Utilization and safety of proton-pump inhibitors and histamine-2 receptor antagonists in children and adolescents: an observational cohort study

Background: Little is known about the use of acid-suppressing treatments and related safety events in children.

Objective: This study compared patient characteristics and safety outcomes among children prescribed acid-suppressing drugs for the first time.

Methods: The Health Improvement Network was used to determine the characteristics of children prescribed a proton pump inhibitor (PPI; esomeprazole or another PPI) or a histamine-2 receptor antagonist (H₂RA) by UK primary care physicians between October 2009 and September 2012. Pre-defined safety outcomes were compared among the treatment groups in up to 18 months of follow-up.

Results: The cohorts comprised 8,172 patients on PPIs (including 24 patients on esomeprazole) and 7,905 on H₂RAs. The baseline characteristics were similar between cohorts, although the children in the PPI cohorts tended to be older. No safety outcomes occurred in the esomeprazole cohort. In the other-PPIs cohort, 92 safety outcomes occurred, most commonly gastroenteritis (n?=?36; 39.1%). In the H₂RAs cohort, 193 safety outcomes occurred, most commonly gastroenteritis (n?=?62; 32.1%). The incidence of most safety outcomes was higher in the H₂RAs cohort than in the other-PPIs cohort, including failure to thrive (3.11 [95% confidence interval (CI)?=?2.25–4.28] vs 0.49 per 1,000 person-years [95% CI?=?0.22–1.07]) and gastroenteritis (5.27 [95% CI?=?4.11–6.75] vs 3.04 per 1,000 person-years [95% CI?=?2.20–4.20]).

Conclusion: Esomeprazole is rarely prescribed to children when they first require acid-suppressing medication, compared with other PPIs/H₂RAs. Overall, more safety outcomes occurred in the H₂RAs cohort than in the PPI cohorts.     

Increased subsequent risk of inflammatory bowel disease association in patients with chronic pancreatitis: a nationwide population-based cohort study

Purpose: To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study.

Methods: Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts.

Results: When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn’s disease (adjusted hazard ratio [aHR]?=?12.9, 95% confidence interval [CI]?=?5.15–32.5) and ulcerative colitis (aHR?=?2.80, 95% CI?=?1.00–7.86).

Conclusions: This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.     

The effect of antibiotic prophylaxis for acute pelvic inflammatory disease after hysterosalpingography: a retrospective cohort study

Aims: Concerns about acute pelvic inflammatory disease (PID) after hysterosalpingography (HSG) have been raised since 1980. However, the effectiveness of prophylactic antibiotics remains unclear. This study investigated the effect of antibiotic prophylaxis in women undergoing HSG.

Methods: Women undergoing HSG between 2000 and 2012 were screened from the Taiwan National Health Insurance Research Database for eligibility. The prophylactic cohort included patients using any antibiotics of 1st-generation cephalosporins, doxycycline, clindamycin, and metronidazole, within 7 days before HSG (n?=?3257). Patients not using any antibiotics were registered as the non-prophylactic cohort (n?=?4662). An unconditional logistic regression model was applied to calculate the odds ratio (OR) and 95% confidence interval (CI) of acute PID after HSG associated with prophylactic antibiotics.

Results: The cumulative incidences of acute PID after HSG were 0.46% and 1.42% in the prophylactic and non-prophylactic cohorts, respectively. Prophylactic patients had a significantly reduced estimated relative risk of acute PID compared with non-prophylactic patients (adjusted OR?=?0.33, 95% CI?=?0.19–0.58; p?=?.001). Doxycycline users had the lowest adjusted OR of 0.20 (95% CI?=?0.04–0.81; p?=?.02), followed by users of 1st-generation cephalosporins (adjusted OR?=?0.35, 95% CI?=?0.18–0.68; p?=?.002). Multivariate sub-group analysis verified this protective effect for almost all sub-groups of prophylactic patients.

Conclusions: Antibiotic prophylaxis is associated with a decreased estimated relative risk of acute PID in HSG patients. Doxycycline and 1st-generation cephalosporins may be effective prophylactic regimens for HSG.     

Pediatric drug safety signal detection of non-chemotherapy drug-induced neutropenia and agranulocytosis using electronic healthcare records

Objectives: This study aimed to develop a procedure to explore the adverse drug reaction signals of drug-induced neutropenia (DIN) or drug-induced agranulocytosis (DIA) in children using an electronic health records (EHRs) database.

Methods: A two-stage design was presented. First, the suspected drugs to induce DIN or DIA were selected. Second, the associations were evaluated by a retrospective cohort study.

Results: Ten and five drugs were potentially identified to be associated with DIN and DIA, respectively. Finally, five (oseltamivir, chlorpheniramine, vancomycin, meropenem, and ganciclovir) and two (chlorpheniramine, and vancomycin) drugs were found to be associated with DIN and DIA, respectively. Of these, the association between oseltamivir and neutropenia (P = 9.83 × 10^–9; OR, 2.10; 95% CI, 1.62?2.69) was considered as a new signal for both adults and children. Chlorpheniramine-induced neutropenia (P = 3.01 × 10^–8; OR, 1.59; 95% CI, 1.35?1.87) and agranulocytosis (P = 3.16 × 10^–7; OR, 3.76; 95% CI, 2.25?6.26) were considered as new signals in children. Other drugs associated with DIN or DIA were confirmed by previous studies.

Conclusion: A method to detect signals for DIN and DIA has been described. Several pediatric drugs were found to be associated with DIN or DIA.     

Association between neurodegenerative diseases and pneumonia: a retrospective population-based study

Purpose: The association between pneumonia and neurodegenerative diseases (NDs) has never been reported in detail. We address this relationship with reference to the general population.

Methods: Using Taiwan’s National Health Insurance Research Database to identify a pneumonia cohort (including the typical and atypical), we established an ND cohort of 19,062 patients and a non-ND cohort of 76,227 people. In both cohorts, the risk of pneumonia was measured using multivariable Cox proportional hazards models.

Results: The adjusted hazard ratio (aHR) (95% confidence interval [CI]) for the pneumonia cohort was 2.10 (1.96–2.24), regardless of age, sex, comorbidities or drug use in the ND cohort. The aHR (95% CI) for adults aged 20–49 years was 2.08 (1.58–2.75), men 2.20 (2.01–2.40). However, older subjects were at greatest risk of pneumonia, (3.41 [2.99–3.88]) if the 20–49 years age group is used as the reference. For the ND and non-ND cohorts, those with comorbidities (with the exception of hyperlipidemia) had higher risk; aHR (95% CI) 2.35 (2.30–2.52). The aHR (95% CI) for those without comorbidities is 3.28 (2.52–4.26). No significant difference was observed in incidence of pneumonia between those who were and were not using statin medications; the aHR (95% CI) was 1.03 (0.93–1.14).

Conclusion: The ND cohort had a higher risk of pneumonia, regardless of age, sex, comorbidities or statin use. The risk of pneumonia was higher in elderly and male patients in the ND cohort.     

Treatment stabilization in children and adolescents with attention-deficit/hyperactivity disorder: data from the Netherlands

Abstract

Objective:

To evaluate the number of patients reaching stable treatment with a stimulant (methylphenidate or dexamphetamine) or non-stimulant (atomoxetine) attention-deficit/hyperactivity disorder (ADHD) medication approved for use in the Netherlands, and the time to treatment stabilization among children and adolescents aged 6–17 years.     

Differences between statins on clinical endpoints: a population-based cohort study

ABSTRACT

Objective: Many studies have shown differences between statins based on surrogate endpoints, but few have studied differences in reaching clinical endpoints.

This study compares the risk of cardiovascular and cerebrovascular events between atorvastatin users and other statin users in daily general practice.

Research design and methods: A cohort study was performed in the Integrated Primary Care Information project database, a longitudinal general practice research database with electronic patient records of more than 500?000 individuals in the Netherlands. All new statin users in the period 1st September 1999 to 31st December 2002 were included. Multivariate Cox-regression analysis was used to compare the occurrence of the primary endpoint between atorvastatin users and other statin users.

Main outcome measures: The primary endpoint was the composite outcome of fatal or non-fatal myocardial infarction, admission for unstable angina pectoris, fatal or non-fatal cerebrovascular accidents, or transient ischaemic events.

Results: 3499 new statin users were identified, including 797 patients with a history of cardiovascular disease. 1341 persons started with simvastatin (38.3%), 1154 with atorvastatin (33.0%), 811 with pravastatin (23.2%) and 193 with other statins (5.5%). The median follow-up was 1.9 years. Two hundred and thirty three patients (6.7%) experienced a primary endpoint. Atorvastatin users had a significantly lower risk of cardiovascular and cerebrovascular events than users of other statins (relative risk [RR]: 0.70, 95% confidence interval [CI]: 0.55–0.96). The relative risks of atorvastatin users compared to simvastatin and pravastatin users individually were 0.70 (95% CI: 0.48–1.02) and 0.78 (95% CI: 0.52–1.16), respectively. The protective effect of atorvastatin was more pronounced in persons without a history of cardiovascular or cerebrovascular events.

Conclusion: Atorvastatin showed a more favourable effect on fatal and non-fatal cardiovascular and cerebrovascular events in the general population than other statins.     

The risk of fractures,acute myocardial infarction,atrial fibrillation and ventricular arrhythmia in geriatric patients exposed to promethazine

ABSTRACT

Objectives: This study aimed to compare the risk of fractures, acute myocardial infarction, atrial fibrillation, and ventricular arrhythmia among Danish citizens aged ≥ 65 which were new users of promethazine or domperidone, triazolam, loratadine, and betahistine. Secondly, the study aimed to perform a risk stratification to identify the most relevant predictors for the study outcomes.

Methods: The study period was 01/01/2015 to 31/12/2016. The data sources were the Danish registers. Each patient was followed for 90 days. A logistic regression model was used to compute the unadjusted and adjusted odds ratios (OR), and a conditional inference tree was used to identify the most relevant predictors for the study outcomes.

Results: Promethazine had a higher risk of hospitalization for atrial fibrillation than loratadine and betahistine (OR 1.58; 95% CI 1.07–2.63 and OR 3.22; 95% CI 1.69–7.14, respectively). For fractures, acute myocardial infarction, and ventricular arrhythmia hospitalizations, no statistically significant differences were found among drugs under investigation. The medical history of cardiac arrhythmia (OR 4.14; 95% CI 2.94–5.78, p < 0.0001) was the most relevant predictor for atrial fibrillation hospitalizations.

Conclusion: This study found an increased risk of atrial fibrillation hospitalization among promethazine users, and the risk was higher among patients with prior cardiac arrhythmia.     

Lung function in oil spill responders 4-6 years after the Deepwater Horizon disaster

ABSTRACT

Oil spill response and clean-up (OSRC) workers were exposed to hazardous airborne chemicals following the 2010 Deepwater Horizon disaster. The aim of this study was to evaluate lung function in workers 4–6 years following the disaster using a prospective cohort. Participants who completed two spirometry test sessions 1–3 years, and 4–6 years after the spill (N = 1,838) were included and forced expiratory volume in 1 s (FEV₁; ml), forced vital capacity (FVC; ml), and ratio (FEV₁/FVC; %) determined. Linear mixed models were utilized to estimate relationships between OSRC exposures and lung function 4–6 years after the spill and changes since the prior measurement. Despite suggestive reduced lung function at 1–3 years, at the 4–6-year exam workers with total hydrocarbon (THC) exposure 1–2.99 ppm and ≥3 ppm compared to those with ≤0.29 ppm exhibited higher FEV₁ (β: 108 ml, 95% CI: 17, 198) and (β: 118 ml, 95% CI: 5, 232), respectively. Compared with support workers, those in higher exposed jobs displayed greater improvement in FEV₁ between visits: cleanup on water (β: 143 ml, 95% CI: 35, 250), operations (β: 132 ml, 95% CI: 30, 234) and response (β: 149 ml, 95% CI: 43, 256). Greater FEV₁ improvement was also associated with higher versus the lowest level THC exposure: 1–2.99 ppm (β: 134 ml, 95% CI: 57, 210) and ≥3 ppm (β: 205 ml, 95% CI: 109, 301). Lung function decrements seen shortly after the spill were no longer apparent 4–6 years later, with the greatest improvement among those with the highest exposures.     

All-cause hospitalization and associated costs in patients with schizophrenia or bipolar disorder initiating long-acting injectable antipsychotics

Objective: To compare all-cause hospitalization and associated costs among patients with schizophrenia or bipolar disorder (BD) treated with long-acting injectable antipsychotics (LAIs).

Methods: The Truven MarketScan Medicaid claims database was used to identify patients with schizophrenia; MarketScan Medicaid and commercial claims databases were used to identify BD. Adult patients with ≥1 LAI claim from January 1, 2013–June 30, 2014 (ID period) were identified. The first day of LAI initiation was the index date; patients were followed for ≥1 year. Logistic and general linear regression models were used to estimate the risk of hospitalization and associated costs.

Results: Adjusted analyses showed that, in the schizophrenia cohort, risks of hospitalization were statistically significantly higher in the haloperidol [OR (95% CI)?=?1.51 (1.05–2.16); HR (95% CI)?=?1.35 (1.05–1.73)] and risperidone [OR (95% CI)?=?1.58 (1.07–2.33); HR (95% CI)?=?1.33 (1.01–1.74)] cohorts than in the aripiprazole once monthly extended release (AOM 400) cohort. Similarly, in patients with BD, risks of hospitalization were significantly higher in haloperidol [OR (95% CI)?=?1.49 (1.01–2.19); HR (95% CI)?=?1.33 (1.03–1.73)] and risperidone [OR (95% CI)?=?1.78 (1.19–2.66); HR (95% CI)?=?1.33 (1.01–1.75)] than in AOM400. No statistically significant differences in hospitalization costs were observed in either disease group.

Conclusions: Although the study results may be subject to confounding variables that are not contained in claims databases, such as disease severity, it appears that AOM400 may be more effective than haloperidol and risperidone LAIs among patients with schizophrenia or BD.     

Clinical and economic outcomes by first-line treatment among women with HR+/HER2– metastatic breast cancer in a large US health plan database

Background: Guidelines recommend that women with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (mBC) initiate hormonal therapy before chemotherapy. This study compared outcomes of women with mBC who received chemotherapy first vs hormonal therapy.

Methods: A retrospective cohort study of women with mBC was conducted using a large US commercial health plan database between January 1, 2008–April 30, 2013. Subjects had evidence of a HR+/HER2– tumor sub-type in a cancer registry and use of chemotherapy or hormonal therapy in claims. Subjects were continuously enrolled for ≥6 months after metastasis and assigned to cohorts for receiving chemotherapy only or hormonal therapy only during first-line (CT-1L vs HT-1L). Adjusted incidence rates of clinically significant events were compared using a negative binomial model, and adjusted healthcare costs were compared using a generalized linear model.

Results: Three hundred and twenty-four women with HR+/HER2– mBC met the selection criteria; 179 (55%) received CT-1L and 145 (45%) received HT-1L. Mortality rates did not differ between cohorts (unadjusted incidence rate ratio (IRR)?=?1.67, 95% CI?=?0.82–3.46; adjusted IRR?=?0.64, 95% CI?=?0.32–1.27). Adjusted average total all-cause healthcare costs were $11?090 for women with CT-1L and $6743 for women with HT-1L (cost ratio =1.64, 95% CI =1.36–1.99).

Conclusions: Observed use of first-line chemotherapy (>50%) was higher than expected given the HR?+?molecular profile of the tumors. Chemotherapy use during first-line did not appear to be associated with a survival benefit, but was associated with significantly higher costs compared with the use of hormonal therapy during first-line; however, this comparison is limited by demographic and baseline characteristic differences between the two cohorts. This study contributes to understanding real-world treatment patterns and the associated clinical and economic outcomes of using chemotherapy vs hormonal therapy as a first-line treatment option for the HR+/HER2– mBC population.     

Predictors of mortality in atypical antipsychotic-treated community-dwelling elderly patients with behavioural and psychological symptoms of dementia: a prospective population-based cohort study from Italy

Purpose

To evaluate the effect of a broad range of covariates on the survival of a real-life long-term follow-up cohort of community-dwelling patients with behavioural and psychological symptoms of dementia who were new users of atypical antipsychotic medications (APMs).

Methods

This was a prospective cohort study of 1,618 subjects aged ≥65 years with dementia and BPSD (“behavioural and psychological symptoms of dementia”) who were new users of atypical APMs and registered in a Dementia Evaluation Unit of Campania Region (Italy) from September 2006 to March 2010. The potential of baseline features to predict mortality was assessed with the Cox proportional hazards model.

Results

The average follow-up was 309 days. Of the 1,618 new users of atypical antipsychotics, 9.3 % experienced at least one adverse event, including death (5.1 %), drug therapeutic failure (3.0 %), extrapyramidal symptoms (0.5 %) and stroke (0.2 %). The crude all-cause mortality rate was 6.0 per 100 person-years [95 % confidence interval (CI) 4.8–7.4]; the rate was higher in patients aged >85 years (9.0 per 100 person-years, 95 % CI 6.4–12.7) and among male patients (7.5 per 100 person-years, 95% CI 5.3–10.6). In the multivariate analysis, only age was associated to all-cause mortality [hazard ratio (HR) 1.1; 95 % CI 1.0–1.1 and HR 1.4; 95 % CI: 0.9–2.2, respectively). In contrast, hallucination (HR 0.4; 95 % CI 0.2–0.6) and dosage change (HR 0.4; 95 % CI 0.2–0.78) were significantly associated with a lower risk of all-cause mortality.

Conclusions

Among our patient cohort, the mortality rate of patients with BPSD receiving long-term treatment with atypical APMs was lower than that reported in other studies, and only age was found to be significant predictor factor of mortality.     

Incidence and risk of proteinuria associated with newly approved vascular endothelial growth factor receptor tyrosine kinase inhibitors in cancer patients: an up-to-date meta-analysis of randomized controlled trials

ABSTRACT

Objective: We performed a meta-analysis to quantify the overall incidence and risk of proteinuria associated with five newly approved VEGFR-TKIs (regorafenib, vandetanib, cabozantinib, lenvatinib, axitinib) in cancer patients.

Methods: Pubmed, Embase, ASCO abstracts, and ESMO abstracts were searched to identify relevant studies. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were estimated using random or fixed effects models according to the heterogeneity of included studies.

Results: A total of 9,446 patients from 20 RCTs were included for the meta-analysis. The use of newly approved VEGFR-TKIs was associated with an increased risk of all-grade (RR 2.35, 95% CI 1.69–3.27, P < 0.001) and high-grade (RR 3.70, 95% CI 2.09–6.54, P < 0.001) proteinuria. On subgroup analysis, lenvatinib, axitinib, and vandetanib significantly increased the risk of all-grade proteinuria, and lenvatinib was associated with an increased risk of high-grade proteinuria. In addition, the risk of developing high-grade proteinuria events was significant for patients with hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), but not for patients with colorectal cancer (CRC) and thyroid cancer (TC).

Conclusion: Treatment with newly approved VEGFR-TKIs significantly increases the risk of developing proteinuria events in cancer patients, especially for patients treated with lenvatinib.     

Characteristics of children and adolescents first prescribed proton pump inhibitors or histamine-2-receptor antagonists: an observational cohort study

Objective: To describe the characteristics of pediatric patients prescribed proton pump inhibitors (PPIs) vs those of pediatric patients prescribed histamine-2-receptor antagonists (H₂RAs).

Methods: Observational studies were conducted using The Health Improvement Network (THIN) and the PHARMO Database Network. Patients aged 0–18 years who were first prescribed a PPI or H₂RA between October 1, 2009 and September 30, 2012 (THIN) or between September 1, 2008 and August 31, 2011 (PHARMO) were included. Patient characteristics were identified and compared between the PPI and H₂RA cohorts using odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age and sex.

Results: The mean age (years) was higher in the PPI than in the H₂RA cohorts (THIN 12.3 [n?=?8204] vs 5.4 [n?=?7937], PHARMO 11.0 [n?=?15 362] vs 7.1 [n?=?6168]). Previous respiratory disease was more common in the PPI than in the H₂RA cohort in THIN (OR?=?1.19, 95% CI?=?1.08–1.30), as were asthma and respiratory medication use in PHARMO (OR?=?1.27, 95% CI?=?1.12–1.45 and OR?=?1.23, 95% CI?=?1.10–1.38, respectively) and oral corticosteroid use in both databases (OR?=?1.45, 95% CI?=?1.10–1.92 [THIN]; OR?=?2.80, 95% CI?=?2.11–3.71 [PHARMO]). Non-steroidal anti-inflammatory drugs, antibiotics, and oral contraceptives were also more common in PPI than in H₂RA cohorts in both databases.

Conclusions: Pediatric patients receiving PPIs and those receiving H₂RAs may represent different patient populations. PPIs may be more commonly prescribed than H₂RAs among patients with respiratory diseases.     

Healthcare resource utilization of second-generation long-acting injectable antipsychotics in schizophrenia: risperidone versus paliperidone palmitate

Objective: This retrospective longitudinal cohort study aimed to compare treatment patterns, healthcare resource utilization (HRU), and costs in patients with schizophrenia treated with second-generation antipsychotic long-acting injectables (SGA-LAIs): biweekly risperidone LAI versus once-monthly paliperidone palmitate.

Methods: Patients who initiated risperidone LAI or paliperidone palmitate between 1 July 2007 and 31 December 2012 (index date) were identified from the Truven MarketScan Commercial, Medicare Supplemental, and Medicaid Multi-State insurance databases. Outcomes were assessed 12 months after the index date. Propensity score matching (1:1) based on patients’ demographics and comorbidities was conducted. Outcome differences between the two cohorts were evaluated using t-tests for continuous variables, chi-square tests for categorical variables, and Wilcoxon rank-sum tests for count and cost variables. Regression models estimated the difference in medication use and adherence, likelihood of HRU, number of HRU events, and healthcare costs when comparing risperidone LAI versus paliperidone palmitate, while further adjusting for patient characteristics and pre-index HRU.

Results: Patient characteristics were well balanced between the two cohorts (n?=?499 each). Significantly lower discontinuation rates (36.5% vs. 53.3%; p?<?0.001) and longer days of LAI coverage (233.6 vs. 131.7 days; p?<?0.001) were observed in the paliperidone palmitate cohort versus the risperidone LAI cohort, respectively. Patients treated with paliperidone palmitate were 12.5 (95% confidence interval [CI]: 9.0–17.8) and 11.7 (95% CI: 8.0–17.4) times more likely to be adherent based on medication possession ratio and proportion of days covered, respectively (p?<?0.001). Patients treated with paliperidone palmitate had reduced likelihood of hospitalization (adjusted odds ratio [95% CI]: 0.72 [0.55–0.95]), fewer emergency department (ED) visits (adjusted incidence rate ratio [aIRR]: 0.67 [0.61–0.73]) and reduced length of inpatient stay (aIRR: 0.86 [0.82–0.90]), which resulted in lower monthly inpatient hospitalization costs (-$77.58; p?=?0.038) and ED visits (-$9.77; p?=?0.021) relative to risperidone LAI.

Limitations: Pharmacy costs were derived from health plan payment in the claims data and do not account for any discounts or rebates. This may have overestimated the branded drug costs in this analysis.

Conclusions: These findings highlight the value of once-monthly paliperidone palmitate in the treatment of patients with schizophrenia.     

Risk of pneumonia and other complications of influenza-like illness in patients treated with oseltamivir

ABSTRACT

Background: Clinical trials suggest that the risk of pneumonia and other sequelae of influenza may be reduced in patients using oseltamivir.

Research design and methods: This retrospective cohort study used U.S. health insurance claims data. Patients were grouped into three cohorts: (1) diagnosed with influenza-like illness (ILI) and received a dispensing of oseltamivir; (2) diagnosed with ILI but received no antiviral medication; and (3) received oseltamivir without a physician diagnosis of ILI. Baseline factors assessed included demographics, history of drug dispensings, diagnoses, and vaccinations.

Main outcome measures: Outcomes included diagnosis of pneumonia, dispensing of an antibiotic, or hospitalization within 30 days after an ILI diagnosis or oseltamivir dispensing.

Results: The adjusted hazard ratio for ILI with oseltamivir compared to ILI without antivirals for pneumonia was 0.72 (95% CI, 0.60–0.86), for antibiotic dispensing was 0.89 (95% CI, 0.86–0.93), and for hospitalization was 0.74 (95% CI, 0.61–0.90). The cohort who received oseltamivir without an ILI diagnosis did not differ significantly in risk of any outcome from the ILI with oseltamivir cohort.

Conclusions: The risk of pneumonia, antibiotic dispensing, and hospitalization was reduced in patients with ILI who received oseltamivir compared to no antiviral therapy. These findings were based on health care claims only and have not been verified through medical record review.     

Regular use of acetaminophen or acetaminophen–codeine combinations and prescription of rescue therapy with non-steroidal anti-inflammatory drugs: a population-based study in primary care

Objective: There are contrasting positions concerning the benefit–risk ratio of acetaminophen use for osteoarthritis (OA)-related pain. To clarify the effectiveness of acetaminophen or acetaminophen–codeine combinations according to their regimen of use, we evaluated whether being a regular user (adherent) of these medications decreased the occurrence of rescue therapy with non-steroidal anti-inflammatory drugs (NSAIDs).

Methods: Using the Health Search IMS Health Longitudinal Patient Database, we formed a cohort of patients aged ≥18 years and newly treated with acetaminophen or acetaminophen–codeine combinations for OA between 1 January 2001 and 31 December 2013. These patients were followed up for one year in which they were categorized as regular or irregular users of these medications according to a variable medication possession ratio (VMPR)?≥?50% or lower. We operationally defined the rescue therapy as the use of any NSAIDs prescribed for OA-related pain.

Results: Overall, 40,029 patients (69.5% females; mean age: 68?±?13.57) treated with acetaminophen or acetaminophen–codeine combinations formed the cohort. After the first year of treatment, regular users showed a statistically significantly lower risk of being prescribed with rescue therapy with NSAIDs (OR?=?0.89; 95% CI 0.84–0.96).

Conclusion: These findings show that regular use of acetaminophen or acetaminophen–codeine combinations may reduce the need for NSAIDs to treat OA-related pain.