[Problems with the availability of drugs in The Netherlands]. / Beschikbasrheidsproblemen van geneesmiddelen in Nederland.

The withdrawal ofa license to trade can result in problems with the availability of drugs. The reasons for withdrawal can be ofan economic nature, but the balance between effectiveness and side effects of a drug can also, after a period of time, prove disappointing and the drug can, as a result, be withdrawn from sale. A scarcity of basic materials, too, can play a role in availability, as can the inability of the manufacturer to meet the standards of the relevant authority.

Pandemic influenza vaccines and neuraminidase inhibitors: efficacy and side effects.

At the time of the outbreak of the pandemic of New Influenza A (H1N1) pandemic influenza vaccines became available via an accelerated registration procedure. In 2005 large stocks of the neuraminidase inhibitor oseltamivir were built up in the Netherlands and other western countries. There was considerable doubt about the efficacy of this medicine. Initially reported positive effects of the drug were largely based on unpublished research, which was sponsored by the manufacturer and was partially written by ghostwriters. There now have been reports of rare and serious side effects. The first reports on the severity of the pandemic in Australia and New Zealand indicated a mild course.

The sponsored pandemic of the Mexican flu?

The first reports of the New Influenza A (H1N1) spoke of a markedly increased morbidity and mortality. Later it turned out that this flu was a very mild flu. Gradually the role of the WHO was questioned. The definition of a pandemic flu had been changed and there rose doubts about the independency of the experts advising the WHO. It showed that some of these experts had a conflict of interest with the pharmaceutical industry, especially with those producing vaccines and neuraminidase inhibitors. As of june 2010 the WHO declared the outbreak to be a pandemic. This provided the momentum to produce vaccines. At the outbreak of the pandemic in the northern hemisphere, there was sufficient evidence that the pandemic would not be so serious, that a single vaccination was sufficient, that there were strong doubts about the efficacy of oseltamivir and that the drug, although rarely, could have serious side effects. With the stockpiling of neuraminidase inhibitors and with the recommendation of the vaccination political decisions were involved. These decisions should be driven and supported by independent scientific advisory bodies with no room for even the semblance of conflicts of interest. Stronger measures to limit the impact of experts with conflicts of interest on the development of, among others, guidelines are necessary.

[The workings of the Drug Bulletin]. / De werkwijze van het Geneesmiddelenbulletin.

The Dutch Drug Bulletin (Geneesmiddelenbulletin) is a monthly journal with a unique approach which, after a hectic period in which its independence and even its right to exist were threatened, has now reached calm water The continued existence of the Dutch Drug Bulletin is now guaranteed, independently of the pharmaceutical industry, the government, professional organizations and patient organizations. Articles appear in the Dutch Drug Bulletin after extensive consultation among various experts. Conclusions are based on the published (and hence controllable) results of randomized, preferably double-blind, studies with an appropriate control group. Departures from these standards are made only in highly exceptional cases. The Dutch Drug Bulletin determines the place of new drugs amongst the already available drugs and compares their effectiveness and side effects with those of the standard therapy. This approach guarantees that dentists and physicians are kept up to date with respect to developments in the field of pharmacology, without the pharmaceutical industry or the government exerting any influence.

Surgical smoke and infection control.

Gaseous byproducts produced during electrocautery, laser surgery or the use of ultrasonic scalpels are usually referred to as 'surgical smoke'. This smoke, produced with or without a heating process, contains bio-aerosols with viable and non-viable cellular material that subsequently poses a risk of infection (human immunodeficiency virus, hepatitis B virus, human papillomavirus) and causes irritation to the lungs leading to acute and chronic inflammatory changes. Furthermore, cytotoxic, genotoxic and mutagenic effects have been demonstrated. The American Occupational Safety and Health Administration have estimated that 500000 workers are exposed to laser and electrosurgical smoke each year. The use of standard surgical masks alone does not provide adequate protection from surgical smoke. While higher quality filter masks and/or double masking may increase the filtration capability, a smoke evacuation device or filter placed near (2-5 cm) the electrocautery blade or on endoscope valves offers additional (and necessary) safety for operating personnel and patients.

The serotonin syndrome.

The serotonin syndrome is a complex of symptoms that are thought to be largely attributable to changes in sensitivity in the serotonin receptor systems in the brainstem and the spinal cord due to drugs. Severe cases are almost always caused by a combination of two or more 'serotonergic' drugs, of which at least one is a selective serotonin reuptake inhibitor or a monoamine oxidase inhibitor. Usually, the syndrome heals spontaneously after withdrawal of the medication. Cessation of 'serotonergic' medication is the preferred treatment as well as supportive care.

The accuracy of physical diagnostic tests for assessing meniscal lesions of the knee: a meta-analysis.

OBJECTIVE: Our systematic review summarizes the evidence about the accuracy of those tests. SEARCH STRATEGY: We performed a literature search of MEDLINE (1966-1999) and EMBASE (1988-1999) with additional reference tracking. SELECTION CRITERIA: Articles written in English, French, German, or Dutch, that addressed the accuracy of at least one physical diagnostic test for meniscus injury with arthrotomy, arthroscopy, or magnetic resonance imaging as the gold standard were included. We excluded studies if no reference group or only test-positives had been included, if the study pertained to cadavers only, or if only physical examination under anesthesia was considered. DATA COLLECTION/ANALYSIS: Two reviewers independently selected studies, assessed the methodologic quality, and abstracted data using a standardized protocol. We calculated sensitivity, specificity, and likelihood ratios for each test, and summary estimates when appropriate and possible. MAIN RESULTS: Of 402 identified studies, 13 met the inclusion criteria. The results of the index and reference tests were assessed independently (blindly) of each other in only 2 studies, and in all studies verification bias seemed to be present. The study results were highly heterogeneous The summary receiver operating characteristic curves of the assessment of joint effusion, the McMurray test and joint line tenderness indicated little discriminative power for these tests. Only the predictive value of a positive McMurray test was favorable. CONCLUSIONS: The methodologic quality of studies addressing the diagnostic accuracy of meniscal tests was poor, and the results were highly heterogeneous. The poor characteristics indicate that these tests are of little value for clinical practice.

Effectiveness of exercise in patients with osteoarthritis of hip or knee: nine months' follow up.

OBJECTIVE: To determine whether the effects of an exercise programme in patients with osteoarthritis of hip or knee are sustained at six and nine months' follow up. METHODS: A randomised, single blind, clinical trial was conducted in a primary care setting. Patients with osteoarthritis of hip or knee (ACR criteria) were selected. Two intervention groups were compared. Both groups received treatment from their general practitioner, including patient education and drug treatment if necessary. The experimental group also received exercise treatment from a physiotherapist in primary care. The treatment period was 12 weeks, with an ensuing 24 week follow up. The main outcome measures were pain, drug use (non-steroidal anti-inflammatory drugs), and observed disability. RESULTS: 201 patients were randomly allocated to the exercise or control group, and 183 patients completed the trial. At 24 weeks exercise treatment was associated with a small to moderate effect on pain during the past week (difference in change between the two groups -11.5 (95% CI -19.7 to -3.3). At 36 weeks no differences were found between the groups. CONCLUSIONS: Beneficial effects of exercise decline over time and finally disappear.

Antidepressant prescription for depression in general practice in The Netherlands.

OBJECTIVE: To evaluate diagnoses and the prescription of antidepressants drugs for depression, based on data from 1993 to 1998 related to consultations for depression in general practice in the Netherlands. METHOD: An exploratory analysis of data provided by IMS Health. Consecutive annual representative samples of 640 GPs regularly registered data on morbidity and (drug) treatment for specific medical problems in special booklets for a period of one week. The data refer to consultations for depression. The diagnoses were initially based on ICD-9 criteria and later ICD-10 criteria for depression. MAIN OUTCOME MEASURES: Number of diagnoses of depression and number of prescriptions for antidepressants. RESULTS: The number of first consultations for depression rose gradually, from 909 in 1993 (95% CI: 774 to 1043), to 1,482 (CI: 1292 to 1672) in 1998: an increase of 63%. For an individual GP, this represents an increase from 18 to 30 in first consultations for depression. The number of prescriptions for antidepressants also increased, mainly during repeat consultations: a 278% increase, from 3,708 in 1993 to 14,024 in 1998 (CIs: 3,504 to 3,912 and 13,252 to 14,796). Antidepressants were prescribed during the first consultation 564 times in 1993 compared with 1,080 times in 1998. The first contact with a GP for depression led to an antidepressant prescription in 62% of cases in 1993 and 73% in 1998. Although the guidelines issued by the Dutch College of General Practitioners in 1994 recommended tricyclic antidepressants (TCAs) for the treatment of depression, paroxetin, fluoxetin, and mirtazapin (SSRIs) accounted for 56% of the prescribed antidepressants. CONCLUSION: Between 1993 and 1998, GPs in the Netherlands prescribed increasingly more antidepressants, and they prescribed more SSRIs than TCAs. Furthermore, GPs diagnose depression more frequently and the number of repeat consultations has increased.

The effectiveness of exercise therapy in patients with osteoarthritis of the hip or knee: a randomized clinical trial.

OBJECTIVE: To determine the effectiveness of exercise therapy in patients with osteoarthritis (OA) of the hip or knee. METHODS: A randomized single blind, clinical trial was conducted in a primary care setting. Patients with hip or knee OA by American College of Rheumatology criteria were selected. Two intervention groups were compared. Both groups received treatment from the patients' general practitioner, including patient education and medication if necessary. The experimental group also received exercise therapy from a physiotherapist in primary care. The treatment period was 12 weeks. The main outcome measures were pain, medication use (nonsteroidal antiinflammatory drugs, NSAID) and observed disability. RESULTS: A total of 201 patients were randomized. Exercise therapy was associated with a reduction of pain in the past week (difference in change -17.0; 95% CI -23.6, -10.4) and observed disability (-0.19; 95% CI -0.38; -0.01). Effect sizes were medium (0.58) and small (0.28), respectively. No effect of exercise therapy was found for the use of NSAID. Additional beneficial effects (p = 0.05) were found for the use of paracetamol (effect size 0.33), global effect as perceived by the patient (effect size 0.68), and muscle strength of the hip (effect size 0.34). CONCLUSION: After 12 weeks, exercise therapy is effective in reducing pain and disability. The size of the effects is medium and small, respectively.

Validity of Cyriax's concept capsular pattern for the diagnosis of osteoarthritis of hip and/or knee.

To analyse the validity of Cyriax's concept of the "capsular pattern" in the diagnosis of osteoarthritis (OA) of hip and knee, data on 200 patients were analysed. The capsular pattern with limitations of medial rotation, flexion, and abduction, was not present as a distinct pattern in patients with OA of the hip. In patients with OA of the knee, an indication of the existence of a capsular pattern of the knee, with limited ranges of motion for both flexion and extension was found in subgroups of patients. It is concluded that the capsular pattern cannot be regarded as a valid test for the diagnosis of OA of the hip or knee. Further investigations in subgroups of patients are recommended.

Prescription changes and drug costs at the interface between primary and specialist care.

OBJECTIVE: To explore the relevance of prescription changes and related drug costs when patients are referred from primary to secondary care. PATIENTS AND METHODS: Secondary analysis of data derived from a study on the quality of referrals, which was performed in 1989-1990. New and non-acute referrals of ambulatory patients were studied for internal medicine, neurology, and dermatology. Diagnoses were coded according to the ICPC, and drug names were coded according to the ATC. Prescription data were collected from referral letters and questionnaires. Drugs were also coded as generic or brand name products. Cost of treatment was calculated on the basis of information in the 1989 edition of the Dutch Public Health Care Drug Compendium taking into account the price of the drug and the duration of the prescription. Potential savings were calculated for those brand name products for which substitution by a similar drug was possible. RESULTS: Data on 289 referrals, representing 289 patients, were available for analysis. In 126 out of the 289 patients (43.6%), specialists added to or changed prescriptions initiated by the general practitioner (GP). Specialist prescribing tended to shift to more chronic use. The costs of specialist prescribing are on average 23% higher than for GP prescriptions. Although specialists had fewer opportunities for generic substitution, the potential for savings was greater than for GPs. In many cases, the specialists changed the diagnosis. Only in neurology was the relative risk of receiving a prescription increased when the diagnosis changed. CONCLUSION: Specialists have considerable influence on prescribing to outpatients. The number of prescriptions and the related costs increased greatly when patients were referred from primary to secondary care. The opportunities for generic substitution, and therefore for possible savings, are not fully exploited by GPs or specialists.

Pseudo-outbreak of multiresistant Pseudomonas aeruginosa in a hematology unit.

OBJECTIVE: To describe the investigation of a pseudo-outbreak of multiresistant Pseudomonas aeruginosa fecal colonization in a hematology unit. DESIGN: Retrospective chart review; prospective environmental sampling and observation of stool culture technique; genotyping by random arbitrary primer polymorphic DNA polymerase chain reaction (RAPD-PCR). SETTING: An academic tertiary-care hospital. PATIENTS: Between August and October 1994, P aeruginosa resistant to imipenem, ceftazidime, ciprofloxacin, and all aminoglycosides was isolated from surveillance stool cultures from 10 neutropenic patients cared for in the hematology unit. P aeruginosa, with an identical susceptibility pattern, was isolated from three patients admitted to the same unit in the year before the "outbreak." Two months before the outbreak, 12 healthcare workers had been added to the staff. RESULTS: Observation of stool sampling techniques as performed by healthcare workers revealed that samples for surveillance cultures were taken from feces in the toilet. When the proper sampling technique was used, P aeruginosa was not isolated from stool samples from 8 of 10 patients with previously positive cultures. P aeruginosa also was isolated from two wash basins, toilet flushing water, and a toilet brush. Genotyping by RAPD-PCR showed that the isolate from the toilet flushing water was identical to the P aeruginosa strains of eight patients from the outbreak. CONCLUSIONS: This pseudo-outbreak emphasizes the importance of proper sampling techniques and that periodic observation may be necessary to verify proper sampling techniques.

Staphylococcus epidermidis catheter-related infections in a short-bowel patient. Persistence of a single strain over a two-year period.

We report the case of a patient with short-bowel syndrome, who lost multiple central venous devices over the course of 2 years while treating his catheter-related septicemia. Genotyping proved that all infectious episodes were caused by a single genotype of a Staphylococcus epidermidis strain, persisting over time.

Pulmonary rehabilitation at moderate altitude: a 1-year follow-up.

BACKGROUND: In order to evaluate a pulmonary rehabilitation program (PRP) at moderate altitude (1560 m) 62 patients with obstructive lung disease were asked to participate; 37 patients completed a 1-year follow-up at sea level, and 25 patients dropped out. The exercise training program lasted for 10 weeks and consisted of a cycling and running program of 20 min daily, 5 days a week. METHODS: Incremental exercise testing, spirometry and histamine provocation tests were performed at sea level before the PRP, on admission to the Dutch Asthma Centre, Davos, after 5 weeks of exercise training, at discharge from the Centre and 6 and 12 months after discharge at sea level. RESULTS: The PRP led to an increase in exercise capacity of the 37 patients who also completed the follow-up as reflected by an increase in Wmax (from 104 +/- 44 watt on admission to 150 +/- 8 at discharge, p < 0.001). HRmax (145 +/- 19/min to 151 +/- 21, p < 0.001), Wmax/HR (0.71 +/- 0.26 watt/beat/min to 0.99 +/- 0.29, p < 0.001), VO2max (1.4 +/- 0.4 l/min to 1.9 +/- 0.6, p < 0.001) and VEmax (49 +/- 18 l/min to 78 +/- 24, p < 0.001) measured at discharge from the Dutch Asthma Centre after the PRP were significantly higher than before the PRP at incremental exercise testing. The group of 25 patients who dropped out showed corresponding improvements in these parameters after the PRP in Davos. The 37 patients who completed the follow-up showed at incremental exercise testing 1 year after the PRP that only two of these parameters were still significantly elevated: VO2max 1.8 +/- 0.6 (p < 0.001) and VEmax 61 +/- 21 (p < 0.001). One year after the PRP arterial PCO2 values at maximum exercise were significantly lower (5.2 +/- 0.8 kPa, p < 0.05) than the baseline values (5.5 +/- 0.9 kPa). CONCLUSIONS: PRP at moderate altitude results in an increase of exercise tolerance in patients with asthma or COPD, but significant long-term effects are few.

Severe bronchial asthma improved on bamifylline. Case report and review.

We describe a 25-year-old patient with severe bronchial asthma, which was difficult to treat with oral theophylline. Bamifylline, a xanthine derivative, clearly improved the clinical signs, symptoms and lung function. We critically review the literature on bamifylline.

Endemic acinetobacter in intensive care units: epidemiology and clinical impact.

AIMS: To assess whether Acinetobacter isolates obtained over 20 months in a tertiary care hospital were epidemiologically related; to establish the clinical importance of the organisms; and to identify the isolates according to the recent taxonomy. METHODS: Fifty eight Acinetobacter isolates from 49 patients collected during 1984 and 1985 were investigated. Most isolates were from respiratory tract specimens from intensive care patients. The organisms were typed by cell envelope protein electrophoresis and by a quantitative carbon source growth assay; patients' charts were reviewed to differentiate between colonisation and infection; representative isolates were identified to species level by DNA-DNA hybridisation. RESULTS: Twelve protein profiles were distinguished in the isolates. Forty two isolates were of the same protein profile (profile I); other profiles were observed in a few or single isolates. Cluster analysis of carbon source growth divided profile I isolates into two groups--one of isolates from 1984 and one from 1985. They were identified as A baumannii and associated with infections in eight patients. Four other infections were caused by acinetobacters with other protein profiles (three of A baumannii; one of the unnamed DNA group 3). CONCLUSIONS: Apart from sporadic strains, two strains of the same protein profile, but distinguishable by carbon source growth, were successively endemic. Cluster analysis was a valuable tool in the interpretation of typing and epidemiological data. The 12 (28%) infections of Acinetobacter in 43 patients in intensive care suggest that the presence of these organisms in wards of severely ill patients should be a cause of concern.

Late asthmatic responses after exercise challenge are reproducible.

In this study the reproducibility of a late asthmatic reaction (LAR) after exercise challenge (EC) has been documented. Eighty-three hospitalized patients with asthma were challenged with exercise. The patients were examined according to a standardized protocol that comprised 8 minutes of bicycling at 90% of predicted heart rate. An LAR after EC was considered to have occurred when there was a fall in peak expiratory flow rate greater than or equal to 20% on three or more time points on the exercise day compared to corresponding clock time on a control day. According to these criteria, 11 patients (13.3%) experienced an LAR. Those patients were rechallenged 21 to 150 days after the first EC, without changing the therapy regimen of the patients, to study its reproducibility. Eight patients (73%) demonstrated a reproducible LAR after EC based on the criteria for a positive LAR. Although the LAR after EC was reproducible, the time points at which the LAR took place after the second EC differed from LARs after the first EC. Our results indicate that the LAR after EC occurs in a considerable number of patients with bronchial asthma and is quite reproducible.