Polypharmacy and pattern of medication use among patients with gastroesophageal reflux disease: results from Pars Cohort study.

BACKGROUND: Gastroesophageal Reflux Disease (GERD) is a common chronic condition. Its chronic nature may affect the pattern of medication use. This study aimed to investigate the prevalence, associated factors, and patterns of polypharmacy and medication use among GERD patients in southwestern Iran. METHODS: We used data from the Pars Cohort Study. We classified drugs using the Anatomical Therapeutic Chemical classification system. The Lexicomp® database was used to assess potential drug-drug interactions. Multivariable Poisson regression was applied. Adjusted prevalence ratio (PR) and its 95% confidence interval (CI) were estimated. RESULTS: A total of 9262 participants were included. Among 2,325 patients with GERD, age-standardized prevalence of polypharmacy was 9.5% (95% CI: 7.5%, 11.6%) in males, and 19.3% (95% CI: 17.2%, 21.4%) in females. The PR of experiencing Polypharmacy by GERD patients compared to non-GERD patients was 1.82 (95% CI: 1.61, 2.05%). Multimorbidity (PR: 3.33; CI: 2.66, 4.15), gender (PR: 1.68; CI: 1.30, 2.18), and metabolic syndrome (PR: 1.77; CI: 1.45, 2.15) were associated with polypharmacy among GERD patients. Drugs for acid-related disorders were the most common used drugs among men, women and elders. We found that 13.9%, 4.2%, and 1.1% of GERD patients had type C, D and X drug interactions, respectively. CONCLUSION: GERD is correlated with a higher prevalence of polypharmacy. Among GERD patients, females, those with multi-morbidities, and those with metabolic syndrome may be affected more by polypharmacy. Considering the fairly high rate of interactions identified, a review of the medication list is essential when approaching GERD patients, and physicians must check for medications that may worsen GERD.

Assessing Google Searches for Toothache during COVID-19 Lockdowns.

Background: Lockdowns due to the coronavirus disease 2019 (COVID-19) pandemic forced many dental offices to be closed. This study aims to investigate the association between COVID-19 imposed lockdowns and online searches for toothache using Google Trends (GT). Methods: We investigated GT online searches for the term "toothache" within the past 5 years. The time frame for data gathering was considered as the initiation and end dates of national/regional lockdowns in each country. We used 1-way analysis of variance to identify statistical differences in relative search volumes (RSVs) between 2020 and 2016-2019 for each country. Results: Overall, 16 countries were included in our analyses. Among all countries, Indonesia (n = 100), Jamaica (n = 56), Philippines (n = 56), Iran (n = 52), and Turkey (47) had the highest RSVs for toothache in the specified period. Compared with the previous 4 years, higher RSVs were seen in the world (as a whole) (2020 RSVs, 94.4; vs 2019 RSVs, 77.8 [ P < 0.001]) and 13 countries (81.3% of the included countries). Conclusion: Generally, searching for the term "toothache" showed an increase during the COVID-19 lockdowns in 2020 compared with the past 4 years. This can imply the importance of dental care as urgent medical care during public health emergencies such as COVID-19.

Population-based pattern of medication use and prevalence of polypharmacy among patients with cardiovascular diseases: results of the Pars cohort study from Iran.

BACKGROUND: Polypharmacy in patients with cardiovascular diseases (CVDs) has been linked to several adverse outcomes. This study aimed to investigate the pattern of medication use and prevalence of polypharmacy among CVDs patients in Iran. METHOD: We used the baseline data of the Pars cohort study (PCS). The participants were asked to bring their medication bags; then, the medications were classified using the Anatomical Therapeutic Chemical classification. Polypharmacy was defined as using five or more medications concurrently. Poisson regression modeling was applied. The adjusted prevalence ratios (PR) and its 95% confidence interval (CI) were estimated. RESULTS: Totally, 9262 participants were enrolled in the PCS, of whom 961 had CVDs. The prevalence of polypharmacy in participants with and without CVDs was 38.9% and 7.1%, respectively. The highest prevalence of polypharmacy (51.5%) was among obese patients. Abnormal waist-hip ratio (PR: 2.79; 95% CI 1.57-4.94), high socioeconomic status (PR: 1.65; 95% CI 1.07-2.54), tobacco-smoking (PR: 1.35; 95% CI 1.00-1.81), patients with more than three co-morbidities (PR: 1.41; 95% CI 1.30-1.53), high physical activity (PR: 0.66; 95% CI 0.45-0.95), use of opiate ever (PR: 0.46; 95% CI 0.26-0.82), and healthy overweight subjects (PR: 0.22; 95% CI 0.12-0.39) were associated with polypharmacy. Cardiovascular drugs (76.1%), drugs acting on blood and blood-forming organs (50.4%), and alimentary tract and metabolism drugs (33.9%) were the most frequently used drugs. Agents acting on the renin-angiotensin system were the mostly used cardiovascular system drugs among men and those above 60 years old, while beta-blocking agents were mostly prevalent among cardiovascular system drugs in women with CVDs. CONCLUSION: Given the high prevalence of polypharmacy among CVDs patients, and subsequent complications, programs to educate both physicians and patients to prevent this issue is crucial.

Knowledge gaps and national research priorities for COVID-19 in Iran.

BACKGROUND: In the present COVID-19 crisis, one of the greatest challenges for research funding at both the international and national level is selecting the best research topic to achieve efficiency and equity in health research and to address the knowledge gap urgently raised due to the event. Despite international recommendations, countries should consider their context-specific situation and define local research priorities. We aimed to exercise a priority-setting activity to identify the knowledge gaps and suggest research priorities in response to the COVID-19 epidemic in Iran. METHODS: First, we tried to identify the contextual knowledge gaps based on an online survey, performing key informant interviews (i.e. health professionals, policy-makers and managers) and media analysis. We also performed a literature review and considered international research priorities for COVID-19. Subsequently, we prepared a list of research questions and challenges to respond to the COVID-19 crisis in Iran using a systems approach. Then we mapped approved COVID-19 research projects in the country to research questions. Finally, we compared the identified research questions (not challenges) with the prioritized research from international organizations and then prioritized them for Iran. RESULTS: We found risk factors and epidemiological dissemination patterns of the virus and its consequences in an epidemiology domain, implementation of clinical and hygiene in a clinical management domain, genetic studies for targeting prevention and treatment in a candidate treatment and vaccine research and development (R&D) knowledge domain, examination of the manifestations of ethics in society instead of ethics in research in an ethics domain, "care, access and health system" and "public health and participation in response to public health and clinical research" as two sub-domains of a social sciences domain, and finally, no new questions in either the virology, transmission, diagnosis or animal and environmental domain. CONCLUSIONS: In the event of global health crises like COVID-19, prioritization of research questions can be done globally, but some of the research priorities are context-specific and may vary by regional needs. To better manage research resources, researchers must respond to the challenges faced in each country based on its political, economic, social and cultural characteristics, and to make evidence-informed decisions, global knowledge gaps must be customized in each country.

Estimation of adverse drug reaction reporting in Iran: Correction for underreporting.

PROPOSE: Underreporting of Adverse Drug Reactions (ADRs) reduces the sensitivity of pharmacovigilance systems. We described ADR reporting and its trend from 1999 to 2017 and estimated the ADR underreporting in the Iranian Pharmacovigilance Center. METHODS: We expressed the number of ADR reporting per inhabitants and admissions and their possible trends. Finally, ADR underreporting percentages were estimated by three approaches: prospective studies, literature review, stratification of the country; and the trend of the proportion of ADR per inhabitants was corrected. RESULTS: The proportion of ADR reporting was 15.3 per 100 000 inhabitants (95% CI: 15.2, 15.8) and 10.0 per 100 000 admissions (95% CI: 9.8, 10.2) in 2017, and its trend was increasing with 16.3% average change per annum during 19 years. The median of estimated percentages of underreporting was 76.0% (IQR: 64.32-81.35). After the correction, the mean proportion of ADR reporting for 19 years reached from 5.87 to 10.33 per 100 000 inhabitants. CONCLUSIONS: The trend of ADRs reporting has been increasing over the 19 years but is still low. This study showed a considerable underreporting of ADR, and about one of four detected ADRs were reported to the pharmacovigilance center from 1999 to 2017.

Assessing research misconduct in Iran: a perspective from Iranian medical faculty members.

BACKGROUND: Research misconduct is a global concern in biomedical science. There are no comprehensive data regarding the perception and situation of scientific misconduct among the Iranian medical faculty members. We conducted a nationwide survey to assess the research misconduct among the medical faculty members in Iran. METHODS: We used the Persian version of the research misconduct questionnaire (PRMQ) on the Google Forms platform. We sent the survey link to a systematic random sample of medical faculty members in Iran (N = 4986). Descriptive analyses were performed on the individual items of the PRMQ, with frequencies and percentages for categorical and Likert-type response items, and means and standard deviation (S.D.) for continuous variables. Chi-square analysis was conducted to test hypotheses examining differences in the frequency of responses related to factors influencing misconduct. We also defined four tenure categories (TC) based on the working years of the participants as tenured faculty members. All the analyses were performed using R 3.6.0. RESULTS: The response rate was 13.8% (692 responses). Nearly 70% of the respondents agreed that their publication output would be of higher quality if there were no publication pressure. Approximately three-quarters (N =499, 72.1%) of the respondents had been aware of some instances of research misconduct during the previous year according to their understanding of misconduct. Among the participants, 18.5% perceived the effectiveness of their associated organisation's rules for reducing research misconduct to be high or very high. Pressure for tenure was identified as the item most frequently perceived with a strong behavioural influence on engaging in research misconduct (80.2%). CONCLUSIONS: This study confirms that research misconduct needs to be actively addressed among the medical faculty members. Making policies with a focus on boosting awareness regarding the occasions of scientific misconduct and its management seems to be indispensable in the future in Iran.

Expectations of Health Researchers From Academic Social Network Sites: Qualitative Study.

BACKGROUND: Today, academic social network sites' role in improving the quality of education and how investigators conduct their research has become more critical. OBJECTIVE: This study aimed to investigate Iranian health researchers' requirements for academic social network sites from a low-income country perspective. METHODS: This qualitative study with a phenomenological approach was done in 2020. In this study, 23 researchers in the health system were selected by purposive sampling. Semistructured interviews were used to collect data. Data were analyzed by MaxQDA-10 software and the content analysis method. RESULTS: We identified 2 categories of functional and technical characteristics in the study participants' expectations. Functional characteristics included facilitating communication and team activities, managing scientific publications, enhancing the process of conducting research, being informative, and sharing and trading laboratory materials and equipment. Technical characteristics of an academic social network include user management capabilities, high security and privacy, being user-friendly, and other technical features. CONCLUSIONS: Health researchers emphasized 2 functional and technical characteristics required to meet academic social network sites' expectations.

Interventions to improve adverse drug reaction reporting: A scoping review.

PURPOSE: Underreporting is the major limitation of a voluntary adverse drug reaction (ADR) reporting system. Many studies have assessed the effectiveness of different interventions designed to improve ADR reporting. The aim of this study was to systematically map interventions and strategies to improve ADR reporting among health care professionals. METHODS: The six-stage methodological framework of Arksey and O'Malley was used to conduct this scoping review. Ovid MEDLINE, EMBASE, All EBM, and Web of Science were systematically searched from 1999 to February 2019, and the reference lists of the included papers were also searched for gray literature to identify any interventions and strategies that aimed to increase ADR reporting. Two reviewers screened the papers for eligibility based on the inclusion criteria and extracted their key data and analyzed them descriptively. RESULTS: Ninety out of 14 501 papers met the selection criteria. Using computerized registration and active surveillance can increase ADR reporting significantly. Educational interventions performed individually or combined with sending reminders and/or feedback, awards, and providing easier reporting channels can improve ADR reporting over a short to medium term. Multiple interventions may have more impact than single-component interventions. CONCLUSION: Multiple interventions could cause a greater increase in ADR reporting rates than single interventions. Although educational interventions appear to be effective, few studies have reviewed their long-term effects to ascertain whether the improvements are sustained over time. Studies with a better methodological quality are required on this subject.

Acupuncture or acupressure for pain management during labour.

BACKGROUND: Many women would like to avoid pharmacological or invasive methods of pain management in labour and this may contribute towards the popularity of complementary methods of pain management. This review examined evidence about the use of acupuncture and acupressure for pain management in labour. This is an update of a review last published in 2011. OBJECTIVES: To examine the effects of acupuncture and acupressure for pain management in labour. SEARCH METHODS: For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, (25 February 2019), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2019, Issue 1), MEDLINE (1966 to February 2019), CINAHL (1980 to February 2019), ClinicalTrials.gov (February 2019), the WHO International Clinical Trials Registry Platfory (ICTRP) (February 2019) and reference lists of included studies. SELECTION CRITERIA: Published and unpublished randomised controlled trials (RCTs) comparing acupuncture or acupressure with placebo, no treatment or other non-pharmacological forms of pain management in labour. We included all women whether nulliparous or multiparous, and in spontaneous or induced labour. We included studies reported in abstract form if there was sufficient information to permit assessment of risk of bias. Trials using a cluster-RCT design were eligible for inclusion, but quasi-RCTs or cross-over studies were not. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 28 trials with data reporting on 3960 women. Thirteen trials reported on acupuncture and 15 trials reported on acupressure. No study was at a low risk of bias on all domains. Pain intensity was generally measured on a visual analogue scale (VAS) of 0 to 10 or 0 to 100 with low scores indicating less pain. Acupuncture versus sham acupuncture Acupuncture may make little or no difference to the intensity of pain felt by women when compared with sham acupuncture (mean difference (MD) -4.42, 95% confidence interval (CI) -12.94 to 4.09, 2 trials, 325 women, low-certainty evidence). Acupuncture may increase satisfaction with pain relief compared to sham acupuncture (risk ratio (RR) 2.38, 95% CI 1.78 to 3.19, 1 trial, 150 women, moderate-certainty evidence), and probably reduces the use of pharmacological analgesia (RR 0.75, 95% CI 0.63 to 0.89, 2 trials, 261 women, moderate-certainty evidence). Acupuncture may have no effect on assisted vaginal birth (very low-certainty evidence), and probably little to no effect on caesarean section (low-certainty evidence). Acupuncture compared to usual care We are uncertain if acupuncture reduces pain intensity compared to usual care because the evidence was found to be very low certainty (standardised mean difference (SMD) -1.31, 95% CI -2.14 to -0.49, 4 trials, 495 women, I2 = 93%). Acupuncture may have little to no effect on satisfaction with pain relief (low-certainty evidence). We are uncertain if acupuncture reduces the use of pharmacological analgesia because the evidence was found to be very low certainty (average RR 0.72, 95% CI 0.60 to 0.85, 6 trials, 1059 women, I2 = 70%). Acupuncture probably has little to no effect on assisted vaginal birth (low-certainty evidence) or caesarean section (low-certainty evidence). Acupuncture compared to no treatment One trial compared acupuncture to no treatment. We are uncertain if acupuncture reduces pain intensity (MD -1.16, 95% CI -1.51 to -0.81, 163 women, very low-certainty evidence), assisted vaginal birth or caesarean section because the evidence was found to be very low certainty. Acupuncture compared to sterile water injection We are uncertain if acupuncture has any effect on use of pharmacological analgesia, assisted vaginal birth or caesarean section because the evidence was found to be very low certainty. Acupressure compared to a sham control We are uncertain if acupressure reduces pain intensity in labour (MD -1.93, 95% CI -3.31 to -0.55, 6 trials, 472 women) or assisted vaginal birth because the evidence was found to be very low certainty. Acupressure may have little to no effect on use of pharmacological analgesia (low-certainty evidence). Acupressure probably reduces the caesarean section rate (RR 0.44, 95% CI 0.27 to 0.71, 4 trials, 313 women, moderate-certainty evidence). Acupressure compared to usual care We are uncertain if acupressure reduces pain intensity in labour (SMD -1.07, 95% CI -1.45 to -0.69, 8 trials, 620 women) or increases satisfaction with pain relief (MD 1.05, 95% CI 0.75 to 1.35, 1 trial, 105 women) because the evidence was found to be very low certainty. Acupressure may have little to no effect on caesarean section (low-certainty evidence). Acupressure compared to a combined control Acupressure probably slightly reduces the intensity of pain during labour compared with the combined control (measured on a scale of 0 to 10 with low scores indicating less pain) (SMD -0.42, 95% CI -0.65 to -0.18, 2 trials, 322 women, moderate-certainty evidence). We are uncertain if acupressure has any effect on the use of pharmacological analgesia (RR 0.94, 95% CI 0.71 to 1.25, 1 trial, 212 women), satisfaction with childbirth, assisted vaginal birth or caesarean section because the certainty of the evidence was all very low. No studies were found that reported on sense of control in labour and only one reported on satisfaction with the childbirth experience. AUTHORS' CONCLUSIONS: Acupuncture in comparison to sham acupuncture may increase satisfaction with pain management and reduce use of pharmacological analgesia. Acupressure in comparison to a combined control and usual care may reduce pain intensity. However, for other comparisons of acupuncture and acupressure, we are uncertain about the effects on pain intensity and satisfaction with pain relief due to very low-certainty evidence. Acupuncture may have little to no effect on the rates of caesarean or assisted vaginal birth. Acupressure probably reduces the need for caesarean section in comparison to a sham control. There is a need for further high-quality research that include sham controls and comparisons to usual care and report on the outcomes of sense of control in labour, satisfaction with the childbirth experience or satisfaction with pain relief.

Health research system resilience: lesson learned from the COVID-19 crisis.

Producing evidence in epidemics is crucial to control the current epidemic and prevent its recurrence in the future. Data must be collected and analyzed rapidly to recognize the most efficient and feasible methods with proper timelines. However, there are many challenges a research system may encounter during a crisis. This article has presented lessons learned from the COVID-19 pandemic for health research system (HRS) to deal with current and future crises. Therefore, a HRS needs to produce and use evidence in such a situation. The components Knowledge Translation Self-Assessment Tool for Research Institutes (SATORI) framework was used to review the actions required and respond to the COVID-19 pandemic in a national HRS. This framework consists of four categories of defining the research question, conducting research, translating the research results, and promoting the use of evidence. The work is proposed actions in response to the COVID-19 crisis and improving a HRS's resilience. While COVID-19 has serious harm to the health and broader socio-economic consequences, this threat should be accounted for as an opportunity to make research systems more accountable and responsible in the timely production and utilization of knowledge. It is time to seriously think about how HRS can build a better back to be resilient to potential shock and prepare for unforeseen emerging conditions.

L-carnosine as an adjuvant to fluvoxamine in treatment of obsessive compulsive disorder: A randomized double-blind study.

BACKGROUND: Dysregulation of glutamate is implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Consistently, glutamate-modulating agents, such as riluzole and memantine have been used in OCD treatment. Previous research has identified some neuroprotective role for L-carnosine potentially via its modulatory effect on glutamate. Here, we assessed the efficacy of L-carnosine as adjuvant to fluvoxamine in OCD treatment. METHODS: Forty-four patients diagnosed with moderate to severe OCD were recruited in a randomized double-blind trial. Patients received either L-carnosine or placebo as adjuvant to fluvoxamine for 10 weeks. The Yale- Brown Obsessive Compulsive Scale (Y-BOCS) was used for assessing the severity of symptoms at baseline and at weeks 4, 8, and 10. RESULTS: General linear model repeated measure showed significant effects for Time × Treatment interaction on total Y-BOCS [F (2.10, 88.42) = 8.66, p < 0.001], obsession [F (1.88, 79.34) = 4.96, p = 0.01] and compulsion [F (1.88, 79.11) = 4.57, p = 0.01]. At week 10, the change from baseline in Y-BOCS scores was 8.86 ± 2.89 (mean ± SD) in the L-carnosine group compared to 5.86 ± 2.88 in the placebo group. CONCLUSION: L-carnosine results in significant reduction of obsessive-compulsive symptoms when used as an adjuvant to fluvoxamine.

Cilostazol adjunctive therapy in treatment of negative symptoms in chronic schizophrenia: Randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase III, as an adjunctive to risperidone in alleviating the negative symptoms of schizophrenia. METHODS: Eighty-four in-patients with diagnosis of chronic schizophrenia participated in a randomized, placebo-controlled trial and underwent 8 weeks of treatment with either cilostazol (50 mg twice a day) or placebo as an adjuvant to risperidone. Participants were assessed using the positive and negative syndrome scale (PANSS) at baseline and at weeks 2, 4, 6, and 8. The primary outcome measure of the trial was to evaluate the efficacy of cilostazol compared to placebo in improving the PANSS negative subscale score. RESULT: General linear model repeated measures demonstrated significant effect for time × treatment interaction on negative subscale scores (p < .001) and PANSS total (p = .006) but did not demonstrate significant effect on the PANSS positive (p = .37) and general (p = .06) subscales. Frequency of adverse events was not significantly different between the 2 treatment groups. No serious adverse event was observed. CONCLUSION: An 8-week course of treatment with cilostazol as an adjunct to risperidone showed a favorable safety and efficacy profile in patients with schizophrenia.

Harms of off-label erythropoiesis-stimulating agents for critically ill people.

BACKGROUND: Anaemia is a common problem experienced by critically-ill people. Treatment with erythropoiesis-stimulating agents (ESAs) has been used as a pharmacologic strategy when the blunted response of endogenous erythropoietin has been reported in critically-ill people. The use of ESAs becomes more important where adverse clinical outcomes of transfusing blood products is a limitation. However, this indication for ESAs is not licensed by regulatory authorities and is called off-label use. Recent studies concern the harm of ESAs in a critical care setting. OBJECTIVES: To focus on harms in assessing the effects of erythropoiesis-stimulating agents (ESAs), alone or in combination, compared with placebo, no treatment or a different active treatment regimen when administered off-label to critically-ill people. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO via OvidSP, CINAHL, all evidence-based medicine (EBM) reviews including IPA and SCI-Expanded, Conference Proceedings Citation Index- Science, BIOSIS Previews and TOXLINE up to February 2017. We also searched trials registries, checked reference lists of relevant studies and tracked their citations by using SciVerse Scopus. SELECTION CRITERIA: We considered randomized controlled trials (RCTs) and controlled observational studies, which compared scheduled systemic administration of ESAs versus other effective interventions, placebo or no treatment in critically-ill people. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and evaluated the eligibility of retrieved records, extracted data and assessed the risks of bias and quality of the included studies. We resolved differences in opinion by consensus or by involving a third review author. We assessed the evidence using GRADE and created a 'Summary of findings' table. We used fixed-effect or random-effects models, depending on the heterogeneity between studies. We fitted three-level hierarchical Bayesian models to calculate overall treatment effect estimates. MAIN RESULTS: Of the 27,865 records identified, 39 clinical trials and 14 observational studies, including a total of 945,240 participants, were eligible for inclusion. Five studies are awaiting classification. Overall, we found 114 adverse events in 33 studies (30 RCTs and three observational studies), and mortality was reported in 41 studies (32 RCTs and nine observational studies). Most studies were at low to moderate risk of bias for harms outcomes. However, overall harm assessment and reporting were of moderate to low quality in the RCTs, and of low quality in the observational studies. We downgraded the GRADE quality of evidence for venous thromboembolism and mortality to very low and low, respectively, because of risk of bias, high inconsistency, imprecision and limitations of study design.It is unclear whether there is an increase in the risk of any adverse events (Bayesian risk ratio (RR) 1.05, 95% confidence interval (CI) 0.93 to 1.21; 3099 participants; 9 studies; low-quality evidence) or venous thromboembolism (Bayesian RR 1.04, 95% CI 0.70 to 1.41; 18,917 participants; 18 studies; very low-quality evidence).There was a decreased risk of mortality with off-label use of ESAs in critically-ill people (Bayesian RR 0.76, 95% CI 0.61 to 0.92; 930,470 participants; 34 studies; low-quality evidence). AUTHORS' CONCLUSIONS: Low quality of evidence suggests that off-label use of ESAs may reduce mortality in a critical care setting. There was a lack of high-quality evidence about the harm of ESAs in critically-ill people. The information for biosimilar ESAs is less conclusive. Most studies neither evaluated ESAs' harm as a primary outcome nor predefined adverse events. Any further studies of ESA should address the quality of evaluating, recording and reporting of adverse events.

A population-based analysis of the risk of drug interaction between clarithromycin and statins for hospitalisation or death.

BACKGROUND: Clarithromycin, known as a potent inhibitor of the cytochrome P450 isoenzyme CYP3A, may increase the plasma concentration of statins metabolized by this pathway; therefore, increase the risk of interaction with statins in reference to pharmacokinetic studies. This study aimed to characterize whether the concomitant use of a statin with clarithromycin is associated with serious outcomes among adult persons. METHODS: Health claims data of adult persons in the Regional Sickness Fund of Burgenland, Austria, who filled a prescription for clarithromycin between July 1, 2009 and June 30, 2012 were reviewed retrospectively. We assumed that the risk of hospitalisation increases acutely with the indication for taking an antibiotic, whereas statin use can be considered a chronic exposure with a low constant effect on hospitalisation. When defining the population as persons taking clarithromycin and the use of statins as the exposure we could achieve a comparable effect in both groups from the acute condition on hospitalisation. Therefore, we defined exposed patients as those who had overlapping treatment with a statin and unexposed controls as those who had filled a prescription for clarithromycin without concomitant statin therapy. Outcome was defined as a composite of hospital admission or death within 30 days after starting clarithromycin. We used generalised linear regression to model an association between outcome and exposure to statins. RESULTS: Among 28,484 prescriptions of clarithromycin, 2317 persons were co-exposed to statins. Co-administration of CYP3A4 metabolized statins and clarithromycin was associated with a 2.11 fold increased risk of death or hospitalisation (95 % confidence interval [CI]: 1.79-2.48). This effect was explained by age, evidence of cardiovascular disease, diabetes mellitus and utilization of other antibiotics (multivariable adjusted risk ratio: 1.02, 95 % CI: 0.85-1.22). The sensitivity analyses did not change the significance of effect. CONCLUSIONS: The risk for hospitalisation or death in persons receiving clarithromycin increases with age and cardiovascular disease but is not causally associated with statin-clarithromycine co-administration.

Age- and gender-specific acute poisoning with drugs and medications affecting nervous system.

BACKGROUND: We investigated acute poisonings resulting from medications affecting the nervous system and illicit substances at Loghman Hakim Hospital in Tehran. METHODS: We retrospectively reviewed patient records at Iran's largest tertiary toxicology referral center between January 2010 and December 2015. We analyzed the prevalence, trend, age and gender distribution of acute poisoning caused by nervous system agents. RESULTS: The present study included 16,657 (57.27%) males and 12,426 (42.73%) females, resulting in 29,083 patients. The median age of men and women was 29 and 26 years, respectively (p < 0.0001). There were 12,071 (72.47%) men and 10,326 (83.10%) women under the age of 40 (p < 0.001). Most cases were intentional (69.38% in men and 79.00% in women, p < 0.001) and 44.10% had a history of poisoning. The proportions of men and women varied significantly between different age groups and nervous system agents. For women, the most common agent was alprazolam, whereas for men, methadone. The overall trend of acute poisoning with drug used in addictive disorders, opioids and alcohol was increasing but decreasing with benzodiazepines and antidepressants. Acute poisoning by nervous system agents led to more deaths in men (1.95% vs. 0.56%; p < 0.001). CONCLUSIONS: Methadone intoxication was common especially among young men and most of these intoxications were intentional. Women and men aged 20-29 most frequently suffer poisoning from alprazolam and clonazepam, respectively. Women over 60 and men over 30 used opium. Illicit drugs caused more than half of the deaths, and opium dominated. This study may create awareness and develop educational and preventive gender and age-specific local programs.

Prevalence and Correlates of Polypharmacy, and Drug Utilization Pattern in a Semi-urban Population: Results from the Pars Cohort Study.

BACKGROUND: Although polypharmacy is considered a major predictor of irrational use of drugs, little is known about polypharmacy in developing regions. We aimed to indicate the prevalence and correlates of polypharmacy and to determine the medication profile at the population level in southern Iran. METHODS: In this cross-sectional study, we analyzed data from participants of the Pars Cohort Study (PCS) (aged above 40 years, N=9269). Polypharmacy was defined as using five or more medications concurrently. A Poisson multivariable model was applied to estimate the adjusted prevalence ratios (APRs) of various risk factors. The Anatomical Therapeutic Chemical (ATC) classification system was used for classifying medications. RESULTS: Prevalence of polypharmacy was 10.4%, (95% CI: 9.75; 11.08) and it was higher among females (15.0%), older adults (age≥65 years) (16.0%), and individuals with more than two chronic conditions (31%). Being female, educated, married, and not having a low socio-economic class were independently associated with a higher likelihood of polypharmacy. The most prevalent medications among female participants were sex hormones and modulators of the genital system (58.4%), drugs for acid-related disorders (14.6%), and anti-anemic preparations (13.6%,). On the other hand, males were using acid-related disorders (14.6%), anti-inflammatory and anti-rheumatic products (7.8%), and beta-blocking agents (6.3%). CONCLUSION: The prevalence of polypharmacy in our sample was relatively low, especially among males. Cardiovascular drugs, acid suppressants, hormonal contraceptives, and anti-anemic preparations are drug classes with the highest contribution to polypharmacy.

Iran Quality of Care in Medicine Program (IQCAMP): Design and Outcomes.

BACKGROUND: Assessment of quality and cost of medical care has become a core health policy concern. We conducted a nationwide survey to assess these measures in Iran as a developing country. To present the protocol for the Iran Quality of Care in Medicine Program (IQCAMP) study, which estimates the quality, cost, and utilization of health services for seven diseases in Iran. METHODS: We selected eight provinces for this nationally representative short longitudinal survey. Interviewers from each province were trained comprehensively. The standard definition of seven high-burden conditions (acute myocardial infarction [MI], heart failure [HF], diabetes mellitus [DM], stroke, chronic obstructive pulmonary (COPD) disease, major depression, and end-stage renal disease [ESRD]) helped customize a protocol for disease identification. With a 3-month follow-up window, the participants answered pre-specified questions four times. The expert panels developed a questionnaire in four modules (demographics, health status, utilization, cost, and quality). The expert panel chose an inclusive set of quality indicators from the current literature for each condition. The design team specified the necessary elements in the survey to calculate the cost of care for each condition. The utilization assessment included various services, including hospital admissions, outpatient visits, and medication. RESULTS: Totally, 156 specialists and 78 trained nurses assisted with patient identification, recruitment, and interviewing. A total of 1666 patients participated in the study, and 1291 patients completed all four visits. CONCLUSION: The IQCAMP study was the first healthcare utilization, cost, and quality survey in Iran with a longitudinal data collection to represent the pattern, quantity, and quality of medical care provided for high-burden conditions.

Search strategies to identify reports on "off-label" drug use in EMBASE.

BACKGROUND: Medications are frequently prescribed outside their regulatory approval (off-label) by physicians particularly where appropriate therapies are not available. However, the risk/benefit ratio of drugs in off-label use needs to be critically appraised because it may differ from approved on-label usage. Therefore, an extensive exploration of current evidence on clinical data is well-advised. The objective of this study was to develop a search strategy that facilitates detection of the off-label drug use documents in EMBASE via OvidSP. METHODS: We constructed two sets of gold standards from relevant records to off-label drug use by a sensitive search of MEDLINE and EMBASE. Search queries, including search words and strings, were conceived based on definition of off-label use of medications as well as text analysis of 500 randomly selected relevant documents. The selected terms were searched in EMBASE (from 1988 to 2011) and their retrieval performance was compared with the gold standards. We developed a sensitivity-maximizing, and a sensitivity- and precision-maximizing search strategy. RESULTS: From 4067 records relevant to off-label drug use in our full gold standard set, 3846 records were retrievable from EMBASE. "off label*.af." was the most sensitive single term (overall sensitivity 77.5%, sensitivity within EMBASE 81.9%, precision 88.1%). The highest sensitive search strategy was achieved by combining 36 search queries with overall sensitivity of 94.0% and precision of 69.5%. An optimal sensitive and precise search strategy was yielded precision 87.4% at the expense of decreasing overall sensitivity to 89.4%. CONCLUSION: We developed highly sensitive search strategies to enhance the retrieval of studies on off-label drug use in OvidSP EMBASE.

Evaluation of Pharmacovigilance System in Iran.

BACKGROUND: Evaluating a pharmacovigilance system helps identify its deficiencies and could facilitate measures to remedy and improve the quantity and quality of adverse drug reaction (ADR) reports and other opportunities for pharmacovigilance systems strengthening. This study aimed to evaluate the status of pharmacovigilance in Iran using the World Health Organization (WHO) pharmacovigilance indicators with the prospect of identifying the gaps and areas for improvement. METHODS: This study was conducted in 2 parts. The first part included a secondary analysis of the national data obtained from the Iranian National Pharmacovigilance Center (PVC) using a structured data collection form based on WHO core pharmacovigilance indicators. In the second part, a 3-month prospective study was carried out to investigate 2 outcome indicators, ie, length of stay and costs of medicine-related hospitalization in all patients of 2 main referral hospitals in the southeast and north of Iran. RESULTS: Iran has a PVC with national policy, trained staff, and a statutory budget. In 2017, the number of ADR reports was 15.0 per 100 000 population, and 262 signals were detected during the preceding 5 years. The average length of stay and costs of medicine-related hospitalization were 5 days and US$817.2 in Afzalipour hospital and 6.6 days and US$306.7 in Razi hospital, respectively. The status of pharmacovigilance in the Iranian public health programs (PHPs) is unknown, and most of the indicators could not be assessed. CONCLUSION: A robust pharmacovigilance system is a pivotal part of the overall medicines regulatory system. The Iranian pharmacovigilance system has relatively the proper structural condition. Though the underreporting of ADRs, especially medicine-related deaths, is an important issue, and some indicators' status was unclear. The Iranian pharmacovigilance program requires a higher prioritization, particularly in the PHPs, a greater allocation of resources, and cross-sectoral cooperation to bolster and achieve the pharmacovigilance objectives.