Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

INTRODUCTION: Burnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear. MATERIALS AND METHODS: We conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of <100% as a clinician. The primary outcome was well-being, as measured by the extended Physician Well-Being Index (ePWBI), an ePWBI ≥3 indicating poor wellbeing. Secondary outcomes included depressive symptoms, mental and physical health, and job satisfaction. We compared outcomes in part-time and full time workers using propensity score-adjusted multivariate regression models. RESULTS: Of 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction. CONCLUSIONS: Full-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.

The impact of pharmacist-led medication reconciliation and interprofessional ward rounds on drug-related problems at hospital discharge.

BACKGROUND: During transitions of care, including hospital discharge, patients are at risk of drug-related problems (DRPs). AIM: To investigate the impact of pharmacist-led services, specifically medication reconciliation at admission and/or interprofessional ward rounds on the number of DRPs at discharge. METHOD: In this retrospective, single-center cohort study, we analyzed routinely collected data of patients discharged from internal medicine wards of a regional Swiss hospital that filled their discharge prescriptions in the hospital's community pharmacy between June 2016 and May 2019. Patients receiving one of the two or both pharmacist-led services (Study groups: Best Care = both services; MedRec = medication reconciliation at admission; Ward Round = interprofessional ward round), were compared to patients receiving standard care (Standard Care group). Standard care included medication history taken by a physician and regular ward rounds (physicians and nurses). At discharge, pharmacists reviewed discharge prescriptions filled at the hospital's community pharmacy and documented all DRPs. Multivariable Poisson regression analyzed the independent effects of medication reconciliation and interprofessional ward rounds as single or combined service on the frequency of DRPs. RESULTS: Overall, 4545 patients with 6072 hospital stays were included in the analysis (Best Care n = 72 hospital stays, MedRec n = 232, Ward Round n = 1262, and Standard Care n = 4506). In 1352 stays (22.3%) one or more DRPs were detected at hospital discharge. The combination of the two pharmacist-led services was associated with statistically significantly less DRPs compared to standard care (relative risk: 0.33; 95% confidence interval: 0.16, 0.65). Pharmacist-led medication reconciliation alone showed a trend towards fewer DRPs (relative risk: 0.75; 95% confidence interval: 0.54, 1.03). CONCLUSION: Our results support the implementation of pharmacist-led medication reconciliation at admission in combination with interprofessional ward rounds to reduce the number of DRPs at hospital discharge.

Detection and resolution of drug-related problems at hospital discharge focusing on information availability - a retrospective analysis.

BACKGROUND: Hospital stays are often associated with medication changes, which may lead to drug-related problems (DRPs). Medication reconciliation and medication reviews are strategies to detect and resolve DRPs. METHODS: A descriptive cohort study was conducted using DRPs collected during routine pharmacist-led medication reconciliation and medication reviews in the hospital's community pharmacy at discharge (Zug Cantonal Hospital, Switzerland). In a simulation experiment, we retrospectively analysed the detection and resolution possibilities of these DRPs and their dependency on different information sources. RESULTS: Overall, 6,087 prescriptions were filled in the hospital's community pharmacy (between June 2016 and May 2019). Among 1,352 prescriptions (with ≥ 1 documented DRP) a total of 1,876 DRPs were detected. The retrospective assessment showed that 1,115 DRPs could have been detected by performing simple medication reviews (based on the discharge prescription and the medication history), whereas in the remaining cases, additional clinical and/or patient-specific information would have been needed. In 944 (84.7 %) DRPs, which are detectable by simple medication reviews, the pharmacist would need to consult the prescriber for resolution. CONCLUSION: The detection of DRPs is strongly influenced by the information available. These results support models with pre-discharge medication reconciliation and pharmacist-led medication review procedures enabling both comprehensive detection and facilitated resolution of DRPs.

[A Rare Cause of Hypercalcemia]. / Eine seltene Ursache der Hyperkalzämie.

A Rare Cause of Hypercalcemia Abstract. Sarcoidosis is a rare cause of hypercalcemia, which is in most cases caused by primary hyperparathyroidism or a malignant tumor. Other rare causes include vitamin D intoxication, other granulomatous diseases (such as tuberculosis, or fungal infection) or mutiple myeloma. Because of the broad differential diagnosis, a systematic diagnostic approach is crucial to establish the correct diagnosis. Therapeutic measures include volume replacement and subsequent administration of bisphosphonates. If hypercalcemia is caused by sarcoidosis, therapy with systemic corticosteroids is indicated.

[Mononeuritis Multiplex: A Diagnostic Challenge]. / Mononeuritis multiplex als diagnostische Herausforderung.

Mononeuritis Multiplex: A Diagnostic Challenge Abstract. Eosinophilic granulomatosis with polyangiitis (EGPA, formerly Churg-Strauss syndrome) is a multifaceted disease. Due to the variability in vascular and organ involvement, EPGA can manifest itself very differently. We report a case of a 60-year-old patient with a known bronchial asthma, pansinusitis and newly blood eosinophilia with a rapid-onset mononeuritis multiplex. The diagnosis was confirmed based on a histological examination. After initiation of therapy the patient can walk independently with a mobility aid.

Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Association with Commonly Prescribed Drugs in Outpatient Care Other than Anti-Epileptic Drugs and Antibiotics: A Population-Based Case-Control Study.

INTRODUCTION: Stevens-Johnson syndrome and toxic epidermal necrolysis have been associated with the use of various drugs, but evidence is scarce. We studied the association between new use of outpatient drugs other than anti-epileptic drugs and antibiotics and Stevens-Johnson syndrome and toxic epidermal necrolysis. METHODS: We conducted a matched (1:4) case-control analysis in 480 previously validated Stevens-Johnson syndrome/toxic epidermal necrolysis cases (1995-2013). We calculated odds ratios with 95% confidence intervals for Stevens-Johnson syndrome/toxic epidermal necrolysis in new users of drugs compared to non-users. For cases of Stevens-Johnson syndrome/toxic epidermal necrolysis diagnosed ≤ 84 days after the first use of a drug, we assessed causality between drug exposure and Stevens-Johnson syndrome/toxic epidermal necrolysis using ALDEN (algorithm of drug causality in epidermal necrolysis). We calculated absolute risks by dividing the number of Stevens-Johnson syndrome/toxic epidermal necrolysis cases ≤ 84 days after new drug exposure by the total number of new users of the drug. RESULTS: There was an association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of allopurinol (odds ratio 24.51, 95% confidence interval 2.94-204.04) and cyclooxygenase-2 inhibitors (odds ratio 24.19, 95% confidence interval 2.91-200.92). Proton pump inhibitors, fluoxetine, mirtazapine, and 5-aminosalicylates (sulfasalazine, mesalamine) were also associated with an increased risk of Stevens-Johnson syndrome/toxic epidermal necrolysis, though with lower odds ratios. ALDEN score application suggests a likely causality for these associations. Absolute risks of Stevens-Johnson syndrome/toxic epidermal necrolysis were 6.0/100,000 new users for allopurinol, and 1.9-4.3/100,000 new users for cyclooxygenase-2 inhibitors and 5-aminosalicylates, and 0.2-1.6/100,000 new users for proton pump inhibitors, fluoxetine, and mirtazapine. We found no association between Stevens-Johnson syndrome/toxic epidermal necrolysis and oxicams, benzodiazepines, citalopram, sertraline, paroxetine, venlafaxine, and phosphodiesterase-5 inhibitors despite > 100,000 new users. CONCLUSIONS: In this observational study, we observed likely causal associations between Stevens-Johnson syndrome/toxic epidermal necrolysis and use of allopurinol, cyclooxygenase-2 inhibitors, and 5-aminosalicylates, and potential associations for proton pump inhibitors, fluoxetine, and mirtazapine.

Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis.

INTRODUCTION: Long-term use of proton pump inhibitors (PPIs) has been associated with an increased risk of Alzheimer's disease (AD) in observational studies. The role of exposure duration, and whether this applies to other dementia subtypes, has not been explored in these studies. OBJECTIVE: The aim was to study the association between long-term use of PPIs (or of histamine-2 receptor antagonists [H2RAs], as a negative control) and the risk of developing AD or vascular dementia (VaD). METHODS: We conducted a case-control analysis on the UK-based Clinical Practice Research Datalink (CPRD). We identified 41,029 patients aged ≥ 65 years with newly diagnosed AD or VaD between 1998 and 2015 and matched them 1:1 to dementia-free controls on age, sex, calendar time, general practice, and number of years of recorded history. We applied conditional logistic regression analyses to calculate adjusted odds ratios (aORs), with 95% confidence intervals (CIs), of developing AD or VaD in relation to previous use of PPIs or H2RAs, categorized by exposure duration. RESULTS: As compared to non-use, long-term PPI use (≥ 100 prescriptions) was not associated with an increased risk of developing AD (aOR 0.88, 95% CI 0.80-0.97) or VaD (aOR 1.18, 95% CI 1.04-1.33). Neither was long-term use of H2RAs (≥ 20 prescriptions) associated with an increased risk of developing AD (aOR 0.94, 95% CI 0.87-1.02) or VaD (aOR 0.99, 95% CI 0.89-1.10). CONCLUSION: In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use.

[Pharmacotherapy in patients with reduced kidney function]. / Besonderheiten der Pharmakotherapie bei eingeschränkter Nierenfunktion.

Pharmacotherapy in patients with reduced kidney function Abstract. Pharmacotherapy in patients with chronic kidney disease (CKD) requires careful assessment of renal function and a profound knowledge of dose adaption principles and pharmacological characteristics of the drugs used. Of importance, non-renal clearance is also affected by impaired kidney function. Direct acting anticoagulants play an increasingly important role in daily clinical practice also in patients with impaired kidney function. Limited data suggest possible use even in end stage renal disease. GLP-1-agonists and SGLT-2-inhibitors are new treatment modalities for type 2 diabetes mellitus. The efficacy of glucose lowering by SGLT-2-inhibitors steadily declines with impaired kidney function; however, positive effects on cardiovascular outcomes seem to be preserved in advanced CKD. NSAIDs affect renal hemodynamics as well as tubular function. Severe renal side effects may be observed especially when used in combination with RAAS-inhibitors and diuretics.

Colorectal cancer and markers of anemia.

Unexplained iron-deficiency anemia is an important marker for colorectal cancer (CRC). Our objectives were as follows: (a) to assess whether the association between anemia and CRC can be detected on the 'Clinical Practice Research Datalink', (b) to evaluate the timing between laboratory changes and CRC detection, and (c) to analyze its association with survival. We conducted a case-control study on patients with an incident CRC diagnosis during 2008-2012 and a 1 : 1-matched control group. We compared anemia markers serum ferritin (SF), hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between cases and controls using conditional logistic regression. We assessed survival in CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95% confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300 ng/ml when restricted to measurements up to 180 days before the CRC diagnosis. For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02 (1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9 g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67), respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively. Low levels of these markers were only weakly associated with survival. Hb, MCV, and SF levels substantially dropped only shortly before the CRC diagnosis. Although slightly more cases had anemia markers compared with controls at 1 year or earlier before the diagnosis, most cases still had normal values. The Clinical Practice Research Datalink is well-suited to detect associations between low Hb, MCV, and SF levels and CRC.

The risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in new users of antiepileptic drugs.

OBJECTIVE: Older antiepileptic drugs (AEDs) are known to cause Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN). However, evidence for newer AED is sparse. We quantified risks of SJS/TEN in association with use of all AEDs in the United Kingdom. METHODS: In a matched case-control study of 480 previously validated SJS/TEN cases (1995-2013) we used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs), and calculated absolute risks of SJS/TEN within separate cohorts of new users of 28 AEDs. We assessed causality between drugs and SJS/TEN in each exposed case, using an adapted version of the algorithm of drug causality for epidermal necrolysis (ALDEN) score. RESULTS: We observed a strong association between SJS/TEN and new use of carbamazepine (OR 92.57, 95% CI 19.89-∞), phenytoin (OR 49.96, 95% CI 10.13-∞), and lamotrigine (OR 26.90, 95% CI 4.88-∞), where causality, according to the ALDEN score, was very probable or probable for most exposed cases. Absolute risks for SJS/TEN were highest for phenytoin (45.86 cases/100,000 exposed), lamotrigine (44.17 cases/100,000 exposed), and carbamazepine (20.38 cases/100,000 exposed). Despite increased ORs for valproate (40,941 exposed), gabapentin (116,037 exposed), pregabalin (59,967 exposed), and clobazam (4,300 exposed), ALDEN suggested no causal association. There were no observed cases of SJS/TEN among new users of levetiracetam (n = 96,77), clonazepam (n = 18,075), or topiramate (n = 11,307). SIGNIFICANCE: The results of our study are consistent with those of previous studies of SJS/TEN, which found increased risks of SJS/TEN in new use of carbamazepine, phenytoin, and lamotrigine. Despite frequent use, no ALDEN-score confirmed cases were observed in new users of valproate, gabapentin, pregabalin, levetiracetam, topiramate, or clonazepam.

The association between thyroid disorders and incident gout: population-based case-control study.

CONTEXT: Thyroid hormones influence kidney function and thereby might alter serum urate levels, a major risk factor for gouty arthritis. OBJECTIVE: To assess the risk of developing incident gout in association with hypothyroidism or hyperthyroidism. DESIGN: Retrospective population-based case-control analysis. SETTING: UK-based Clinical Practice Research Datalink, a primary care research database. PATIENTS: We identified adult patients with a diagnosis of incident gout between 1990 and 2014. We matched one control to each gout case in terms of age, sex, general practice, calendar time, and years of active history in the database. MAIN OUTCOME MEASURE: We used conditional logistic regression to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for developing gout in association with hypo- or hyperthyroidism and adjusted for potential confounders. RESULTS: The study population encompassed 68,159 incident gout cases, of whom 78.8% were male, and the same number of matched controls. There was no increased risk of gout in patients with hypothyroidism: adjusted OR of gout of 1.12 (95% CI 1.05-1.20) compared with no hypothyroidism. Current short-term treatment of thyroid hormone replacement therapy was associated with an adjusted OR of gout of 1.54 (95% CI 1.24-1.92), compared with no treatment. Neither hyperthyroidism nor current treatment with thyroid suppression therapy was associated with gout (adjusted OR, 1.08 [95% CI 0.95-1.22] and 0.82 [95% CI 0.57-1.17], respectively). CONCLUSION: This large observational study does not provide evidence that hypothyroidism or hyperthyroidism, irrespective of treatment, is associated with a clinically relevant increased risk of developing incident gout. There may be an exception among patients with newly diagnosed and treated hypothyroidism.

The Epidemiology of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the UK.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but life-threatening mucocutaneous diseases. SJS/TEN mostly manifest as a reaction to new drug use, but little is known about their incidence and epidemiology. We conducted a large observational study on the epidemiology of SJS/TEN using data from the UK-based Clinical Practice Research Datalink. Among 551 validated SJS/TEN patients, we calculated an incidence rate of 5.76 SJS/TEN cases per million person-years between 1995 and 2013, which was consistent throughout the study period and was highest in patients aged 1-10 years and 80 years or older. Within a 1:4 matched case-control analysis, black and Asian patients were at a 2-fold risk of SJS/TEN when compared with white patients. Among patients with epilepsy and gout, odds ratios for SJS/TEN were significantly increased only in the presence of recent new drug treatment with antiepileptics or allopurinol, respectively. We observed statistically significant associations between SJS/TEN and pre-existing depression, lupus erythematosus, recent pneumonia, chronic kidney disease, and active cancer, but confounding by drug use needs to be followed up. This large and longitudinal observational study on the epidemiology of SJS/TEN contributes to the understanding of this still underinvestigated severe skin disease in a European and largely white study population.

Mistaking 2C-P for 2C-B: What a Difference a Letter Makes.

2,5-Dimethoxy-4(n)-propylphenethylamine (2C-P) is a synthetic phenethylamine derivative belonging to the large family of the so-called 2C drugs. These compounds can differ significantly in receptor affinity, potency and duration of action, and an important structural difference is the ligand in the 4 position of the phenyl ring, such as propyl in 2C-P or bromine in 2,5-dimethoxy-4-bromophenethylamine (2C-B). The 2C drugs are known for their hallucinogenic properties. We present a case of a 19-year-old male admitted to the emergency department with severe hallucinations, mydriasis, tachycardia, agitation and confusion following the use of a substance sold as 2C-B. By using liquid chromatography-mass spectrometry, the more potent substance 2C-P was detected and quantified. On the basis of two blood sample concentrations, the estimated elimination half-life was 19 h. This case report illustrates and discusses the differences in potency and duration of action of 2C drugs.

Metformin and the risk of renal cell carcinoma: a case-control analysis.

Metformin use has been associated previously with a decreased risk of cancer, but its association with renal cell carcinoma has not yet been investigated in observational studies. We aimed to explore the association between the use of metformin and other antidiabetic drugs and the risk of renal cell carcinoma (RCC). We carried out a case-control analysis in the UK-based Clinical Practice Research Datalink. We included individuals with an incident RCC between January 1995 and December 2013 younger than the age of 90 years. Six controls per case were matched on age, sex, calendar time, general practice, and number of years of active history in the Clinical Practice Research Datalink before the index date. We included BMI, smoking, alcohol consumption, hypertension, and diabetes mellitus as potential confounders in a multivariate model using conditional logistic regression to calculate odds ratios with 95% confidence intervals, and we carried out a sensitivity analysis restricted only to diabetic cases and controls. Long-term use of metformin was not associated with an altered relative risk of RCC (≥30 prescriptions, adjusted odds ratio 1.18, 95% confidence interval 0.88-1.58), nor was use of other antidiabetic drugs. Results in the sensitivity analysis including only diabetic cases and controls were largely the same. Use of metformin or other antidiabetic drugs was not associated with a materially altered risk of RCC. Further studies are warranted.

Validation of Stevens-Johnson syndrome or toxic epidermal necrolysis diagnoses in the Clinical Practice Research Datalink.

PURPOSE: To evaluate the validity of recorded diagnoses of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in the Clinical Practice Research Datalink (CPRD). METHODS: We identified patients with a diagnosis of SJS or TEN between 1995 and 2013 in the CPRD. We reviewed information from patient records, free text, and hospital episode statistics (HES) data, and excluded patients with no indication of a secondary care referral. Remaining patients were classified as probable, possible, or unlikely cases of SJS/TEN by two specialised clinicians or based on pre-defined classification criteria. We quantified positive predictive values (PPV) for all SJS/TEN patients and for patients categorised as 'probable/possible' cases of SJS/TEN, based on a representative subsample of 118 patients for whom we had unequivocal information (original discharge letters or HES data). RESULTS: We identified 1324 patients with a diagnosis of SJS/TEN, among whom 638 had a secondary care referral recorded. Of those, 565 were classified as probable or possible cases after expert review. We calculated a PPV of 0.79 (95% CI, 0.71-0.86) for all SJS/TEN patients with a recorded secondary care referral, and a PPV of 0.87 (95% CI, 0.81-0.93) for probable/possible cases. After excluding 14 false positive patients, our study population consisted of 551 SJS/TEN patients. CONCLUSIONS: Diagnoses of SJS/TEN are recorded with moderate diagnostic accuracy in the CPRD, which was substantially improved by additional expert review of all available information. We established a large population-based SJS/TEN study population of high diagnostic validity from the CPRD. Copyright © 2016 John Wiley & Sons, Ltd.