Improving healthcare for patients with HIV, tuberculosis and hepatitis C in eastern Europe: a review of current challenges and important next steps.

OBJECTIVES: In some eastern European countries, serious challenges exist to meet the HIV-, tuberculosis (TB)- and hepatitis-related target of the United Nations Sustainable Development Goals. Some of the highest incidence rates for HIV and the highest proportion of multi-drug-resistant (MDR) tuberculosis worldwide are found in the region. The purpose of this article is to review the challenges and important next steps to improve healthcare for people living with TB, HIV and hepatitis C (HCV) in eastern Europe. METHODS: References for this narrative review were identified through systematic searches of PubMed using pre-idientified key word for articles published in English from January 2000 to August 2020. After screening of titles and abstracts 37 articles were identified as relevant for this review. Thirty-eight further articles and sources were identified through searches in the authors' personal files and in Google Scholar. RESULTS: Up to 50% of HIV/MDR-TB-coinfected individuals in the region die within 2 years of treatment initiation. Antiretroviral therapy (ART) coverage for people living with HIV (PLHIV) and the proportion virological suppressed are far below the UNAIDS 90% targets. In theory, access to various diagnostic tests and treatment of drug-resistant TB exists, but real-life data point towards inadequate testing and treatment. New treatments could provide elimination of viral HCV in high-risk populations but few countries have national programmes. CONCLUSION: Some eastern European countries face serious challenges to achieve the sustainable development goal-related target of 3.3 by 2030, among others, to end the epidemics of AIDS and tuberculosis. Better integration of healthcare systems, standardization of health care, unrestricted substitution therapy for all people who inject drugs, widespread access to drug susceptibility testing, affordable medicines and a sufficiently sized, well-trained health workforce could address some of those challenges.

Delayed diagnosis of tuberculosis in persons living with HIV in Eastern Europe: associated factors and effect on mortality-a multicentre prospective cohort study.

BACKGROUND: Early diagnosis of tuberculosis (TB) is important to reduce transmission, morbidity and mortality in people living with HIV (PLWH). METHODS: PLWH with a diagnosis of TB were enrolled from HIV and TB clinics in Eastern Europe and followed until 24 months. Delayed diagnosis was defined as duration of TB symptoms (cough, weight-loss or fever) for ≥ 1 month before TB diagnosis. Risk factors for delayed TB diagnosis were assessed using multivariable logistic regression. The effect of delayed diagnosis on mortality was assessed using Kaplan-Meier estimates and Cox models. FINDINGS: 480/740 patients (64.9%; 95% CI 61.3-68.3%) experienced a delayed diagnosis. Age ≥ 50 years (vs. < 50 years, aOR = 2.51; 1.18-5.32; p = 0.016), injecting drug use (IDU) (vs. non-IDU aOR = 1.66; 1.21-2.29; p = 0.002), being ART naïve (aOR = 1.77; 1.24-2.54; p = 0.002), disseminated TB (vs. pulmonary TB, aOR = 1.56, 1.10-2.19, p = 0.012), and presenting with weight loss (vs. no weight loss, aOR = 1.63; 1.18-2.24; p = 0.003) were associated with delayed diagnosis. PLWH with a delayed diagnosis were at 36% increased risk of death (hazard ratio = 1.36; 1.04-1.77; p = 0.023, adjusted hazard ratio 1.27; 0.95-1.70; p = 0.103). CONCLUSION: Nearly two thirds of PLWH with TB in Eastern Europe had a delayed TB diagnosis, in particular those of older age, people who inject drugs, ART naïve, with disseminated disease, and presenting with weight loss. Patients with delayed TB diagnosis were subsequently at higher risk of death in unadjusted analysis. There is a need for optimisation of the current TB diagnostic cascade and HIV care in PLWH in Eastern Europe.

Long-term outcomes after tuberculosis for people with HIV in eastern Europe.

BACKGROUND: Eastern Europe has a high burden of tuberculosis (TB)/HIV coinfection with high mortality shortly after TB diagnosis. This study assesses TB recurrence, mortality rates and causes of death among TB/HIV patients from Eastern Europe up to 11 years after TB diagnosis. METHODS: A longitudinal cohort study of TB/HIV patients enrolled between 2011 and 2013 (at TB diagnosis) and followed-up until end of 2021. A competing risk regression was employed to assess rates of TB recurrence, with death as competing event. Kaplan-Meier estimates and a multivariable Cox-regression were used to assess long-term mortality and corresponding risk factors. The Coding Causes of Death in HIV (CoDe) methodology was used for adjudication of causes of death. RESULTS: Three hundred and seventy-five TB/HIV patients were included. Fifty-three (14.1%) were later diagnosed with recurrent TB [incidence rate 3.1/100 person-years of follow-up (PYFU), 95% confidence interval (CI) 2.4-4.0] during a total follow-up time of 1713 PYFU. Twenty-three of 33 patients with data on drug-resistance (69.7%) had multidrug-resistant (MDR)-TB. More than half with recurrent TB ( n  = 30/53, 56.6%) died. Overall, 215 (57.3%) died during the follow-up period, corresponding to a mortality rate of 11.4/100 PYFU (95% CI 10.0-13.1). Almost half of those (48.8%) died of TB. The proportion of all TB-related deaths was highest in the first 6 ( n  = 49/71; 69%; P  < 0.0001) and 6-24 ( n  = 33/58; 56.9%; P  < 0.0001) months of follow-up, compared deaths beyond 24 months ( n  = 23/85; 26.7%). CONCLUSION: TB recurrence and TB-related mortality rates in PWH in Eastern Europe are still concerningly high and continue to be a clinical and public health challenge.

Possible Tacrolimus-Related Neuropsychiatric Symptoms: One Year After Allogeneic Hematopoietic Cell Transplantation: A Case Report.

Tacrolimus is a calcineurin inhibitor (CNI), an immunosuppressive agent used to prevent graft versus host disease following allogeneic hematopoietic cell transplantation (HCT). Side-effects of tacrolimus treatment include neuropsychiatric symptoms, for example, affective disturbances, psychosis, and akinetic mutism. The onset of side-effects is independent of tacrolimus blood concentration and can occur years after treatment initiation. To our knowledge, case-reports describing tacrolimus-induced neuropsychiatric symptoms following HCT are sparse. This article reports the case of a 60-year-old woman with T-cell prolymphocytic leukemia, who developed memory loss, affective disturbances, and delusions, 1-year after HCT, and tacrolimus treatmentinitiation. Upon hospital admission, she was motionless and mute, albeit easily roused. The routine physical examination was without pathological findings. Blood work and microbiological analyses of blood and cerebrospinal fluid were normal. The neuroimaging showed chronic structural changes without relation to the debut of neuropsychiatric symptoms. Tacrolimus was discontinued on suspicion of tacrolimus-induced neuropsychiatric symptoms. The patient recovered within 48 hours of discontinuation. She was switch to prednisone treatment, and there has been no reemergence of neuropsychiatric symptoms since.

The long-term effect of an exercise and diet intervention in asthma patients: a 1-year follow-up on a randomised controlled trial.

BACKGROUND: In the EFFORT (Effects of Exercise and Diet in Nonobese Asthma Patients - A Randomized Controlled Trial) study, maximum exercise capacity (V'O2 max) increased significantly within a 2-month high-intensity spinning period. Furthermore, the study concluded that only the combined exercise and diet intervention improved asthma control, significantly. This study examined whether original improvements in V'O2 max and asthma control were present 1 year after intervention completion. METHOD: In the original trial, 149 patients were randomised into four study groups. Participants were assessed with an incremental cycle ergometer test and the Asthma Control Questionnaire (ACQ). Of the 149 patients, 66 accepted the follow-up invitation. Participants were distributed in their original groups: exercise group (n=18), diet group (n=117), combined diet and exercise group (n=115) and the control group (n=110). Patients were assessed with original procedures. Though, upon measuring V'O2 max, the original four study groups were merged into one spinning group (n=127) and one nonspinning group (n=133). RESULTS: Comparing the spinning and nonspinning group, there was no significant between-group difference in V'O2 max, at 1-year follow-up (p=0.3). In addition, there was no significant between-group difference in ACQ score (p=0.6). Hence, in the combined group, the initial improvement in the ACQ score had regressed to pre-intervention values within 1 year from study completion. CONCLUSION: There were no measurable long-lasting effects on V'O2 max 1 year after the intervention was completed. Furthermore, there was no long-lasting effect of the combined intervention on asthma control.