Comparing the long-term outcomes in chronic coronary syndrome patients with prior ST-segment and non-ST-segment elevation myocardial infarction: findings from the TIGRIS registry.

OBJECTIVES: Compared with ST-segment elevation myocardial infarction (STEMI) patients, non-STEMI (NSTEMI) patients have more comorbidities and extensive coronary artery disease. Contemporary comparative data on the long-term prognosis of stable post-myocardial infarction subtypes are needed. DESIGN: Long-Term rIsk, clinical manaGement and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS) was a multinational, observational and longitudinal cohort study. SETTING: Patients were enrolled from 350 centres, with >95% coming from cardiology practices across 24 countries, from 19 June 2013 to 31 March 2017. PARTICIPANTS: This study enrolled 8277 stable patients 1-3 years after myocardial infarction with ≥1 additional risk factor. OUTCOME MEASURES: Over a 2 year follow-up, cardiovascular events and deaths and self-reported health using the EuroQol 5-dimension questionnaire score were recorded. Relative risk of clinical events and health resource utilisation in STEMI and NSTEMI patients were compared using multivariable Poisson regression models, adjusting for prognostically relevant patient factors. RESULTS: Of 7752 patients with known myocardial infarction type, 46% had NSTEMI; NSTEMI patients were older with more comorbidities than STEMI patients. NSTEMI patients had significantly poorer self-reported health and lower prevalence of dual antiplatelet therapy at hospital discharge and at enrolment 1-3 years later. NSTEMI patients had a higher incidence of combined myocardial infarction, stroke and cardiovascular death (5.6% vs 3.9%, p<0.001) and higher all-cause mortality (4.2% vs 2.6%, p<0.001) compared with STEMI patients. Risks were attenuated after adjusting for other patient characteristics. Health resource utilisation was higher in NSTEMI patients, although STEMI patients had more cardiologist visits. CONCLUSIONS: Post-NSTEMI chronic coronary syndrome patients had a less favourable risk factor profile, poorer self-reported health and more adverse cardiovascular events during long-term follow-up than individuals post STEMI. Efforts are needed to recognise the risks of stable patients after NSTEMI and optimise secondary prevention and care. TRIAL REGISTRATION NUMBER: NCT01866904.

Mind the gap: analysis of two pilot projects of a home telehealth service for persons with complex conditions in a Swedish hospital.

BACKGROUND: Developing and implementing home telehealth (HTH) services for patients with chronic conditions is a challenge. HTH services provide continuous and integrated care to patients, but very often pilot projects face non-adoption and abandonment issues. Change processes in healthcare are often complex and require learning to adapt to non-linear and unpredictable events. Complexity science can thus provide a complementary view to the predominant Quality Improvement (QI) approach in healthcare. In this study of two pilot projects in a Swedish hospital, we explore how a theory-driven approach can be used (a) to support the development of a self-monitoring HTH service in hospital care and (b) to evaluate staff and patients' experiences from early adoption. METHODS: To plan and evaluate the service for the recipients (i.e., patients and healthcare providers), we used the Plan-Do-Study-Act (PDSA) tool in combination with two complexity-informed frameworks: the Non-adoption, Abandonment, Scale-up, Spread and Sustainability (NASSS) framework, and the joint Complexity Assessment Tool (CAT). The theory-informed development process led to two pilot projects of an HTH service for patients with heart failure and COVID-19. We collected data from multiple sources (project documents, a survey on readiness for change among staff, and semi-structured interviews with patients and staff) and analyzed the data using descriptive statistics and qualitative content analysis with a deductive approach. RESULTS: Patients and staff perceived the services as valuable as they enabled rapid feedback, and improved communication and collaboration between patients and healthcare providers. Yet, despite the extensive development efforts, there was a perceived gap between how individuals valued the service and the capacity of adopters, the organization, and the wider system to effectively integrate these services into routine care. CONCLUSIONS: The combined use of PDSA, NASSS, and CAT can support the development and evaluation of HTH services that are perceived as valuable by individual patients and staff. For successful adoption, the value for individuals must be supported by organizational efforts to learn how to integrate new routines and tasks into clinical practice and daily life, and how to coordinate multiple providers within and outside the hospital walls.

Risk Analysis of Nonunion After First Metatarsophalangeal Joint Arthrodesis.

Objective: The standard therapy for a symptomatic hallux rigidus is still the arthrodesis of the first metatarsophalangeal (MTP) joint. A nonunion of the arthrodesis is a possible postoperative complication. This study aimed to evaluate the incidence of nonunion associated with first MTP joint arthrodesis and identify risk factors influencing this. Methods: This retrospective study included 197 patients who were treated with an isolated first MTP joint arthrodesis. The severity of MTP-related osteoarthritis was assessed clinically and radiologically prior to surgery according to the Waizy classification. Patient characteristics and radiological parameters were evaluated postoperatively. Results: A full clinical and radiological data set was collected from 153 out of 197 patients. We identified 14 cases of nonunion and found that nonunion was associated with higher incidence of male gender (P = .29), comorbidity (P = .035), higher grade of osteoarthritis (P = .01), and increased postoperative great toe dorsiflexion (P = .022). Conclusions: Arthrodesis of the first MTP joint is a safe operative treatment, as demonstrated by a nonunion rate of 9.2%. Negative influencing factors were the presence of preexisting diseases, higher grades of osteoarthritis, and a relative increased dorsiflexion position of the great toe after surgery. These factors should be considered during pre-, intra-, and postoperative planning.Levels of Evidence: Therapeutic, Level IV: Retrospective.

Comparison of Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction With Versus Without Hyperuricemia or Gout.

Hyperuricemia and gout are common in patients with heart failure (HF) and are associated with poor outcomes. Data describing hyperuricemia and gout in patients with HF with preserved ejection fraction (HFpEF) are limited. We used data from the Duke University Health System to describe characteristics of patients with HFpEF and hyperuricemia (serum uric acid >6 mg/dl) or gout (gout diagnosis or gout medication within the previous year) and to explore associations with 5-year outcomes (death and hospitalization). We identified 7,004 patients in the Duke University Health System with a known diagnosis of HFpEF who underwent transthoracic echocardiography between January 1, 2005 and December 31, 2017. A total of 1,136 (16.2%) patients with HFpEF also had hyperuricemia or gout. Patients with HFpEF and hyperuricemia or gout had a greater co-morbidity burden, more echocardiographic findings of cardiac remodeling, and higher unadjusted rates of all-cause death, all-cause hospitalization, and HF hospitalization compared with those with HFpEF without hyperuricemia or gout. After multivariable adjustment, patients with HFpEF and hyperuricemia or gout had a significantly higher rates of first all-cause hospitalization (adjusted hazard ratio 1.10 [95% confidence interval 1.02 to 1.19]; p = 0.020) and recurrent all-cause hospitalization (associated rate ratio 1.13 [95% confidence interval 1.01 to 1.25]; p = 0.026). After adjustment, no significant differences in death or HF hospitalization were observed. In conclusion, patients with HFpEF and hyperuricemia or gout were found to have a higher burden of co-morbidities and a higher rate of all-cause hospitalization, even after multivariable adjustment, compared to patients with HFpEF without hyperuricemia or gout.

Impact of ischaemic heart disease severity and age on risk of cardiovascular outcome in diabetes patients in Sweden: a nationwide observational study.

OBJECTIVES: To compare short-term cardiovascular (CV) outcome in type 2 diabetes (T2D) patients without ischaemic heart disease (IHD), with IHD but no prior myocardial infarction (MI), and those with prior MI; and assess the impact on risk of age when initiating first-time glucose-lowering drug (GLD). DESIGN: Cohort study linking morbidity, mortality and medication data from Swedish national registries. PARTICIPANTS: First-time users of GLD during 2007-2016. OUTCOMES: Predicted cumulative incidence for the CV outcome (MI, stroke and CV mortality) was estimated. A Cox model was developed where age at GLD start and CV risk was modelled. RESULTS: 260 070 first-time GLD users were included, 221 226 (85%) had no IHD, 16 294 (6%) had stable IHD-prior MI and 22 550 (9%) had IHD+MI. T2D patients without IHD had a lower risk of CV outcome compared with the IHD populations (±prior MI), (3-year incidence 4.78% vs 5.85% and 8.04%). The difference in CV outcome was primarily driven by a relative greater MI risk among the IHD patients. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger (<60 years) patients had a relative greater risk compared with older patients. CONCLUSIONS: T2D patients without IHD had a lower risk of the CV outcome compared with the T2D populations with IHD, primarily driven by a greater risk of MI. For T2D patients without IHD, an almost linear association between age at start of GLD and relative risk was observed, whereas in IHD patients, the younger patients had a relative greater risk compared with older patients. Our findings suggest that intense risk prevention should be the key strategy in the management of T2D patients, especially for younger patients.

The significance of walking from the perspective of people with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with progressive mobility and walking difficulties. Although these aspects have been found to be central from a patient perspective, the perceived significance of walking is less well understood. OBJECTIVE: To explore the significance of walking as perceived and experienced by individuals with PD. METHODS: Eleven persons with PD (seven men; median age, 71 years; median PD duration, 7 years) participated. Data were collected through semi-structured interviews, which were recorded and transcribed verbatim. Data were qualitatively analysed by systematic text condensation. RESULTS: The ability to walk had a complex and multifaceted impact on the participants, including physical, psychological and emotional aspects as well as on the ability to be active in daily life and to participate in society. The central role of coping strategies was prominent in filtering emotional reactions to physical changes, and when managing the activities and participation in everyday situations. The sense of unpredictability, uncertainty and loss of control were underlying phenomena in all categories. Furthermore, inability to manage walking difficulties had a negative impact on the participants' self-concept. CONCLUSIONS: The central meaning of being able to walk appears to be intimately linked to an individual's social identity, emotional well-being and integrity. Consequently, being able to walk independently was a prerequisite to an autonomous life and participation in society. This implies that rehabilitation and other mobility interventions also need to consider individual emotional, psychological, and social implications, and to facilitate appropriate compensatory and coping strategies.

Reducing dispensing errors in Swedish pharmacies: the impact of a barrier in the computer system.

BACKGROUND: Since 2004, a web-based reporting system enables monitoring of dispensing errors in all Swedish pharmacies. The adoption of this system was followed by an overall increase in reports, mainly explained by the dispensing of medicines of improper strength. In 2006 an intervention was implemented, aimed at reducing these errors. The objective of this study was to assess the impact of the intervention on the number of errors. METHODS: Monthly data on the reported number of dispensing errors from July 2004 until December 2007 were used. These were analysed in total and subdivided by type and cause of error. A time-series design was applied, and linear segmented regression analysis used to analyse whether changes in slope or level occurred; shifts in intercept or slope where p<0.01 were considered as statistically significant. RESULTS: The intervention coincided with a distinct decrease in error reports and a statistically significant change in slope that switched from a slight increase, 0.09, to a decrease, -0.26 (p = 0.0035). Medicines dispensed with wrong strength also displayed a significant change in slope, from 0.08 to -0.27 (p<0.0001), as well as dispensing errors caused by registration failure, that is, failure of the registration of a prescription in pharmacy computers, which changed from 0.05 to -0.29 (p<0.0001). CONCLUSION: The intervention was associated with a decrease in the number of reports on drugs dispensed with the wrong strength, but also had a decreasing effect on errors caused by registration failure and on the dispensing errors in total as well.

Socioeconomic determinants of psychotropic drug utilisation among elderly: a national population-based cross-sectional study.

BACKGROUND: Psychotropic drugs are commonly utilised among the elderly. This study aimed to analyse whether two socioeconomic determinants - income and marital status - are associated with differences in utilisation of psychotropic drugs and potentially inappropriate psychotropic drugs among elderly in Sweden. METHODS: All individuals aged 75 years and older who had purchased a psychotropic drug in Sweden during 2006 were included (68.7% women, n = 384712). Data was collected from national individual-based registers. Outcome measures were utilisation of three or more psychotropic drugs and utilisation of potentially inappropriate psychotropic drugs, as classified by the Swedish National Board of Health and Welfare. RESULTS: Individuals with low income were more likely to utilise three or more psychotropic drugs compared to those with high income; adjusted odds ratio (aOR) 1.12 (95% confidence interval [CI] 1.10-1.14). The non-married had a higher probability for utilising three or more psychotropic drugs compared to the married (aOR 1.22; CI 1.20-1.25). The highest probability was observed among the divorced and the never married. Potentially inappropriate psychotropic drugs were more common among individuals with low compared to high income (aOR 1.14; CI 1.13-1.16). Compared to the married, potentially inappropriate psychotropic drug utilisation occurred more commonly among the non-married (aOR 1.08; CI 1.06-1.10). The never married and the divorced had the highest probability. CONCLUSIONS: There was an association between socioeconomic determinants and psychotropic drug utilisation. The probability for utilising potentially inappropriate psychotropics was higher among individuals with low income and among the non-married.

A comparative analysis of remuneration models for pharmaceutical professional services.

OBJECTIVES: Pharmacists provide a wide range of professional services to support the appropriate use of medicines by patients. This study aims to conduct an international, comparative analysis of remuneration models for pharmaceutical professional services. METHODS: Information about remuneration models was derived from a literature review and a semi-structured questionnaire completed by experts. RESULTS: Remuneration models differ in the way that pharmacists are paid for professional services beyond dispensing medicines. Also, the scope of services that are remunerated varies. The majority of countries regulate remuneration for services only when the medicine is paid for under the reimbursement scheme. Remuneration of services implies a commitment to assure their quality in some countries. Collaborative practice models have been set up where pharmacists work together with other health care professionals to deliver diagnosis-specific services or services based on the patient's use of medicines. The remuneration of services is influenced by the value of services, budgetary constraints, the payer perspective, and the attitude of physicians, pharmacists and patients. CONCLUSIONS: Professional organisations need to formulate a clear strategy for developing and gaining remuneration for pharmaceutical professional services. This implies that pharmacists not only demonstrate the value of services, but also assure their quality.

Multifaceted national and regional drug reforms and initiatives in ambulatory care in Sweden: global relevance.

It is a continual challenge trying to improve the quality of prescribing while concurrently trying to address increasing pharmaceutical development, utilization and expenditure. National and regional reforms and initiatives in Sweden have moderated growth in ambulatory drug expenditure to 2.7% per annum in recent years despite increasing volumes. National reforms include mandatory generic substitution and value-based pricing alongside devolution of drug budgets to the regions. Regional initiatives include strengthening the role of the regional Drug and Therapeutic Committees, further budget devolution as well as strategies incorporating prescribing guidance and monitoring coupled with financial incentives. The extent and nature of the regional initiatives vary depending on their characteristics. In this article, we compare initiatives undertaken in two major counties, Stockholm and Ostergötland, and their outcomes. Outcomes include annual drug budget savings while achieving agreed quality as well as increased adherence to prescribing targets and guidance; the latter associated with savings. Appraising these multifaceted reforms can provide guidance to other countries and regions in view of their diversity. Future steps must incorporate measures to improve the utilization of new expensive drugs, which should include horizon scanning and forecasting activities as well as post-launch activities involving monitoring of prescribing and registries. This may well require cooperation with other European countries.

Prescribing behaviour after the introduction of decentralized drug budgets: is there an association with employer and type of care facility?

OBJECTIVE: To analyse whether prescribing patterns changed after introduction of drug budgets and whether there is an association between drug prescribing patterns and the type of employer and care facility. METHODS: Data analysed encompassed information on dispensed medicines, by workplaces, prescribed in the Region Vastra Gotaland, Sweden, for the years 2003 and 2006. Workplaces (n = 969) were categorized according to type of employer and type of care facility. Five prescribing indicators reflecting goals for cost-containing prescribing in Region Vastra Gotaland were assessed. Changes over time and differences between different types of employer and care facility were analysed by Mann-Whitney tests. RESULTS: In 2003, workplaces with a public employer had a significantly higher adherence to three of the prescribing indicators compared with private practitioners. Two of these differences remained in 2006. In 2003, none of the prescribing indicators differed between primary care and other care facilities. Three years later workplaces in primary care had a significantly higher adherence to three of the prescribing indicators than other care facilities. There was a statistically significant difference in change between 2003 and 2006 between primary care and other care facilities; there were no differences in change between workplaces with public and private employers. CONCLUSIONS: Adherence to three of the prescribing indicators increased after the introduction of decentralized drug budgets. Workplaces with a public employer showed greater adherence to two of the prescribing indicators than private sector workplaces.

To what extent does the indicator "concurrent use of three or more psychotropic drugs" capture use of potentially inappropriate psychotropics among the elderly?

PURPOSE: The indicator "concurrent use of three or more psychotropic drugs" has been used as a measure of quality in drug use among the elderly. The aim of our study was to assess to what extent the indicator captures the use of specific psychotropics associated with an increased risk of adverse events among the elderly, i.e., potentially inappropriate psychotropic drugs (PIP). METHODS: All individuals aged 75 years and older in Sweden purchasing prescribed psychotropic drugs in 2006 constituted the study population (n = 384,904). Data on purchased psychotropic drugs from the Swedish Prescribed Drug Register were used. The overlap between individuals with the indicator and individuals using PIP was assessed with sensitivity, specificity, positive and negative predictive values and likelihood ratio as outcome measures. RESULTS: Among the psychotropic drug users, 15% had the indicator and 39% used PIP. The proportion of individuals with the indicator among all individuals using PIP was 27% (sensitivity). The proportion of individuals without the indicator among all individuals not using PIP was 93% (specificity). The positive predictive value was 72%, and the negative predictive value was 67%. Differences in outcome measures were observed between different categories of PIP. CONCLUSIONS: The indicator "concurrent use of three or more psychotropics" can be technically easy to use, but PIP is more specific. Three quarters of all individuals who used PIP in this study were not captured by the indicator. However, two thirds of all individuals with the indicator used PIP. When selecting instruments to assess appropriateness in drug therapy in the elderly, clinical relevance should be balanced against convenience of use.

Recent national and regional drug reforms in Sweden: implications for pharmaceutical companies in Europe.

With an aging population and increased prevalence of chronic diseases, such as obesity and diabetes mellitus, drug reforms are needed across Europe to ensure the continued provision of comprehensive healthcare. It is also a challenge, with the limited resources available, to fund new innovative drugs that significantly improve patient health. Recent national and regional reforms in Sweden have moderated the rate of increase in drug expenditure, despite increased volumes of drug use and the launch of new, expensive drugs. National reforms include the adoption of economic principles when assessing the value and subsequent reimbursement of new and existing drugs, as well as reforms to obtain low prices for generic drugs. Regional reforms aim to encourage the rational use of medicines through the establishment of drug and therapeutic committees, development of guidelines, academic detailing, continuous benchmarking of prescribing patterns, and financial incentives. Some of these reforms provide examples to other European countries, whilst others duplicate existing measures. As such, we believe other European countries can benefit from an analysis of the Swedish reforms. We believe the pharmaceutical industry can also benefit from this analysis by working with key regional payers involved with developing and implementing the reforms as they moderate and refine their future activities, including finding acceptable ways of introducing new expensive drugs.

Influence of mandatory generic substitution on pharmaceutical sales patterns: a national study over five years.

BACKGROUND: Mandatory generic substitution was introduced in Sweden in October 2002 in order to try to curb escalating pharmaceutical expenditure. The aim of this study was to investigate how sales patterns for substitutable and non-substitutable pharmaceuticals have developed since the introduction of mandatory generic substitution; furthermore, to compare sales patterns in different groups of the population, based on patients' age and gender. METHODS: Five therapeutic groups comprising both substitutable and non-substitutable pharmaceuticals were included. The study period was from January 2000 to June 2005. National sales data were used, covering volumes of dispensed prescription medicines (expressed in defined daily doses per 1000 inhabitants and day) of each pharmacological substance in the therapeutic groups for each age and gender group. Sales patterns for substitutable and non-substitutable pharmaceuticals were compared using a descriptive approach. RESULTS: In most therapeutic groups there has been an increase in the volumes of substitutable pharmaceuticals sold since the introduction of the reform, ranging from one third to three times the initial volume; whereas the volumes of non-substitutable pharmaceuticals have levelled out or declined. There were few gender differences in sales patterns of substitutable and non-substitutable drugs. In three therapeutic groups, sales patterns differed across different age groups, and there was a tendency for volumes of recently introduced non-substitutable pharmaceuticals to be proportionally higher in the youngest age groups. CONCLUSION: Since the introduction of the reform, there has been a proportionally larger increase in sales of substitutable pharmaceuticals compared with sales of non-substitutable pharmaceuticals. This indicates that the reform might have contributed to larger sales of less expensive pharmaceuticals.

Impact of a generic substitution reform on patients' and society's expenditure for pharmaceuticals.

Sweden's pharmaceutical expenditure has increased during the last decades. On 1 October 2002 mandatory generic substitution was introduced in Sweden with the purpose to reduce the growth in pharmaceutical expenditure. The aim of the present study was to investigate if the implementation of generic substitution was associated with changes in patients' expenses and reimbursed cost for prescribed pharmaceuticals included in the Swedish Pharmaceutical Benefits Scheme (PBS). Monthly pharmacy sales data was obtained from the National Corporation of Swedish Pharmacies (Apoteket AB). The study period ranged between 1 January 2000 and 31 December 2004. Changes in pharmaceutical expenditure associated with the introduction of generic substitution were analysed with a linear segmented regression. The study comprised outpatient prescription pharmaceuticals encompassed by PBS for Sweden in total and each county council. Two different data sets were analysed. The first comprised all prescribed pharmaceuticals. The second contained only pharmaceuticals on regular prescriptions (i.e. exclusion of multidose dispensed drugs). Changes in patient co-payment per 1000 inhabitants and working day and subsidised cost per 1000 inhabitants and working day associated with the introduction of generic substitution were analysed. Expenditure was expressed in Swedish krona, SEK (SEK 1=US$ 0.14/euro 0.11, 7 July 2006). The Swedish Consumer Price Index was used to inflation-adjust expenditures with 2004 as base. The introduction of generic substitution was associated with a significant change in slope for patient co-payment in both all prescribed pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.005) for Sweden in total. The slope shifted direction from a slight increase before the reform into a decline after the reform was implemented. This was also found for the average slope of patient co-payment for all county councils (p<0.0001). The introduction of generic substitution was associated with a statistically significant shift in slope for subsidised cost for Sweden in total (p<0.001). The slope shifted from a monthly increase before October 2002 to a monthly decline for all prescribed pharmaceuticals afterwards. Similar results were found for the average slope of subsidised cost for all county councils both for all prescribed pharmaceuticals and pharmaceuticals on regular prescriptions (p<0.0001). The introduction of generic substitution was associated with a shift in trend from an increase into a decrease both for patients' and society's expenditures. This suggests that generic substitution has contributed to a reduction in the growth of pharmaceutical expenditure.

Physicians' opinions and experiences of the Pharmaceutical Benefits Reform.

AIM: To investigate opinions on and experiences of the new Pharmaceutical Benefits Reform (PBR) among physicians working in the Swedish county council of Region Västra Götaland. METHODS: Questionnaires were sent to all private practitioners who had contracts with the county council of Region Västra Götaland (n = 320) and a random sample of 25% of the doctors employed by the same county council (n = 1,068). The questionnaire comprised questions on how the physicians had received information on the PBR and sought opinions on the introduction of generic substitution in pharmacies, workplace codes, individual prescriber codes, and the Pharmaceutical Benefits Board. Analyses were performed with logistic regression. RESULTS: The response rate was 65%. The majority of doctors had received sufficient information about the reform, most often from their employer, followed by the Drug and Therapeutics Committees. More than half of the respondents were positive about the introduction of generic substitution, which was associated with the respondent's age, experiences, and employer. Most of the doctors thought that generic substitution could reduce the health system's pharmaceutical expenditure, which was associated with the employer. One-third reported that generic substitution had caused problems for their patients in the past month. The probability of being mainly positive towards the newly created Pharmaceutical Benefits Board, which decides on reimbursement, increased with increasing age. CONCLUSIONS: Most participating doctors had received sufficient information about the reform and thought that generic substitution could save money for society. Age, employer, and experiences appeared to influence opinions on several issues.

Beliefs about medicines among Swedish pharmacy employees.

OBJECTIVE: The aim of this study was to describe the beliefs about medicines among pharmacy employees. A further aim was to analyse whether these beliefs were associated with any background characteristics, such as age, professional category or medication use. METHOD: The study subjects were pharmacy employees at 24 community pharmacies in Göteborg, Sweden. The participating pharmacies had a total of 372 employees (pharmacists, dispensing pharmacists, and pharmacy technicians). Data was collected at the weekly pharmacy information meetings with a questionnaire comprising background questions and the Beliefs about Medicines Questionnaire (BMQ). The general part of the BMQ was used. For each statement in the BMQ, respondents marked their degree of agreement on a five-point Likert scale (1=strongly disagree, 2=disagree, 3=uncertain, 4=agree and 5=strongly agree). MAIN OUTCOME MEASURE: The three subscales of BMQ General: General Harm, General Overuse and General Benefit. RESULTS: The majority of the 292 respondents were dispensing pharmacists. More than half of the respondents were aged 45 years or older and had worked in a pharmacy for 20 years or more. Compared to the other professional categories, a higher proportion of dispensing pharmacists stated that they currently used traditional medicines. The pharmacy employees had a mean score for General Benefit of 4.31 and a mean score for General Harm of 1.81. Pharmacists and dispensing pharmacists in general regarded medicines as somewhat more beneficial, whereas pharmacy technicians viewed medicines as slightly more harmful. Those who had worked in a pharmacy for 30-34 years regarded medicines as less harmful compared to those who had worked 0-4 years. Compared to non-users, current users of prescription drugs regarded medicines as more beneficial. When controlling for background characteristics, no confounders were detected for any of the three subscales (ANCOVA analyses). CONCLUSION: Results of the study of 292 Swedish pharmacy employees show that they regard medicines as beneficial rather than harmful and that there are differences in beliefs between the professional categories. However, the reasons for these differences remain unclear. Nevertheless, the positive beliefs among pharmacy employees may have an impact on the communication with clients and, eventually, clients' adherence to medicines.

Do policy changes in the pharmaceutical reimbursement schedule affect drug expenditures? Interrupted time series analysis of cost, volume and cost per volume trends in Sweden 1986-2002.

The last decades increasing pharmaceutical expenditures in Sweden and other western countries have created a need for reforms to reduce the trend. The aim was to analyse if reforms concerning the pharmaceutical reimbursement scheme in Sweden during the years 1986-2002 were associated with changes in cost, volume and cost per volume of pharmaceuticals. Effects of changes in the reimbursement schedule during the study period were evaluated for all registered pharmaceuticals in Sweden and for five indicator drug groups. Five policy changes during the study period were assessed. Three concerned increased patient co-payment (January 1, 1991; January 1, 1995 and June 1, 1999), one the introduction of reference based pricing and increased co-payment (January 1, 1993) and one a new structure of the reimbursement schedule (January 1, 1997). The National Corporation of Swedish Pharmacies provided pharmaceutical delivery data for all Swedish pharmacies. Possible breaks in the trend associated with the investigated reforms were analysed with linear segmented regression analysis. This showed that increased co-payments were not associated with changed level or slope of cost and volume. The new reimbursement schedule was associated with a decreased level of cost and volume, both for all drugs combined and for several of the indicator drug groups. It was also associated with an increased slope for both volume and cost in some indicator drug groups and for all drugs. Introduction of reference based pricing was associated with a reduced slope of cost/defined daily doses (DDD) in all of the indicator drug groups and for all drugs. The analysis showed that major changes in the reimbursement system such as the introduction of a new reimbursement schedule and reference based pricing were associated with reductions in cost and volume for the new reimbursement schedule and cost per volume for reference based pricing.

Posttranscriptional regulation of TNFalpha expression via eukaryotic initiation factor 4E (eIF4E) phosphorylation in mouse macrophages.

Resident mouse macrophages secrete Tumor necrosis factor alpha (TNFalpha) upon challenge with LPS. The production of TNFalpha is controlled not only at the transcription of the gene, but also by strong posttranscriptional regulation. When macrophages are stimulated with LPS different signal transduction pathways become activated. Here we show that the combination of the 2 kinases p38 and MEK and presumably ERK1/2 regulate translation of TNFalpha, through the downstream kinase Mnk1. TNFalpha production is inhibited in a concentration-dependent manner by CGP57380 (Mnk1 inhibitor). The corresponding mRNA results show that the inhibition targets posttranscriptional regulation and is paralleled by inhibition of the phosphorylation of eukaryotic initiation factor 4E (eIF4E). Unexpectedly, the activation/inhibition of MAPKAP kinase-2 (MK2) does not parallel TNFalpha production, arguing against a direct/immediate role for this kinase. On the basis of the present and previous results we propose that ARE-containing TNFalpha mRNA requires phosphorylation of eIF4E for initiation of translation.

What are the obstacles to generic substitution? An assessment of the behaviour of prescribers, patients and pharmacies during the first year of generic substitution in Sweden.

PURPOSE: The aim of the present study was to investigate obstacles to generic substitution and savings achieved during the first year after Sweden introduced generic substitution in October 2002. METHODS: Normal prescriptions encompassed by generic substitution were included. Data on dispensed prescriptions in the Vastra Gotaland region was obtained from the National Corporation of Swedish Pharmacies. The outcome variables were investigated in three categories of drugs represented by two indicator drugs each. RESULTS: In total, 501,400 dispensed prescriptions of six indicator drugs were analysed. The prescriber opposed substitution in 1-8% of the dispensed prescriptions, varying between the indicator drugs. Patients declined substitution more frequently when the average saving per substitution was low. Substitution occurred most frequently in indicator drugs where the average saving per substitution was high. The total possible saving was 26 million Swedish krona (Swedish krona 1=U.S. $0.13) for the indicator drugs. The actual saving achieved by substitution was on average 60% of the total possible savings and was largely dependent on the extent to which the pharmacies kept the cheapest brand in stock. CONCLUSIONS: Generic substitution has been implemented in practice although it did not reach full dividend during the first year. The potential savings from extended use of generic substitution are substantial.