Thomas Cars

Small-area variations in sales of TNF inhibitors in Sweden between 2000 and 2009

Objective: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors. Methods: For 2000–2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden. Results: From 2000 to 2009, annual TNF inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7–5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold in 2009 (24%). During the same period, total drug expenditure per capita remained at a 1.2-fold county variation (4–6%). Sales per capita variations of non-biologic treatments against chronic inflammatory diseases ranged from 1.5 to 1.8 (12–16%). For trastuzumab, a 3.2-fold variation (30%) was observed in 2009. At the patient level, there was a 2-fold county variation (from 10% to 21%) in biologic penetration in RA. County-specific sales per capita were associated with mean RA duration (r = −0.52, p = 0.015) and C-reactive protein at treatment initiation (r = −0.49, p = 0.025), while pain was borderline significant (r = −0.43, p = 0.055). Conclusions: Despite universal access to treatment, substantial but decreasing small-area variations were observed. Although geographic variations are anticipated initially, their persistence calls for investigation of patient equity and treatment appropriateness as counties seem to have different initiation thresholds.

Most common diseases diagnosed in primary care in Stockholm, Sweden, in 2011

BACKGROUND The most commonly reported diagnoses in primary care are useful to identify and meet health care needs in society. We estimated the rates of the most common diagnoses in primary health care in total and also by gender. METHODS This was a cross-sectional study including all 2.0 million inhabitants living in Stockholm County, Sweden, on 1 January 2009. Data on all health care appointments made in primary care in 2011 and during 2009-11 were extracted from the Stockholm County Council data warehouse VAL (Vårdanalysdatabasen; Stockholm regional health care data warehouse). Primary care data were analysed by underlying population and age. Appropriate specialist open care and inpatient data were used for comparison. RESULTS The five most common diagnoses in primary care (in 2011) were acute upper respiratory tract infections (6.0% of the population), essential hypertension (5.6%), coughing (2.6%), dorsalgia (2.6%) and acute tonsillitis (2.4%). Female-to-male ratios were higher for 27 of the 30 most common diagnoses, the exceptions being type 2 diabetes, unspecified types of diabetes and multiple wounds. CONCLUSIONS The 30 most common diagnoses in primary care reflect the complexity of disorders cared for in the first line of health care. Knowledge of these patterns is important when aiming at using primary health care resources in a proper way.

Extraction of Electronic Health Record Data in a Hospital Setting : Comparison of Automatic and Semi-Automatic Methods Using Anti-TNF Therapy as Model

There is limited experience and methods for extractions of drug therapy data from electronic health records (EHR) in the hospital setting. We have therefore developed and evaluated completeness and consistency of an automatic versus a semi‐automatic extraction procedure applied on prescribing and administration of the TNF inhibitor infliximab using a hospital EHR system in Karolinska University Hospital, Sweden. Using two different extraction methods (automatic and semi‐automatic), all administered infusions of infliximab between 2007 and 2010 were extracted from a database linked to the EHR system. Extracted data included encrypted personal identity number (PIN), date of birth, sex, time of prescription/administration, healthcare units, prescribed/administered dose and time of admission/discharge. The primary diagnosis (ICD‐10) for the treatment with infliximab was extracted by linking infliximab infusions to their corresponding treatment episode. A total of 13,590 infusions of infliximab were administered during the period of 2007 to 2010. Of those were 13,531 (99.6%) possible to link to a corresponding treatment episode, and a primary diagnosis was extracted for 13,530 infusions. Information on encrypted PIN, date of birth, time of prescription/administration, time of admission/discharge and healthcare unit was complete. Information about sex was missing in one patient only. Calculable information about dosage was extracted for 13,300 (98.3%) of all linked infusions. This methodological study showed the potential to extract drug therapy data in a hospital setting. The semi‐automatic procedure produced an almost complete pattern of demographics, diagnoses and dosages for the treatment with infliximab.

Dabigatran - a continuing exemplar case history demonstrating the need for comprehensive models to optimize the utilization of new drugs.

Background: There are potential conflicts between authorities and companies to fund new premium priced drugs especially where there are effectiveness, safety and/or budget concerns. Dabigatran, a new oral anticoagulant for the prevention of stroke in patients with non-valvular atrial fibrillation (AF), exemplifies this issue. Whilst new effective treatments are needed, there are issues in the elderly with dabigatran due to variable drug concentrations, no known antidote and dependence on renal elimination. Published studies showed dabigatran to be cost-effective but there are budget concerns given the prevalence of AF. These concerns resulted in extensive activities pre- to post-launch to manage its introduction. Objective: To (i) review authority activities across countries, (ii) use the findings to develop new models to better manage the entry of new drugs, and (iii) review the implications based on post-launch activities. Methodology: (i) Descriptive review and appraisal of activities regarding dabigatran, (ii) development of guidance for key stakeholder groups through an iterative process, (iii) refining guidance following post launch studies. Results: Plethora of activities to manage dabigatran including extensive pre-launch activities, risk sharing arrangements, prescribing restrictions and monitoring of prescribing post launch. Reimbursement has been denied in some countries due to concerns with its budget impact and/or excessive bleeding. Development of a new model and future guidance is proposed to better manage the entry of new drugs, centering on three pillars of pre-, peri-, and post-launch activities. Post-launch activities include increasing use of patient registries to monitor the safety and effectiveness of new drugs in clinical practice. Conclusion: Models for introducing new drugs are essential to optimize their prescribing especially where concerns. Without such models, new drugs may be withdrawn prematurely and/or struggle for funding.

A MiniReview of the Use of Hospital-based Databases in Observational Inpatient Studies of Drugs

The majority of pharmacoepidemiological data resources are based on data generated in primary health care. Although inpatient data resources have existed since the 1960s, inpatient pharmacoepidemiological studies are relatively scarce. The objectives of this MiniReview were to describe pharmacoepidemiological studies in hospital settings and the underlying databases to provide an overview of research questions addressed by such databases. The studies were retrieved by chain searching. We included pharmacoepidemiological studies in hospital settings containing data on inpatient drug use. Twelve inpatient databases in Asia, the United States and Europe were found. Most databases were automatically collected from claims data or generated from electronic medical records. The contents of the databases varied as well as the potential for linkage with other data sources such as laboratory and outpatient data. Twenty studies were selected and discussed to illustrate the diversity of inpatient pharmacoepidemiological studies. Hospital-based databases had mainly been used for drug utilization studies and research in adverse drug reactions. Five studies within comparative effectiveness were found. The number of pharmacoepidemiological studies in inpatient settings was low compared with studies from primary healthcare settings. These resources may be under-utilized.

Cell-wall-inhibiting antibiotic combinations with activity against multidrug-resistant Klebsiella pneumoniae and Escherichia coli

The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is rapidly limiting the options for effective antibiotic therapy. Systematic studies on combinations of already available antibiotics that could provide an effective treatment against MDR bacteria are needed. We tested combinations of antibiotics that target one important physiological function (peptidoglycan synthesis) at several steps, and studied Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) for which multidrug resistance associated with ESBL-producing plasmids has become a major problem. To measure the effectiveness of antibiotics alone and in combination, we used checkerboard assays, static antibiotic concentration time-kill assays, and an improved in-vitro kinetic model that simulates human pharmacokinetics of multiple simultaneously administered antibiotics. The target strains included an MDR K. pneumoniae isolate responsible for a recent major hospital outbreak. A double combination (fosfomycin and aztreonam) and a triple combination (fosfomycin, aztreonam and mecillinam) were both highly effective in reducing bacterial populations in all assays, including the in vitro kinetic model. These combinations were effective even though each of the MDR strains was resistant to aztreonam alone. Our results provide an initial validation of the potential usefulness of a combination of antibiotics targeting peptidoglycan synthesis in the treatment of MDR Gram-negative bacteria. We suggest that a combination of fosfomycin with aztreonam could become a useful treatment option for such infections and should be further studied.

Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease

BACKGROUND AND AIMS Crohns disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. METHODS This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. RESULTS A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. CONCLUSIONS This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients.

Anti-TNF treatment in Crohn's disease and risk of bowel resection-a population based cohort study

TNF inhibitors (TNFi) have been shown to reduce the need for surgery in Crohns disease, but few studies have examined their effect beyond the first year of treatment.

Antibiotic use and bacterial complications following upper respiratory tract infections: a population-based study

Objectives To investigate if use of antibiotics was associated with bacterial complications following upper respiratory tract infections (URTIs). Design Ecological time-trend analysis and a prospective cohort study. Setting Primary, outpatient specialist and inpatient care in Stockholm County, Sweden. All analyses were based on administrative healthcare data on consultations, diagnoses and dispensed antibiotics from January 2006 to January 2016. Main outcome measures Ecological time-trend analysis: 10-year trend analyses of the incidence of URTIs, bacterial infections/complications and respiratory antibiotic use. Prospective cohort study: Incidence of bacterial complications following URTIs in antibiotic-exposed and non-exposed patients. Results The utilisation of respiratory tract antibiotics decreased by 22% from 2006 to 2015, but no increased trend for mastoiditis (p=0.0933), peritonsillar abscess (p=0.0544), invasive group A streptococcal disease (p=0.3991), orbital abscess (p=0.9637), extradural and subdural abscesses (p=0.4790) and pansinusitis (p=0.3971) was observed. For meningitis and acute ethmoidal sinusitis, a decrease in the numbers of infections from 2006 to 2015 was observed (p=0.0038 and p=0.0003, respectively), and for retropharyngeal and parapharyngeal abscesses, an increase was observed (p=0.0214). Bacterial complications following URTIs were uncommon in both antibiotic-exposed (less than 1.5 per 10 000 episodes) and non-exposed patients (less than 1.3 per 10 000 episodes) with the exception of peritonsillar abscess after tonsillitis (risk per 10 000 tonsillitis episodes: 32.4 and 41.1 in patients with no antibiotic treatment and patients treated with antibiotics, respectively). Conclusions Bacterial complications following URTIs are rare, and antibiotics may lack protective effect in preventing bacterial complications. Analyses of routinely collected administrative healthcare data can provide valuable information on the number of URTIs, antibiotic use and bacterial complications to patients, prescribers and policy-makers.

Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example

Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different from those treated in clinical practice. Therefore, it is important to optimize real‐time postmarketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases from a well‐defined region with universal access to healthcare, we have built a framework for real‐time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.