Comparing healthcare cost associated with the use of enzyme-inducing and non-enzyme active antiepileptic drugs in elderly patients with epilepsy in the UK: a long-term retrospective, matched cohort study.

BACKGROUND: In elderly patients (≥65 years of age) with epilepsy who take medications for comorbid conditions, some antiepileptic drugs (AEDs) may alter the metabolism of other treatments and increase the risk of adverse consequences and healthcare utilisation. This analysis compares healthcare costs associated with enzyme-inducing AEDs (EIAEDs) and non-enzyme active AEDs (nEAAEDs) use in elderly patients with epilepsy. METHODS: This retrospective matched cohort study used the Clinical Practice Research Datalink (CPRD) of UK primary care medical records, linked to the Hospital Episode Statistics (HES) database. Selected patients with epilepsy were ≥ 65 years and prescribed an EIAED or nEAAED between 2001 and 2010 (index) after ≥1 year without AEDs (baseline) and followed until the first occurrence of the following: end of HES data coverage, end of GP registration, or death; practice's up-to-standard status or addition of an AED belonging to another cohort or discontinuation of the last AED of that cohort. Propensity score matching reduced confounding factor effects between cohorts. Key outcomes included time to cohort treatment failure, time to index AED treatment failure, and direct healthcare costs in 2014 Pound Sterling (£) values. RESULTS: Overall, 1425 elderly patients were included: 964 with EIAEDs and 461 with nEAAEDs. At baseline, the EIAED cohort was older (mean age, 76.2 vs. 75.1 years) and a higher proportion were male. Baseline direct healthcare costs were similar. After matching (n = 210 each), and over the entire follow-up period, median monthly direct healthcare costs were higher for patients taking EIAEDs than nEAAEDs (£403 vs. £317; p = 0.0150, Mann-Whitney U). Costs were higher for patients remaining in the EIAED cohort after 3 follow-up years. The median time to cohort treatment failure for the EIAED cohort was 1110 days vs. 1175 days for the nEAAED cohort. CONCLUSION: Newly treated elderly patients with epilepsy were more likely to be prescribed EIAEDs than nEAAEDs. In matched cohorts, elderly patients with epilepsy treated with EIAEDs had higher average total direct and epilepsy-related healthcare costs than nEAAED-treated patients; this difference was greater than previously reported in the overall adult population. Changing treatment practices could improve patient care and reduce costs.

Electronic medical record systems: A pathway to sustainable public health insurance schemes in sub-Saharan Africa.

Pubic health insurance schemes are usually set up by governments to provide cover for their insured populations against healthcare costs. These schemes are usually administered by a government agency and vary both in how they are funded and provide their services. A number of developing countries have introduced such schemes to minimise the impact of financial barriers to healthcare access by their populations. These schemes are expected to bridge the inequality in healthcare. A National Health Insurance Scheme has been in operation in Nigeria since 2005 to provide health cover for government employees and those in private institutions with no less than ten workers. There are similar schemes in a number of countries in sub-Saharan Africa. We conducted a literature review of publications on public health insurance schemes in sub-Saharan Africa to identify the challenges they encounter. We found 76 relevant publications. Although much have been published on these schemes, few have addressed the critical obstacles to effective implementation, management and sustenance in the unique environments we find in sub-Saharan Africa - where poor technological infrastructures, acts of forgery, counterfeiting and other forms of fraud are common. We highlight these challenges, using the scheme in Nigeria for reference. We discuss the potential role of robust electronic medical record (EMR) systems for sustainable schemes in such environments and describe some of the ways robust EMR systems could be used to mitigate the challenges posed by most of the peculiar problems associated with poor infrastructures.

Health care cost associated with the use of enzyme-inducing and non-enzyme-active antiepileptic drugs in the UK: a long-term retrospective matched cohort study.

BACKGROUND: Some antiepileptic drugs (AEDs) induce expression of hepatic enzymes. This can contribute to comorbidities via interference with metabolic pathways and concomitant drug metabolization, thereby increasing the likelihood of health care interventions. Using medical records, we compared the direct health care cost in patients initiating epilepsy therapy with enzyme-inducing AEDs (EIAEDs) vs non-enzyme-active AEDs (nEAAEDs) over up to 12 years. METHODS: Patients with untreated epilepsy were indexed in the UK Clinical Practice Research Datalink and Hospital Episode Statistics database when prescribed a new EIAED or nEAAED between January 2001 and December 2010. Propensity score matching reduced confounding factors between cohorts. Patients were followed until cohort treatment failure or data cut-off. The primary outcome was the median standardized monthly direct health care cost during follow-up in 2014 £GBP, calculated using published reference costs and compared using a Mann-Whitney U test. RESULTS: The unmatched EIAED cohort (n = 2752) was older (54 vs 46 years), more likely to be male, had more comorbidities, and higher health care resource use/cost during the 1-year pre-index period (median £3014 vs £2516) than the nEAAED cohort (n = 2,137). The most common index EIAED and nEAAED were carbamazepine (63.3%) and lamotrigine (58.0%), respectively. After matching, cohorts had similar features (n = 951 each). Over up to 12 years of follow-up, the median standardized monthly direct health care cost was £229 for the EIAED and £188 for the nEAAED cohorts (p = 0.0091). The median cost was higher for the EIAED cohort in every year of follow-up. In the two cohorts, 25.1% and 20.1% of total mean cost during follow-up was epilepsy-related, with approximately 4.6% and 3.0% for AED acquisition, respectively. The median time to cohort treatment failure was shorter in the matched EIAED cohort (468 vs 1194 days). CONCLUSIONS: Patients in the UK who initiated epilepsy therapy with an EIAED appeared to be at higher risk of complications associated with enzyme induction. In long-term matched cohort analyses, the median total direct health care cost associated with EIAED therapy was higher than with nEAAEDs. Changing current treatment practices could potentially improve patient outcomes and reduce costs.

Self-Medication Practices and Associated Factors in the Prevention and/or Treatment of COVID-19 Virus: A Population-Based Survey in Nigeria.

Background: The anxiety caused by the emergence of the novel coronavirus disease (COVID-19) globally has made many Nigerians resort to self-medication for purported protection against the disease, amid fear of contracting it from health workers and hospital environments. Therefore, this study aimed to estimate the knowledge level, causes, prevalence, and determinants of self-medication practices for the prevention and/or treatment of COVID-19 in Nigeria. Methods: A web-based cross-sectional survey was conducted between June and July 2020 among the Nigerian population, using a self-reported questionnaire. Statistical analysis of descriptive, bivariate, and multivariate analyses was done using STATA 15. Results: A total of 461 respondents participated in the survey. Almost all the respondents had sufficient knowledge about self-medication (96.7%). The overall prevalence of self-medication for the prevention and treatment of COVID-19 was 41%. The contributing factors were fear of stigmatization or discrimination (79.5%), fear of being quarantine (77.3%), and fear of infection or contact with a suspected person (76.3%). The proximal reasons for self-medication were emergency illness (49.1%), delays in receiving hospital services (28.1%), distance to the health facility (23%), and proximity of the pharmacy (21%). The most commonly used drugs for self-medication were vitamin C and multivitamin (51.8%) and antimalarials (24.9%). These drugs were bought mainly from pharmacies (73.9%). From the multivariable logistic regression model, males (OR: 0.79; 95% CI: 0.07-0.54), and sufficient knowledge on SM (OR: 0.64; 95% CI: 0.19-0.77) were significantly associated with self-medication. Conclusion: The key finding of this study was the use of different over-the-counter medications for the prevention (mainly vitamin C and multivitamins) and treatment (antibiotics/antimicrobial) of perceived COVID-19 infection by Nigerians with mainly tertiary education. This is despite their high knowledge and risk associated with self-medication. We suggest that medication outlets, media and community should be engaged to support the rational use of medication.

An Explainable Multimodal Neural Network Architecture for Predicting Epilepsy Comorbidities Based on Administrative Claims Data.

Epilepsy is a complex brain disorder characterized by repetitive seizure events. Epilepsy patients often suffer from various and severe physical and psychological comorbidities (e.g., anxiety, migraine, and stroke). While general comorbidity prevalences and incidences can be estimated from epidemiological data, such an approach does not take into account that actual patient-specific risks can depend on various individual factors, including medication. This motivates to develop a machine learning approach for predicting risks of future comorbidities for individual epilepsy patients. In this work, we use inpatient and outpatient administrative health claims data of around 19,500 U.S. epilepsy patients. We suggest a dedicated multimodal neural network architecture (Deep personalized LOngitudinal convolutional RIsk model-DeepLORI) to predict the time-dependent risk of six common comorbidities of epilepsy patients. We demonstrate superior performance of DeepLORI in a comparison with several existing methods. Moreover, we show that DeepLORI-based predictions can be interpreted on the level of individual patients. Using a game theoretic approach, we identify relevant features in DeepLORI models and demonstrate that model predictions are explainable in light of existing knowledge about the disease. Finally, we validate the model on independent data from around 97,000 patients, showing good generalization and stable prediction performance over time.

Recent trends in lung cancer and its association with COPD: an analysis using the UK GP Research Database.

BACKGROUND: The association between lung cancer and COPD has not been investigated in the primary care setting. METHOD: We determined the recent trends of lung cancer in COPD patients in the UK during the period 1991-2004, by investigating the population aged 45 and over in the General Practice Research Database. RESULTS: The annual-incidence rates of lung cancer per 10,000 person-years were at least four-fold higher in patients with prior COPD (increasing from 45 to 64 in men; 29 to 48 in women) compared with the general population (from 10 to 15 in men; 5 to 10 in women). These lung cancer trends had significant annual increases that were similar in men (5%) and in women (5.5%) with prior COPD; in contrast, the annual increases of lung cancer incidence rates in the general population differed by gender, being 4% in men but double in women (8%). The three-year survival for lung cancer patients among those with prior COPD was almost half that of the general population (15% versus 26%; p<0.01) and the highest mortality was observed in men aged 45-64 (83.79 per 100 person-years; 95% CI: 69.66-97.92). CONCLUSION: These results support the association of COPD and lung cancer observed in other settings.

Trends in antiepileptic drug treatment and effectiveness in clinical practice in England from 2003 to 2016: a retrospective cohort study using electronic medical records.

OBJECTIVE: To assess the evolution of antiepileptic drug (AED) treatment patterns and seizure outcomes in England from 2003 to 2016. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of electronic medical records from Clinical Practice Research Datalink and National Health Service Digital Hospital Episode Statistics databases. Patients newly diagnosed with epilepsy were identified and followed until end of data availability. Three eras were defined starting 1 April 2003 (first National Institute for Health and Care Excellence (NICE) guideline); 1 September 2007 (Standard and New Antiepileptic Drugs publication); and 1 January 2012 (second NICE guideline). OUTCOME MEASURES: Time from diagnosis to first AED; AED sequence; time from first AED to first 1-year remission period (no new AED attempts and no seizure-related healthcare events); time from first AED to refractoriness (third AED attempt regardless of reason); Kaplan-Meier analysis of time-to-event variables. RESULTS: 4388 patients were included (mean follow-up: 6.8, 4.2 and 1.7 years by era). 84.6% of adults (≥16 years), 75.5% of children (<16) and 89.1% of elderly subgroup (65+) received treatment within 1 year; rates were generally stable over time. Treatment trends included reduced use of carbamazepine (adult first line, era 1: 34.9%; era 3: 10.7%) and phenytoin, earlier line and increased use of levetiracetam (adult first line, era 1: 2.6%; era 3: 26.2%) and lamotrigine (particularly in adults and elderly subgroup), and a larger number of different AEDs used. Valproate use shifted somewhat to later lines. Rates of 1-year remission within 2 years of starting treatment increased in adults (era 1: 71.9%; era 3: 81.4%) and elderly (era 1: 76.1%; era 3: 81.7%). Overall, 55.5% of patients relapsed after achieving 1-year remission. Refractoriness rates remained stable over time (~26% of adults within 5 years). CONCLUSION: Treatment trends often were not aligned with era-relevant guidance. However, our results suggest a slight improvement in epilepsy treatment outcomes over the 13-year period.

Assessment and effect of a gap between new-onset epilepsy diagnosis and treatment in the US.

OBJECTIVE: To estimate the treatment gap between a new epilepsy diagnosis and antiepileptic drug (AED) initiation in the United States. METHODS: Retrospective claims-based cohort study using Truven Health MarketScan databases (commercial and supplemental Medicare, calendar years 2010-2015; Medicaid, 2010-2014) and a validation study using PharMetrics Plus Database linked to LRx claims database (2009-2014). Persons met epilepsy diagnostic criteria, had an index date (first epilepsy diagnosis) with a preceding 2-year baseline (1 year for persons aged 1 to <2 years; none for persons <1 year), and continuous medical and pharmacy enrollment without epilepsy/seizure diagnosis or AED prescription during baseline. Outcomes included percentage of untreated persons (no AED prescription) up to 3 years' follow-up and comparative outcomes (incidence rate ratio: untreated persons/treated persons), including medical events and health care resource utilization. RESULTS: In the primary study, 59,970 persons met selection (or inclusion) criteria; 36.7% of persons with newly diagnosed epilepsy remained untreated up to 3 years after diagnosis. In the validation study (N = 30,890), 31.8% of persons remained untreated up to 3 years after diagnosis. Lack of AED treatment was associated with an adjusted incidence rate ratio (95% confidence interval) of 1.2 (1.2-1.3) for medical events, 2.3 (2.2-2.3) for hospitalizations, and 2.8 (2.7-2.9) for emergency department visits. CONCLUSIONS: One-third of newly diagnosed persons remain untreated up to 3 years after epilepsy diagnosis. The increased risk of medical events and health care utilization highlights the consequences of delayed treatment after epilepsy diagnosis, which might be preventable.

Description of an incidence-based model for Assessing comorbidity patterns in disease natural history.

BACKGROUND: Patients with a chronic disease often suffer from other diseases called comorbidities, which can be important factors in the assessment of risks associated with the disease and its management. However, comorbidities can pose important methodological issues because factors such as time, age, duration and the disease can influence their impact on the risk of interest. METHODS: To identify comorbidities of a chronic disease, it is common practice to construct 2 separate cohorts of patients-a set with the disease and another as a random sample of patients free of the disease-and compare the event rates for each candidate's comorbidity over a specific period between the 2, while accounting for factors which may confound the results. We describe an incidence-based alternative approach that exploits the longitudinal properties of observational databases to track incident event rates along the natural history of the chronic disease. We illustrate it in a retrospective cohort of patients with chronic obstructive pulmonary disease (COPD) aged 50 and above-each patient with COPD was matched with another without COPD on certain confounding factors. RESULTS: We obtained 24 079 matched pairs. We found that chronic conditions such as lung cancer, asthma, fracture and osteoporosis were more common in patients with COPD. We also found evidence of time-varying associations. CONCLUSIONS: Our findings in COPD suggest that time is an important factor and comorbidity studies which are based on information in a single fixed period (such as first year postdiagnosis of COPD) are more likely to report spurious associations.

A Comparison of 2 Practical Cooling Methods on Cycling Capacity in the Heat.

CONTEXT: Cooling the torso and neck can improve exercise performance and capacity in a hot environment; however, the proposed mechanisms for the improvements often differ. OBJECTIVE: To directly compare the effects of cooling the neck and torso region using commercially available devices on exercise capacity in a hot environment (temperature = 35°C ± 0.1°C, relative humidity = 50.1% ± 0.7%). DESIGN: Crossover study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: Eight recreationally active, nonheat-acclimated men (age = 24 ± 4 years, height = 1.82 ± 0.10 m, mass = 80.3 ± 9.7 kg, maximal power output = 240 ± 25 W). INTERVENTION(S): Three cycling capacity tests at 60% maximal power output to volitional exhaustion: 1 with no cooling (NC), 1 with vest cooling (VC), and 1 with a neck cooling collar (CC). MAIN OUTCOME MEASURE(S): Time to volitional exhaustion, rectal temperature, mean skin temperature, torso and neck skin temperature, body mass, heart rate, rating of perceived exertion, thermal sensation, and feeling scale were measured. RESULTS: Participants cycled longer with VC (32.2 ± 9.5 minutes) than NC (27. 6 ± 7.6 minutes; P = .03; d = 0.54) or CC (30.0 ± 8.8 minutes; P = .02; d = 0.24). We observed no difference between NC and CC (P = .12; d = 0.31). Neck and torso temperature and perceived thermal sensation were reduced with the use of cooling modalities (P < .001), but no other variables were affected. CONCLUSIONS: Cycling capacity in the heat improved when participants used a commercially available cooling vest, but we observed no benefit from wearing a commercially available CC. The vest and the collar did not alter the heart rate, rectal temperature, skin temperature, or sweat-loss responses to the cycling bout.

Inhaled corticosteroids are more effective in COPD patients when used with LABA than with SABA.

Adding long-acting beta agonists (LABA) to inhaled corticosteroids (ICS) has been associated with beneficial effects in COPD patients in randomized controlled trials and observational studies. However, it is not known whether adding short-acting beta agonists (SABA) to ICS instead of LABA will be similarly effective in COPD. We compared the effectiveness of combination therapies involving ICS with LABA versus ICS with SABA in reducing risk of re-hospitalization or death among COPD patients within a year of discharge from a first COPD hospitalization. Using the UK General Practice Research Database, we obtained 437 pairs of patients who either used ICS plus LABA or ICS plus SABA, each pair having been matched on disease severity. We found that 12.1% of patients prescribed ICS with LABA experienced re-hospitalization or death within 12 months compared with 18.1% among those given ICS with SABA. In multivariate analyses, we found a 38% risk reduction (P<0.007) among patients given ICS with LABA relative to those given ICS with SABA. Models stratified by SABA use generated a risk reduction of 35% (P=0.02) among those given ICS and LABA with SABA in the 90-day period, and of 49% (P<0.05) among those given ICS and LABA without any SABA compared with the combination users of ICS and SABA. We conclude that in moderate to severe COPD patients, the combined use of ICS with LABA is more effective in reducing the risk of re-hospitalization or death than the combined use of ICS with SABA.

Gender differences in the management and experience of Chronic Obstructive Pulmonary Disease.

Whether women receive the same medical care for COPD as men and if they are at risk of different outcomes as a result, is not known. The Confronting COPD International Survey was performed in the USA, Canada, France, Italy, Germany, The Netherlands, Spain and the UK in 2000 with 3265 COPD participants. Forty-one per cent were women; mean age in women and men was 61.2 (SD 10.5) and 64.4 (11.0) years, mean pack-years of smoking 36 (29) and 46 (35) years, respectively. After adjusting for age, pack-years, country and severe dyspnea (MRC scores 5 and 4), women were less likely to have had spirometry (OR 0.84, 95% C.I. 0.72-0.98) but more likely to get smoking cessation advice (OR 1.57, 1.33-1.86). Despite significantly lower pack-years of smoking, women were more likely to report severe dyspnea than men (OR 1.30, 1.10-1.54), with similar cough (OR 1.08, 0.92-1.27) and less sputum (OR 0.84, 0.72-0.98). There were no differences in the risk of hospitalisation or emergency room visit. This study indicates that gender differences in COPD care and outcomes exist.

A pathway to improved prospective observational post-authorization safety studies.

Randomized controlled trials (RCTs) are the gold standard for assessing the efficacy of drugs but not necessarily so for drug safety where inadequate power to detect either multiple or rare adverse events is a major handicap. Furthermore, the conditions under which drugs are approved for market use are often different from the settings in actual use. Indeed, with their control mechanisms, trials are by design largely inadequate for the identification of potential safety signals, especially of the rare type, hence the value of postmarketing surveillance and risk management plan-based activities. Today, clinical trials constitute only a part of the research that goes into assessing the safety of drugs. Observational studies, where the investigators merely collect data on treatments received by patients and their health status in routine clinical practice are increasing in uptake because they reflect the real-life utility of drugs, despite the absence of random treatment assignment. Although such studies generally provide less compelling evidence than RCTs, they can be far more useful to drug safety assessment activities than generally acknowledged. An increasing number of post-authorization safety studies (PASS) within the European Medicines Agency's jurisdiction are of the observational type - considered perhaps as more appropriate vehicles for exploring and documenting how products perform in the real world. A similar trend is emerging in the US following the FDA Amendments Act of 2007; since early 2010, an increasing number of post-approval commitments mandated by the FDA include observational studies. However, despite this pattern, not much is known about ongoing efforts to address many of the recognized inadequacies associated with existing methodologies and practices currently adopted in observational PASS. This current opinion presents an overview of some of the main challenges we face in prospective observational PASS, mainly from practical experience, and proposes certain steps for improvement.

How real is intention-to-treat (ITT) analysis in non-interventional post authorization safety studies? We can do better.

Although cohort studies which are based on intention-to-treat (ITT) approach offer a simple design with data which are simpler to analyse and results easier to interpret, such studies also intrinsically assume that any time-varying treatment effect that exits can be adequately estimated by a fixed-effect component. However, such an assumption may not reflect real-life drug use. Reflection of real-life clinical practice is a major strength of epidemiologic safety studies. The failure to properly reflect reality may result in effect under-estimation leading to false and irreproducible conclusions due to exposure misclassification. In effect, the use of nested case-control design is a concesion that ITT in cohort design may not be adequate. But the nested design also has its own sources of bias, including confounding by indication. We present an overview of the counter-matched version of the nested case-control, case-crossover, case-in-time, case series and case-cohort designs as alternatives in prospective post-authorization safety studies.

Inhaled corticosteroids and risk of lung cancer among COPD patients who quit smoking.

RATIONALE AND OBJECTIVES: COPD is associated with an increased risk of lung cancer. We examined whether inhaled corticosteroids (ICS) used concomitantly with long-acting beta(2)-agonists (LABA) were associated with reduction in lung cancer risk in COPD patients. METHODS: We conducted a retrospective cohort study of patients with a first-time diagnosis of COPD (index date) between 1989 and 2003 who were initially free of lung cancer, had quit smoking, were aged >or=50 years at time of diagnosis, and were regular users of ICS, ICS/LABA concomitantly, or short-acting bronchodilators (SABD). A nested case-control design was applied to overcome the time-varying nature of treatment. RESULTS: We identified 7079 COPD patients who were regular users of the therapies of interest, of whom 127 subsequently had lung cancer and were matched to 1470 controls of same gender and age. Lung cancer was diagnosed in 6.0% of concomitant ICS/LABA users compared with 7.3% of ICS and 10.9% of SABD users. In multivariate analyses, reductions in lung cancer risk were observed, with hazard ratio (HR) 0.50 (95% confidence interval, 0.27-0.90) in ICS/LABA users and 0.64 (0.42-0.98) in ICS users, compared with SABD users. In assessing 'dose-response' relationships, we found risk reductions: HR of 0.75 (0.33-1.75) and 0.39 (0.19-0.79) in ICS/LABA users with 1-2 and 3+ prescriptions/year, respectively, and 0.88 (0.51-1.52) and 0.51 (0.30-0.84) in ICS users with 1-2 and 3+ prescriptions/year, respectively. CONCLUSIONS: Regular use of ICS, with and without LABA, may reduce the risk of lung cancer among former smokers with diagnosed COPD.

Chronic obstructive pulmonary disease and hospitalizations for pneumonia in a US cohort.

OBJECTIVE: To better understand risk factors for pneumonia hospitalizations in people with impaired lung function. METHODS: We analyzed longitudinal data from participants in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). We limited our analysis to 20,375 participants aged 45 and older at baseline. We stratified the sample based on prebronchodilator baseline lung function data, according to modified GOLD criteria, including a "restrictive" category (FEV(1)/FVC>70% and FVC<80%). We defined "pneumonia" as a hospitalization with a pneumonia discharge diagnosis (ICD-9 codes 480-486) within 36 months. We used Cox proportional hazard models to determine pneumonia risk associated with COPD stage, adjusting for age, sex, race, smoking status and comorbid disease (diabetes mellitus or cardiovascular disease at the baseline examination). RESULTS: Pneumonia hospitalization risk was associated with older age, male gender, comorbid conditions, smoking status, and level of lung function impairment. Overall, people with normal lung function had the lowest pneumonia hospitalization rate (1.5 per 1000 person-years) and those with GOLD stage 3 or 4 COPD had the highest rate (22.7 per 1000 person-years). After adjusting for other potential confounding factors, GOLD stages 3 or 4 and 2 COPD were associated with an increased risk of pneumonia (hazard ratio [HR] 5.65, 95% confidence interval [CI] 3.29, 9.67 and 2.25 (1.35, 3.75), respectively) relative to normal lung function. CONCLUSION: COPD severity (GOLD stage) is an important and independent predictor of pneumonia hospitalizations in this cohort.