Primary headache disorders in the adult general population of Pakistan – a cross sectional nationwide prevalence survey

Back Ground: The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include almost all of Eastern Mediterranean Region (EMR). We report a nationwide population-based study in Pakistan, an EMR country with the sixth largest population in the world, conducted as a project within the Global Campaign against Headache. Methods: We surveyed six locations from the four provinces of Pakistan: Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. We randomly selected and visited rural and urban households in each. One adult member (18-65 years) of each household, also randomly selected, was interviewed by a trained non-medical interviewer from the same location using a previously-validated structured questionnaire translated into Urdu, the national language. We estimated 1-year prevalences of the headache disorders of public-health importance and examined their associations with demographic variables using multivariate analysis. Results: There were 4223 participants (mean age 34.4 ± 11.0 years; male 1957 [46.3%], female 2266 [53.7%]; urban 1443 [34.2%], rural 2780 [65.8%]). Participation proportion was 89.5%. Headache in the previous year was reported by 3233 (76.6% [95% CI: 75.3-77.8%]). The age- and gender-adjusted 1-year prevalence of migraine was 22.5% [21.2-23.8%] (male 18.0% [16.8-19.2%], female 26.9% [25.6-28.2%]), of tension-type headache (TTH) 44.6% [43.1-46.1%] (male 51.2% [49.7-52.7%], female 37.9% [36.4-39.4%]), of probable medication-overuse headache 0.7% [0.5-1.0%] (male 0.7% [0.5-1.0%], female 0.8% [0.5-1.1%]) and of other headache on ≥15 days/month 7.4% [6.6-8.2%] (male 4.4% [3.8-5.0%], female 10.4% [9.5-11.3%]). Migraine was more prevalent in females by a factor of 3:2 although this association barely survived (P = 0.039) after correcting for other factors. TTH was more prevalent in males by about 4:3 (P = 0.026). All headache and migraine were age-related, peaking in the age group 40-49 years; TTH peaked a decade earlier. Higher education (P = 0.004) and income (P = 0.001) were negatively associated with prevalence of migraine. Conclusion: With three quarters of its population affected, headache disorders must be on the public-health agenda of Pakistan. Worldwide, these disorders are the third leading cause of disability; information from specific enquiry into the burden attributable to headachedisorders in this country is needed to inform health policy and priority-setting, and will be reported soon

Fraud in a population-based study of headache: prevention, detection and correction

BACKGROUND: In medicine, research misconduct is historically associated with laboratory or pharmaceutical research, but the vulnerability of epidemiological surveys should be recognized. As these surveys underpin health policy and allocation of limited resources, misreporting can have far-reaching implications. We report how fraud in a nationwide headache survey occurred and how it was discovered and rectified before it could cause harm. METHODS: The context was a door-to-door survey to estimate the prevalence and burden of headache disorders in Pakistan. Data were collected from all four provinces of Pakistan by non-medical interviewers and collated centrally. Measures to ensure data integrity were preventative, detective and corrective. We carefully selected and trained the interviewers, set rules of conduct and gave specific warnings regarding the consequences of falsification. We employed two-fold fraud detection methods: comparative data analysis, and face-to-face re-contact with randomly selected participants. When fabrication was detected, data shown to be unreliable were replaced by repeating the survey in new samples according to the original protocol. RESULTS: Comparative analysis of datasets from the regions revealed unfeasible prevalences and gender ratios in one (Multan). Data fabrication was suspected. During a surprise-visit to Multan, of a random sample of addresses selected for verification, all but one had been falsely reported. The data (from 840 cases) were discarded, and the survey repeated with new interviewers. The new sample of 800 cases was demographically and diagnostically consistent with other regions. CONCLUSION: Fraud in community-based surveys is seldom reported, but no less likely to occur than in other fields of medical research. Measures should be put in place to prevent, detect and, where necessary, correct it. In this instance, had the data from Multan been pooled with those from other regions before analysis, a damaging fraud might have escaped notice

The burden of headache disorders in Pakistan: methodology of a population-based nationwide study, and questionnaire validation

Background Large geographical gaps in our knowledge of the prevalence and burden of headache disorders include Pakistan, a country with major problems of poverty, illiteracy and security. We report implementation in this country of standard methods developed by Lifting The Burden (LTB) for population-based burden-of-headache studies. Methods We surveyed six locations from the four provinces: Lahore and Multan (Punjab), Karachi and Sukkur (Sindh), Abbottabad (Khyber Pakhtunkhwa) and Gwadar (Baluchistan). We randomly selected rural and urban households in each, which were visited by trained non-medical interviewers from the same locations. One randomly selected adult member (18–65 years) of each household was interviewed using LTB’s structured questionnaire translated into Urdu, the national language. Validation was performed among patients and accompanying attendants in three (urban and rural) medical facilities. After responding to the questionnaire, these participants were re-interviewed and diagnosed by a neurologist (gold standard). Results The survey was completed by 4,223 respondents (1,957 [46.3%] male, 2,266 [53.7%] female, 1,443 [34.2%] urban, 2,780 [65.8%] rural, mean age 34.4 ± 11.0 years). The participation rate was 89.5%. There were 180 participants (46.1% male, 53.9% female, 41.7% urban, 58.3% rural, mean age 39.4 ± 14.2 years) in the validation sample, of whom 147 (81.7%) reported headache in the last year. The questionnaire was 100% sensitive in screening for headache and for headache on ≥15 days/month, and showed good agreement with the gold-standard diagnoses (kappa = 0.77). It was relatively insensitive for TTH. The questionnaire’s default diagnosis of probable MOH when medication overuse accompanied headache on ≥15 days/month was not supported by evidence of causation in most cases seen by the neurologist. In public-health terms, precise diagnosis in these cases matters less than reliably detecting the coexistence of these disorders. Conclusion In conclusion, the methods developed by LTB were applied successfully in Pakistan, despite problems unique to this country

Profile of plecanatide in the treatment of chronic idiopathic constipation: design, development, and place in therapy

Amol Sharma, Anam Asif Herekar, Jigar Bhagatwala, Satish SC Rao  Division of Gastroenterology and Hepatology, Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, USA  Abstract: Constipation is a multifactorial disorder that can cause significant psychological distress to patients and economic burden on the health care system. Many patients are not satisfied with their current established treatment, highlighting the need for new and improved therapeutic options. Guanylate cyclase-C (GC-C)/cyclic guanosine monophosphate agonists have emerged as a safe and efficacious class of drugs for the treatment of chronic idiopathic constipation (CIC). Plecanatide, a second-in-class, US FDA-approved, synthetic GC-C agonist, has recently been approved in the US for the treatment of irritable bowel syndrome with constipation at doses of 3 and 6 mg and CIC at the 3 mg dosage. In this study, we summarize the design of this novel 16-amino acid uroguanylin analog, drug development through Phase I, II, and III clinical studies, and its role in the treatment of CIC.  Keywords: plecanatide, uroguanylin, constipatio

Primary headache disorders in the adult general population of Pakistan - a cross sectional nationwide prevalence survey

Background The large geographical gaps in our knowledge of the prevalence and burden of headache disorders include almost all of Eastern Mediterranean Region (EMR). We report a nationwide population-based study in Pakistan, an EMR country with the sixth largest population in the world, conducted as a project within the Global Campaign against Headache. Methods We surveyed six locations from the four provinces of Pakistan: Punjab, Sindh, Khyber Pakhtunkhwa and Baluchistan. We randomly selected and visited rural and urban households in each. One adult member (18–65 years) of each household, also randomly selected, was interviewed by a trained non-medical interviewer from the same location using a previously-validated structured questionnaire translated into Urdu, the national language. We estimated 1-year prevalences of the headache disorders of public-health importance and examined their associations with demographic variables using multivariate analysis. Results There were 4223 participants (mean age 34.4 ± 11.0 years; male 1957 [46.3%], female 2266 [53.7%]; urban 1443 [34.2%], rural 2780 [65.8%]). Participation proportion was 89.5%. Headache in the previous year was reported by 3233 (76.6% [95% CI: 75.3–77.8%]). The age- and gender-adjusted 1-year prevalence of migraine was 22.5% [21.2–23.8%] (male 18.0% [16.8–19.2%], female 26.9% [25.6–28.2%]), of tension-type headache (TTH) 44.6% [43.1–46.1%] (male 51.2% [49.7–52.7%], female 37.9% [36.4–39.4%]), of probable medication-overuse headache 0.7% [0.5–1.0%] (male 0.7% [0.5–1.0%], female 0.8% [0.5–1.1%]) and of other headache on ≥15 days/month 7.4% [6.6–8.2%] (male 4.4% [3.8–5.0%], female 10.4% [9.5–11.3%]). Migraine was more prevalent in females by a factor of 3:2 although this association barely survived (P = 0.039) after correcting for other factors. TTH was more prevalent in males by about 4:3 (P = 0.026). All headache and migraine were age-related, peaking in the age group 40–49 years; TTH peaked a decade earlier. Higher education (P = 0.004) and income (P = 0.001) were negatively associated with prevalence of migraine. Conclusion With three quarters of its population affected, headache disorders must be on the public-health agenda of Pakistan. Worldwide, these disorders are the third leading cause of disability; information from specific enquiry into the burden attributable to headache disorders in this country is needed to inform health policy and priority-setting, and will be reported soon. Keyword

The World Health Organization ACTION-I (Antenatal CorTicosteroids for Improving Outcomes in preterm Newborns) Trial: a multi-country, multi-centre, two-arm, parallel, double-blind, placebo-controlled, individually randomized trial of antenatal corticosteroids for women at risk of imminent birth in the early preterm period in hospitals in low-resource countries

BACKGROUND: Antenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries. METHODS/DESIGN: The trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up). DISCUSSION: Findings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization's global recommendations on ACS use. TRIAL REGISTRATION: ACTRN12617000476336 . Registered on 31 March 2017