Factors associated with loss to follow-up among TB patients in rural Papua New Guinea

BACKGROUND: Papua New Guinea (PNG) is a lower middle-income country that has struggled to contain TB. The loss of patients to follow-up is a major contributing factor towards the high disease burden.OBJECTIVE: To describe persons with drug-susceptible TB (DS-TB) registered for treatment at the Gaubin Rural Hospital (GRH) on Karkar Island, Madang Province, PNG, and to investigate factors associated with patient loss to follow-up (LTFU).DESIGN: A retrospective cohort study was conducted using data from GRH DS-TB registers. Factors associated with LTFU were investigated using univariable and multivariable logistic regression.RESULTS: A total of 722 patients were registered for DS-TB treatment and eligible for inclusion between 1 January 2014 and 30 June 2018, of whom 97 (13.4%) were lost to follow-up. Male sex was associated with an increased odds of LTFU (adjusted OR [aOR] 1.9, 95% CI 1.2–3.0; P = 0.005), as was travel time to GRH >3 h (aOR 3.7, 95%, CI 2.2–6.3; P < 0.001).CONCLUSION: A high LTFU rate has been identified in patients with TB in PNG. This study found male sex and increased travel time from treatment location to be associated with unsuccessful treatment adherence, highlighting the need for further interventions to improve adherence.

Evaluation of Biological Effect in Breast Cell Irradiated with Dose 2 Gy in Radiotherapy

Introduction: Breast cancer (BC) is the most common female malignancy worldwide. For the definitive treatment of MC, radiotherapy can be used, as an important component, and uses ionizing radiation (IR). Studies reveal the potential capacity of IR to promote metastasis. The clinical response of BC to radiotherapy is related to radiosensitivity and resistance of irradiated cells, which is associated with clonogenic activity and sensitivity to radiation. Unsuccessful treatment increases the risk of local and distant recurrence.Methodology: Three breast cell lines (MCF-10A, MCF-7, and MDA-MB-231) were irradiated with 2 Gy and after 72 hours following markers were evaluated: E-cadherin, fibronectin, vimentin, and Snail. The processes of invasion, degradation of MMP2 and MMP9, and transendothelial migration were then assessed. Double-strand DNA breaks (DSBs), apoptosis, and colony formation were quantified. Result: The detection of γH2AX histone of irradiated cells showed that MCF-10A non-tumor cell is more radiosensitive while the MDA-MB-231 tumor cell is more radioresistant. The dose 2 Gy altered the formation of colonies to any of the cell lines. Tumorigenic cells exhibited a markedly increase in apoptosis, 24 h after irradiation while MCF-10A cells only after 72 h. A single dose of 2 Gy does not induce changes in the cellular microenvironment that lead to changes in the mesenchymal epithelium in breast BC.Conclusion: A dose of 2 Gy induces apoptosis and consequently an alteration in cell survival. However, a single dose of 2 Gy does not induce changes in the cellular microenvironment that lead to changes in the mesenchymal epithelium.

Impact of socio-economic factors on Tuberculosis treatment outcomes in north-eastern Uganda: a mixed methods study

Background Tuberculosis (TB) is a major public health problem and at 48%, Karamoja in North-Eastern Uganda has the lowest treatment success rate nationally. Addressing the social determinants of TB is crucial to ending TB. This study sought to understand the extent and ways in which socio-economic factors affect TB treatment outcomes in Karamoja. Methods We conducted a convergent parallel mixed methods study in 10 TB Diagnostic and Treatment Units. The study enrolled former TB patients diagnosed with drug-susceptible TB between April 2018 and March 2019. Unit TB and laboratory registers were reviewed to identify pre-treatment losses to follow-up. Four focus group discussions with former TB patients and 18 key informant interviews with healthcare workers were conducted. Principle component analysis was used to generate wealth quintiles that were compared to treatment outcomes using the proportion test. The association between sociodemographic characteristics and TB treatment outcomes was evaluated using the chi-square test and multiple logistic regression. Results A total of 313 participants were randomly selected from 1184 former TB patients recorded in the unit TB registers. Of these, 264 were contacted in the community and consented to join the study: 57% were male and 156 (59.1%) participants had unsuccessful treatment outcomes. The wealthiest quintile had a 58% reduction in the risk of having an unsuccessful treatment outcome (adj OR = 0.42, 95% CI 0.18–0.99, p = 0.047). People who were employed in the informal sector (adj OR = 4.71, 95% CI 1.18–18.89, p = 0.029) and children under the age of 15 years who were not in school or employed (adj OR = 2.71, 95% CI 1.11–6.62, p = 0.029) had significantly higher odds of unsuccessful treatment outcome. Analysis of the pre-treatment loss to follow-up showed that 17.2% of patients with pulmonary bacteriologically confirmed TB did not initiate treatment with a higher proportion among females (21.7%) than males (13.5%). Inadequate food, belonging to migratory communities, stigma, lack of social protection, drug stock-outs and transport challenges affected TB treatment outcomes. Conclusions This study confirmed that low socio-economic status is associated with poor TB treatment outcomes emphasizing the need for multi- and cross-sectoral approaches and socio-economic enablers to optimise TB care.

Achieving a “step change” in the tuberculosis epidemic through comprehensive community-wide intervention: a model-based analysis

Background Global progress towards reducing tuberculosis (TB) incidence and mortality has consistently lagged behind the World Health Organization targets leading to a perception that large reductions in TB burden cannot be achieved. However, several recent and historical trials suggest that intervention efforts that are comprehensive and intensive can have a substantial epidemiological impact. We aimed to quantify the potential epidemiological impact of an intensive but realistic, community-wide campaign utilizing existing tools and designed to achieve a “step change” in the TB burden. Methods We developed a compartmental model that resembled TB transmission and epidemiology of a mid-sized city in India, the country with the greatest absolute TB burden worldwide. We modeled the impact of a one-time, community-wide screening campaign, with treatment for TB disease and preventive therapy for latent TB infection (LTBI). This one-time intervention was followed by the strengthening of the tuberculosis-related health system, potentially facilitated by leveraging the one-time campaign. We estimated the tuberculosis cases and deaths that could be averted over 10 years using this comprehensive approach and assessed the contributions of individual components of the intervention. Results A campaign that successfully screened 70% of the adult population for active and latent tuberculosis and subsequently reduced diagnostic and treatment delays and unsuccessful treatment outcomes by 50% was projected to avert 7800 (95% range 5450–10,200) cases and 1710 (1290–2180) tuberculosis-related deaths per 1 million population over 10 years. Of the total averted deaths, 33.5% (28.2–38.3) were attributable to the inclusion of preventive therapy and 52.9% (48.4–56.9) to health system strengthening. Conclusions A one-time, community-wide mass campaign, comprehensively designed to detect, treat, and prevent tuberculosis with currently existing tools can have a meaningful and long-lasting epidemiological impact. Successful treatment of LTBI is critical to achieving this result. Health system strengthening is essential to any effort to transform the TB response.

Tuberculosis Treatment Outcome and Predictors in Africa: A Systematic Review and Meta-Analysis

This review aimed to summarize and estimate the TB treatment success rate and factors associated with unsuccessful TB treatment outcomes in Africa. Potentially eligible primary studies were retrieved from PubMed and Google Scholar. The risk of bias and quality of studies was assessed using The Joanna Briggs Institute’s (JBI) appraisal criteria, while heterogeneity across studies was assessed using Cochran’s Q test and I2 statistic. Publication bias was checked using the funnel plot and egger’s test. The protocol was registered in PROSPERO, numbered CRD42019136986. A total of 26 eligible studies were considered. The overall pooled estimate of TB treatment success rate was found to be 79.0% (95% CI: 76–82%), ranging from 53% (95% CI: 47–58%) in Nigeria to 92% (95% CI: 90–93%) in Ethiopia. The majority of unsuccessful outcomes were attributed to 48% (95% CI: 40–57%) death and 47% (95% CI: 39–55%) of defaulter rate. HIV co-infection and retreatment were significantly associated with an increased risk of unsuccessful treatment outcomes compared to HIV negative and newly diagnosed TB patients with RR of 1.53 (95% CI: 1.36–1.71) and 1.48 (95% CI: 1.14–1.94) respectively. TB treatment success rate was 79% below the WHO defined threshold of 85% with significant variation across countries. Countries need to explore contextual underlining factors and more effort is required in providing TB preventive treatment, improve case screening and linkage for TB treatment among HIV high-risk groups and use confirmatory TB diagnostic modality. Countries in Africa need to strengthen counseling and follow-up, socio-economic support for patients at high risk of loss to follow-up and poor treatment success is also crucial for successful TB control programs.

Exploring the Role of Alcohol Metabolizing Genotypes in a 12-Week Clinical Trial of Naltrexone for Alcohol Use Disorder

Background: The efficacy of naltrexone in the treatment of alcohol use disorder (AUD) has been associated with a set of variables not directly related with the expression of opioid receptors. All the variables have been found to be highly associated with AUD itself or more severe clinical levels of AUD. Objectives: Given the high association between alcohol metabolizing enzymes (AME) and the outcome of AUD, the present study aims to investigate the role of AME genotype variants in the treatment of AUD with naltrexone. Methods: We carried out a 12-week longitudinal clinical trial based on the treatment of AUD patients with naltrexone (N = 101), stratified by different alcohol metabolization genotypes. Genotyping was performed after the inclusion of the patients in the study, based on the individual presence of single nucleotide polymorphisms (SNPs) in the ADH (alcohol dehydrogenase)1B (ADH1B*2 and ADH1B*3), ADH1C (ADHC*1) and ALDH (aldehyde dehydrogenase) 2 (ALDH2*2) genes. The outcome of alcohol use has been monitored employing the timeline follow-back during the treatment. Results: The ADH1C*1 (Ile350Val, rs698) and ALDH2*2 (Glu504Lys, rs671) polymorphisms were associated with a better response to naltrexone treatment, whereas the ADH1B*3 (Arg370Cys, rs2066702) allelic variant showed a negative outcome. Conclusions: The present study explores a genomic setting for the treatment of AUD with naltrexone. According to our findings, the association between ADH1C*1 and ALDH2*2 variants and better outcomes suggests a successful treatment, whereas the ADH1B*3 mutated allele might lead to an unsuccessful treatment. Further studies should be performed to investigate the relationship between alcohol metabolizing genotypes, the family history of alcohol use disorders and the effect of naltrexone on the outcomes. Genotyping may be a valuable tool for precision-medicine and individualized approach, especially in the context of alcohol use disorders. The small number of subjects was the main limitation of the present study.

The Use of Hydroxyurea in the Treatment of COVID-19

Introduction The rapid worldwide spread of COVID-19 motivated medical professionals to pursue and authenticate appropriate remedies and treatment protocols. This article aims to analyze the potential benefits of one treatment protocol developed by a group of care providers caring for severe COVID-19 patients. Methods The clinical findings of COVID-19 patients who were transferred to a specialized care hospital after unsuccessful treatment in previous institutions, were analyzed. The specialized care hospital used a treatment protocol including hydroxyurea, a medication commonly used for sickle cell treatment, to improve respiratory distress in the COVID-19 patients. None of the COVID-19 patients included in the analyzed data were diagnosed with sickle cell, and none had previously taken hydroxyurea for any other conditions. Results In all presented cases, patients reverted to their baseline respiratory health after treatment with the hydroxyurea protocol. There was no significant difference in the correlation between COVID-19 and hydroxyurea. However, deaths were extremely low for those taking hydroxyurea. Conclusions Fatality numbers were extremely low for those taking hydroxyurea; death could be attributed to other underlying issues.

Sequential Blood Purification for Pediatric Fatal Toxic Epidermal Necrolysis: A Case Series

<b><i>Background:</i></b> Extracorporeal therapy that included therapeutic plasma exchange (TPE) or continuous hemofiltration (CHF) for toxic epidermal necrolysis (TEN) syndrome was used in small number of patients. We aimed to describe the sequential mode of combined application of CHF and TPE in 3 TEN patients with multiple organ dysfunction (MODS) in pediatric intensive care unit. <b><i>Methods:</i></b> Three patients with fatal TEN received sequential CHF and TPE due to unsatisfactorily conventional treatments. CHF was initiated and performed on a daily basis with 35–50 mL/kg.h replacement fluid at the rate of 3–5 mL/kg.min blood flow. CHF was temporarily interrupted for TPE, which was performed with exchange 1–1.5-fold of one body calculated plasma volume in each section. <b><i>Results:</i></b> All 3 fatal TEN (with &#x3e;30% involvement of body surface and MODS) following unsuccessful treatment with corticosteroids and intravenous immunoglobulin. Antibiotics were suspected in the TEN-triggered drugs. The range number of TPE sessions was 3–5 and the duration of CHF was from 120 h to 202 h. After initiation of TPE and CHF, blistering with extensive epidermal necrosis halted and the skin re-epithelialized within 2 weeks. Serum C-reactive protein, procalcitonin, tumor necrosis factor-α , and interlukin-6 decreased and percentage of natural killer cells increased in surviving children. Two patients survived to discharge and one case died due to nosocomial infection with multidrug-resistant <i>Acinetobacter baumannii.</i> <b><i>Conclusion:</i></b> After sequential TPE and CHF, skin lesions and inflammatory response improved in TEN. Our result indicates extracorporeal therapy could be used as an alternative modality for fatal pediatric TEN.

Lived experience perspectives on labeling and defining long-standing anorexia nervosa

Objective Since efforts to stage anorexia nervosa (AN) revealed the existence of various presentations, research into the long-standing subgroup has increased. A change in treatment has been proposed with the intention to use more effective evidence-based methods that target symptoms of the long-standing presentation and improve prognosis. A barrier in achieving this goal in both research and clinical contexts is the lack of a consistent label and definition. This makes the ability to assess, recruit and treat these presentations difficult. Investigations into how this subgroup may be differentiated from other stages of the disorder have included the opinions of practitioners and researchers with little consideration for the perspectives of individuals living with this illness. It was the aim of the current study to investigate lived experience perspectives on the way long-standing AN should be labeled and defined. Methods Data were collected through a semi-structured interview within a narrative inquiry framework. This approach is beneficial when examining processes that occur over time, such as investigations into a long-term illness. A total of 11 women with a presentation of long-standing AN participated in an interview. Data were divided into two categories for analysis based on the association to labeling or defining the features of the long-standing AN illness. Results Two labels emerged during the analysis with participants describing a preference for the use of ‘severe and enduring’ over ‘chronic’ when referring to their presentation of AN. When defining the illness, the most preferred criterion was illness duration with mixed perspectives for the use of previously failed treatment attempts. Participants described a consistent dislike for the use of low body weight as a feature in the defining of the illness. Conclusions The current study describes how individuals with a lived experience prefer to have the long-standing AN presentation labeled and defined. It is the hope of the authors that these insights will be adopted into any guidelines developed to ensure individuals most affected by this disorder have a voice and continue to be given the opportunity to contribute to topics related to their illness. Plain English summary Anorexia nervosa (AN) is a complex illness that has been divided into stages based on the severity of symptoms. Little is known about the AN stage that persists over lengthy periods of time with research pursuits underway to determine characteristics that allow this disorder to persevere. A barrier in researching and treating these individuals is the lack of a consistent label to refer to these presentations and criteria that will allow us to identify this stage of AN. The aim of the current study was to determine how individuals with a lived experience of long-standing AN prefer to have their illness labeled and defined. A total of 11 women who had experienced this stage of AN were interviewed with the majority of participants reporting to prefer the label ‘severe and enduring’ over the term ‘chronic’. Additionally, most of the participants had a preference for defining their illness based on the duration of time the illness had persisted with mixed opinions for using the number of previously unsuccessful treatment attempts as criterion. The authors are hopeful that any guidelines established for labeling and defining long-standing AN will incorporate the perspectives of individuals with a lived experience of the illness.