[Pain medications for acute and chronic low back pain]. / Medikamentöse Therapie bei akuten und chronischen lumbalen Rückenschmerzen.

Low back pain is common. In the acute (duration <6 weeks) and subacute pain phases (6-12 weeks) the main goal of pharmacological pain treatment is to enable patients to move and to stay as active as possible. In the chronic phase, pain medications can support non-pharmacological measures and improve physical function. Although almost every person will experience low back pain at least once in a lifetime, for many pain medications no clinical studies on their efficacy exist. Most data are available on the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) in acute and chronic low back pain; however, potential adverse effects and contraindications for NSAIDs need to be taken into account when the medication is prescribed. For other non-opioid medications (e. g. paracetamol, metamizole) the efficacy is not well studied. Weak and strong opioids have been shown to be effective compared to placebo in the short term; however, there is increasing evidence that opioids are no more effective than non-opioid medications in the treatment of acute and chronic low back pain. Furthermore, gastrointestinal and central nervous system adverse effects of opioids should be considered. Conclusion: in low back pain, the choice of a specific pain medications is based on the individual patient preferences, contraindications, and potential adverse effects. The main goal of pain medications is to enable patients to stay active. In persisting pain, non-pharmacological measures are important and should complement pharmacological pain treatment.

Cost-effectiveness of conservative versus surgical treatment strategies of lumbar spinal stenosis in the Swiss setting: analysis of the prospective multicenter Lumbar Stenosis Outcome Study (LSOS).

PURPOSE: To evaluate the cost-effectiveness of conservative versus surgical treatment strategies for lumbar spinal stenosis (LSS). METHODS: Patients prospectively enrolled in the multicenter Lumbar Stenosis Outcome Study (LSOS) with a minimum follow-up of 12 months were included. Quality adjusted life years (QALY) were calculated based on EQ-5D data. Cost data were retrieved retrospectively. Cost-effectiveness was calculated via decision tree analysis. RESULTS: A total of 434 patients were included, treated surgically (n = 170) or conservatively (n = 264) for LSS. The majority of surgically treated patients underwent decompression (n = 141, 82.9%), and 17.1% (n = 29) additionally underwent fusion. A reoperation was required in 13 (7.6%) surgically treated patients. In 27 (10.2%) conservatively treated patients, a single infiltration was successful, with no further infiltration or surgery within the follow-up. However, 46 patients (17.4%) required multiple infiltrations, and in 191 (72.4%) initially conservatively treated patients a subsequent surgery was needed. The area under the curve was 0.776 QALY in the surgical arm (0.776 and 0.790, decompression or additional fusion, respectively), compared to 0.778 in the conservative arm. Treatment costs were estimated at CHF 12,958 and 13,637 (USD 13,465 and 14,169) in surgically and initially conservatively treated patients, respectively [base-case incremental cost-effectiveness ratio (ICER): CHF 392,145, USD 407,831], per QALY gained. Probabilistic sensitivity analysis identified surgery as the preferred strategy in 67.1%. CONCLUSIONS: Both the surgical and the conservative treatment approach resulted in a comparable health-related quality of life within the first year after study inclusion. Due to slightly higher costs, mostly because the majority of initially conservatively treated patients underwent multiple infiltrations or a subsequent surgery, decompressive surgery was identified as the most cost-effective approach for LSS in this setting.

A novel use of the Spine Tango registry to evaluate selection bias in patient recruitment into clinical studies: an analysis of patients participating in the Lumbar Spinal Stenosis Outcome Study (LSOS).

PURPOSE: Patients enrolled in clinical studies typically represent a sub-set of all who are eligible, and selection bias may compromise the generalizability of the findings. Using Registry data, we evaluated whether surgical patients recruited by one of the referring centres into the Lumbar Spinal Stenosis Outcome Study (LSOS; a large-scale, multicentre prospective observational study to determine the probability of clinical benefit after surgery) differed in any significant way from those who were eligible but not enrolled. METHODS: Data were extracted for all patients with lumbar spinal stenosis registered in our in-house database (interfaced to Eurospine's Spine Tango Registry) from 2011 to 2013. Patient records and imaging were evaluated in relation to the admission criteria for LSOS to identify those who would have been eligible for participation but were not enrolled (non-LSOS). The Tango surgery data and Core Outcome Measures Index (COMI) data at baseline and 3 and 12 months after surgery were analysed to evaluate the factors associated with LSOS enrolment or not. RESULTS: 514 potentially eligible patients were identified, of which 94 (18%) were enrolled into LSOS (range 2-48% for the 6 spine surgeons involved in recruiting patients) and 420 (82%) were not; the vast majority of the latter were due to non-referral to the study by the surgeon, with only 5% actually refusing participation. There was no significant difference in gender, age, BMI, smoking status, or ASA score between the two groups (p ≥ 0.18). Baseline COMI was significantly (p = 0.002) worse in the non-LSOS group (7.4 ± 1.9) than the LSOS group (6.7 ± 1.9). There were no significant group differences in any Tango surgery parameters (additional spine patholothegies, operation time, blood loss, complications, etc.) although significantly more patients in the non-LSOS group had a fusion procedure (38 vs 18% in LSOS; p = 0.0004). Postoperatively, neither the COMI nor its subdomain scores differed significantly between the groups (p > 0.05). Multiple logistic regression revealed that worse baseline COMI (p = 0.021), surgeon (p = 0.003), and having fusion (p = 0.014) predicted non-enrolment in LSOS. CONCLUSION: A high proportion of eligible patients were not enrolled in the study. Non-enrolment was explained in part by the specific surgeon, worse baseline COMI status, and having a fusion. The findings may reflect a tendency of the referring surgeon not to overburden more disabled patients and those undergoing more extensive surgery with the commitments of a study. Beyond these factors, non-enrolment appeared to be somewhat arbitrary, and was likely related to surgeon forgetfulness, time constraints, and administrative errors. Researchers should be aware of potential selection bias in their clinical studies, measure it (where possible) and discuss its implications for the interpretation of the study's findings.

Validity of outcome measures used in randomized clinical trials and observational studies in degenerative lumbar spinal stenosis.

It is unclear whether outcome measures used in degenerative lumbar spinal stenosis (DLSS) have been validated for this condition. Cross-sectional analysis of studies for DLSS included in systematic reviews (SA) and meta-analyses (MA) indexed in the Cochrane Library. We extracted all outcome measures for pain and disability. We assessed whether the studies provided external references for the validity of the outcome measures and the quality of the validation studies. Out of 20 SA/MA, 95 primary studies used 242 outcome measures for pain and/or disability. Most commonly used were the VAS (n = 69), the Oswestry Disability Index (n = 53) and the Zurich Claudication Questionnaire (n = 22). Although validation references were provided in 45 (47.3%) primary studies, only 14 validation studies for 9 measures (disability n = 7, pain and disability combined n = 2) were specifically validated in a DLSS population. The quality of the validation studies was mainly poor. The Zurich Claudication Questionnaire was the only disease specific tool with adequate validation for assessing treatment response in DLSS. To compare results from clinical studies, outcome measures need to be validated in a disease specific population. The quality of validation studies need to be improved and the validity in studies adequately cited.

Association between depression and anxiety on symptom and function after surgery for lumbar spinal stenosis.

Evidence on the role of depression and anxiety in patients undergoing surgical treatment for symptomatic degenerative lumbar spinal stenosis (DLSS) is conflicting. We aimed to assess the association between depression and anxiety with symptoms and function in patients undergoing surgery for DLSS. Included were patients with symptomatic DLSS participating in a prospective multicentre cohort study who underwent surgery and completed the 24-month follow-up. We used the hospital anxiety and depression scale (HADS) to assess depression/anxiety. We used mixed-effects models to quantify the impact on the primary outcome change in the spinal stenosis measure (SSM) symptoms/function subscale from baseline to 12- and 24-months. Logistic regression analysis was used to quantify the odds of the SSM to reach a minimal clinically important difference (MCID) at 24 months follow-up. The robustness of the results in the presence of unmeasured confounding was quantified using a benchmarking method based on a multiple linear model. Out of 401 patients 72 (17.95%) were depressed and 80 anxious (19.05%). Depression was associated with more symptoms (ß = 0.36, 95% confidence interval (CI) 0.20 to 0.51, p < 0.001) and worse function (ß = 0.37, 95% CI 0.24 to 0.50, p < 0.001) at 12- and 24-months. Only the association between baseline depression and SSM symptoms/function was robust at 12 and 24 months. There was no evidence for baseline depression/anxiety decreasing odds for a MCID in SSM symptoms and function over time. In patients undergoing surgery for symptomatic DLSS, preoperative depression but not anxiety was associated with more severe symptoms and disability at 12 and 24 months.

A systematic review of treatment options for dermal photosensitivity in erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a rare inherited disease characterized by dermal photosensitivity due to the accumulation of photosensitizer protoporphyrin IX. We performed a systematic database search on studies related to treatment of EPP. A total of 25 relevant studies were retrieved, 16 of them dealing with the application of beta-carotene. Two studies were found on each of the three substances, n-acetyl-cysteine (NAC), cysteine, and dihydroxyacetone/Lawson (henna). In addition, single studies on vitamin C, canthaxanthin and UVB treatment respectively, were located. The total number of patients in the 25 studies was 454, including 337 patients in the various beta-carotene trials. Most studies were published in the 1970's. Efficacy criteria were not standardized. Only 5 of the 25 studies were randomized and controlled trials; the rest were either open-label, uncontrolled studies or retrospective case reports. Four of the five well-designed studies suggested lack of efficacy of beta-carotene, NAC and vitamin C. The results of the beta-carotene studies were strongly contradictory and efficacy was inversely correlated with study quality. Our data confirm the opinion of experts in the field who are much more skeptical as to its efficacy than were early proponents of treatment with this agent. We conclude, that the available data are insufficient to prove efficacy of any treatments studied so far in EPP. We emphasize the necessity of high quality efficacy studies in porphyrias and in other rare diseases.

[Research in medicine]. / Forschung in der Medizin.

Research is defined as "seeking of knowledge, data, or the truth about something". Research in the field of medicine can be divided in "basic science" oriented and "patient oriented" research. The starting point of most research is one or a set of yet unanswered questions. The research question should be formulated precisely and in the field of patient oriented research the answer to the question should be clinically relevant. A research question includes the main occurrence relation, the determinant(s) and the outcome as well as the domain in which the relation will be investigated.

[Managerial considerations in research]. / Management eines Forschungsprojektes.

Basics for proper research are good ideas, know how and adequate resources. Essential to accomplish a research project in an efficient way is thorough planning. A research project can be divided in four organizational units. Writing of the protocol, which includes details about all relevant aspects, e.g. the research question, study design, time table and budget, second, details on data collection, third, data analysis and fourth, writing a report or manuscript for publication. A thoroughly developed protocol facilitates the communication between all involved persons and permits an efficient management of a research project.

Patient education in asthma: a survey of physicians' knowledge of the principles and implementation of self management in practice.

BACKGROUND: Therapeutic patient education, particularly when including written instructions in self-management, improves outcomes in asthma. The education of patients in self-management requires specific knowledge and skills, which are not generally taught in under- or postgraduate training programmes. PURPOSE: To investigate physicians' knowledge of the principles and implementation of self-management in asthma care. METHOD: A 14-item questionnaire was developed, piloted and subsequently sent to 1039 general physicians (general practitioners and internists) and pulmonologists registered as members of the Medical Society of Zurich. RESULTS: 368 (35%) of the physicians returned the questionnaire. 352 (96%) stated that they care for patients with asthma, 312 (87%) provided asthma education, 264 (75%) gave information about the mechanisms of illness, 272 (77%) provided instructions on how to use inhalers although only 212 (60%) checked inhaler technique. 170 (48%) instructed patients in home measurement of peak flow recordings (PEFR). 21% of general physicians and 52% of pulmonologists provided written action plans outlining what actions to take if PEFR or symptoms deteriorated. The majority of physicians were aware of positive benefits of patient education and over 80% stated that all asthmatic patients should be offered education. Only 32% felt that they should personally be educating the patients whilst two-thirds expressed a preference for the education to be provided by a specialist centre. 66% of the physicians expressed a desire to undertake further training in effective patient education. CONCLUSION: Whilst most physicians in this study state to be aware of the benefits of patient education in asthma, only 24% actually provide their patients with asthma self-management plans. With a low response rate, our study is likely to be biased towards those physicians with a greater interest in asthma; hence actual use of self-management plans is likely be lower than in our sample.

The Effect of Epidural Steroid Injection on Postoperative Outcome in Patients From the Lumbar Spinal Stenosis Outcome Study.

STUDY DESIGN: Retrospective analysis of data from patients participating in the Lumbar Spinal Stenosis Outcome Study (LSOS). OBJECTIVE: The aim of LSOS was to assess clinical outcomes after surgical or nonoperative treatment in patients with and without prior epidural steroid injections. SUMMARY OF BACKGROUND DATA: Epidural steroid injections (ESI), a common treatment modality, reduce symptoms in the short-term, but according to a subgroup analysis from the Spine Patient Outcomes Research Trial (SPORT) they reduce the amount of improvement after subsequent surgical or nonoperative treatment. METHODS: The data of 281 patients with lumbar spinal stenosis who had completed baseline and 6-month follow-up assessments were analyzed. Patients completed the Spinal Stenosis Measure (SSM). Changes in the SSM scores from baseline to follow-up were compared between patients with and without prior ESI, for the surgical and nonsurgical treatment groups. RESULTS: The mean (SD) age of the patients was 75 (8.7) years. 229 patients underwent surgery and 111 of these had received an ESI in the 12 months before surgery. Of the 52 patients treated nonoperatively, 29 had received a prior ESI. The unadjusted changes (improvement) in the SSM-symptom scores between baseline and 6 months' follow up were: surgery and prior ESI 0.95, surgery and no prior ESI 0.78 (P = 0.15); no surgery and prior ESI 0.28, no surgery and no prior ESI 0.29 (P = 0.85). When adjusted for confounding factors, the reduction in SSM-symptom score was greater for surgery than for nonoperative treatment by 0.41 points (P < 0.001); the effect of having had an ESI prior to study entry was -0.08 (P = 0.40). CONCLUSION: The analysis of outcomes in the LSOS cohort provided no evidence that ESIs have a negative effect on the short-term outcome of surgery or nonoperative treatment in patients with lumbar spinal stenosis. LEVEL OF EVIDENCE: 3.

Long-term experience in percutaneous transluminal dilatation of renal artery stenosis.

Percutaneous transluminal dilatation was attempted in 65 patients with renovascular hypertension. In five cases (8 percent), percutaneous transluminal dilatation could not be performed for technical reasons. In the remaining 60 patients (35 with atherosclerotic stenosis and 25 with fibromuscular dysplasia), both mean systolic and diastolic pressure fell immediately after percutaneous transluminal dilatation and remained significantly lower for a period of up to five years. Cure rates after a mean control period of 21.6 months were higher in patients with fibromuscular dysplasia (50 percent) than in those with atherosclerotic stenosis (29 percent). Improvement of blood pressure was observed in 32 percent of patients with fibromuscular dysplasia and in 48 percent of patients with atherosclerotic stenosis. Follow-up angiography in 33 cases showed occlusion of the dilated artery in two patients and recurrence of slight renal artery stenosis in nine patients. Successful redilatation could be performed in five of these cases. Furthermore, renal vein renin determinations were only of limited diagnostic or prognostic value. These results document the good long-term effect of percutaneous transluminal dilatation in patients with renal artery stenosis. Percutaneous transluminal dilatation should, therefore, be the favored procedure in patients with renovascular hypertension.

What is the impact of the ACE gene insertion/deletion (I/D) polymorphism on the clinical effectiveness and adverse events of ACE inhibitors?--Protocol of a systematic review.

BACKGROUND: The Angiotensin Converting Enzyme (ACE) insertion/deletion (I/D) polymorphism has received much attention in pharmacogenetic research because observed variations in response to ACE inhibitors might be associated with this polymorphism. Pharmacogenetic testing raises the hope to individualise ACE inhibitor therapy in order to optimise its effectiveness and to reduce adverse effects for genetically different subgroups. However, the extent of its effect modification in patients treated with ACE inhibitors remains inconclusive. Therefore our objective is to quantify the effect modification of the insertion/deletion polymorphism of the angiotensin converting enzyme gene on any surrogate and clinically relevant parameters in patients with cardiovascular diseases, diabetes, renal transplantation and/or renal failure. METHODS: Systematic Review. We will perform literature searches in six electronic databases to identify randomised controlled trials comparing the effectiveness and occurrence of adverse events of ACE inhibitor therapy against placebo or any active treatment stratified by the I/D gene polymorphism. In addition, authors of trials, experts in pharmacogenetics and pharmaceutical companies will be contacted for further published or unpublished data. Hand searching will be accomplished by reviewing the reference lists of all included studies. The methodological quality of included papers will be assessed. Data analyses will be performed in clinically and methodologically cogent subgroups. The results of the quantitative assessment will be pooled statistically where appropriate to produce an estimate of the differences in the effect of ACE inhibitors observed between the three ACE genotypes. DISCUSSION: This protocol describes a strategy to quantify the effect modification of the ACE polymorphism on ACE inhibitors in relevant clinical domains using meta-epidemiological research methods. The results may provide evidence for the usefulness of pharmacogenetic testing for individualised ACE inhibitor therapy.

Serum and dialyzate concentrations of intraperitoneal cephalothin in patients undergoing continuous ambulatory peritoneal dialysis.

The pharmacokinetics of cephalothin sodium were studied in seven patients with chronic renal failure undergoing continuous ambulatory peritoneal dialysis. 100 mg of cephalothin per liter dialyzate were administered intraperitoneally during nine dialysis cycles with 2 liters of dialysis fluid per cycle. Serum levels of the antibiotic, measured microbiologically during the first, fifth and ninth dwell time, revealed peak values of 3.5 +/- 1.7 mg/l, 5.6 +/- 2.2 mg/l and 5.3 +/- 2.5 mg/l, respectively. The mean concentration in the dialysis outflow was 23.6 +/- 15.6 mg/l (range: 2.0-78.7 mg/l). Intraperitoneally administered cephalothin is well tolerated. Serum levels exceeded the minimal inhibitory concentrations of most gram positive bacteria causing peritonitis in these patients.

Platelet aggregation and beta-thromboglobulin levels in nephrotic patients with and without thrombosis.

Platelet aggregation and beta-thromboglobulin levels were studied in 17 patients with the nephrotic syndrome. Thrombosis or thromboembolic complications occurred in 4 of these patients with serum albumin levels below 2 g/100 ml. Pathologic platelet aggregation assessed by estimating alpha 2-angle values derived from platelet aggregation curves was seen in the 4 patients with thromboembolic complications (alpha 2-angle 69.5 degrees +/- 10.1 degrees), whereas patients without thrombosis showed normal alpha 2-angle values (less than 30 degrees) with only one exception. In addition, patients with thromboembolic complications demonstrated significantly elevated beta-thromboglobulin levels, when compared with those not having thrombosis or thromboembolic complications (76.8 +/- 14.3 ng/ml vs 44.8 +/- 8.6 ng/ml, P less than 0.001). The decrease in serum albumin concentration showed an inverse relationship with both, alpha 2-angle values (r = -0.82, P less than 0.001) and beta-thromboglobulin levels (r = -0.83, P less than 0.001) indicating a regulatory role of serum albumin in platelet aggregation. We conclude, that altered platelet aggregation as well as hypercoagulability may be involved in the pathogenesis of thrombosis and thromboembolic complications in the course of the nephrotic syndrome.

Use of the Internet by medical doctors in Switzerland.

QUESTIONS UNDER STUDY: To investigate the utilisation of the Internet by primary care physicians for medical purposes during their daily practice, and to clarify the reasons for use or non-use of this technology. METHODS: Cross-sectional postal survey in German-speaking Switzerland employing a purpose-designed pre-validated 69-item questionnaire. A random sample of 2009 primary care physicians participated in the investigation. MAIN OUTCOME MEASURES: Number of primary care physicians with access to the Internet; reasons for using the Internet during consultations; sources of information in solving medical problems arising from concurrent patient care. RESULTS: 55% of the physicians returned the completed questionnaire. 75% of respondents reported access to the Internet. Only 7% use the Internet during patient consultations. The main reasons for not using the Internet were time pressure and concerns about potential negative interaction with physician-patient communication. To solve patient-specific problems arising during daily practice, 59% of the practitioners consult text-books or colleagues. Only 14% of respondents report regularly finding useful information on the Internet. Internet users assess information quality by checking on authorship, institution, publishing company, or whether the information is sponsored by a third party with a potential conflict of interest. CONCLUSIONS: Access to the Internet is widespread amongst German-speaking Swiss primary care physicians. Only a small minority use the Internet for information retrieval during consultation hours. Electronic information systems need to be tailored to the needs of primary care physicians.

Skin hyperemia in a habitual blusher.

Blushing, a vascular skin response to emotion is difficult to investigate since subjects are not able to blush on demand in a laboratory setting. Laser Doppler fluxmetry measures blood flux changes noninvasively. In a 28 year old lady distressed by habitual blushing we were able to document changes in skin blood flux during blushing. Forehead skin blood flux increased suddenly from 20 to 45 arbitrary units and returned to baseline values after about 3 minutes. It is the first time that emotionally provoked hyperemia in head skin is documented.

[Chronic anterior tibial syndrome]. / Chronisches Tibialis anterior-Syndrom.

In two young athletic men we made the diagnosis of chronic tibialis anterior syndrome. Pain during strenuous exercise was localized in the anterolateral aspect of both calves. After stopping exercise the complaints disappeared within 15-20 minutes and not in 2-3 minutes as it would be typical for patients with atherosclerotic peripheral arterial occlusive disease. Diagnosis is based on patient history, normal clinical examination (systolic ankle pressure determined by Doppler-Sonography, electronic segmental oscillography) and increased intramuscular pressure at rest (> 10 mmHg) and after exercise (42 and 35 mmHg). Bilateral fasciotomy was performed in both patients. They are free of pain after 3 respectively 6 months postoperatively.

Reversal of atherosclerotic obstructions by percutaneous transluminal angioplasty raises high-density lipoprotein cholesterol.

Variation of high-density lipoprotein cholesterol (HDL) levels in man show a strong inverse relationship to the incidence of atherosclerotic vascular disease. Conversely, effects of atherosclerosis and ischemia on lipoprotein metabolism are unclear. We investigated 41 patients, 10 women and 31 men, undergoing percutaneous transluminal angioplasty by measuring fasting lipoprotein cholesterol including high-density lipoprotein subfraction analysis before and one as well as 12 weeks after the procedure. Successful reopening of a haemodynamically significant iliac, femoral or popliteal obstruction was achieved in all patients. A highly significant (p < 0.001) increase of HDL cholesterol from 1.10 +/- 0.05 to 1.31 +/- 0.06 mmol/l was revealed 12 weeks later. This was due to a significant (p < 0.001) increase in HDL3 cholesterol by 26%, whereas HDL2 cholesterol did not change significantly. We conclude that HDL cholesterol levels increase after recanalization of a significant atherosclerotic obstruction which may be a direct effect of reperfusion or an indirect effect due to an increase in exercise tolerance.

[Description of Internet-based models for continuing medical education. First results and experiences with asthma patients]. / Beschreibung eines internetbasierten Modells für die ärztliche Fortbildung. Erste Resultate und Erfahrungen bei Patienten mit Asthma.

The Pilot study "Quality Development through the Internet" by the Horten Center is an integral part of a concept on dissemination of medical knowledge. It offers participants the possibility to compare interactively their own and their peers' performance with their competence and with accepted guidelines within a web-based Audit-Cycle. The participants can discuss the evidence-based recommendations which are offered. In addition, changes in behavior and care can be documented objectively.

Conception of an XML-based ontology for a Web-based medical information service.

In order to be useful for practice, medical information on the World Wide Web must be relevant, reliable, well designed, and easy accessible. Approaches towards improving these requirements include evidence-based medical information services such as EVIMED. This research paper considers the question of how a user can be supported in accessing requested information from EVIMED and how further, semantically related information can easily be retrieved. The presented method of resolution is based on Schmid's concept of media and on Gruber's concept of the ontology. The use of the emerging Web standard eXtensible Markup Language (XML) in order to implement it, allows for the design of a component-based solution supporting an easy adaptation of the representational vocabulary in accordance with the conceptualization of the user, i.e., the practitioner.