[A man with a curved deformity of the hand]. / Een man met een kromme hand.

A 63-year-old male was seen at the rheumatology outpatient clinic because of a curved deformity of his left hand, with fixed flexion of the MCP joints and hyperextension of the PIP and DIP joints. This so-called striatal hand, a feature of Parkinson's disease, can easily be confused with rheumatoid arthritis or Dupuytren's contracture.

Longitudinal study of udder cleft dermatitis in 5 Dutch dairy cattle herds.

Udder cleft dermatitis (UCD) is a skin lesion in dairy cows, most often located between anterior parts of the udder and abdomen, but also found between the front quarters. A few recent studies have investigated the prevalence of UCD, but relatively little is known about its pathogenesis, clinical course, and duration. Therefore, the aim of this study was to investigate the incidence and recovery of UCD on high-prevalence herds. Five Dutch dairy herds with a UCD prevalence of at least 6% were visited weekly for 19 wk, followed by visits every other week for 26 wk. During each visit, all dry and lactating cows were inspected for the presence of UCD signs. If a UCD case was detected, the affected skin was photographed and the photo was subsequently examined by a research assistant. Cows were then classified according to the appearance of the skin into 3 categories: healthy (no photo: no signs), mild (photo: affected skin but no wound), or severe (photo: open wound). The overall mean within-herd prevalence of UCD was 38% and the overall mean incidence was 1.94 UCD episodes per 100 cow-weeks at risk. Incidence of UCD was significantly higher in cows in third or higher parity and significantly increased with DIM. Median observed duration of UCD was 16 wk. The UCD recovery was 3 times more likely for mild than for severe lesions. The probability of moving from one category to another between 2 consecutive visits was very low, indicating that rapid changes in appearance did not occur. The observed incidence of UCD was rather low, and the relatively high prevalence in the selected herds was most likely due to the long duration of lesions rather than a high incidence of new UCD cases.

Safety and efficacy of a fully covered large-diameter self-expanding metal stent for the treatment of upper gastrointestinal perforations, anastomotic leaks, and fistula.

Upper gastrointestinal perforations, fistula, and anastomotic leaks are severe conditions with high mortality. Temporary endoscopic placement of fully covered self-expanding metal stent (fSEMS) has emerged as treatment option. Stent migration is a major drawback of currently used stents. Migration is often attributed to a relatively too small stent diameter as esophageal stents were initially intended for the treatment of strictures. This study aimed to investigate the safety and efficacy of a large-diameter fSEMS for treatment of these conditions. Data were retrospectively collected from patients who received this stent in the Netherlands between March 2011 and August 2013. Clinical success was defined as sufficient leak closure after stent removal as confirmed by endoscopy or X-ray with oral contrast without surgical intervention or placement of another type of stent. Adverse events were graded according a standardized grading system. Stent placement was performed in 34 patients for the following indications: perforation (n = 6), anastomotic leak (n = 26), and fistula (n = 2). Technical success rate was 97% (33/34). Clinical success rate was 44% (15/34) after one stent and 50% (17/34) after an additional stent. There were no severe adverse events and stent-related mortality. The overall adverse event rate was 50% (all graded 'moderate'). There were 14 (41%) stent migrations (complete n = 8, partial n = 6). Other adverse events were bleeding (n = 2) and aspiration pneumonia (n = 1). Reinterventions for failure of the large-diameter fSEMS were placement of another type of fSEMS (n = 4), surgical repair (n = 3), or esophagectomy (n = 1). Eleven patients (32%) died in-hospital because of persisting intrathoracic sepsis (n = 10) or preexistent bowel ischemia (n = 1). This study suggests that temporary placement of a large-diameter fSEMS for the treatment of upper gastrointestinal perforations, fistula, and anastomotic leaks is safe in terms of severe adverse events and stent-related mortality. The larger diameter does not seem to prevent stent migration.

Cyclo-oxygenase-2 inhibitors or nonselective NSAIDs plus gastroprotective agents: what to prescribe in daily clinical practice?

BACKGROUND: Two strategies for prevention of upper gastrointestinal (UGI) events for nonselective nonsteroidal anti-inflammatory drug (nsNSAID) users are replacement of the nsNSAID by a cyclo-oxygenase-2-selective inhibitor (coxib) or co-prescription of a gastroprotective agent (GPA). AIM: To identify whether and in whom either of these strategies should be preferred in daily practice. METHODS: A nested case-control study was conducted using three European primary care databases. We selected a cohort including all naive nsNSAID+GPA (≥80% GPA adherence) and coxib users (without GPA use) aged ≥50 years. Cases with an UGI event (i.e. symptomatic UGI ulcer or bleeding) were matched to cohort members without an UGI event on age, sex and number of individual UGI risk factors (i.e. UGI event history, age ≥65 years, concomitant use of anticoagulants, antiplatelets, or glucocorticoids) and calendar time. Conditional logistic regression analysis was used to calculate odds ratios (ORs) with 95% CI, while adjusting for potential confounders. RESULTS: Within the NSAID cohort (n = 617,220), 398 UGI cases were identified. The risk of UGI events was equivalent for coxib and nsNSAID+GPA (≥80% adherence) users (OR: 1.02; 95%CI: 0.77-1.37). In concurrent glucocorticoid users, the risk of UGI events was significantly elevated for nsNSAID+GPA (≥80% adherence) compared with coxib users (OR: 9.01; 95%CI: 1.61-50.50). CONCLUSIONS: The risk of UGI events was similar in nsNSAID+GPA (≥80% adherence) and coxibs users. In patients concurrently using glucocorticoids, a significant increase in the risk of UGI events for nsNSAID+GPA users was observed and coxibs should be preferred.

Prescription of nonselective NSAIDs, coxibs and gastroprotective agents in the era of rofecoxib withdrawal - a 617,400-patient study.

BACKGROUND: Gastroprotective strategies are recommended for nonsteroidal anti-inflammatory drug (NSAID) users at risk of upper gastrointestinal (UGI) complications. AIM: To compare the use of gastroprotective strategies in NSAID users in three countries, and the subsequent impact of rofecoxib withdrawal. METHODS: We conducted a population-based cohort study in three general practice (GP) databases: (i) United Kingdom's (UK) GP Research Database (1998-2008); (ii) Italy's (IT) Health Search/CSD Longitudinal Patient Database (2000-2007); and (iii) the Dutch (NL) Integrated Primary Care Information database (1996-2006). Study cohorts comprised incident NSAID users ≥50 years. Preventive strategies included: (i) co-prescription of gastroprotective agents; or (ii) cyclooxygenase-2-selective inhibitor use. Under-use was defined as no gastroprotection in patients with ≥1 UGI risk factor (history of UGI event, age ≥65 years, concomitant use of anticoagulants, antiplatelets or glucocorticoids). Interrupted time-series analysis was performed to assess the impact of rofecoxib withdrawal on preventive strategies. RESULTS: The study populations consisted of 384 649 UK, 177 747 IT and 55 004 NL NSAID users. In UK, under-use of preventive strategies fell from 91% to 71% [linear trend (lt) P = 0.001], in NL from 92% to 58% (lt P < 0.001) and in IT from 90% to 76% (lt P = 0.38) in high-risk NSAID users. In 2000 and 2006, under-use was significantly lower in NL compared with UK and IT (P < 0.001) in high-risk users. After rofecoxib's withdrawal, under-use increased significantly in UK and NL. CONCLUSIONS: The prescription of gastropreventive strategies followed a similar pattern across countries. Despite a temporary negative effect of rofecoxib withdrawal on under-use, improvement of gastroprotection with nonsteroidal anti-inflammatory drugs was observed.

Incidence of multiple sclerosis in the general population in the Netherlands, 1996-2008.

BACKGROUND: We estimated the multiple sclerosis (MS) incidence in the Netherlands for better active monitoring of potential vaccine safety signals. METHODS: A retrospective cohort study (1996-2008) was conducted using a population-based general practice research database containing electronic medical records. Additional information was collected to validate incident probable cases. RESULTS: In the source population (648,656 persons), 146 incident probable MS cases were identified. Overall incidence rate was 6.3/100,000 person years (py; 95% CI, 5.2-7.2). In the subgroup in which MS could be fully validated, the incidence increased from 4/100,000 py (95% CI, 3-5) in 1996-2004 to 9/100,000 py in 2007/8 (95% CI, 6-16). This increase was highest among women, but not statistically significantly different by gender. The median lag time between first recorded symptoms and MS diagnosis decreased from 32 months (<1998) to 2 months (>2005). CONCLUSIONS: MS is rare in the Netherlands. In recent years, there was a slight increase in the incidence especially among women during the fertile age. This increase coincided with a decrease in lag time between symptoms and diagnosis, both for men and women. This trend should be taken into account in the interpretation of MS cases occurring in a population where new vaccinations will be introduced shortly.

Risk of recurrent myocardial infarction with the concomitant use of clopidogrel and proton pump inhibitors.

BACKGROUND: The association between myocardial infarction (MI) and co-administration of proton pump inhibitors (PPIs) and clopidogrel remains controversial. AIM: To quantify the association between concomitant use of PPIs and clopidogrel and occurrence of recurrent MI. METHODS: We conducted a case-control study within a cohort of acute MI patients in PHARMO Record Linkage System (1999-2008). The cases were patients readmitted for MI. PPI exposure was categorized as current (3-1 days before MI), past (30-3 days before MI), or no use (>30 days before MI). We used conditional logistic regression analyses. RESULTS: Among 23 655 patients hospitalized following MI, we identified 1247 patients readmitted for MI. Among clopidogrel users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.62, 95% CI: 1.15-2.27) when compared with no PPI use, but not when compared with past PPI use (OR: 0.95, 95% CI: 0.38-2.41). Among clopidogrel non-users, current PPI use was associated with an increased risk of recurrent MI (OR: 1.38, 95% CI: 1.18-1.61) when compared with no PPI use. CONCLUSIONS: The apparent association between recurrent MI and use of PPIs with clopidogrel depends on the design, and is affected by confounding by indication. The association is not present when (un)measured confounding is addressed by design.

Time-trends in gastroprotection with nonsteroidal anti-inflammatory drugs (NSAIDs).

BACKGROUND: Preventive strategies are advocated in patients at risk of upper-gastrointestinal complications associated with nonsteroidal anti-inflammatory drugs (NSAIDs). AIM: To examine time-trends in preventive strategies. METHODS: In a study population comprising 50 126 NSAID users > or =50 years from the Integrated Primary Care Information database, we considered two preventive strategies: co-prescription of gastroprotective agents and prescription of a cyclooxygenase-2-selective inhibitor. In patients with > or =1 risk factor (history of upper-gastrointestinal bleeding/ulceration, age >65 years, use of anticoagulants, aspirin, or corticosteroids), correct prescription was defined as the presence of a preventive strategy and under-prescription as the absence of one. In patients with no risk factors, correct prescription was defined as the lack of a preventive strategy, and over-prescription as the presence of one. RESULTS: Correct prescription rose from 6.9% in 1996 to 39.4% in 2006 (P < 0.01) in high-risk NSAID users. Under-prescription fell from 93.1% to 59.9% (P < 0.01). In the complete cohort, over-prescription rose from 2.9% to 12.3% (P < 0.01). CONCLUSIONS: Under-prescription of preventive strategies has steadily decreased between 1996 and 2006; however, 60% of NSAID users at increased risk of NSAID complications still do not receive adequate protection.

Gastro-oesophageal reflux, medical resource utilization and upper gastrointestinal endoscopy in patients at risk of oesophageal adenocarcinoma.

BACKGROUND: Early identification of patients at risk of oesophageal adenocarcinoma (OAC) might improve survival. AIM: To assess the medical resource utilization in the 3 years before OAC diagnosis as potential markers for early identification and intervention. METHODS: We identified 65 incident OAC within the Integrated Primary Care Information database. For comparison, we randomly selected 260 age- and gender-matched population controls. We abstracted the use of gastric acid inhibitors, general practitioner (GP) and specialist care, and gastroscopies in the 3 years before the detection of OAC. RESULTS: Approximately 20% of the cases used gastric acid inhibitors in the third and second year before OAC, which increased to almost 50% in the last year, compared to approximately 10% among controls. Only in the 6 months before OAC, the proportion of patients visiting a GP (97%) or specialist (41%) increased compared to controls. Of 13 gastroscopies performed in the 3 years, six (46%) were not suspect for a malignancy. CONCLUSIONS: Only a minority of all OAC patients used acid inhibitors before diagnosis. The use of medical care between cases and controls differed only in the final year before OAC diagnosis. Detection of early neoplastic changes proves to be difficult.

[A patient with repeated, life-threatening gastro-intestinal haemorrhages treated by means of medication, open surgery, endoscopic surgery, intervention radiology and conservative methods]. / Een patiënt met recidiverende levensbedreigende darmbloedingen behandeld met medicamenteuze, chirurgische, endoscopische, interventieradiologische en conservatieve methoden.

A 56-year-old man with Henoch Schönlein purpura vasculitis suffered from repeated and multiple life-threatening gastrointestinal haemorrhages. Over recent years a number of interventions for the treatment of gastrointestinal haemorrhaging have become available; choosing which option to use can present difficulties. The available interventions are carried out by different disciplines and include haemostatic drugs, endoscopic intervention, intervention radiology, and surgery. In this patient, following a severe drop in haemoglobin levels, CT and angiography revealed active bleeding in the distal jejunum. Transarterial embolization by means of a coiling procedure halted the bleeding. The patient was also given tranexamic acid, a fibrinolysis inhibitor. More episodes of bleeding subsequently followed which necessitated further coiling procedures, two bowel resections, the endoscopic clipping of a bleeding artery, treatment with the recombinant activated factor VII (rFVIIa) at a dosage of 90 microg/kg, as well as conservative treatment with multiple transfusions of filtered erythrocytes and fresh plasma. The patient eventually recovered.

Adherence to gastroprotection and the risk of NSAID-related upper gastrointestinal ulcers and haemorrhage.

BACKGROUND: Upper gastrointestinal (UGI) complications are a well-recognized risk of NSAID treatment, requiring preventive measures in high-risk patients. Adherence to gastroprotective agents (GPAs) in NSAID users has been suggested to be suboptimal. AIM: To investigate the association between adherence to GPAs (proton pump inhibitors or H(2)-receptor antagonists) and the risk of NSAID-related UGI ulcers or haemorrhage in high-risk patients. METHODS: A population-based nested case-control study was conducted within a cohort of new NSAID users with at least one risk factor for a NSAID-related UGI complication, identified in the Dutch IPCI database during 1996-2005. Adherence to GPAs was calculated as the proportion of NSAID treatment days covered (PDC) by a GPA prescription. Multivariate conditional logistic regression analysis was used to calculate odds ratios with 95% confidence intervals (95% CI). RESULTS: Fifteen percent of the non-selective NSAID users received GPAs. The risk of a NSAID-related UGI complication among NSAID users increased 16% for every 10% decrease in adherence. Compared to patients with a PDC of >80%, patients with PDCs of 20-80% and <20% had a 2.5-fold (95% CI: 1.0-6.7) respectively 4.0-fold (95% CI: 1.2-13.0) increased risk. CONCLUSION: There is a strong inverse relationship between adherence to GPAs and the risk of UGI complications in high-risk NSAID users.

[A woman with shock as first sign of Zollinger-Ellison syndrome]. / Een vrouw met shock als eerste uiting van een zollinger-ellisonsyndroom.

A 49-year-old woman presented at the emergency ward in shock with upper gastrointestinal bleeding. Extensive ulceration confirmed by gastroduodenoscopy was suggestive of Zollinger-Ellison syndrome. Further evaluation by fasting gastrin assessment, CT, endosonography with cytological biopsy and somatostatin-receptor scintigraphy confirmed the diagnosis ofgastrinoma. Three enlarged lymph nodes near the pancreatic head were surgically removed; each was found to contain neuroendocrine tumour cells. The patient recovered rapidly after surgery and the gastrin level normalised. Zollinger-Ellison syndrome is uncommon but should be considered as a possible cause of upper gastrointestinal bleeding. Shock is very rarely the first sign ofZollinger-Ellison syndrome. In this case, the use of a proton-pump inhibitor may have masked the disease for years.

Persistence and adherence to proton pump inhibitors in daily clinical practice.

BACKGROUND: Proton pump inhibitors are widely used, but little is known about the usage pattern in different indications. AIM: To analyse proton pump inhibitor usage patterns in the general population. METHODS: A cohort of 16 311 incident proton pump inhibitor users was identified in the Integrated Primary Care Information database, a Dutch general practice research database. Persistence and adherence were calculated by indication. Risk factors were identified by logistic regression analysis. RESULTS: One-year persistence was 31% in patients using proton pump inhibitors for gastro-oesophageal reflux. Persistence was higher in oesophagitis grade A/B (54%), grade C/D (73%) and Barrett's oesophagus (72%), compared to patients with only reflux symptoms (27%). Approximately 25% of patients with non-reflux dyspepsia or Helicobacter pylori-associated indications used proton pump inhibitors for more than 6 months. Half of all patients used proton pump inhibitors <80% of time indicating intermittent use, which was independent of indication. Exception were patients with Barrett's oesophagus, who were most adherent. CONCLUSIONS: A substantial proportion of patients with indications not requiring long-term treatment use proton pump inhibitors for an extended period. Half of the patients used proton pump inhibitors on-demand or intermittently. Such usage pattern is probably sufficient for most patients, but may be inadequate if proton pump inhibitors are used for serious diseases, such as severe oesophagitis or Barrett's oesophagus.

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.

Occupational health risks in veterinary nursing: an exploratory study.

OBJECTIVES: The aims of this exploratory study were to survey the prevalence of certain exposures and health problems among a group of veterinary nurses attending the International Veterinary Nurses' Conference in Brisbane, Australia, 2003 and to identify the main concerns among those veterinary nurses with regard to occupational health hazards they may face. METHODS AND MATERIALS: An anonymous self-administered questionnaire was distributed among all attendees of the International Veterinary Nurses' Conference 2003, Brisbane, Australia (N=147 respondents among 215 surveyed). RESULTS: The prevalence of exposure to X-radiation (97%), anaesthetics (96%), disinfectants (96%) and vaccines (85%) was high. More than 70% of the nurses were exposed to formaldehyde (76%) and pesticides/insecticides (71%). For all exposures except vaccines, about 50% of the nurses exposed were worried about negative health consequences. Acute injuries were common with 98% of the nurses experiencing dog/cat bites/scratches, 71% experiencing needle stick injuries and 43% experiencing lacerations. More than half of the nurses (52%) suffered from chronic back/neck pain and 39% reported having allergy or hay fever. Sixteen cases (11%) of Cat Scratch Fever were reported. Job related affective well-being was similar to a large sample of workers in comparable level jobs. CONCLUSION: Among attendees of a veterinary nurses conference, the proportion of this group of nurses exposed to hazards in their work environment was high and acute and chronic injuries were common. Considering that nurses account for more than 40% of total employment in the veterinary service industry, the results of this study show that the occupational health hazards of this professional group require further study.

Effect of recombinant human osteogenic protein-1 on the healing of a freshly closed diaphyseal fracture.

Osteogenic protein-1 (OP-1), or bone morphogenetic protein-7, is an osteoinductive morphogen that is involved in embryonic skeletogenesis and in bone repair. In bone defect models without spontaneous healing, local administration of recombinant human OP-1 (rhOP-1) induces complete healing. To investigate the ability of rhOP-1 to accelerate normal physiologic fracture healing, an experimental study was performed. In 40 adult female goats a closed tibial fracture was made, stabilized with an external fixator, and treated as follows: (1) no injection; (2) injection of 1 mg rhOP-1 dissolved in aqueous buffer; (3) injection of collagen matrix; and (4) injection of 1 mg rhOP-1 bound to collagen matrix. The test substances were injected in the fracture gap under fluoroscopic control. At 2 and 4 weeks, fracture healing was evaluated with radiographs, three-dimensional computed tomography (CT), dual-energy X-ray absorptiometry, biomechanical tests, and histology. At 2 weeks, callus diameter, callus volume, and bone mineral content at the fracture site were significantly increased in both rhOP-1 groups compared with the no-injection group. As signs of accelerated callus maturation, bending and torsional stiffness were higher and bony bridging of the fracture gap was observed more often in the group with rhOP-1 dissolved in aqueous buffer than in uninjected fractures. Treatment with rhOP-1 plus collagen matrix did not result in improved biomechanical properties or bony bridging of the fracture gap at 2 weeks. At 4 weeks there were no differences between groups, except for a larger callus volume in the rhOP-1 plus collagen matrix group compared with the control groups. All fractures showed an advanced stage of healing at 4 weeks. In conclusion, the healing of a closed fracture in a goat model can be accelerated by a single local administration of rhOP-1. The use of a carrier material does not seem to be crucial in this application of rhOP-1.

[Diagnostic image (86). A man with thirst and diplopia]. / Diagnose in beeld (86). Een man met dorst en dubbelzien. Multipel myeloom met N.-abducensparese links.

A 71-year-old man was thirsty, had bone pains and a double vision. Multiple myeloma with hypercalcemia was diagnosed. One tumour in the clivus turned out to be compressing the left N. abducens.