Miriam Sturkenboom

The incidence of complex regional pain syndrome: a population-based study.

Abstract The complex regional pain syndrome (CRPS) is a painful disorder that can occur in an extremity after any type of injury, or even spontaneously. Data on the incidence of CRPS are scarce and mostly hospital based. Therefore the size of the problem and its burden on health care and society are unknown. The objective of the present study was to estimate the incidence of CRPS in the general population. A retrospective cohort study was conducted during 1996–2005 in the Integrated Primary Care Information (IPCI) project, a general practice research database with electronic patient record data from 600,000 patients throughout the Netherlands. Potential CRPS cases were identified by a sensitive search algorithm including synonyms and abbreviations for CRPS. Subsequently, cases were validated by electronic record review, supplemented with original specialist letters and information from an enquiry of general practitioners. The estimated overall incidence rate of CRPS was 26.2 per 100,000 person years (95% CI: 23.0–29.7). Females were affected at least three times more often than males (ratio: 3.4). The highest incidence occurred in females in the age category of 61–70 years. The upper extremity was affected more frequently than the lower extremity and a fracture was the most common precipitating event (44%). The observed incidence rate of CRPS is more as four times higher than the incidence rate observed in the only other population‐based study, performed in Olmsted County, USA. Postmenopausal woman appeared to be at the highest risk for the development of CRPS.

Increasing incidence of Barrett’s oesophagus in the general population

Background: Barrett’s oesophagus (BO) predisposes to oesophageal adenocarcinoma. Epidemiological data suggest that the incidence of BO is rising but it is unclear whether this reflects a true rise in incidence of BO or an increase in detection secondary to more upper gastrointestinal endoscopies performed. This study aimed to examine the changes in BO incidence relative to the number of upper gastrointestinal endoscopies performed in the general population. Methods: We conducted a cohort study using the Integrated Primary Care Information database. This general practice research database contains the complete and longitudinal electronic medical records of more than 500 000 persons. Results: In total, 260 incident cases of BO were identified during the study period. The incidence of BO increased from 14.3/100 000 person years in 1997 (95% confidence interval (CI) 8.6–22.4) to 23.1/100 000 person years (95% CI 17.2–30.6) in 2002 (r2 = 0.87). The number of upper gastrointestinal endoscopies decreased from 7.2/1000 person years (95% CI 6.7–7.7) to 5.7/1000 person years (95% CI 5.4–6.1) over the same time period. This resulted in an overall increase in detected BO per 1000 endoscopies from 19.8 (95% CI 12.0–31.0) in 1997 to 40.5 (95% CI 30.0–53.5) in 2002 (r2 = 0.93). The incidence of adenocarcinoma increased from 1.7/100 000 person years (95% CI 0.3–5.4) in 1997 to 6.0/100 000 person years (95% CI 3.3–10.2) in 2002 (r2 = 0.87). Conclusion: The incidence of diagnosed BO is increasing, independent of the number of upper gastrointestinal endoscopies that are being performed. This increase in BO incidence will likely result in a further increase in the incidence of oesophageal adenocarcinomas in the near future.

Incidence rates and treatment of neuropathic pain conditions in the general population.

&NA; Incidence rate estimates of neuropathic pain are scanty and mostly address single types whereas the scope of the disease is wide. We aimed to calculate the incidence rates of neuropathic pain conditions in the Dutch general population and to assess treatment strategies in primary care. The study population included persons registered for at least one year in the Integrated Primary Care Information (IPCI) database between 1996 and 2003. Neuropathic pain was ascertained and classified by systematic review of computerized longitudinal medical records. Incidence rates (IR) were calculated, and the treatment for pain was compared to age and gender matched controls. Among 362,693 persons contributing 1,116,215 person years (PY), we identified 9135 new cases of neuropathic pain (IR: 8.2/1000 PY, 95%CI: 8.0–8.4). Mononeuropathy and carpal tunnel syndrome were the most frequent types with 4.3 and 2.3 cases/1000 PY followed by diabetic peripheral neuropathy and post‐herpetic neuralgia at 0.72 and 0.42/1000 PY. Neuropathic pain was 63% more common in women than in men and peaked between the ages 70 and 79. More than 50% of cases received pain medication within 6 months after diagnosis, mostly consisting of NSAIDs or aspirin. Anticonvulsants and tricyclic antidepressants were only used by 4.8 and 4.7% of cases. Neuropathic pain is a rather frequent condition with an annual incidence of almost 1% of the general population and affecting women and middle‐aged persons more often. The treatment mostly consisted of regular analgesics suggesting that pharmacological treatment of neuropathic pain is suboptimal.

Genome-wide association study of intracranial aneurysm identifies three new risk loci

Saccular intracranial aneurysms are balloon-like dilations of the intracranial arterial wall; their hemorrhage commonly results in severe neurologic impairment and death. We report a second genome-wide association study with discovery and replication cohorts from Europe and Japan comprising 5,891 cases and 14,181 controls with ∼832,000 genotyped and imputed SNPs across discovery cohorts. We identified three new loci showing strong evidence for association with intracranial aneurysms in the combined dataset, including intervals near RBBP8 on 18q11.2 (odds ratio (OR) = 1.22, P = 1.1 × 10−12), STARD13-KL on 13q13.1 (OR = 1.20, P = 2.5 × 10−9) and a gene-rich region on 10q24.32 (OR = 1.29, P = 1.2 × 10−9). We also confirmed prior associations near SOX17 (8q11.23–q12.1; OR = 1.28, P = 1.3 × 10−12) and CDKN2A-CDKN2B (9p21.3; OR = 1.31, P = 1.5 × 10−22). It is noteworthy that several putative risk genes play a role in cell-cycle progression, potentially affecting the proliferation and senescence of progenitor-cell populations that are responsible for vascular formation and repair.

Combining electronic healthcare databases in Europe to allow for large-scale drug safety monitoring: the EU-ADR Project

In this proof‐of‐concept paper we describe the framework, process, and preliminary results of combining data from European electronic healthcare record (EHR) databases for large‐scale monitoring of drug safety.

Incidence of facial pain in the general population

ABSTRACT Facial pain has a considerable impact on quality of life. Accurate incidence estimates in the general population are scant. The aim was therefore to estimate the incidence rate (IR) of trigeminal neuralgia (TGN), postherpetic neuralgia (PHN), cluster headache (CH), occipital neuralgia (ON), local neuralgia (LoN), atypical facial pain (AFP), glossopharyngeal neuralgia (GPN) and paroxysmal hemicrania (PH) in the Netherlands. In the population‐based Integrated Primary Care Information (IPCI) medical record database potential facial pain cases were identified from codes and narratives. Two medical doctors reviewed medical records, questionnaires from general practitioners and specialist letters using criteria of the International Association for the Study of Pain. A pain specialist arbitrated if necessary and a random sample of all cases was evaluated by a neurologist. The date of onset was defined as date of first specific symptoms. The IR was calculated per 100,000 PY. Three hundred and sixty‐two incident cases were ascertained. The overall IR [95% confidence interval] was 38.7 [34.9–42.9]. It was more common among women compared to men. Trigeminal neuralgia and cluster headache were the most common forms among the studied diseases. Paroxysmal hemicrania and glossopharyngeal neuralgia were among the rarer syndromes. The IR increased with age for all diseases except CH and ON, peaking in the 4th and 7th decade, respectively. Postherpetic neuralgia, CH and LoN were more common in men than women. From this we can conclude that facial pain is relatively rare, although more common than estimated previously based on hospital data.

Adverse drug reaction-related hospitalisations: a nationwide study in The Netherlands.

AbstractBackground: The incidence of adverse drug reaction (ADR)-related hospitalisations has usually been assessed within hospitals. Because of the variability in results and methodology, it is difficult to extrapolate these results to a national level. Objectives: To evaluate the incidence and characteristics of ADR-related hospitalisations in The Netherlands in 2001. Methods: We conducted a nationwide study of all hospital admissions in 2001. Data were retrieved from a nationwide computer database for hospital discharge records. All acute, non-planned admissions to all Dutch academic and general hospitals in 2001 were included in the study (n = 668 714). From these admissions we selected all hospitalisations that were coded as drug-related, but intended forms of overdose, errors in administration and therapeutic failures were excluded. Hence, we extracted all ADR-related hospitalisations. We compared age, sex and the risk of a fatal outcome between patients admitted with ADRs and patients admitted for other reasons, as well as the most frequent main diagnoses in ADR-related hospitalisations and which drugs most frequently caused the ADRs. In addition, we evaluated to what extent these ADRs were reported to the Netherlands Pharmacovigilance Centre Lareb for spontaneous ADR reporting. Results: In 2001, 12 249 hospitalisations were coded as ADR related. This was 1.83% of all acute hospital admissions in The Netherlands (95% CI 1.80, 1.86). The proportion increased with age from 0.8% (95% CI 0.75, 0.85) in the <18 years group to 3.2% in the ≥80 years group (95% CI 3.08, 3.32). The most frequent ADR-related diagnoses of hospitalisations were bleeding (n = 1048), non-specified ‘unintended effect of drug’ (n = 438), hypoglycaemia (n = 375) and fever (n = 347). The drugs most commonly associated with ADR-related hospitalisations were anticoagulants (n = 2185), cytostatics and immunosuppressives (n = 1809) and diuretics (n = 979). Six percent of the ADR-related hospitalisations had a fatal outcome (n = 734). Older age and female gender were associated with ADR-related hospitalisations. Only approximately 1% of the coded ADRs causing hospitalisation were reported to our national centre for spontaneous ADR reporting. Conclusion: The proportion of ADR-related hospitalisations is substantial, especially considering the fact that not all ADRs may be recognised or mentioned in discharge letters. Under-reporting of ADRs that result in hospital admission to our national centre for spontaneous ADR reporting was considerable.

Patterns of persistence with antihypertensive medications in newly diagnosed hypertensive patients in Italy: a retrospective cohort study in primary care.

Objective To describe patterns of persistence and related primary care costs associated with first antihypertensive treatment. Design and setting Retrospective cohort study during 2000–2001, using information from 320 Italian general practitioners. Participants We studied 13 303 patients with newly diagnosed hypertension, who received a first single antihypertensive prescription within 3 months after diagnosis. Main outcome measures Persistence with first-line single treatment, categorized as follows: continuers: patients continuing the first-line medication for at least 1 year; combiners: patients receiving an additional antihypertensive drug and continuing the initial medication; switchers: patients changing from the first-line to another class of antihypertensive drug and discontinuing the initial treatment; discontinuers: patients stopping the first-line treatment without having another prescription until the end of the follow-up. Primary care costs were expressed as the cost of hypertension management per person-year of follow-up. Results In the study cohort, 19.8% were continuers, 22.1% were combiners, 15.4% were switchers, and 42.6% were discontinuers. Continuation was greatest with angiotensin II type 1 receptor blocking agents (25.2%), calcium channel blockers (23.9%) and angiotensin-converting enzyme inhibitors (23.3%). Severe hypertension [hazards ratio 1.30; 95% confidence interval (CI) 1.18 to 1.43] and severe health status (hazards ratio 1.22; 95% CI 1.15 to 1.30) increased the risk of discontinuation. The likelihood of needing an additional antihypertensive drug was associated with mild-to-severe baseline blood pressure, diabetes (hazards ratio 1.20; 95% CI 1.06 to 1.36), and familial history of cardiovascular disease (hazards ratio 1.24; 95% CI 1.10 to 1.39). Discontinuers accounted for 22.4% of the total primary care cost. Initial treatment with angiotensin II type 1 receptor blocking agents and β-blockers resulted in incremental primary care costs of &U20AC;145.2 and &U20AC;144.2, respectively, compared with diuretics. Combiners and switchers increased the primary care cost by &U20AC;140.1 and &U20AC;11.7, compared with continuers. Conclusion Persistence with first-line single antihypertensive drugs is extremely low during the first year of treatment. Potential cost saving should be possible by reducing the high frequency of discontinuation. Diuretics represent the least expensive therapeutic option, although further investigations in the long-term are needed to analyse the effects of persistence on therapeutic effectiveness and related costs.

The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns

BACKGROUND In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification. METHODS We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000-2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom. RESULTS Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90-0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women>men) and around 60 years of age. In the age group 5-19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1-3.1) in Denmark, 6.4 (95% CI: 4.2-9.7) in Finland and 7.5 (95% CI: 5.2-10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time. CONCLUSIONS The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.

Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice.

Objectives To evaluate antihypertensive drug discontinuation among newly diagnosed hypertensive patients. Methods This was a population-based cohort study using the UK General Practice Research Database (GPRD). Patients newly diagnosed with hypertension between 1991 and 2001 and subsequently treated with antihypertensive drugs were included. Overall antihypertensive drug discontinuation was evaluated from a patients first-ever antihypertensive prescription. Class-specific discontinuations were evaluated from a patients first-ever prescriptions of angiotensin-converting enzyme (ACE) inhibitors (ACE-I), alpha antagonists, angiotensin-2 antagonists (AIIA), β blockers, calcium-channel blockers (CCB), miscellaneous, potassium-sparing diuretics, and thiazides. Discontinuation occurred when no antihypertensive prescription was issued within 90 days following the most recent prescription expiration. Results The study population comprised 109 454 patients, with 223 228 antihypertensive drug-class episodes contributing to the class-specific analysis. Overall antihypertensive drug discontinuation was 20.3% [95% confidence interval (CI): 20.0, 20.5%] at 6 months and 28.5% (95% CI: 28.2, 28.7%) at 1 year, with a median time to discontinuation of 3.07 years. The median time to antihypertensive class discontinuation was longest for AIIAs (2.90 years) followed by ACE-I (2.24), CCB (1.86), β blockers (1.50), thiazides (1.50), alpha antagonists (1.35), potassium-sparing diuretics (0.40), and miscellaneous (0.39). One-year discontinuation ranged from 29.4% (95% CI: 28.0, 30.7) for AIIAs to 64.1% (95% CI: 62.1, 66.3) for potassium-sparing diuretics. Forty-four percent who discontinue their first-ever antihypertensive drug class failed to switch to a different drug class within 90 days of discontinuation. Conclusion It is important that general practitioners (GPs) monitor patients closely in the first year following antihypertensive drug initiation, due to the high early risk of discontinuation, and the low percentage of patients who switch to a different antihypertensive drug class after a drug-class discontinuation. AIIA, followed by ACE-I and CCB, had the lowest risk of discontinuation among antihypertensive drug classes.