being married (odds ratio (OR) = 2.17, 95% confidence interval (CI) 1.01, 4.66), resistance to second-line drugs (OR = 2.61, 95% CI 1.61, 4.21) and presence of extensively drug-resistant TB (OR = 7.82, 95% CI 2.90, 21.07). CONCLUSIONS: Approximately 75% of the treatment success rate set by the Global Plan to Stop TB was achieved. Resistance to second-line drugs and presence of extensively drug-resistant TB are the main risk factors for poor treatment outcomes.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Survival of HIV-positive individuals with hepatitis B and C infection in Michigan.

We sought to estimate mortality and associated factors in HIV-hepatitis co-infected individuals in Michigan using a retrospective cohort study. For the study period of 1 January 2006 to 31 December 2009, all HIV-infected individuals were matched to hepatitis B and C cases. In the final Cox proportional hazards regression model, individuals of other [hazard ratio (HR) 2·2, 95% confidence interval (CI) 1·4-3·2] and black (HR 1·3, 95% CI 1·1-1·6) race had decreased survival compared to white race. Similarly, injecting drug users (IDUs) (HR 2·1, 95% CI 1·6-2·6), men who have sex with men (MSM)/IDUs (HR 1·5, 95% CI 1·1-2·2), individuals with undetermined risk (HR 1·5, 95% CI 1·2-1·9) and heterosexual practices (HR 1·4, 95% CI 1·1-1·8) had decreased survival compared to MSM. Additionally, an interaction was found between current HIV status and co-infection. Mortality in HIV-hepatitis co-infected individuals remains a continuing problem. Our study can help in planning interventions to reduce mortality in HIV-infected individuals.

Hepatitis B and C co-infection in HIV/AIDS population in the state of Michigan.

A retrospective cohort study was conducted from 1 January 2006 to 31 December 2009 in Michigan to estimate the prevalence of HIV and hepatitis co-infection and identify associated factors. The prevalence of co-infection was 4.1% [95% confidence interval (CI) 3.8-4.5]. Multivariable logistic regression analysis revealed a significant association between co-infection and being male and: of Black race [odds ratio (OR) 2.0, 95% CI 1.2-3.6] and of Other race (OR 3.5, 95% CI 1.7-7.0) compared to Hispanic race. A significant association was found between co-infection and risk categories of blood products (OR 11.1, 95% CI 6.2-20.2), injecting drug user (IDU) (OR 3.6, 95% CI 2.7-4.8) and men who have sex with men/IDU (OR 3.4, 95% CI 2.4-4.9) in addition to two interactions; one between sex and current HIV status and the other between current HIV status and age at HIV diagnosis. Our results document the changing epidemiology of HIV-hepatitis co-infection which can guide preventive measures and interventions to reduce the prevalence of hepatitis co-infection.

Relationship of family and personal history to the occurrence of depression in persons with Alzheimer's disease.

The authors tested the associations of family history and personal history of depression with mood disorders among patients with Alzheimer's disease (AD; N=161). Considered individually, a positive family history and a positive personal history each conferred increased risk for depression in AD. Conjointly, neither family nor personal history accounted for a substantial amount of the variance in syndromal depression after the onset of AD. Most depressed AD patients in this sample did not have a positive family history or a previous episode of depression. Our understanding of the etiology and course of depression and dementia may be augmented with further neuropsychological and brain-imaging studies of the neuropathological substrates shared by these illnesses.

Do health professionals' attitudes interfere with the treatment of depression?

Might the attitudes of health care professionals help to explain why most persons with a depressive disorder do not receive adequate care? To assess this question, the authors surveyed the faculty and staff of a midwestern university. One hundred percent of the social workers who responded found psychotherapy or counseling to be extremely or quite effective in treating persons with a major depressive episode, compared to 55% of the psychologists and 31% of the psychiatrists. For medication, the corresponding figures were 88% of psychiatrists, 64% of psychologists, and 46% of social workers. Many respondents noted problems with interprofessional communication, while most psychiatrists felt that individuals treated by two or more professionals for their depression usually receive poorer care. If future studies indicate that nonmedical therapists who view antidepressants as relatively ineffective are less likely to refer depressed clients for medication evaluation, these findings might help to explain why many depressed individuals who could benefit from medication do not receive it. Concerns about interprofessional communication, as well as psychiatrists' beliefs about the quality of care received by persons treated by more than one professional, might also explain why joint treatment occurs less often than would be desirable. The authors discuss some of the implications that these findings may have for the education of health care professionals.

Orbital neurilemmoma: report of seven cases.

Neurilemmoma (schwannoma) has a predilection for the head and neck, especially the eighth cranial nerve in the cerebellopontine angle. It rarely occurs in the orbit, representing only 1% of orbital tumours. We report seven cases. The nerve of origin was identifiable in four cases. Two occurred within the inferior oblique muscle. Five were treated successfully by anterior or lateral orbitotomy without craniotomy and two required a combined cranio-orbitotomy. The majority of orbital neurilemmomas occur as discrete intraorbital lesions without intracranial extension and can be safely removed via orbitotomy alone.

Extracolonic features of familial adenomatous polyposis in patients with sporadic colorectal cancer.

We have investigated the occurrence of attenuated extracolonic manifestations (AEMs) of familial adenomatous polyposis (FAP) in patients with non-polyposis colorectal cancer. In a prospective case-control study, we observed that significantly more colorectal cancer patients exhibited AEM than did age and sex-matched controls (19.5% vs 7.5%, P < 0.004). However patients with AEMs do not have occult FAP, as we found no heterozygous adenomatous polyposis coli (APC) gene mutations despite extensive analysis of constitutional DNA. Genome-wide DNA replication errors (RERs) occur in a proportion of colorectal cancers, particularly right-sided lesions and in almost all tumours from hereditary non-polyposis colorectal cancer (HNPCC) patients. As AEMs have been reported in familial colon cancer cases, we investigated the relationship of AEMs to tumour RER phenotype. There was indeed an excess of AEMs in patients with right-sided tumours (30.2% of 53 patients vs 14.7% of 116 patients, P < 0.03) and in those with RER tumours (3 out of 12 patients with RER tumours vs none out of 21 patients with non-RER tumours, P < 0.05). Two patients with AEM were from HNPCC families compared with none of those without AEM (P < 0.05). The association of AEMs with colorectal cancer is intriguing, and we speculate that it may be a manifestation of mutational mosaicism of the APC gene, perhaps associated with a constitutional defect in DNA mismatch pair.

Warming lignocaine reduces the pain of injection during local anaesthetic eyelid surgery.

The injection of local anaesthetic solutions is frequently a painful and unpleasant experience for patients. A double-masked randomised controlled trial was performed to study the potential benefit of warming lignocaine during local anaesthetic minor surgical procedures on the eyelids. The pain of subcutaneous injection of 1.5 ml of 2% lignocaine at room temperature (cold) and body temperature (warm) was compared in 60 patients during the surgical incision of solitary meibomian cysts of one eyelid. Patients were randomly allocated to receive either warm or cold lignocaine. Pain was assessed subjectively by the use of a linear analogue pain scale ranging from 0 to 100. The median pain score for the group receiving cold anaesthetic (19.5) was found to be greater than that for the warm group (10.0; p = 0.02). In conclusion, the simple process of warming lignocaine to 37 degrees C was found to reduce the pain associated with its injection significantly. It is recommended that this technique be more widely adopted in order to minimise patients' discomfort.

Warming lignocaine reduces the pain of injection during peribulbar local anaesthesia for cataract surgery.

AIMS: To test if the simple technique of warming lignocaine reduces the pain of injection during local anaesthetic cataract surgery. METHODS: Sixty patients undergoing peribulbar local anaesthesia for cataract surgery were allocated randomly to receive either warm (37 degrees C) or cold (room temperature) plain 2% lignocaine for the injection. Pain was assessed subjectively by asking the patients to score their pain from 0 (no pain) to 10 (most severe pain imaginable). RESULTS: The mean pain score for the warm group was 2.3 (SD 1.3) in comparison with a mean score of 5.5 (1.0) for the cold group (p < 0.01). CONCLUSIONS: The process of warming lignocaine to 37 degrees C has been found to reduce significantly the pain of injection during peribulbar local anaesthesia. It is recommended that this technique be more widely adopted in order to minimise patient's discomfort.

Triple therapy and incidence of de novo cancer in renal transplant recipients.

Some 27 (5.5 per cent) of 492 renal transplant recipients developed de novo cancer between January 1975 and December 1991. Patients administered triple therapy of prednisolone, cyclosporin A and azathioprine had a significantly higher incidence of cancer (seven of 40 patients; 17.5 per cent) than those given prednisolone with cyclosporin (14 of 319; 4.4 per cent) and azathioprine with prednisolone (six of 133; 4.5 per cent) (P = 0.005). In a prospective study between January 1989 and December 1992, 110 renal transplant patients were randomized into three immunosuppressive regimens at the time of transplantation. The incidence of cancer in patients receiving low-dose cyclosporin, azathioprine and prednisolone was three of 45, in those given high-dose cyclosporin and prednisolone none of 23 and in those administered high-dose cyclosporin, nifedipine and prednisolone one of 29. The addition of azathioprine to ongoing maintenance cyclosporin and prednisolone therapy is useful in a subgroup of patients with graft dysfunction, but there are possibly higher risks in the development of de novo carcinoma.