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.

Is Inhaler Technique Adequately Assessed and Reported in Clinical Trials of Asthma and Chronic Obstructive Pulmonary Disease Therapy? A Systematic Review and Suggested Best Practice Checklist.

BACKGROUND: Inhaled medications are central to treating asthma and chronic obstructive pulmonary disease (COPD), yet critical inhaler technique errors are made by up to 90% of patients. In the clinical research setting, recruitment of subjects with poor inhaler technique may give a false impression of both the benefits and the necessity of add-on treatments such as biologic therapies. OBJECTIVE: To assess the frequency with which inhaler technique is assessed and reliably optimized before and during patient enrollment into randomized controlled trials (RCTs) addressing the efficacy of topical therapy, and the escalation of therapy for asthma and COPD. METHODS: Systematic searches were conducted of PubMed and Embase for RCTs published in the past 10 years involving patients with a diagnosis of asthma or COPD undergoing escalation of baseline inhaled therapy (stepping up, changing, adding, switching, increasing, etc) or the introduction of biologic agents. RESULTS: Searches highlighted 1,014 studies, 118 of which were eligible after the removal of duplicates as well as screening and full text review. Of these, only 14 (11.9%) included accessible information in the methods section or referred to such information in online supplements or protocols concerning assessment of participants' inhaler technique. We therefore developed the proposed Best Practice Inhaler Technique Assessment and Reporting Checklist. CONCLUSIONS: Our study identifies a concerning lack of checking and correcting inhaler technique, or at least reporting that this was undertaken, before enrollment in asthma and COPD RCTs, which may affect the conclusions drawn. Mandating the use of a standardized checklist in RCT protocols and ensuring all published RCTs report checking and correcting inhaler technique before enrollment are important next steps.

Sleep apnea in early childhood associated with preterm birth but not small for gestational age: a population-based record linkage study.

STUDY OBJECTIVES: Investigate the relationship between gestational age and weight for gestational age and sleep apnea diagnosis in a cohort of children aged up to 6 years old. DESIGN: A cohort study, using record linked population health data. SETTING: New South Wales, Australia. PARTICIPANTS: 398,961 children, born between 2000 and 2004, aged 2.5 to 6 years. MEASUREMENTS: The primary outcome was sleep apnea diagnosis in childhood, first diagnosed between 1 and 6 years of age. Children with sleep apnea were identified from hospital records with the ICD-10 code G47.3: sleep apnea, central or obstructive. RESULTS: A total of 4,145 (1.0%) children with a first diagnosis of sleep apnea were identified. Mean age at first diagnosis was 44.2 months (SD 13.9). Adenoidectomy, tonsillectomy, or both were common among the children diagnosed with sleep apnea (85.6%). Children born preterm compared to term were significantly more likely to be diagnosed with sleep apnea (< 32 weeks versus term hazard ratio 2.74 [95% CI: 2.16, 3.49]) this remained even after adjustment for known confounding variables. Children born small for gestational age were not at increased risk of sleep apnea compared to children born appropriate for gestational age, hazard ratio 0.95 (95% CI 0.86-1.06). CONCLUSIONS: This is the largest study investigating preterm birth and sleep apnea diagnosis and suggests that diagnosis of sleep disordered breathing is more prevalent in children born preterm, but not those who are small for gestational age.

Quality of data in perinatal population health databases: a systematic review.

BACKGROUND: Administrative or population health datasets (PHDS) are increasingly being used for research related to maternal and infant health. However, the accuracy and completeness of the information in the PHDS is important to ensure validity of the results of this research. OBJECTIVE: To compile and review studies that validate the reporting of conditions and procedures related to pregnancy, childbirth, and newborns and provide a tool of reference for researchers. METHODS: A systematic search was conducted of Medline and EMBASE databases to find studies that validated routinely collected datasets containing diagnoses and procedures related to pregnancy, childbirth, and newborns. To be included datasets had to be validated against a gold standard, such as review of medical records, maternal interview or survey, specialized register, or laboratory data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and/or κ statistic for each diagnosis or procedure code were calculated. RESULTS: Forty-three validation studies were included. Under-enumeration was common, with the level of ascertainment increasing as time from diagnosis/procedure to birth decreased. Most conditions and procedures had high specificities indicating few false positives, and procedures were more accurately reported than diagnoses. Hospital discharge data were generally more accurate than birth data, however identifying cases from more than 1 dataset further increased ascertainment. CONCLUSIONS: This comprehensive collection of validation studies summarizing the quality of perinatal population data will be an invaluable resource to all researchers working with PHDS.

A prevalence survey of every-day activities in pregnancy.

BACKGROUND: Research into the effects of common activities during pregnancy is sparse and often contradictory. To examine whether common activities are an acute trigger of pregnancy complications the prevalence of these activities are necessary to determine sample size estimates. The aim of this study is to ascertain the prevalence of selected activities in any seven day period during pregnancy. METHODS: The study was conducted in the antenatal clinic of a teaching hospital with tertiary obstetric and neonatal care in Sydney, Australia between August 2008 and April 2009. Women who were at least 20 weeks pregnant and able to read English completed a questionnaire to assess whether they had performed a list of activities in the seven days prior to survey completion. Results were analysed using frequency tabulations, contingency table analyses and chi square tests. RESULTS: A total of 766 surveys were completed, 29 surveys were excluded as the women completing them were less than 20 weeks pregnant, while 161 women completed the survey more than once. Ninety seven per cent of women completed the survey when approached for the first time, while 87% completed the survey when approached a subsequent time. In the week prior to completing the survey 82.6% of women had consumed a caffeinated beverage, 42.1% had had sexual intercourse, 32.7% had lifted something over 12 kilograms, 21.4% had consumed alcohol and 6.4% had performed vigorous exercise. The weekly prevalence of heavy lifting was higher for multiparous women compared to nulliparous women. CONCLUSIONS: The results of this study can be used to inform future research into activities as acute triggers of pregnancy complications.

Is there an association between endometriosis and the risk of pre-eclampsia? A population based study.

BACKGROUND: An association between endometriosis and reduced risk of pre-eclampsia has recently been reported. Longitudinally-linked electronic hospital records are a valuable resource for investigating such findings in a large, population-based sample. Our aim was to determine whether women with a history of endometriosis were at modified risk for pregnancy hypertension or pre-eclampsia. METHODS: A population-based, longitudinal study of all women in the Australian state of New South Wales, aged from 15 to 45 years of age with a singleton birth during the period 2000-2005. Endometriosis was identified using ICD-10 codes. Endometriosis subgroups were analysed based on: (i) site of endometriosis (ovary or peritoneum), (ii) multiple (i.e. two or more) sites affected and (iii) infertility. To investigate the association between pregnancy hypertension and endometriosis, number of weeks gestation at birth and maternal age, we used logistic regression. RESULTS: In the 3239 (1.6%) women with endometriosis diagnosed before their first birth, 352 (10.9%) had a diagnosis of pregnancy hypertension compared with 23,186/205,640 (11.3%) in women with no endometriosis diagnosis (OR 0.96; 95% CI 0.9-1.3). The frequency of pregnancy hypertension and pre-eclampsia was not significantly different in women with more severe endometriosis or endometriosis in conjunction with infertility when compared with those with no endometriosis. After adjusting for maternal age and weeks gestation there was still no altered risk. CONCLUSIONS: We have found no evidence for an association between endometriosis and subsequent risk of either pregnancy hypertension or pre-eclampsia in this large population-based dataset.

The impact of the Baby Bonus payment in New South Wales: who is having "one for the country"?

OBJECTIVE: To assess the change in birth rates, both overall and in age, parity, socioeconomic and geographical subgroups of the population, after the introduction of the Baby Bonus payment in Australia on 1 July 2004. DESIGN AND SETTING: Population-based study using New South Wales birth records and Australian Bureau of Statistics population estimates for the period 1 January 1997 - 31 December 2006. PARTICIPANTS: All 853 606 women aged 15-44 years with a pregnancy resulting in a birth at > or = 20 weeks' gestation or a baby > or = 400 g birthweight. MAIN OUTCOME MEASURE: Change in birth rate in 2005 and 2006 compared with the trend in birth rates before the introduction of the Baby Bonus. RESULTS: The crude annual birth rate showed a downward trend from 1997 to 2004; after 2004 this trend reversed with a sharp increase in 2005 and a further increase in 2006. All age-specific birth rates increased after 2004, with the greatest increase in birth rate, relative to the trend before the Baby Bonus, being seen in teenagers. Rates of first births were not significantly affected by the bonus; however, rates of third or subsequent births increased across all age, socioeconomic and geographical subgroups. CONCLUSIONS: In the first 2 years after the introduction of the Baby Bonus, birth rates increased, especially among women having a third or subsequent birth. This could represent an increase in family size and/or a change in the timing of births.

Are babies getting bigger? An analysis of birthweight trends in New South Wales, 1990-2005.

OBJECTIVE: To determine whether the proportion of babies born large for gestational age (LGA) in New South Wales has increased, and to identify possible reasons for any increase. DESIGN AND SETTING: Population-based study using data obtained from the NSW Midwives Data Collection, a legislated surveillance system of all births in NSW. PARTICIPANTS: All 1 273 924 live-born singletons delivered at term (> or = 37 complete weeks' gestation) in NSW from 1990 to 2005. MAIN OUTCOME MEASURES: LGA, defined as > 90th centile for sex and gestational age using 1991-1994 Australian centile charts; maternal factors associated with LGA were assessed using logistic regression. RESULTS: The proportion of babies born LGA increased from 9.2% to 10.8% (18% increase) for male infants and from 9.1% to 11.0% (21% increase) for female infants. The mean birthweight increased by 23 g for boys and 25 g for girls over the study period. Increasing maternal age, higher rates of gestational diabetes and a decline in smoking contributed significantly to these increases, but did not fully explain them. CONCLUSIONS: There is an increasing trend in the proportion of babies born LGA, which is only partly attributable to decreasing maternal smoking, increasing maternal age and increasing gestational diabetes.

How accurate is the reporting of obstetric haemorrhage in hospital discharge data? A validation study.

BACKGROUND: Routinely collected datasets are frequently used for population-based research but their accuracy needs to be assured. AIM: This study aims to assess the accuracy of hospital discharge data in identifying obstetric haemorrhage diagnoses and procedures, and estimate their population incidence. METHODS: The medical records of 1200 randomly selected women were reviewed and compared with obstetric haemorrhage diagnoses and procedures in the hospital discharge data. Sensitivity, specificity, and positive and negative predictive values were calculated using the medical records as the 'gold standard'. Estimates of population incidence were calculated and weighted by the sampling probabilities. RESULTS: Estimated population incidence for any antepartum haemorrhage was 1.8 per 100, and post partum haemorrhage was 7.2 per 100 women. Obstetric haemorrhage diagnosis and procedure codes tended to be underreported, with sensitivities ranging from 28.3% to 100%. All codes had specificities of 98.9% or greater. The identification of obstetric haemorrhage differed between levels of severity. CONCLUSION: The results indicate that population health datasets can be a reliable information source; however, these datasets could be improved with more complete documentation in medical records.

The accuracy of reporting of the hypertensive disorders of pregnancy in population health data.

OBJECTIVE: To assess the accuracy of hypertensive disorders of pregnancy reporting in birth and hospital discharge data compared with data abstracted from medical records. METHODS: Data from a validation study of 1200 women provided the 'gold standard' for hypertension status. The validation data were linked to both hospital discharge and birth databases. Hypertension could be reported in one, both, or neither database. RESULTS: Of the 1184 records available for review, 8.3% of women had pregnancy-related hypertension and 1.3% had chronic hypertension. Reporting sensitivities ranged from 23% to 99% and specificities from 96% to 100%. Using broad rather than specific categories of hypertension and more than one source to identify hypertension improved case ascertainment. Women with severe preeclampsia or adverse outcomes were more likely to have their pregnancy-related hypertension reported. When the hypertension reporting was discordant on the birth and hospital discharge data, the hospital data were more accurate. CONCLUSIONS: Pregnancy-related hypertension is reported with a reasonable level of accuracy, but chronic hypertension is markedly under-ascertained, even when cases were identified from more than one source. Milder forms of hypertension are more likely to go unreported. Studies utilizing population health data may overestimate the proportion of more severe forms of disease and any risk these conditions contribute to other outcomes.

Birth at hospitals with co-located paediatric units for infants with correctable birth defects.

OBJECTIVES: To determine the percentage of liveborn infants with selected antenatally identifiable and correctable birth defects who were delivered at hospitals with co-located paediatric surgical units (co-located hospitals). Additionally, to determine the survival rates for these infants. PATIENTS AND METHODS: Data were from linked New South Wales hospital discharge records from 2001 to 2004. Livebirths with one of the selected defects were included if they underwent an appropriate surgical repair, or died during the first year of life. Infants with multiple lethal birth defects were excluded. Deliveries at co-located hospitals were identified, but no data on antenatal diagnosis were available. RESULTS: The study identified 287 eligible livebirths with the selected defects. The highest rates of delivery at co-located hospitals were for gastroschisis (88%), exomphalos (71%), spina bifida (63%) and diaphragmatic hernia (61%), and the lowest for transposition of the great arteries (43%) and oesophageal atresia (40%). Mothers resident outside of metropolitan areas, where the co-located hospitals are located, had a similar rate of delivery at co-located hospitals as metropolitan women. For the non-metropolitan mothers of infants with a birth defect, this represented a 30-fold increase over the baseline delivery rate of 1.8%. Post-surgery survival rates were 87% or higher. Overall survival rates were > or = 86% except for infants with a diaphragmatic hernia. CONCLUSIONS: Delivery rates at co-located hospitals were high for mothers of infants with these correctable birth defects. Regionalised health care appears to work well for these pregnancies, as women living outside metropolitan areas had a similar rate of delivery at co-located hospitals to that of urban women.

The prevalence of maternal medical conditions during pregnancy and a validation of their reporting in hospital discharge data.

Population health datasets are a valuable resource for studying maternal and obstetric health outcomes. However, their validity has not been thoroughly examined. We compared medical records from a random selection of New South Wales (NSW) women who gave birth in a NSW hospital in 2002 with coded hospital discharge records. We estimated the population prevalence of maternal medical conditions during pregnancy and found a tendency towards underreporting although specificities were high, indicating that false positives were uncommon.