Quality of life, daily functioning, and symptoms in hypothyroid patients on thyroid replacement therapy: A Dutch survey.

Objective: To explore the nature and extent of possible residual complaints among Dutch hypothyroid patients using thyroid replacement therapy, we initiated a comprehensive study measuring health-related quality of life (QoL), daily functioning, and hypothyroidism-associated symptoms in patients and control persons. Methods: An online survey measuring thyroid-specific QoL (ThyPRO), daily functioning, and hypothyroidism-associated symptoms (ThySHI) was distributed among treated hypothyroid patients and control individuals. The advertising text was formulated in an open-ended manner. Patients also provided their most recent thyroid blood values and their thyroid medication. Results: There was a large-sized impairment of QoL (Cohen's d = 1.04, +93 % ThyPRO score) in hypothyroid patients on thyroid replacement therapy (n = 1195) as compared to controls (n = 236). Daily functioning was significantly reduced i.e., general health (-38 %), problems with vigorous- (+64 %) and moderate activities (+77 %). Almost 80 % of patients reported having complaints despite thyroid medication and in-range thyroid blood values, with 75 % expressing a desire for improved treatment options for hypothyroidism (total n = 1194). Hypothyroid patients experienced 2.8 times more intense hypothyroidism-associated symptoms than controls (n = 865, n = 203 resp). Patients' median reported serum concentrations were: TSH 0.90 mU/L, FT4 17.0 pmol/L, and FT3 2.67 pmol/L, with 52 % having low T3 levels (<3.1 pmol/L). The QoL was not found to be related to age, sex, BMI, menopausal status, stress, serum thyroid parameters, the origin and duration of hypothyroidism, the type of thyroid medication, or the LT4 dose used. Conclusions: Our study revealed major reductions in quality of life and daily functioning, and nearly three times more intense hypothyroidism-associated symptoms in treated hypothyroid patients as compared to controls, despite treatment and largely in-range serum TSH/FT4 concentrations. The QoL was not associated with serum thyroid parameters. We recommend future research into the origin of persisting complaints and the development of improved treatment modalities for hypothyroidism.

A European community pharmacy-based survey to investigate patterns of prescription fraud through identification of falsified prescriptions.

AIM: To identify prescription drugs involved in falsified prescriptions in community pharmacies in 6 European countries. METHODS: A cross-sectional survey among 2,105 community pharmacies in Belgium, France, Italy, the Netherlands, Spain and Sweden was carried out to collect all suspect prescription forms. For each reported drug, the number of reported falsified prescriptions per thousand inhabitants was estimated. A falsification ratio was calculated by dividing the number of reports by the number of defined daily doses per 1,000 inhabitants per day for this drug, computed from national sale or reimbursement data. RESULTS: On 862 prescription forms, benzodiazepines (zolpidem, bromazepam, alprazolam), buprenorphine (as an opioid maintenance drug) and tramadol were the most frequently reported. Depending on their level of use in each country, methylphenidate, morphine and flunitrazepam presented the highest falsification ratios, particularly in Spain, Belgium and France. CONCLUSIONS: Stimulants, opioids and some benzodiazepines were the most frequently reported drugs in this survey on falsified prescriptions, but differences between countries were observed.

Ineffectiveness and adverse events of nitrofurantoin in women with urinary tract infection and renal impairment in primary care.

PURPOSE: To determine whether treatment with nitrofurantoin in women with urinary tract infection (UTI) and renal impairment in primary care is associated with a higher risk of ineffectiveness and/or serious adverse events than in women without renal impairment. METHODS: A cohort of 21,317 women treated with nitrofurantoin and a cohort of 7,926 women treated with trimethoprim, identified from the Pharmo Record Linkage System, were analysed. The primary outcome was ineffectiveness of treatment of nitrofurantoin defined as the start of a second antibacterial within 1 month after the start of nitrofurantoin. The secondary outcome was the occurrence of serious adverse events of nitrofurantoin leading to hospitalization within 90 days. A cohort of trimethoprim users was used to determine if the associations found for nitrofurantoin were mainly related to nitrofurantoin itself. The association between renal impairment and the risk of these outcomes was determined with Cox regression and expressed as hazard ratios (HRs). RESULTS: Overall, the incidence density for ineffectiveness was 5.4 per 1,000 person-days, and moderate renal impairment was not associated with ineffective treatment [HR 1.1, 95 % confidence interval (CI) 0.74-1.51]. The overall incidence density for adverse events was 0.02 per 1,000 person-days. In patients with renal impairment (<50 ml/min/1.73 m²) the risk of pulmonary adverse events leading to hospitalization was significantly increased (HR 4.1, 95 % CI 1.31-13.09) CONCLUSIONS: Nitrofurantoin treatment was not associated with a higher risk of ineffectiveness in women with UTI and moderate renal impairment (30-50 ml/min/1.73 m²). However, we did find a significant association between renal impairment (<50 ml/min/1.73 m²) and pulmonary adverse events leading to hospitalization.

Trends in incidence and characteristics of children, adolescents, and adults initiating immediate- or extended-release methylphenidate or atomoxetine in the Netherlands during 2001-2006.

BACKGROUND: Previous Dutch studies showed increasing psychostimulant use, especially methylphenidate immediate-release (MPH-IR), between 1995 and 2003. In 2003 the extended-release (ER) formulation of MPH and in 2005 atomoxetine (ATX) were introduced in The Netherlands, which increased treatment options. OBJECTIVE: The aim of this study was to describe the change in incidence of attention-deficit/hyperactivity disorder (ADHD) drugs and the prescription profiles of patients younger than 45 years starting treatment with these medicines between 2001 and 2006. METHODS: Data were obtained from Dutch community pharmacies as collected by the Foundation for Pharmaceutical Statistics, covering 97% of all dispenses for prescription medicines to outpatients in The Netherlands. RESULTS: The overall incidence of ADHD drugs use increased 6.5-fold from 2001 to 2006 in men as well as in women. The absolute incidence was highest among 6- to 11-year-old boys. The percentage of first-time MPH-IR users decreased from 98.3% in 2001 to 75.9% in 2006. Likewise, MPH-ER use increased from 0% in 2001 to 18.9% in 2006, and ATX use increased from 0% in 2001 to 3.9% in 2006. The new nonstimulant drug ATX was prescribed more often to adults if they had been previously treated with selective serotonin reuptake inhibitors (SSRIs), benzodiazepines, or antipsychotics. Youngsters <17 years initiated on ATX were often previously treated with antipsychotics or clonidine/guanfacine. CONCLUSION: These findings demonstrate an increase in incidence in use of ADHD drugs between 2001 and 2006 in The Netherlands. The major proportion of all treated patients comprised boys, 6-11 years old; most of them were treated with MPH-IR. In a few years time, the use of extended-release drugs as part of all ADHD drug prescriptions increased considerably, despite the lack of full reimbursement of these extended-release drugs. Psychostimulants and atomoxetine in children, adolescents, and adults are probably used to address different treatment needs.

The use of driving impairing medicines: a European survey.

AIM: To analyse the consumption of a number of medicines with a known potential for increasing the risk of road traffic accidents in the general population of Europe. METHODS: Questionnaires were distributed through the European Drug Utilization Research Group (EuroDURG) and Post-Innovation Learning through Life-events of drugs (PILLS) networks. A total of 30 countries (the current EU Member States, Iceland, Norway and Switzerland) were asked to supply data on the use of driving impairing medicines for the period 2000-2005, aggregated at the level of the active substance and presented in Defined Daily Doses (DDDs) per 1000 inhabitants per day. RESULTS: National utilization data were provided by 12 of the 30 countries. Based on these data, a considerable increase in consumption was only seen for the antidepressants and the selective serotonin reuptake inhibitors. A slight increase, decrease or no increase was seen for the rest of the drugs studied (i.e. opioids, antipsychotics, anxiolytics, hypnotics and sedatives, drugs that are used in addictive disorders and antihistamines). Limitations were encountered when data on driving impairing medicines were compared between countries (e.g. variation in the data sources and providers, population coverage, inclusion of hospital data, use of divergent ATC/DDD versions) and, therefore, a cross-national comparison could not be performed. CONCLUSIONS: During the study period, trends within countries showed slight to no increase in the consumption of selected medicinal drug groups, with the exception of the antidepressants and the selective serotonin reuptake inhibitors: they showed a remarkable increased use during the study time-frame. Our results illustrate that it is still difficult to perform a valid and comprehensive collection of drug utilization data on driving impairing medicines. Therefore, efforts to harmonize data collection techniques are required and recommended.

Furthering patient adherence: a position paper of the international expert forum on patient adherence based on an internet forum discussion.

BACKGROUND: As the problem of patient non-adherence persists and a solution appears hard to be found, it continues to be important to look for new ways to further the issue. We recently conducted a meta-review of adherence intervention studies which yielded a preliminary agenda for future research, practice and theory development in patient adherence. The objective of the present project was to find out to what extent adherence experts consider this agenda relevant and feasible. METHODS: The thirty-five corresponding authors of the review studies included in the meta-review were invited to join the International Expert Forum on Patient Adherence and to participate in a four-week web-based focus group discussion. The discussion was triggered by the points on the preliminary agenda presented as propositions to which forum members could react. Two researchers analysed the transcripts and selected relevant phrases. RESULTS: Twenty adherence experts participated. Various ideas and viewpoints were raised. After the closure of the web-site, the expert forum was asked to authorize the synthesis of the discussion, to list the propositions in order of priority and to answer a few questions on the use of the web-based focus group as a tool to obtain expert opinions. Their ranking showed that the development of simple interventions is the most promising step to take in fostering patient adherence, preferably within a multidisciplinary setting of medical, pharmaceutical, social and technical science and, not in the least, by incorporating patients' perspectives. CONCLUSION: For enhancing adherence, the development of simple interventions originating from a multidisciplinary perspective including patients' input, appears most promising. Disclosing patients' perspectives requires open communication about patients' expectations, needs and experiences in taking medication and about what might help them to become and remain adherent.

Patient adherence to medical treatment: a review of reviews.

BACKGROUND: Patients' non-adherence to medical treatment remains a persistent problem. Many interventions to improve patient adherence are unsuccessful and sound theoretical foundations are lacking. Innovations in theory and practice are badly needed. A new and promising way could be to review the existing reviews of adherence to interventions and identify the underlying theories for effective interventions. That is the aim of our study. METHODS: The study is a review of 38 systematic reviews of the effectiveness of adherence interventions published between 1990 and 2005. Electronic literature searches were conducted in Medline, Psychinfo, Embase and the Cochrane Library. Explicit inclusion and exclusion criteria were applied. The scope of the study is patient adherence to medical treatment in the cure and care sector. RESULTS: Significant differences in the effectiveness of adherence interventions were found in 23 of the 38 systematic reviews. Effective interventions were found in each of four theoretical approaches to adherence interventions: technical, behavioural, educational and multi-faceted or complex interventions. Technical solutions, such as a simplification of the regimen, were often found to be effective, although that does not count for every therapeutic regimen.Overall, our results show that, firstly, there are effective adherence interventions without an explicit theoretical explanation of the operating mechanisms, for example technical solutions. Secondly, there are effective adherence interventions, which clearly stem from the behavioural theories, for example incentives and reminders. Thirdly, there are other theoretical models that seem plausible for explaining non-adherence, but not very effective in improving adherence behaviour. Fourthly, effective components within promising theories could not be identified because of the complexity of many adherence interventions and the lack of studies that explicitly compare theoretical components. CONCLUSION: There is a scarcity of comparative studies explicitly contrasting theoretical models or their components. The relative weight of these theories and the effective components in the interventions designed to improve adherence, need to be assessed in future studies.