Development and internal validation of a prediction model for long-term opioid use-an analysis of insurance claims data.

ABSTRACT: In the United States, a public-health crisis of opioid overuse has been observed, and in Europe, prescriptions of opioids are strongly increasing over time. The objective was to develop and validate a multivariable prognostic model to be used at the beginning of an opioid prescription episode, aiming to identify individual patients at high risk for long-term opioid use based on routinely collected data. Predictors including demographics, comorbid diseases, comedication, morphine dose at episode initiation, and prescription practice were collected. The primary outcome was long-term opioid use, defined as opioid use of either >90 days duration and ≥10 claims or >120 days, independent of the number of claims. Traditional generalized linear statistical regression models and machine learning approaches were applied. The area under the curve, calibration plots, and the scaled Brier score assessed model performance. More than four hundred thousand opioid episodes were included. The final risk prediction model had an area under the curve of 0.927 (95% confidence interval 0.924-0.931) in the validation set, and this model had a scaled Brier score of 48.5%. Using a threshold of 10% predicted probability to identify patients at high risk, the overall accuracy of this risk prediction model was 81.6% (95% confidence interval 81.2% to 82.0%). Our study demonstrated that long-term opioid use can be predicted at the initiation of an opioid prescription episode, with satisfactory accuracy using data routinely collected at a large health insurance company. Traditional statistical methods resulted in higher discriminative ability and similarly good calibration as compared with machine learning approaches.

Elevated TSH Levels: A Database Study of General Practitioners' Course of Action.

OBJECTIVE: To investigate general practitioners' course of action after detection of elevated thyroid stimulating hormone (TSH) levels regarding repeat testing, direct levothyroxine replacement, or neither. METHODS: We conducted a retrospective study of adults without prior evidence of thyroid disease and with a first detection of elevated TSH levels from January 1, 2015, to December 31, 2020, using data from electronic medical records of a Swiss primary care database. We determined the occurrence of either repeat TSH testing or direct levothyroxine initiation in primary care during 12-month follow-up and determined associations with demographic and clinical factors. RESULTS: Of the 1 591 patients included (median age 65 years, 64.4% female, median TSH 5.7 mIU/L), 34.3% received repeat TSH testing and 12.4% received direct levothyroxine replacement in primary care during follow-up. Repeat TSH testing showed the strongest association with overt hypothyroidism and was more common among patients with high primary care utilization and among patients aged 40-64 years compared to patients aged <40 years. Direct levothyroxine initiation was more likely for TSH levels >7 mIU/L, overt hypothyroidism, female patients, and nonurban practices. CONCLUSIONS: While the degree of thyroid dysfunction was the main driver of follow-up, we identified important gaps in the primary care-based monitoring of elevated TSH levels in young patients and in patients with infrequent consultations. We also observed potential overtreatment of women and patients in nonurban areas. Our findings highlight the need for standardization and dissemination of guidelines for the management of elevated TSH levels among general practitioners.

Importance of different electronic medical record components for chronic disease identification in a Swiss primary care database: a cross-sectional study.

BACKGROUND: Primary care databases collect electronic medical records with routine data from primary care patients. The identification of chronic diseases in primary care databases often integrates information from various electronic medical record components (EMR-Cs) used by primary care providers. This study aimed to estimate the prevalence of selected chronic conditions using a large Swiss primary care database and to examine the importance of different EMR-Cs for case identification. METHODS: Cross-sectional study with 120,608 patients of 128 general practitioners in the Swiss FIRE ("Family Medicine Research using Electronic Medical Records") primary care database in 2019. Sufficient criteria on three individual EMR-Cs, namely medication, clinical or laboratory parameters and reasons for encounters, were combined by logical disjunction into definitions of 49 chronic conditions; then prevalence estimates and measures of importance of the individual EMR-Cs for case identification were calculated. RESULTS: A total of 185,535 cases (i.e. patients with a specific chronic condition) were identified. Prevalence estimates were 27.5% (95% CI: 27.3-27.8%) for hypertension, 13.5% (13.3-13.7%) for dyslipidaemia and 6.6% (6.4-6.7%) for diabetes mellitus. Of all cases, 87.1% (87.0-87.3%) were identified via medication, 22.1% (21.9-22.3%) via clinical or laboratory parameters and 19.3% (19.1-19.5%) via reasons for encounters. The majority (65.4%) of cases were identifiable solely through medication. Of the two other EMR-Cs, clinical or laboratory parameters was most important for identifying cases of chronic kidney disease, anorexia/bulimia nervosa and obesity whereas reasons for encounters was crucial for identifying many low-prevalence diseases as well as cancer, heart disease and osteoarthritis. CONCLUSIONS: The EMR-C medication was most important for chronic disease identification overall, but identification varied strongly by disease. The analysis of the importance of different EMR-Cs for estimating prevalence revealed strengths and weaknesses of the disease definitions used within the FIRE primary care database. Although prioritising specificity over sensitivity in the EMR-C criteria may have led to underestimation of most prevalences, their sex- and age-specific patterns were consistent with published figures for Swiss general practice.

The Effect of Paraspinal Fatty Muscle Infiltration and Cumulative Lumbar Spine Degeneration on the Outcome of Patients With Lumbar Spinal Canal Stenosis: Analysis of the Lumbar Stenosis Outcome Study (LSOS) Data.

STUDY DESIGN: Prospective. OBJECTIVE: To investigate the influence of paraspinal fatty muscle infiltration (FMI) and cumulative lumbar spine degeneration as assessed by magnetic resonance imaging on long-term clinical outcome measures in patients with lumbar spinal canal stenosis (LSCS) of the Lumbar Stenosis Outcome Study (LSOS) cohort. SUMMARY OF BACKGROUND DATA: Past studies have tried to establish correlations of morphologic imaging findings in LSCS with clinical endpoints. However, the impact of FMI and overall lumbar spinal degeneration load has not been examined yet. MATERIALS AND METHODS: Patients from the LSOS cohort with moderate to severe LSCS were included. Two radiologists assessed the degree of LSCS as well as cumulative degeneration of the lumbar spine. FMI was graded using the Goutallier scoring system. Spinal Stenosis Measure (SSM) was used to measure the severity level of symptoms and disability. European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) was used to measure health-related quality of life. RESULTS: The nonsurgically treated group consisted of 116 patients (age 74.8±8.5 yr), whereas the surgically treated group included 300 patients (age 72.3±8.2 yr). Paraspinal FMI was significantly different between the groups (54.3% vs. 32.0% for Goutallier grade ≥2; P <0.001). Total degeneration score was comparable in both groups (9.5±2.0 vs. 9.3±2.0; P =0.418). FMI was associated with lower SSM function and lower EQ-5D-3L (all P <0.05), but not with SSM symptoms. Total degeneration of the lumbar spine was associated neither with SSM symptoms, nor with SSM function, nor with EQ-5D-3L (all P >0.05). CONCLUSIONS: FMI is associated with higher disability and worse health-related quality of life of LSCS patients in the LSOS cohort. There was no significant association between total cumulative lumbar spine degeneration and the outcome of either surgically or nonsurgically treated patients. LEVEL OF EVIDENCE: 3.

Incidence of Revision Surgery After Decompression With vs Without Fusion Among Patients With Degenerative Lumbar Spinal Stenosis.

Importance: Only limited data derived from large prospective cohort studies exist on the incidence of revision surgery among patients who undergo operations for degenerative lumbar spinal stenosis (DLSS). Objective: To assess the cumulative incidence of revision surgery after 2 types of index operations-decompression alone or decompression with fusion-among patients with DLSS. Design, Setting, and Participants: This cohort study analyzed data from a multicenter, prospective cohort study, the Lumbar Stenosis Outcome Study, which included patients aged 50 years or older with DLSS at 8 spine surgery and rheumatology units in Switzerland between December 2010 and December 2015. The follow-up period was 3 years. Data for this study were analyzed between October and November 2021. Exposures: All patients underwent either decompression surgery alone or decompression with fusion surgery for DLSS. Main Outcomes and Measures: The primary outcome was the cumulative incidence of revision operations. Secondary outcomes included changes in the following patient-reported outcome measures: Spinal Stenosis Measure (SSM) symptom severity (higher scores indicate more pain) and physical function (higher scores indicate more disability) subscale scores and the EuroQol Health-Related Quality of Life 5-Dimension 3-Level questionnaire (EQ-5D-3L) summary index score (lower scores indicate worse quality of life). Results: A total of 328 patients (165 [50.3%] men; median age, 73.0 years [IQR, 66.0-78.0 years]) were included in the analysis. Of these, 256 (78.0%) underwent decompression alone and 72 (22.0%) underwent decompression with fusion. The cumulative incidence of revisions after 3 years of follow-up was 11.3% (95% CI, 7.4%-15.1%) for the decompression alone group and 13.9% (95% CI, 5.5%-21.5%) for the fusion group (log-rank P = .60). There was no significant difference in the need for revision between the 2 groups over time (unadjusted absolute risk difference, 2.6% [95% CI, -6.3% to 11.4%]; adjusted absolute risk difference, 3.9% [95% CI, -5.2% to 17.0%]; adjusted hazard ratio, 1.40 [95% CI, 0.63-3.13]). The number of revisions was significantly associated with higher SSM symptom severity scores (ß, 0.171; 95% CI, 0.047-0.295; P = .007) and lower EQ-5D-3L summary index scores (ß, -0.061; 95% CI, -0.105 to -0.017; P = .007) but not with higher SSM physical function scores (ß, 0.068; 95% CI, -0.036 to 0.172; P = .20). The type of index operation was not significantly associated with the corresponding outcomes. Conclusions and Relevance: This cohort study showed no significant association between the type of index operation for DLSS-decompression alone or fusion-and the need for revision surgery or the outcomes of pain, disability, and quality of life among patients after 3 years. Number of revision operations was associated with more pain and worse quality of life.

Prescription Rates, Polypharmacy and Prescriber Variability in Swiss General Practice-A Cross-Sectional Database Study.

Purpose: The frequency of medication prescribing and polypharmacy has increased in recent years in different settings, including Swiss general practice. We aimed to describe patient age- and sex-specific rates of polypharmacy and of prescriptions of the most frequent medication classes, and to explore practitioner variability in prescribing. Methods: Retrospective cross-sectional study based on anonymized electronic medical records data of 111 811 adult patients presenting to 116 Swiss general practitioners in 2019. We used mixed-effects regression analyses to assess the association of patient age and sex with polypharmacy (≥5 medications) and with the prescription of specific medication classes (second level of the Anatomical Therapeutic Chemical Classification System). Practitioner variability was quantified in terms of the random effects distributions. Results: The prevalence of polypharmacy increased with age from 6.4% among patients aged 18-40 years to 19.7% (41-64 years), 45.3% (65-80 years), and 64.6% (81-92 years), and was higher in women than in men, particularly at younger ages. The most frequently prescribed medication classes were antiinflammatory and antirheumatic products (21.6% of patients), agents acting on the renin-angiotensin system (19.9%), analgesics (18.7%), and drugs for acid related disorders (18.3%). Men were more often prescribed agents targeting the cardiovascular system, whereas most other medications were more often prescribed to women. The highest practitioner variabilities were observed for vitamins, for antiinflammatory and antirheumatic products, and for mineral supplements. Conclusion: Based on practitioner variability, prevalence, and risk potential, antiinflammatory drugs and polypharmacy in older patients appear to be the most pressing issues in current drug prescribing routines.

Testing and Prescribing Vitamin B12 in Swiss General Practice: A Survey among Physicians.

Testing and prescribing vitamin B12 (also known as cobalamin) is increasing in Switzerland but substantial variation among general practitioners (GPs) with respect to testing has been noted. In this study, we aimed at exploring GPs' mindsets regarding vitamin B12 testing and prescribing. A cross-sectional study was conducted using an online survey distributed by e-mail to Swiss GPs. The questionnaire explored mindsets related to testing and prescribing vitamin B12 in specific clinical situations, as well as testing and prescribing strategies. The questionnaire was sent to 876 GPs and 390 GPs responded (44.5%). The most controversial domains for testing and prescribing vitamin B12 were idiopathic fatigue (57.4% and 43.4% of GPs agreed, respectively) and depressive symptoms (53.0% and 35.4% of GPs agreed, respectively). There was substantial variation among GPs with regard to testing strategies (89.5% of GPS used a serum cobalamin test, 71.3% of GPS used holotranscobalamin, and 27.6% of GPs used homocysteine or methylmalonic acid). Intramuscular injection was the predominantly prescribed route of application (median of 87.5% of the prescriptions). In this study, we focus on discordant mindsets that can be specifically targeted by using educational interventions, and research questions that still need answering specifically about the effectiveness of vitamin B12 for idiopathic fatigue.

Effects of Vitamin B12 Supplementation on Cognitive Function, Depressive Symptoms, and Fatigue: A Systematic Review, Meta-Analysis, and Meta-Regression.

Vitamin B12 is often used to improve cognitive function, depressive symptoms, and fatigue. In most cases, such complaints are not associated with overt vitamin B12 deficiency or advanced neurological disorders and the effectiveness of vitamin B12 supplementation in such cases is uncertain. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to assess the effects of vitamin B12 alone (B12 alone), in addition to vitamin B12 and folic acid with or without vitamin B6 (B complex) on cognitive function, depressive symptoms, and idiopathic fatigue in patients without advanced neurological disorders or overt vitamin B12 deficiency. Medline, Embase, PsycInfo, Cochrane Library, and Scopus were searched. A total of 16 RCTs with 6276 participants were included. Regarding cognitive function outcomes, we found no evidence for an effect of B12 alone or B complex supplementation on any subdomain of cognitive function outcomes. Further, meta-regression showed no significant associations of treatment effects with any of the potential predictors. We also found no overall effect of vitamin supplementation on measures of depression. Further, only one study reported effects on idiopathic fatigue, and therefore, no analysis was possible. Vitamin B12 supplementation is likely ineffective for improving cognitive function and depressive symptoms in patients without advanced neurological disorders.

[Increase in New Approvals of Strong Opioid Medications in Switzerland]. / Starker Anstieg der Neuzulassungen von Opioiden in der Schweiz.

Increase in New Approvals of Strong Opioid Medications in Switzerland Abstract. Consumption of pain medication, especially opioids, has risen sharply since 2000, both worldwide and in Switzerland. However, it is unknown whether this increased use is associated with an increase in new approvals of pain medications. An analysis of new approvals of painkillers in Switzerland showed a significant increase from the year 2000 onwards. The majority of new registrations were strong opioid preparations, while the trend in new registrations of non-opioid painkillers was decreasing. Furthermore, the treatment duration of newly approved strong opioids increased significantly from the year 2000 onwards, which may lead to a higher risk of overdoses or dependence.

Increased risk of adverse events in non-cancer patients with chronic and high-dose opioid use-A health insurance claims analysis.

BACKGROUND: Chronic and high dose opioid use may result in adverse events. We analyzed the risk associated with chronic and high dose opioid prescription in a Swiss population. METHODS: Using insurance claims data covering one-sixth of the Swiss population, we analyzed recurrent opioid prescriptions (≥2 opioid claims with at least 1 strong opioid claim) between 2006 and 2014. We calculated the cumulative dose in milligrams morphine equivalents (MED) and treatment duration. Excluded were single opioid claims, opioid use that was cancer treatment related, and opioid use in substitution programs. We assessed the association between the duration of opioid use, prescribed opioid dose, and benzodiazepine use with emergency department (ED) visits, urogenital and pulmonary infections, acute care hospitalization, and death at the end of the episode. RESULTS: In 63,642 recurrent opioid prescription episodes (acute 38%, subacute 7%, chronic 25.8%, very chronic (>360 days) episodes 29%) 18,336 ED visits, 30,209 infections, 19,375 hospitalizations, and 9,662 deaths occurred. The maximum daily MED dose was <20 mg in 15.8%, 20-<50 mg in 16.6%, 50-<100 mg in 21.6%, and ≥100 mg in 46%. Compared to acute episodes (<90 days), episode duration was an independent predictor of ED visits (chronic OR 1.09 (95% CI 1.03-1.15), very chronic (>360 days) OR 1.76 (1.67-1.86)) for adverse effects; infections (chronic OR 1.74 (1.66-1.82), very chronic 4.16 (3.95-4.37)), and hospitalization (chronic: OR 1.22 (1.16-1.29), very chronic OR 1.82 (1.73-1.93)). The risk of death decreased over time (very chronic OR 0.46 (0.43-0.50)). A dose dependent increased risk was observed for ED visits, hospitalization, and death (≥100mg daily MED OR 1.21 (1.13-1.29), OR 1.29 (1.21-1.38), and OR 1.67, 1.50-1.85, respectively). A concomitant use of benzodiazepines increased the odds for ED visits by 46% (OR 1.46, 1.41-1.52), infections by 44% (OR 1.44, 1.41-1.52), hospitalization by 12% (OR 1.12, 1.07-1.1), and death by 45% (OR 1.45, 1.37-1.53). CONCLUSION: The length of opioid use and higher prescribed morphine equivalent dose were independently associated with an increased risk for ED visits and hospitalizations. The risk for infections, ED visits, hospitalizations, and death also increased with concomitant benzodiazepine use.

Long-term Results After Surgical or Nonsurgical Treatment in Patients With Degenerative Lumbar Spinal Stenosis: A Prospective Multicenter Study.

STUDY DESIGN: Prospective, multicenter cohort study. OBJECTIVE: The aim of our study was to assess the course of patients over a period of 3 years undergoing surgical or nonsurgical treatments for degenerative lumbar spinal stenoses (DLSS) based on data from the Lumbar Stenosis Outcome Study (LSOS), prospectively performed in eight hospitals. SUMMARY OF BACKGROUND DATA: The optimal treatment strategy for patients with DLSS is still debated. METHODS: The outcomes of patients with verified DLSS were quantified by Spinal Stenosis Measure (SSM) symptoms- and SSM function-scores, and EQ-5D-3L (quality of life) summary index (SI) over time (up to 36-month follow-up), and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and EQ-5D-3L SI from baseline to 36-month follow-up. RESULTS: For this study, 601 patients met the inclusion criteria; 430 underwent surgery, 18 of them only after more than a year after enrolment, 171 received nonsurgical treatment only. At baseline, patients in the surgical and nonsurgical groups had similar values for the SSM symptoms and SSM function scores, but patients in the surgical group suffered significantly more from buttocks pain and reported more worsening symptoms over the last 3 months before enrollment in the study. Surgically treated patients (except changers) performed significantly better in all clinical outcome measures (P < 0.001) with a plateau at 12-month follow-up staying constant until the follow-up ended. Further, two-thirds of patients in the surgical group had a relevant improvement in function, symptoms, and quality of life, compared with only about half of those in terms of symptoms and even less in terms of function and quality of life with nonsurgical treatment. CONCLUSIONS: Surgical treatment of DLSS results in more favorable clinical outcomes with a sustained effect over time, compared to nonsurgical treatment. LEVEL OF EVIDENCE: 3.

Two-year outcome comparison of decompression in 14 lipomatosis cases with 169 degenerative lumbar spinal stenosis cases: a Swiss prospective multicenter cohort study.

PURPOSE: Spinal epidural lipomatosis (SEL) is defined as an abnormal and extensive accumulation of unencapsulated adipose tissue within the spinal epidural space. To date, there is a lack of high-level evidence studies reporting the outcome of surgical treatment of symptomatic SEL in patients with lumbar spinal stenosis (LSS). The aim was to compare clinical outcomes in patients with symptomatic LSS with and without SEL who underwent decompression surgery alone at the 12- and 24-month follow-up. METHODS: One hundred and eighty-three patients met the inclusion criteria, of which 14 had mainly SEL on at least one level operated in addition to possible degenerative changes on other levels and 169 degenerative LSS only. The main outcomes were pain (Spinal Stenosis Measure (SSM) symptoms), disability (SSM function), and quality of life [EQ-5D-3L summary index (SI)] at 24-month follow-up, and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and EQ-5D-3L SI. RESULTS: The multiple regression linear models showed that SEL was associated with worse SSM symptoms (p = 0.045) and EQ-5D-3L SI scores (p = 0.026) at 24-month follow-up, but not with worse SSM function scores. Further, depression (in all models) was negatively associated with better clinical outcomes at 24-month follow-up. In the outcomes SSM symptoms and EQ-5D-3L SI, distinctly more patients in the classical LSS group reached MCID than in the SEL group (71.3% and 62.3% vs. 50.0% and 42.9%). CONCLUSIONS: Our study demonstrated that decompression alone surgery was associated with significant improvement in disability in both groups at 2 years, but not in pain and quality of life in patients with SEL.

Datasets describing the introduction of the high-sensitive troponin in the emergency department.

Chest pain is a common clinical condition in the emergency department. A high sensitive (hs) troponin test assay may help to identify patients with acute coronary syndrome earlier compared to conventional tests but also entails the risk of a high proportion of positive test results in patients without cardiac disease. We assessed the impact of the introduction of the hs-troponin test in clinical practice in an emergency department. We compared December 1, 2009 until November 30, 2010 (standard test period) to December 1, 2010 - the date of the introduction of the hs-troponin assay - until December 31, 2011 (hs troponin test period) of patients presenting with chest pain to one of the ten largest hospitals in Switzerland. We identified electronic health records using the following ICD-10 codes: R06.4 (hyperventilation), R07.1 (chest pain when breathing), R07.2 (precordial pain), R07.3 (other chest pain), and R07.4 (chest pain not specified), I20 (angina pectoris), I21 (acute MI), I22 (recurrent MI), I23 (complications after acute MI), and I24 (other acute ischemic heart disease). Included were all medical records of adult patients (≥18 years) presenting to the ED with chest pain and with ≥1 troponin test. Excluded were records without troponin test, pregnancy, trauma patients/life-threatening conditions, malignant disease, current fracture, renal replacement therapy/severe kidney failure (creatinine clearance <30ml/min/1.73m2), patients with disability, or patients disagreeing that their data will be used for scientific purposes. Two researchers screened all records for in-/exclusion. The first presentation for chest pain to the ED and all presentations within the following three months extracted. Presentations after >3 months due to chest pain were defined as a new index visit of a second episode. The extraction form with predefined variables was pilot-tested in 20 records. Additional diagnostic tests were ECG, treadmill test, coronary angiography, MIBI scintigraphy, echocardiography, chest X-ray, computer tomography (CT) of the chest or abdomen, sonography of the abdomen or pleura, gastroscopy, and lung function tests. We compared the number of non-invasive / invasive cardiac diagnostic tests in troponin positive and negative patients and the number of diagnostic tests after the exclusion of patients with STEMI diagnosis. Non-invasive / invasive cardiac tests included treadmill test, coronary angiography, MIBI scintigraphy, and echocardiography. We calculated average monthly tests per patient and compared mean tests per patient between groups. We used a t-test to quantify the evidence for differential number of diagnostic tests per patient in each period. Between-group differences were estimated with 95% confidence intervals. All analyses were performed with the statistical software R for windows [1]. Interpretation of this data can be found in a research article titled Impact of the introduction of high-sensitive troponin assay on the evaluation of chest pain patients in the emergency department: a retrospective study [2]).

The influence of endplate (Modic) changes on clinical outcomes in lumbar spinal stenosis surgery: a Swiss prospective multicenter cohort study.

PURPOSE: To investigate if the presence or absence of preoperative endplate Modic changes (MC) is predictive for clinical outcomes in degenerative lumbar spinal stenosis (DLSS) patients undergoing decompression-alone or decompression with instrumented fusion surgery. METHODS: Two hundred five patients were included and categorized into four groups; 102 patients into the decompression-alone group with MCs, 41 patients into the fusion group with MCs, 46 patients into the decompression-alone group without MCs, and 16 patients into the fusion group without MCs. Clinical outcome was quantified with changes in spinal stenosis measure (SSM) symptoms, SSM function, NRS pain, and EQ-5D-3L sum score over time (measured at baseline, 12-, 24-, and 36-month follow-up) and minimal clinically important difference (MCID) in SSM symptoms, SSM function, and NRS pain from baseline to 36-month follow-up. To investigate if possible effects of MCs had been modified or hidden by confounding variables, we used the group LASSO method to search for good prognostic models. RESULTS: There were no obvious differences in any of the clinical outcome measures between groups at baseline. At 12 months, most patients have improved in all outcomes and maintained improved conditions over time (no significant group differences). Between 70 and 90 percent of the patients maintained a clinically important improvement up to 36 months. CONCLUSIONS: Endplate MCs have no significant influence on clinical outcome parameters in patients with lumbar spinal stenosis compared to patients without MCs, independent of the chosen surgical strategy. All patients benefitted from surgical therapy up to 36-month follow-up. These slides can be retrieved under Electronic Supplementary Material.

Evaluating the Minimal Clinically Important Difference of EQ-5D-3L in Patients With Degenerative Lumbar Spinal Stenosis: A Swiss Prospective Multicenter Cohort Study.

STUDY DESIGN: Analysis of a prospective, multicenter cohort study. OBJECTIVE: The aim of our study was to compare thresholds of published minimal clinically important differences (MCID) for the three-level EuroQol-5D health survey (EQ-5D-3L) summary index (range -0.53 to 1.00) with our anchor-based estimate and evaluate how useful these thresholds are in determining treatment success in patients undergoing surgery for degenerative lumbar spinal stenosis (DLSS). SUMMARY OF BACKGROUND DATA: MCID values for EQ-5D-3L are specific to the underlying disease and only three studies have been published for DLSS patients reporting different values. METHODS: Patients of the multicenter Lumbar Stenosis Outcome Study with confirmed DLSS undergoing first-time decompression or fusion surgery with 12-month follow-up were enrolled in this study. To calculate MCID we used the Spinal Stenosis Measure satisfaction subscale as anchor. RESULTS: For this study, 364 patients met the inclusion criteria; of these, 196 were very satisfied, 72 moderately satisfied, 43 somewhat satisfied, and 53 unsatisfied 12 months after surgery. The MCID calculation estimated for EQ-5D-3L a value of 0.19. Compared with published MCID values (ranging from 0.30 to 0.52), our estimation is less restrictive. CONCLUSIONS: In patients with LSS undergoing surgery, we estimated an MCID value for EQ-5D-3L summary index of 0.19 with the help of the average change anchor-based method, which we find to be the most suitable method for assessing patient change scores. LEVEL OF EVIDENCE: 3.

Impact of the Introduction of High-Sensitive Troponin Assay in the Emergency Department: A Retrospective Study.

BACKGROUND: Compared with troponin T/I test, the introduction of a high-sensitive (hs) troponin test may result in a higher proportion of positive test results in patients with chest pain and over-testing in patients without acute coronary syndrome. We assessed the impact of the introduction of the hs-troponin assay on the discharge diagnoses and the number of diagnostic tests in patients presenting with chest pain in a real-life setting in an emergency department. METHODS: Retrospective chart review of patients presenting with chest pain to one of the largest hospitals in Switzerland. We compared the standard troponin period (December 2009 to November 2010) with the hs-troponin period (December 2010 to December 2011). RESULTS: Data from 1274 patients (standard 597 [46.9%], hs-troponin 677 [53.1%]) were analyzed. The proportion of patients with non-ST-segment elevation myocardial infarction increased (hs-troponin 14.9%, compared with 9.7%); the proportion in unstable angina (1.5% to 4.0%) and other cardiac illnesses (8.1% to 11.7%) decreased. Although the proportion of noncardiac chest pain illnesses (67%) remained unchanged, the proportion of positive hs-troponin was higher (6.1% vs 2.0%). The average number of additional tests/person decreased in troponin-positive patients (2.0 to 1.7 test per patient; P = .02) and troponin-negative patients (3.1 to 2.8 tests; P < .0001). CONCLUSION: Although the introduction of the hs-troponin test resulted in a higher proportion of positive hs-troponin tests in patients with noncardiac chest pain, the average number of diagnostic tests decreased in patients with chest pain presenting to an emergency department, indicating an increased confidence of clinicians in their diagnosis.

Opioid Prescription in Switzerland: Appropriate Comedication use in Cancer and Noncancer Pain.

BACKGROUND: In Europe, limited information on the use of opioids is available. OBJECTIVES: To assess how guideline recommendations to manage opioid-related adverse events were followed in cancer- and noncancer-related opioid use. STUDY DESIGN: Analysis of health insurance data of one of the major health insurers in Switzerland. SETTING: All opioid claims between 2006 and 2014. METHODS: Opioid episodes were cancer-related when cancer treatments were used within ± 3 months of the first opioid claim. Recurrent strong episodes were defined as >/= 2 opioid claims with at least one strong opioid claim. Episode duration were acute (< 90 days), subacute, or chronic (>/= 120 days >/= 90 days +>/= 10 claims). RESULTS: Out of 591,633 opioid episodes 76,968 (13%) were recurrent episodes: 94% were noncancer related (83% in recurrent episodes) and 6% cancer related (17% recurrent). Chronic opioid use was observed in 55% (noncancer) and 58% (cancer) recurrent episodes. Recommended laxatives were used in 50% noncancer and in 67% cancer episodes. Antiemetic drugs were used in 54% noncancer and in 83% cancer episodes. Not recommended coprescription of benzodiazepines was observed in 34% recurrent noncancer and 46% cancer episodes. LIMITATIONS: No clinical information was available to assess the indication for opioid use. CONCLUSIONS: In this study, opioids were primarily used outside the context of cancer-related treatment. In noncancer-related opioid use, we found a substantial higher proportion without recommended laxative and antiemetic medications. Coprescription of benzodiazepines may increase the risk for opioid overdose and was present in one-third of the noncancer episodes and in almost every second cancer episode. KEY WORDS: Pain medications, opioids, nonopioids, benzodiazepines, health insurance claims data, cancer pain, noncancer pain, chronic opioid use, adverse events prevention, guideline recommendations.

Appetite-Suppressing and Satiety-Increasing Bioactive Phytochemicals: A Systematic Review.

The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.

Serious adverse events in patients with target-oriented blood pressure management: a systematic review.

: On the basis of the benefits of antihypertensive treatment, progressively intensive treatment is advocated. However, it remains controversial whether intensive blood pressure control might increase the frequency of serious adverse events (SAEs) compared with moderate control. This review assessed the occurrence of SAEs in blood pressure treatment with predefined blood pressure targets. Seven original studies and eight post hoc analyses (derived from two original studies) met the inclusion criteria. Compared with moderate blood pressure treatment, intensive treatment was associated with a significant increase in treatment-related SAEs (Sign-test: P = 0.0002, Wilcoxon signed-rank test: P = 0.001). However, comparability between studies was limited, due to unclear determinations about the treatment-relatedness of adverse events, missing definitions of SAEs and variations in recording methods. Thus, a meta-analysis was not justified. The definitions of serious adverse events and methods of recording and reporting need to be improved and standardized to facilitate the comparison of results.

Outcome of unilateral versus standard open midline approach for bilateral decompression in lumbar spinal stenosis: is "over the top" really better? A Swiss prospective multicenter cohort study.

OBJECTIVEIn this retrospective analysis of a prospective multicenter cohort study, the authors assessed which surgical approach, 1) the unilateral laminotomy with bilateral spinal canal decompression (ULBD; also called "over the top") or 2) the standard open bilateral decompression (SOBD), achieves better clinical outcomes in the long-term follow-up. The optimal surgical approach (ULBD vs SOBD) to treat lumbar spinal stenosis remains controversial.METHODSThe main outcomes of this study were changes in a spinal stenosis measure (SSM) symptoms score, SSM function score, and quality of life (sum score of the 3-level version of the EQ-5D tool [EQ-5D-3L]) over time. These outcome parameters were measured at baseline and at 12-, 24-, and 36-month follow-ups. To obtain an unbiased result on the effect of ULBD compared to SOBD the authors used matching techniques relying on propensity scores. The latter were calculated based on a logistic regression model including relevant confounders. Additional outcomes of interest were raw changes in main outcomes and in the Roland and Morris Disability Questionnaire from baseline to 12, 24, and 36 months.RESULTSFor this study, 277 patients met the inclusion criteria. One hundred forty-nine patients were treated by ULBD, and 128 were treated by SOBD. After propensity score matching, 128 patients were left in each group. In the matched cohort, the mean (95% CI) estimated differences between ULBD and SOBD for change in SSM symptoms score from baseline to 12 months were -0.04 (-0.25 to 0.17), to 24 months -0.07 (-0.29 to 0.15), and to 36 months -0.04 (-0.28 to 0.21). For change in SSM function score, the estimated differences from baseline to 12 months were 0.06 (-0.08 to 0.21), to 24 months 0.08 (-0.07 to 0.22), and to 36 months 0.01 (-0.16 to 0.17). Differences in changes between groups in EQ-5D-3L sum scores were estimated to be -0.32 (-4.04 to 3.40), -0.89 (-4.76 to 2.98), and -2.71 (-7.16 to 1.74) from baseline to 12, 24, and 36 months, respectively. None of the group differences between ULBD and SOBD were statistically significant.CONCLUSIONSBoth surgical techniques, ULBD and SOBD, may provide effective treatment options for DLSS patients. The authors further determined that the patient outcome results for the technically more challenging ULBD seem not to be superior to those for the SOBD even after 3 years of follow-up.