Availability, cost and affordability of essential medicines for chronic respiratory diseases in low-income and middle-income countries: a cross-sectional study.

Contemporary data on the availability, cost and affordability of essential medicines for chronic respiratory diseases (CRDs) across low-income and middle-income countries (LMICs) are missing, despite most people with CRDs living in LMICs. Cross-sectional data for seven CRD medicines in pharmacies, healthcare facilities and central medicine stores were collected from 60 LMICs in 2022-2023. Medicines for symptomatic relief were widely available and affordable, while preventative treatments varied widely in cost, were less available and largely unaffordable. There is an urgent need to address these issues if the Sustainable Development Goal 3 is to be achieved for people with asthma by 2030.

Severe Falciparum and Vivax Malaria on the Thailand-Myanmar Border: A Review of 1503 Cases.

BACKGROUND: The northwestern border of Thailand is an area of low seasonal malaria transmission. Until recent successful malaria elimination activities, malaria was a major cause of disease and death. Historically the incidences of symptomatic Plasmodium falciparum and Plasmodium vivax malaria were approximately similar. METHODS: All malaria cases managed in the Shoklo Malaria Research Unit along the Thailand-Myanmar border between 2000 and 2016 were reviewed. RESULTS: There were 80 841 consultations for symptomatic P. vivax and 94 467 for symptomatic P. falciparum malaria. Overall, 4844 (5.1%) patients with P. falciparum malaria were admitted to field hospitals, of whom 66 died, compared with 278 (0.34%) with P. vivax malaria, of whom 4 died (3 had diagnoses of sepsis, so the contribution of malaria to their fatal outcomes is uncertain). Applying the 2015 World Health Organization severe malaria criteria, 68 of 80 841 P. vivax admissions (0.08%) and 1482 of 94 467 P. falciparum admissions (1.6%) were classified as severe. Overall, patients with P. falciparum malaria were 15 (95% confidence interval, 13.2-16.8) times more likely than those with P. vivax malaria to require hospital admission, 19 (14.6-23.8) times more likely to develop severe malaria, and ≥14 (5.1-38.7) times more likely to die. CONCLUSIONS: In this area, both P. falciparum and P. vivax infections were important causes of hospitalization, but life-threatening P. vivax illness was rare.

"Asthma is a very bully disease" - patient experiences of living with chronic respiratory diseases in Cape Town, South Africa.

BACKGROUND: Chronic respiratory diseases are common in Cape Town, South Africa. Yet the experiences of how adults with these conditions, such as asthma or COPD (chronic obstructive pulmonary disease), negotiate the health system are poorly understood. Qualitative methodology lends itself to investigate this question. AIM OF STUDY: To explore the "emic" experiences of adults with CRDs in Cape Town when they were negotiating the health system using semi-structured interviews. METHODS: Interviews were conducted following informed consent with purposively sampled adults who had attended public hospitals in Cape Town with chronic respiratory disease flare-ups. This work was nested in the quantitative "Diagnosing Airways Disease" study. The topic guide explored patients' experiences of accessing healthcare including receiving and interpretations of the diagnosis and management, and impacts on daily life. Interviews were conducted in Afrikaans, isiXhosa, or English; transcribed, and translated into English and thematically analysed until saturation. RESULTS: Thirty-two interviews (16 in Afrikaans, 8 in isiXhosa, 8 in English) were completed in 2022. 17 women and 15 men participated. Most participants were older than 50 years (25/32), and most were unemployed (13/32) or retired (11/32). The identified themes were: Perceived causes of illness; experiences of healthcare; perceived risks and barriers when accessing healthcare; and impact on earnings. The perceived causes of their illness and risks were structural, and included air pollution, poor quality housing, occupational exposures, limited healthcare services, and fear of violence. These factors led to self-treatment, sharing of medicines, and delay in receiving a diagnosis. Many paid privately for treatments or services to overcome identified shortcomings of the public healthcare system, and many reported additional significant indirect costs. Being ill had a profound impact on income. The identified themes were explored through the lens of "structural violence", where "social structures stop individuals … from reaching their full potential" (Galtung, 1969). CONCLUSION: In Cape Town structural elements such as stretched healthcare professionals, insufficiently enforced policies on e.g., housing or work-place exposures, poverty and crime made it difficult for participants to successfully navigate their illness experience. It forced some to pay out of pocket to receive perceived better healthcare privately.

Does antibiotic treatment duration affect the outcomes of exacerbations of asthma and COPD? A systematic review.

Asthma and chronic obstructive pulmonary disease (COPD) cause significant morbidity and mortality worldwide, primarily through exacerbations. Exacerbations are often treated with antibiotics but their optimal course duration is uncertain. Reducing antibiotic duration may influence antimicrobial resistance but risks treatment failure. The objective of this article is to review published literature to investigate whether shorter antibiotic therapy duration affects clinical outcomes in the treatment of asthma and COPD exacerbations. We systematically searched electronic databases (MEDLINE, EMBASE, CINAHL, World Health Organisation International Clinical Trial Registry Platform, the Cochrane library, and ISRCTN) with no language, location, or time restrictions. We retrieved observational and controlled trials comparing different durations of the same oral antibiotic therapy in the treatment of acute exacerbations of asthma or COPD in adults. We found no applicable studies for asthma exacerbations. We included 10 randomized, placebo-controlled trials for COPD patients, all from high-income countries. The commonest studied antibiotic class was fluoroquinolones. Antibiotic courses shorter than 6 days were associated with significantly fewer overall adverse events (risk ratio (RR): 0.84, 95% confidence interval (CI): 0.75-0.93, p = 0.001) when compared with those of 7 or more days. There was no statistically significant difference for clinical success or bacteriological eradication in sputum (RR: 1.00, 95% CI: 0.88-1.13 and RR: 1.06, 95% CI: 0.79-1.44, respectively). Shorter durations of antibiotics for COPD exacerbations do not seem to confer a higher risk of treatment failure but are associated with fewer adverse events. This is in keeping with previous studies in community acquired pneumonia, but studies were heterogeneous and differed from usual clinical practice. Further observational and prospective work is needed to explore the significance of antibiotic duration in the treatment of asthma and COPD exacerbations.

The availability, cost, and affordability of essential medicines for asthma and COPD in low-income and middle-income countries: a systematic review.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) cause a considerable burden of morbidity and mortality in low-income and middle-income countries (LMICs). Access to safe, effective, quality-assured, and affordable essential medicines is variable. We aimed to review the existing literature relating to the availability, cost, and affordability of WHO's essential medicines for asthma and COPD in LMICs. METHODS: A systematic review of the literature was done by searching seven databases to identify research articles published between Jan 1, 2010, and June 30, 2022. Studies on named essential medicines for asthma and COPD in LMICs were included and review articles were excluded. Two authors (MS and HT) screened and extracted data independently, and assessed bias using Joanna Briggs Institute appraisal tools. The main outcome measures were availability (WHO target of 80%), cost (compared with median price ratio [MPR]), and affordability (number of days of work of the lowest paid government worker). The study was registered with PROSPERO, CRD42021281069. FINDINGS: Of 4742 studies identified, 29 met the inclusion criteria providing data from 60 LMICs. All studies had a low risk of bias. Six of 58 countries met the 80% availability target for short-acting beta-agonists (SABAs), three of 48 countries for inhaled corticosteroids (ICSs), and zero of four for inhaled corticosteroid-long-acting beta-agonist (ICS-LABA) combination inhalers. Costs were reported by 12 studies: the range of MPRs was 1·1-351 for SABAs, 2·6-340 for ICSs, and 24 for ICS-LABAs in the single study reporting this. Affordability was calculated in ten studies: SABA inhalers typically cost around 1-4 days' wages, ICSs 2-7 days, and ICS-LABAs at least 6 days. The included studies showed heterogeneity. INTERPRETATION: Essential medicines for treating asthma and COPD were largely unavailable and unaffordable in LMICs. This was particularly true for inhalers containing corticosteroids. FUNDING: WHO and Wellcome Trust.

Diagnostic accuracy of combined thoracic and cardiac sonography for the diagnosis of pulmonary embolism: A systematic review and meta-analysis.

OBJECTIVES: Computed tomography pulmonary angiography (CTPA) is the diagnostic standard for pulmonary embolism (PE), but is unavailable in many low resource settings. We evaluated the evidence for point of care ultrasound as an alternative diagnostic. METHODS: Using a PROSPERO-registered, protocol-driven strategy (https://www.crd.york.ac.uk/PROSPERO, ID = CRD42018099925), we searched MEDLINE, EMBASE, and CINHAL for observational and clinical trials of cardiopulmonary ultrasound (CPUS) for PE. We included English-language studies of adult patients with acute breathlessness, reported according to PRISMA guidelines published in the last two decades (January 2000 to February 2020). The primary outcome was diagnostic accuracy of CPUS compared to reference standard CTPA for detection of PE in acutely breathless adults. RESULTS: We identified 260 unique publications of which twelve met all inclusion criteria. Of these, seven studies (N = 3872) were suitable for inclusion in our meta-analysis for diagnostic accuracy (two using CTPA and five using clinically derived diagnosis criterion). Meta-analysis of data demonstrated that using cardiopulmonary ultrasound (CPUS) was 91% sensitive and 81% specific for pulmonary embolism diagnosis compared to diagnostic standard CTPA. When compared to clinically derived diagnosis criterion, CPUS was 52% sensitive and 92% specific for PE diagnosis. We observed substantial heterogeneity across studies meeting inclusion criteria (I2 = 73.5%). CONCLUSIONS: Cardiopulmonary ultrasound may be useful in areas where CTPA is unavailable or unsuitable. Interpretation is limited by study heterogeneity. Further methodologically rigorous studies comparing CPUS and CTPA are important to inform clinical practice.

Screening Heroin Smokers Attending Community Drug Clinics for Change in Lung Function: A Cohort Study.

BACKGROUND: Heroin smokers have high rates of COPD, respiratory morbidity, hospital admission, and mortality. We assessed the natural history of symptoms and lung function in this population over time. METHODS: A cohort of heroin smokers with COPD was followed for 18 to 24 months. At baseline and follow-up, respiratory symptoms were measured by the Medical Research Council Dyspnea Scale (MRC) and the COPD Assessment Tool (CAT), and postbronchodilator spirometry was performed. Frequency of health-care-seeking episodes was extracted from routine health records. Parametric, nonparametric, and linear regression models were used to analyze the change in symptoms and lung function over time. RESULTS: Of 372 participants originally recruited, 161 were assessed at follow-up (mean age, 51.0 ± 5.3 years; 74 women [46%]) and 106 participants completed postbronchodilator spirometry. All participants were current or previous heroin smokers, and 122 (75.8%) had smoked crack. Symptoms increased over time (MRC score increased by 0.48 points per year, P < .001; CAT score increased by 1.60 points per year, P < .001). FEV1 declined annually by 90 ± 190 mL (P < .001). This deterioration was not associated with change in tobacco or heroin smoking status or use of inhaled medications. CONCLUSIONS: Heroin smokers experience a high and increasing burden of chronic respiratory symptoms and a decline in FEV1 that exceeds the normal age-related decline observed among tobacco smokers with COPD and healthy nonsmokers. Targeted COPD diagnostic and treatment services hosted within opiate substitution services could benefit this vulnerable, relatively inaccessible, and underserved group of people.

Antibiotics for COPD exacerbations: does drug or duration matter? A primary care database analysis.

Introduction: Antibiotics are routinely given to people with chronic obstructive pulmonary disease (COPD) presenting with lower respiratory tract infection (LRTI) symptoms in primary care. Population prescribing habits and their consequences have not been well-described. Methods: We conducted a retrospective analysis of antibiotic prescriptions for non-pneumonic exacerbations of COPD from 2010 to 2015 using the UK primary care Optimum Patient Care Research Database. As a proxy of initial treatment failure, second antibiotic prescriptions for LRTI or all indications within 14 days were the primary and secondary outcomes, respectively. We derived a model for repeat courses using univariable and multivariable logistic regression analysis. Results: A total of 8.4% of the 9042 incident events received further antibiotics for LRTI, 15.5% further courses for any indication. Amoxicillin and doxycycline were the most common index and second-line drugs, respectively (58.7% and 28.7%), mostly given for 7 days. Index drugs other than amoxicillin, cardiovascular disease, pneumococcal vaccination and more primary care consultations were statistically significantly associated with repeat prescriptions for LRTI (p<0.05). The ORs and 95% CIs were: OR 1.28, 95% CI 1.10 to 1.49; OR 1.37, 95% CI 1.13 to 1.66; OR 1.33, 95% CI 1.14 to 1.55 and OR 1.05, 95% CI 1.02 to 1.07, respectively. Index duration, inhaled steroid use and exacerbation frequency were not statistically significant. The derived model had an area under the curve of 0.61, 95% CI 0.59 to 0.63. Discussion: The prescription of multiple antibiotic courses for COPD exacerbations was relatively common-one in twelve patients receiving antibiotics for LRTI had a further course within 2 weeks. The findings support the current preference for amoxicillin as index drug within the limitations of this observational study. Further clinical trials to determine best practice in this common clinical situation appear required.

Antibiotic Choice and Duration Associate with Repeat Prescriptions in Infective Asthma Exacerbations.

BACKGROUND: Patients with asthma who present with lower respiratory tract infections (LRTIs) often receive antibiotics. There is uncertainty about the need for and consequences of antibiotic administration. OBJECTIVE: To describe the demographic characteristics of and antibiotic prescriptions for adult patients with asthma with LRTI and investigate factors associated with repeat antibiotic courses. METHODS: We analyzed prescriptions of antibiotics for LRTIs in UK primary care from 2010 to 2015 using the Optimum Care Database. The primary outcome was a second antibiotic prescription for an LRTI code within 14 days of index prescription, as a proxy of initial treatment failure. A model for repeat prescriptions was derived using univariable and multivariable logistic regression analyses. RESULTS: We assessed 28,289 cases with complete data sets, 6.5% of which received a second antibiotic course. Amoxicillin and clarithromycin respectively were used most commonly as index and second agents. The most frequent course length was 7 days for both index and repeat prescriptions. Multivariable analysis demonstrated that age, index antibiotic and duration, smoking status, location, and number of consultations and oral steroid courses in the previous year were significantly associated with repeat prescriptions. The derived model predicted the binary outcome adequately (Cox-Snell R2, 0.012; area under curve, 0.62; 95% CI, 0.61-0.63). Comorbidities, vaccinations, asthma treatment, and number of exacerbations were significant only in the univariable analysis. CONCLUSIONS: The current index prescribing preference of 7 days of amoxicillin correlated to fewer repeat courses. Baseline asthma treatment was not associated with risk of further prescriptions. Antibiotic administration in older patients with a smoking history could be a target for future studies.

The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas.

CONTEXT: Mutations have been identified in the aryl hydrocarbon receptor-interacting protein (AIP) gene in familial isolated pituitary adenomas (FIPA). It is not clear, however, how this molecular chaperone is involved in tumorigenesis. OBJECTIVE: AIP sequence changes and expression were studied in FIPA and sporadic adenomas. The function of normal and mutated AIP molecules was studied on cell proliferation and protein-protein interaction. Cellular and ultrastructural AIP localization was determined in pituitary cells. PATIENTS: Twenty-six FIPA kindreds and 85 sporadic pituitary adenoma patients were included in the study. RESULTS: Nine families harbored AIP mutations. Overexpression of wild-type AIP in TIG3 and HEK293 human fibroblast and GH3 pituitary cell lines dramatically reduced cell proliferation, whereas mutant AIP lost this ability. All the mutations led to a disruption of the protein-protein interaction between AIP and phosphodiesterase-4A5. In normal pituitary, AIP colocalizes exclusively with GH and prolactin, and it is found in association with the secretory vesicle, as shown by double-immunofluorescence and electron microscopy staining. In sporadic pituitary adenomas, however, AIP is expressed in all tumor types. In addition, whereas AIP is expressed in the secretory vesicle in GH-secreting tumors, similar to normal GH-secreting cells, in lactotroph, corticotroph, and nonfunctioning adenomas, it is localized to the cytoplasm and not in the secretory vesicles. CONCLUSIONS: Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis.

Amoxicillin is associated with a lower risk of further antibiotic prescriptions for lower respiratory tract infections in primary care - A database analysis spanning over 30 years.

Antibiotic prescriptions for lower respiratory tract infections occur commonly in primary care but there is uncertainty about the most effective initial treatment strategy. Both increasing antimicrobial resistance and awareness of preventable harm from medicines make resolving this uncertainty a priority. Pragmatic, real-life epidemiological investigations are needed to inform future interventional studies. In this cross-sectional database study we analysed antibiotic prescriptions for non-pneumonic, lower respiratory tract infections (LRTI) in primary care as captured in the Optimum Care Database from 1984 to 2017. The primary outcome was a second antibiotic prescription for a LRTI code within 14 days of index prescription, the secondary outcome further antibiotic prescription for any indication. Only individuals without chronic respiratory diseases were included. We conducted univariable analysis to identify factors associated with repeat prescriptions and generate hypotheses for forthcoming projects. We analysed 367,188 index prescriptions for LRTI. Amoxicillin was the commonest used index drug (65.1%). In 6% a second antibiotic course coded for a further LRTI was prescribed (11.2% without this coding restriction). Further antibiotic prescriptions for LRTI were significantly associated with older age, previous smoking, seven day index courses and not using amoxicillin initially. The largest effect size was seen when amoxicillin was not used as index drug (odds ratio (OR) 1.15, p < 0.001). This would support current prescribing practice for amoxicillin as index drug in those without respiratory disease. Prospective studies are needed to explore the observed differences.

The Early Recognition and Management of Sepsis in Sub-Saharan African Adults: A Systematic Review and Meta-Analysis.

Sepsis is a common cause of morbidity and mortality in sub-Saharan African adults. Standardised management pathways have been documented to improve the survival of adults with sepsis from high-resource settings. Our aim was to assess the current evidence base for early sepsis interventions (recognition, empirical antibiotics, and resuscitation) in resource-poor settings of sub-Saharan Africa. We searched MEDLINE, EMBASE and CINHAL Plus databases to identify interventional studies for the early recognition and management of sepsis in sub-Saharan Africa (1 January 2000 to 1 August 2018) using a protocol-driven search strategy: adults, protocolised care pathway, and sub-Saharan Africa. We identified 725 publications of which three met criteria for final selection. Meta-analysis from two randomised controlled trials demonstrated that mortality was increased by 'early goal-directed therapy' interventions that increased fluid resuscitation (R.R. 1.26, 95% C.I. 1.00⁻1.58, p = 0.045; I² 53%). The third observational cohort study demonstrated improved survival after implementation of protocolised management for sepsis (mortality 33.0% vs. 45.7%, p = 0.005). No study incorporated standardised protocols for empirical antibiotic administration. High rates of pneumonia and mycobacteraemia were reported. There has been little research into the early recognition and management of sepsis in sub-Saharan Africa. Interventional trials of early goal-directed therapy have, to date, increased mortality. There is an urgent need to develop effective strategies to improve outcomes for adults with sepsis in sub-Saharan Africa.

Predictors of repeated acute hospital attendance for asthma in children: A systematic review and meta-analysis.

BACKGROUND: Asthma attacks are common and have significant physical, psychological, and financial consequences. Improving the assessment of a child's risk of subsequent asthma attacks could support front-line clinicians' decisions on augmenting chronic treatment or specialist referral. We aimed to identify predictors for emergency department (ED) or hospital readmission for asthma from the published literature. METHODS: We searched MEDLINE, EMBASE, AMED, PsycINFO, and CINAHL with no language, location, or time restrictions. We retrieved observational studies and randomized controlled trials (RCT) assessing factors (personal and family history, and biomarkers) associated with the risk of ED re-attendance or hospital readmission for acute childhood asthma. RESULTS: Three RCTs and 33 observational studies were included, 31 from Anglophone countries and none from Asia or Africa. There was an unclear or high risk of bias in 14 of the studies, including 2 of the RCTs. Previous history of emergency or hospital admissions for asthma, younger age, African-American ethnicity, and low socioeconomic status increased risk of subsequent ED and hospital readmissions for acute asthma. Female sex and concomitant allergic diseases also predicted hospital readmission. CONCLUSION: Despite the global importance of this issue, there are relatively few high quality studies or studies from outside North America. Factors other than symptoms are associated with the risk of emergency re-attendance for acute asthma among children. Further research is required to better quantify the risk of future attacks and to assess the role of commonly used biomarkers.

Health Risks Associated with Occupational Exposure to Ambient Air Pollution in Commercial Drivers: A Systematic Review.

Ambient air pollution is a major global health problem and commercial drivers are particularly exposed to it. As no systematic assessment of the health risks associated with occupational exposure to ambient air pollution in this population had yet been carried out, we conducted a systematic review using a protocol-driven strategy. Papers published from inception to April 20, 2018 in MEDLINE, EMBASE, CINAHL, African journals online, the Cochrane library, ISRCTN WHO ICTRP, and the Web of Science and Scopus databases were screened for inclusion by two independent reviewers. Original articles with at least an available abstract in English or French were included. The initial search retrieved 1454 published articles of which 20 articles were included. Three studies reported a significant difference in white blood cells (106/L) among commercial motorcyclists compared to rural inhabitants (5.041 ± 1.209 vs. 5.900 ± 1.213, p = 0.001), an increased risk of lung cancer (RR = 1.6, 95%CI 1.5⁻1.8) in bus drivers and an increased standardized mortality ratio (SMR) in bus drivers from Hodgkin's lymphoma (SMR 2.17, 95%CI 1.19⁻3.87) compared to white-collar workers. Other studies also found that drivers had more oxidative DNA damage and chromosome breaks. Four papers failed to demonstrate that the drivers were more exposed to air pollution than the controls. Three other studies also reported no significant difference in lung function parameters and respiratory symptoms. The genetic polymorphisms of detoxifying enzymes were also not homogeneously distributed compared to the controls. There is some evidence that occupational exposure to ambient air pollution among commercial drivers is associated with adverse health outcomes, but the existing literature is limited, with few studies on small sample size, methodological weaknesses, and contradictory findings-thus, further research is recommended.

A tool to improve competence in the management of emergency patients by rural clinic health workers: a pilot assessment on the Thai-Myanmar border.

BACKGROUND: Shoklo Malaria Research Unit has been providing health care in remote clinics on the Thai-Myanmar border to refugee and migrant populations since 1986 and 1995, respectively. Clinics are staffed by local health workers with a variety of training and experience. The need for a tool to improve the competence of local health workers in basic emergency assessment and management was recognised by medical faculty after observing the case mix seen at the clinic and reviewing the teaching programme that had been delivered in the past year (Jan-13 to March-14). AIMS: To pilot the development and evaluation of a simple teaching tool to improve competence in the assessment and management of acutely unwell patients by local health workers that can be delivered onsite with minimal resources. METHODS: A structured approach to common emergencies presenting to rural clinics and utilizing equipment available in the clinics was developed. A prospective repeated-measures observed structured clinical examination (OSCE) assessment design was used to score participants in their competence to assess and manage a scenario based 'emergency patient' at baseline, immediately post-course, and 8 weeks after the delivery of the teaching course. The assessment was conducted at 3 clinic sites and staff participation was voluntary. Participants filled out questionnaires on their confidence with different scenario based emergency patients. RESULTS: All staff who underwent the baseline assessment failed to carry out the essential steps in initial emergency assessment and management of an unconscious patient scenario. Following delivery of the teaching session, all groups showed improved competence in both objective assessment and subjective confidence levels. CONCLUSIONS: Structured and practical teaching and learning with minimal theory in this resource limited setting had a positive short-term effect on the competence of individual staff to carry out an initial assessment and manage an acutely unwell patient. Health-worker confidence likewise improved. Workplace assessments are needed to determine if this type of skills training impacts upon mortality or near miss mortality patients at the clinic.