Heterogeneity after harmonisation: A retrospective cohort study of bleeding and stroke risk after the introduction of direct oral anticoagulants in four Western European countries.

PURPOSE: Database heterogeneity can impact effect estimates. Harmonisation provided by common protocols and common data models (CDMs) can increase the validity of pharmacoepidemiologic research. In a case study measuring the changes in the safety and effectiveness of stroke prevention therapy after the introduction of direct oral anticoagulants (DOACs), we performed an international comparison. METHODS: Using data from Stockholm, Denmark, Scotland and Norway, harmonised with a common protocol and CDM, two calendar-based cohorts were created: 2012 and 2017. Patients with a diagnosis code of atrial fibrillation 5 years preceding the 1-year cohort window were included. DOAC, vitamin K antagonist and aspirin treatment were assessed in the 6 months prior to the start of each year while strokes and bleeds were assessed during the year. A Poisson regression generated incidence rate ratios (IRRs) to compare outcomes from 2017 to 2012 adjusted for changes in individual-level baseline characteristics. RESULTS: In 280 359 patients in the 2012 cohort and 356 779 in the 2017 cohort, treatment with OACs increased on average from 45% to 65%, while treatment with aspirin decreased from 30% to 10%. In all countries except Scotland, there were decreases in the risk of stroke and no changes in bleeding risk, after adjustment for changes in baseline characteristics. In Scotland, major bleeding (IRR 1.09, 95% confidence interval [CI] [1.00; 1.18]) and intracranial haemorrhage (IRR 1.31, 95% CI [1.13; 1.52]) increased from 2012 to 2017. CONCLUSIONS: Stroke prevention therapy improved from 2012 to 2017 with a corresponding reduction in stroke risk without increasing the risk of bleeding in all countries, except Scotland. The heterogeneity that remains after methodological harmonisation can be informative of the underlying population and database.

A national, multicentre, web-based point prevalence survey of antimicrobial use and quality indices among hospitalised paediatric patients across South Africa.

OBJECTIVES: Data on antimicrobial consumption among the paediatric population in public hospitals in South Africa are limited. This needs to be addressed to improve future antimicrobial use and reduce antimicrobial resistance rates. This study aimed to quantify antimicrobial usage and to identify and classify which antimicrobials are used in the paediatric population in public sector hospitals in South Africa according to the World Health Organization (WHO) AWaRe list of antimicrobials. METHODS: A point prevalence survey was conducted among 18 public sector hospitals from nine provinces using a newly developed web-based application. Data were analysed according to the WHO AWaRe list to guide future quality improvement programmes. RESULTS: A total of 1261 paediatric patient files were reviewed, with 49.7% (627/1261) receiving at least one antimicrobial and with 1013 antimicrobial prescriptions overall. The top five antimicrobials included ampicillin (16.4%), gentamicin (10.0%), amoxicillin/enzyme inhibitor (9.6%), ceftriaxone (7.4%) and amikacin (6.3%). Antimicrobials from the 'Access' classification were the most used (55.9%), with only 3.1% being from the 'Reserve' classification. The most common infectious conditions for which an antimicrobial was prescribed were pneumonia (14.6%; 148/1013) and clinical sepsis (11.0%; 111/1013). Parenteral administration (75.6%; 766/1013) and prolonged surgical prophylaxis (66.7%; 10/15) were common concerns. Only 28.0% (284/1013) of prescribed antimicrobials had cultures requested; of which only 38.7% (110/284) of culture results were available in the files. CONCLUSION: Overall, antimicrobial prescribing is common among paediatric patients in South Africa. Interventions should be targeted at improving antimicrobial prescribing, including surgical prophylaxis, and encouraging greater use of oral antibiotics.

A point prevalence survey of antimicrobial utilisation patterns and quality indices amongst hospitals in South Africa; findings and implications.

Objectives: Antimicrobial use is growing, driven mainly by rising demands in developing countries. Knowing how antimicrobials are prescribed is important. Consequently, we undertook a point prevalence survey (PPS) quantifying antimicrobial consumption among 18 public sector hospitals across South Africa.Method: A purpose-built web-based application was used to collect PPS data.Results: Out of 4407 adult patients surveyed, 33.6% were treated with an antimicrobial. The most frequently prescribed groups were a combination of penicillins including ß-lactamase inhibitors. Amoxicillin combined with an enzyme inhibitor accounted for 21.4% total DDDs. In the medical and surgical wards, Access antimicrobials (54.1%) were mostly used, while in the ICU, Watch antimicrobials (51.5%) were mostly used. Compliance with the South African Standard Treatment Guidelines and Essential Medicines List was 90.2%; however, concerns with extended use of antimicrobials for surgical prophylaxis (73.2% of patients).Conclusion: The web-based PPS tool was easy to use and successful in capturing PPS data since the results were comparable to other PPS studies across Africa. High use of amoxicillin combined with an enzyme inhibitor, possibly because it was among the broad-spectrum antimicrobials in the Access group. The findings will assist with future targets to improve antimicrobial prescribing among public sector hospitals in South Africa.

Development of a web-based application to improve data collection of antimicrobial utilization in the public health care system in South Africa.

OBJECTIVE: Determining antimicrobial utilization patterns in hospitals can be a challenge given personnel and resource constraints with paper-based systems. A web-based application (APP) was developed in South Africa to address this, building on a recent point prevalence survey (PPS) using a paper-based system. Consequently, there was a need to test and evaluate the ease of use of a newly developed app and potential time saving versus paper-based methods for PPS. The findings can be used to further refine the APP. METHODS: The developed app was tested in a large academic public hospital in a PPS in South Africa. During data collection, the app was evaluated for functionality on 35 variables and subsequently refined. After data collection, the app was evaluated in terms of its time-saving potential and ease of use. RESULTS: 181 patient's files were surveyed across 13 wards in the hospital, with the antimicrobial usage findings similar to the previous paper-based study in the same hospital. The median age for males was 45.5 years and 42 years for females. Overall 80 out of 181 (44%) patients received antibiotics. Whilst 38% (12 out of 31) of patients in the adult surgical ward received antimicrobials, the prevalence was the highest (78%) in the pediatric medical wards. All the data collectors were confident in using the app after training and found the tool is not complex at all to use. In addition, the time taken to plan for the study and to collect data was considerably reduced. Reduced time spent in data collection and analysis is important for timely instigation of quality improvement programs in resource limited settings. CONCLUSIONS: All data collectors would recommend the app for future PPSs. Several concerns with data entry were identified, which have now been addressed. The app development has been successful and is now being deployed across South Africa as part of a national PPS as well as wider.

Cost burden of Clostridioides difficile infection to the health service: A retrospective cohort study in Scotland.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with high healthcare demands and related costs. AIM: To evaluate the healthcare and economic burden of CDI in hospitalized patients with community- (HOCA-CDI) or hospital-associated CDI (HOHA-CDI) in the National Health Service in Scotland. METHODS: A retrospective cohort study was conducted, examining data between August 2010 and July 2013 from four patient-level Scottish datasets, linked to death data. Data examined included prior antimicrobial prescriptions in the community, hospitalizations, length of stay and mortality. Each CDI case was matched to three hospital-based controls on the basis of age, gender, hospital and date of admission. Descriptive economic evaluations were based on bed-day costs for different types of wards. FINDINGS: Overall, 3304 CDI cases were included in the study. CDI was associated with additional median lengths of stay of 7.2 days for HOCA-CDI and 12.0 days for HOHA-CDI compared with their respective, matched controls. The 30-day mortality rate was 6.8% for HOCA-CDI and 12.4% for HOHA-CDI. Overall, recurrence within 90 days of the first CDI episode occurred in 373/2740 (13.6%) survivors. The median additional expenditure for each initial CDI case compared with matched controls was £1713. In the 6 months after the index hospitalization, the cost associated with a CDI case was £5126 higher than for controls. CONCLUSION: Using routinely collected national data, we demonstrated the substantial burden of CDI on healthcare services, including lengthy hospital stays and readmissions, which increased the costs of managing patients with CDI compared with matched controls.

Residual effect of community antimicrobial exposure on risk of hospital onset healthcare-associated Clostridioides difficile infection: a case-control study using national linked data.

BACKGROUND: Associations between antimicrobial exposure in the community and community-associated Clostridioides difficile infection (CA-CDI) are well documented but associations with healthcare-associated CDI (HA-CDI) are less clear. This study estimates the association between antimicrobial prescribing in the community and HA-CDI. METHODS: A matched case-control study was conducted by linking three national patient level datasets covering CDI cases, community prescriptions and hospitalizations. All validated cases of HA-CDI (August 2010 to July 2013) were extracted and up to three hospital-based controls were matched to each case on the basis of gender, age, hospital and date of admission. Conditional logistic regression was applied to estimate the association between antimicrobial prescribing in the community and HA-CDI. A sensitivity analysis was conducted to consider the impact of unmeasured hospital antimicrobial prescribing. RESULTS: Nine-hundred and thirty unique cases of HA-CDI with onset in hospital and no hospital discharge in the 12 weeks prior to index admission were linked with 1810 matched controls. Individuals with prior prescription of any antimicrobial in the community had an odds ratio (OR) = 1.41 (95% confidence interval (CI) 1.13-1.75) for HA-CDI compared with those without. Individuals exposed to high-risk antimicrobials (cephalosporins, clindamycin, co-amoxiclav or fluoroquinolones) had an OR = 1.86 (95% CI: 1.33-2.59). After accounting for the likely impact of unmeasured hospital prescribing, the community exposure, particulary to high-risk antimicrobials, was still associated with elevated HA-CDI risk. CONCLUSIONS: Community antimicrobial exposure is an independent risk factor for HA-CDI and should be considered as part of the risk assessment of patients developing diarrhoea in hospital.

Statin use in Brazil: findings and implications.

INTRODUCTION AND OBJECTIVES: Statins have become an integral part of treatment to reduce cardiac events in patients with cardiovascular disease. However, their use within the public healthcare system in Brazil is unknown. Consequently, we sought to determine and characterize statin use in primary healthcare delivered by the public health system (SUS) in Brazil and evaluate associated patient factors to improve future use. METHODS: Cross-sectional study with a national representative sample from five Brazilian regions, derived from the National Survey on Access, Use and Promotion of Rational Use of Medicines using a multi-stage complex sampling plan. Patients over 18 years old were interviewed from July 2014 to May 2015. The prevalences of statin use and self-reported statin adherence were determined amongst medicine users. The associations between statin use and sociodemographic/health condition variables were assessed using logistic regression. RESULTS: A total of 8803 patients were interviewed, of whom 6511 were medicine users. The prevalence of statin use was 9.4% with simvastatin (90.3%), atorvastatin (4.7%) and rosuvastatin (1.9%) being the most used statins. Poor adherence was described by 6.5% of patients. Statin use was significantly associated with age ≥65 years old, higher educational level, residence in the South, metabolic and heart diseases, alcohol consumption and polypharmacy. CONCLUSIONS: This is the first population based study in Brazil to assess statin use in SUS primary healthcare patients. Addressing inequalities in access and use of medicines including statins is an important step in achieving the full benefit of statins in Brazil, with the findings guiding future research and policies.

Influence of multiple initiatives in Sweden to enhance ARB prescribing efficiency following generic losartan; findings and implications for other countries.

BACKGROUND: Encouraging the prescribing of ACEIs first line vs. angiotensin receptor blockers (ARBs) has been a health authority focus with generic ACEIs as ACEIs and ARBs have similar effectiveness and there is limited coughing with ACEIs. This includes Sweden with its multiple initiatives keeping expenditure on renin-angiotensin inhibitor drugs similar between 2001 and 2007 despite appreciably increased volumes. Generic losartan became available and was reimbursed in March 2010 providing further opportunities for the authorities in Sweden to save costs with all ARBs seen as similar in managing hypertension and CHF at appropriate doses. AIMS: The main aim of this study was to assess changes in the utilisation of losartan vs. other single ARBs after generic losartan alongside accompanying demand-side measures. Additional aims were to (i) assess changes in the price of generic losartan and single ARB expenditure over time; (ii) suggest additional programmes, if needed; and (iii) analyse utilisation of ARB FDCs and compare with ACEI FDCs. METHODS: Retrospective observational study using an interrupted time series design. RESULTS: Multiple demand-side measures introduced among the 21 Counties in Sweden significantly enhanced the utilisation of generic losartan, growing from 26% to 27% of total ARBs (DDD basis) before generic losartan to 40% by August 2011. Losartan was principally generics (97% by August 2011). Expenditure/DDD for generic losartan was 10% of the pre-patent loss price in August 2011. This reduced total single ARB expenditure by 26% by the study end despite a 16% increase in utilisation. Greater utilisation of ARB FDCs than seen with ACEI FDCs. This may be due to similarities in prices between single and FDC ARBs. DISCUSSION: Multiple demand-side measures appreciably enhanced ARB prescribing efficiency, mirroring other studies. No significant increase in losartan utilisation following generics was seen in European countries where no specific measures were instigated. Losartan price reduction was in line with expectations. CONCLUSION: Multiple and intensive demand-side measures are needed to change physician prescribing habits. Authorities cannot rely on physicians transferring their activities from one class to another without interventions.

Are specific initiatives required to enhance prescribing of generic atypical antipsychotics in Scotland?: International implications.

BACKGROUND: National and regional authorities in Scotland have introduced multiple measures to appreciably enhance prescribing efficiency for the proton pump inhibitors (PPIs), statins and renin-angiotensin inhibitor drugs. Generic oral risperidone recently became available in Scotland; however, schizophrenia is a complex disease with advice from respected authorities suggesting that treatment should be individualised. AIMS: To assess (i) changes in atypical antipsychotic drug (AAP) utilisation and expenditure following the availability of oral generic risperidone in Scotland; (ii) to determine (a) current INN prescribing rates for risperidone following generic availability and (b) decrease in expenditure/DDD for generic risperidone; (iii) to suggest additional measures that could possibly be introduced in Scotland to further enhance prescribing of generic AAPs; and (iv) to provide guidance to NHS Scotland as well as other European authorities on the implications. METHODS: Retrospective observational study and an interrupted time series design. RESULTS: No appreciable change in the utilisation patterns of risperidone pre- and postgeneric availability. Appreciable INN prescribing averaged 93-98% of total oral risperidone. Generic risperidone was 84% below prepatent loss prices by study end, reducing annual expenditure for oral risperidone in 2010 by GB£3.19mn compared with prepatent loss situation. However, overall expenditure on AAPs increased by 42% from 2005 to 2010. DISCUSSION: As expected, there was no change in utilisation patterns for risperidone, although potential to influence prescribing patterns. Continued high INN prescribing suggests no problems with generic risperidone in practice. Costs will start to decrease as more AAPs lose their patents (olanzapine and quetiapine). There is the possibility to accelerate this reduction through educational activities. CONCLUSION: There is potential to realise some savings with generic AAPs. However, this is limited by the complexity of the disease area. Any measures introduced must aim at increasing the prescribing of generic AAPs first line in suitable patients.

Equity and efficiency: striving for a solution for the introduction of new medicines.

The aim of this study was to describe the evolution of mechanisms to manage the introduction of new medicines and their impact on the health-care system in Scotland. The study was a review of published and unpublished national audits and surveys on the introduction of new medicines in Scotland. Before the Scottish Medicines Consortium (SMC) was established, Area Drug and Therapeutics Committees (ADTCs) played a key role in advising National Health Service (NHS) Boards in Scotland on the use of new medicines. There was evidence of variation in the medicines evaluated and, in some cases, the evidence used leading to different decisions for the same medicine. After the SMC was established, ADTC decisions had become more consistent and comprehensive. The role of ADTCs evolved from evaluation of medicines to assessment of local implications and implementation of SMC advice. There was increased recognition of the importance of monitoring medicine use. This review demonstrated a clear evolution in the evaluation and implementation of new medicines by ADTCs across NHS Scotland. After the SMC was established, more medicines were considered by ADTCs and there was greater consistency in those considered for local implementation. ADTCs have moved from evaluation of new medicines to other aspects of medicine management, including assessment of local implications and implementation of SMC advice.

Bronchogastric fistula successfully treated with the insertion of a covered bronchial stent.

We present what we believe to be the first case of a bronchogastric fistula successfully treated with a plastic-covered metallic bronchial stent. This developed 5 years after a transhiatal oesophagectomy with gastric pull-up for carcinoma of the oesophagus. The successful outcome in this case suggests that this method of treatment should be considered in patients in whom this post-operative complication cannot be managed easily by other means.

Bradyarrhythmias in acute myocardial infarction: should thrombolysis lower the decision threshold for temporary pacing?

Both acute myocardial infarction and reperfusion therapy with thrombolytic agents may be associated with bradyarrhythmias, and there may be a case for 'prophylactic' insertion of a temporary pacing wire in selected patients. We describe 4 patients in whom clinical decisions had to be made concerning the appropriateness and timing of temporary pacing, and discuss the implications for modern guidelines on the indications for pacing in such a setting.