Integrating Pharmacomechanical Treatments for Pulmonary Embolism Management within a Hub-and-Spoke System in the Swiss Ticino Region.

The Swiss Ticino regional pulmonary embolism response team (PERT) features direct access to various pharmacomechanical PE management options within a hub/spoke system, by integrating evidence, guidelines' recommendations and personal experiences. This system involves a collaborative management of patients among the hospitals distributed throughout the region, which refer selected intermediate-high or high PE patients to a second-level hub center, located in Lugano at Cardiocentro Ticino, belonging to the Ente Ospedaliero Cantonale (EOC). The hub provides 24/7 catheterization laboratory activation for catheter-based intervention (CBI), surgical embolectomy and/or a mechanical support system such as extracorporeal membrane oxygenation (ECMO). The hub hosts PE patients after percutaneous or surgical intervention in two intensive care units, one specialized in cardiovascular anesthesiology, to be preferred for patients without relevant comorbidities or with hemodynamic instability and one specialized in post-surgical care, to be preferred for PE patients after trauma or surgery or with relevant comorbidities, such as cancer. From April 2022 to December 2023, a total of 65 patients were referred to the hub for CBI, including ultrasound-assisted catheter-directed thrombolysis (USAT) or large-bore aspiration intervention. No patient received ECMO or underwent surgical embolectomy.

A Population-Based Scoring System to Assess the Impact of Individual Risk Factors on Vascular Health.

Arterial stiffness is an indicator of vascular health, influenced by both pathological conditions and physiological determinants, noticeably age. Augmentation index (AI) and pulse wave velocity (PWV) are used among others to assess arterial stiffness. Several risk factors may contribute to pathologically increase arterial stiffness and produce early vascular aging. Our study aims to assess the impact of individual risk factors on vascular health, evaluating the distribution of PWV and AI values in a cohort of adult people without modifiable cardiovascular risk factors while analyzing their role in accelerating vascular ageing. We performed a secondary analysis of a Swiss population-based research project, which took place in 2017 and 2018. Of the 1202 participants originally enrolled, 1097 were included in the final sample. The population was divided into without (n=388) and with risk factors (n=709), based on the presence of the following: smoking, diabetes, previous cardiovascular disease (CVD), chronic kidney disease stage 3 or more, LDL cholesterol ≥ 4.11 or treatment with hypolipidemic drugs, hypertension or treatment with antihypertensive drugs, and metabolic syndrome. Tonometric and oscillometric devices were employed to assess PWV, and the 75th percentiles of PWV and AI in the population without risk factors were calculated to identify cut-offs for the logistic regression analysis. We developed nomograms by assigning a numerical score to each independent prognostic factor; the total score estimating the probability of PWVs and AIs being over the defined cut-offs. Patients with hypertension, diabetes, and obesity showed higher PWV values (p < 0.001). In the univariate logistic regression, factors predictive for higher PWV values were diabetes, CVDs, hypercholesterolemia, and hypertension, while CVDs, antihyperlipidemic treatment, hypertension, and increased BMI were predictive in the multivariate logistic regression. Smoking did not significantly influence arterial stiffness parameters. The present study provides reference values for PWV and AI in subjects without modifiable cardiovascular risk factors and, through nomograms, a risk score stratification to assess the impact of individual risk factors on vascular health.

Perioperative costs of local or regional anesthesia versus general anesthesia in the outpatient setting: a systematic review of recent literature

Abstract Background and objectives: In this systematic review, we carried out an assessment of perioperative costs of local or regional anesthesia versus general anesthesia in the ambulatory setting. Methods: A systematic literature search was conducted to find relevant data on costs and cost-effectiveness analyses of anesthesia regimens in outpatients, regardless of the medical procedure they underwent. The hypothesis was that local or regional anesthesia has a lower economic impact on hospital costs in the outpatient setting. The primary outcome was the average total cost of anesthesia calculated on perioperative costs (drugs, staff, resources used). Results: One-thousand-six-hundred-ninety-eight records were retrieved, and 28 articles including 27,581 patients were selected after reviewing the articles. Data on the average total costs of anesthesia and other secondary outcomes (anesthesia time, recovery time, time to home readiness, hospital stay time, complications) were retrieved. Taken together, these findings indicated that local or regional anesthesia is associated with lower average total hospital costs than general anesthesia when performed in the ambulatory setting. Reductions in operating room time and postanesthesia recovery time and a lower hospital stay time may account for this result. Conclusions: Despite the limitations of this systematic review, mainly the heterogeneity of the studies and the lack of cost-effectiveness analysis, the economic impact of the anesthesia regimes on healthcare costs appears to be relevant and should be further evaluated.

Contribution margin per hour of operating room to reallocate unutilized operating room time: a cost-effectiveness analysis

Abstract Background and objectives: Contribution margin per hour (CMH) has been proposed in healthcare systems to increase the profitability of operating suites. The aim of our study is to propose a simple and reproducible model to calculate CMH and to increase cost-effectiveness. Methods: For the ten most commonly performed surgical procedures at our Institution, we prospectively collected their diagnosis-related group (DRG) reimbursement, variable costs and mean procedural time. We quantified the portion of total staffed operating room time to be reallocated with a minimal risk of overrun. Moreover, we calculated the total CMH with a random reallocation on a first come-first served basis. Finally, prioritizing procedures with higher CMH, we ran a simulation by calculating the total CMH. Results: Over a two-months period, we identified 14.5 hours of unutilized operating room to reallocate. In the case of a random ''first come -first serve'' basis, the total earnings were 87,117 United States dollars (USD). Conversely, with a reallocation which prioritized procedures with a high CMH, it was possible to earn 140,444 USD (p < 0.001). Conclusion: Surgical activity may be one of the most profitable activities for hospitals, but a cost-effective management requires a comprehension of its cost profile. Reallocation of unused operating room time according to CMH may represent a simple, reproducible and reliable tool for elective cases on a waiting list. In our experience, it helped improving the operating suite cost-effectiveness.

Differential impact of transfusion guidelines on blood transfusion practices within a health network.

Whether clinical practice guidelines have a significant impact on practice is unclear. The effect of guideline recommendations on clinical practice often a lags behind the date of publication. We evaluated by means of a data-driven approach if and when the guidelines on red blood cell transfusions (RBCTs) issued by Swiss Smarter Medicine in 2016 had an impact on RBCTs practice within a hospital network, where awareness of guidelines was promoted mainly among internal medicine specialties. Data on RBCTs performed in a Swiss hospital network from January 2014 to April 2021 were analyzed by hospital site and specialty to assess whether guidelines led to a decrease in inappropriate RBCTs. RBCTs were defined as "inappropriate" if patients had a hemoglobin level ≥ 70 g/L without or ≥ 80 g/L with significant cardiovascular comorbidities. Changes in the rate of inappropriate transfusions were analyzed with an advanced statistical approach that included generalized additive models. Overall prior to March 2017 there were more inappropriate than appropriate RBCTs, but after October 2017 the opposite could be observed. A change-point in the time trend was estimated from transfusion data to occur in the time interval between March and October 2017. This change was mainly driven by practice changes in the medical wards, while no significant change was observed in the critical care, surgical and oncology wards. Change in practice varied by hospital site. In conclusion, our results show that a significant change in the RBCTs practice at the hospital level occurred approximately 18 months after national guidelines were issued.

New-onset cutaneous sarcoidosis under tocilizumab treatment for giant cell arteritis: a quasi-paradoxical adverse drug reaction. Case report and literature review.

BACKGROUND: New-onset sarcoidosis has been previously described in three case reports in patients affected by rheumatoid arthritis treated with tocilizumab (TCZ). The existence of a cause-effect mechanism between the biological treatment and the onset of the illness is still being debated. PATIENT CONCERNS: A 74-year-old woman was diagnosed with giant cell arteritis (GCA). The first-line treatment with glucocorticoids; and the second-line with methotrexate and low-dose glucocorticoids were stopped due to multiple pathological vertebral fractures and insufficient biological and clinical response. The cytotoxic agent, cyclophosphamide, was then introduced and in turn stopped, because of gastrointestinal side effects. Thereafter a treatment with TCZ was begun. The patient experienced good clinical response; however, 8 months later she developed painful hyper-pigmented reddish cutaneous micronodular lesions localized to the abdomen and thorax. A cutaneous biopsy was performed, and histological analysis showed noncaseating epithelioid granulomas in the hypodermis. The diagnosis of cutaneous sarcoidosis was made. INTERVENTIONS: Topical corticosteroids were administered and, as requested by the patient, TCZ was discontinued with slow but complete resolution of the skin lesions. After TCZ discontinuation however, the GCA flared and the patient's symptoms and biological abnormalities reappeared. Thus, after a 6-month suspension, TCZ was re-administered. At 2 months later the skin lesions compatible with cutaneous sarcoidosis reappeared. Topical corticosteroids were once again prescribed and as suggested by the patient the TCZ posology was reduced. The patient's symptoms disappeared, and the cutaneous lesions resolved. LESSONS: The time elapsed from TCZ treatment start and the onset of cutaneous sarcoidosis, as well as its recurrence after TCZ suspension and rechallenge supported the diagnosis of a drug-induced reaction. To the best of our knowledge, this case report represents the first instance of cutaneous sarcoidosis most likely induced by TCZ in patients affected by GCA. In addition, our case emphasizes that although TCZ in monotherapy confirms to be an effective treatment for GCA, further immunological disorders could be unmasked, and the discussed side effect of the drug could be dose-dependent.

Choosing wisely in oncology: necessity and obstacles.

In the last decades, the survival of many patients with cancer improved thanks to modern diagnostic methods and progresses in therapy. Still for several tumours, especially when diagnosed at an advanced stage, the benefits of treatment in terms of increased survival or quality of life are at best modest when not marginal, and should be weighed against the potential discomfort caused by medical procedures. As in other specialties, in oncology as well the dialogue between doctor and patient should be encouraged about the potential overuse of diagnostic procedures or treatments. Several oncological societies produced recommendations similar to those proposed by other medical disciplines adhering to the Choosing Wisely (CW) campaign. In this review, we describe what was reported in the medical literature concerning adequacy of screening, diagnostic, treatment and follow-up procedures and the potential impact on them of the CW. We only marginally touch on the more complex topic of treatment appropriateness, for which several evaluation methods have been developed (including the European Society for Medical Oncology-magnitude of clinical benefit scale). Finally, we review the possible obstacles for the development of CW in the oncological setting and focus on the strategies which could allow CW to evolve in the cancer field, so as to enhance the therapeutic relationship between medical professionals and patients and promote more appropriate management.

Combining prescription monitoring, benchmarking, and educational interventions to reduce benzodiazepine prescriptions among internal medicine inpatients; a multicenter before and after study in a network of Swiss Public Hospitals.

OBJECTIVES: Reducing the inappropriate benzodiazepine (BZD) prescriptions represents a challenge for health care systems worldwide. The 'Choosing Wisely' campaign recommends against the use of BZD in the elderly as the first choice for insomnia, agitation, or delirium. We aimed to determine whether a transparent monitoring-benchmarking together with educational interventions, on top of the internal publication of a targeted recommendation, could be effective in curbing BZD prescriptions. METHODS: Multicenter before and after study in a network of five southern-Switzerland teaching hospitals. An intervention based on a transparent continuous monitoring-benchmarking system, called 'Reporting Wisely', able to collect, analyze, and report data on BZD prescriptions and educational interventions focused on themed meetings, audit, and feedback, was implemented. The intervention was limited to the Internal Medicine. The impact of the intervention on new BZD prescriptions and de-prescribing at hospital discharge, was assessed using segmented regression analyses of interrupted time-series and comparing Internal Medicine to Surgery. RESULTS: Between July 1st2014, and June 30th2017, data of 45,597 hospital admissions, from Internal Medicine and Surgery departments were analyzed. Before the intervention (July 1st2014 to December 31st2015), the mean monthly new BZD prescription rate was 7.2%; value dropping to 5.5% (24% relative reduction; p < 0.001) in the intervention phase (January 1st2016 to June 30th2017). At the end of the intervention a 15% relative increase of BZD de-prescribing was also found (p < 0.01). The use of atypical antipsychotic (AAP) and other potentially harmful sedative drugs did not increase. In the surgery department, exposed to the recommendation but not to the intervention, a constant upward trend with a slope of 0.129 new prescriptions per 100 admissions per month (95% CI 0.08-0.17; p < 0.001) was seen. CONCLUSIONS: The implementation of a dual intervention based on transparent monitoring-benchmarking and multidisciplinary education has proved useful in curbing new BZD prescriptions and in promoting BZD de-prescribing in the hospital setting.

Multifaceted intervention to curb in-hospital over-prescription of proton pump inhibitors: A longitudinal multicenter quasi-experimental before-and-after study.

BACKGROUND: Proton pump inhibitors (PPIs) are indicated for a restricted number of clinical conditions, and their misuse can lead to several adverse effects. Despite that, the proportion of overuse is alarmingly high. OBJECTIVE: To test the efficacy of a multifaceted strategy in order to achieve a significant reduction of new PPI prescriptions at discharge in hospitalized patients. DESIGN: Multicenter longitudinal quasi-experimental before-and-after study conducted from July 1st, 2014 to June 30th, 2017. PARTICIPANTS: 44,973 admissions in a network of 5 public teaching hospitals of the Italian-speaking region of Switzerland. INTERVENTION: Multifaceted strategy consisting in a continuous transparent monitoring-benchmarking and in capillary educational interventions applied in the internal medicine departments. To confirm the causality of the results we monitored the trend of new PPI prescriptions in the, not exposed to the intervention, surgery departments of the same hospital network. MAIN MEASURES: New PPI prescriptions at hospital discharge. KEY RESULTS: Over the 36month study period 44,973 patient files were analyzed. At admission, comparing internal medicine vs. surgery departments, 44.9% vs. 23.3% of patients were already being treated with a PPI. The annual rate of new PPI prescriptions, for internal medicine showed a decreasing trend: 19, 19, 18, 16% in years 2014, 2015, 2016, 2017, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001), while an increasing rate was found in the surgery departments in the same years: 30, 29, 36, 36%, respectively (p<0.001, 2014 vs. 2017; p-for-trend <0.001). The case mix was significantly associated with the probability of new PPI prescriptions in both departments (OR1.35, 95% CI 1.26-1.44 for internal medicine and 1.24, 95% CI 1.19-1.30 for surgery). CONCLUSIONS: The introduction of a multifaceted intervention significantly reduced the time trend of PPI prescriptions at hospital discharge in internal medicine departments. Further studies are needed to confirm whether the strategy proposed could contribute to optimize the in-hospital drug prescription behavior in other healthcare settings as well.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 µmol/kg/24 hours in men and 151 ± 38 µmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Prevalence of obesity and overweight and associated nutritional factors in a population-based Swiss sample: an opportunity to analyze the impact of three different European cultural roots.

PURPOSE: Obesity represents a growing public health concern worldwide. The latest data in Switzerland rely on self-reported body mass index (BMI), leading to underestimation of prevalence. We reassessed the prevalence of obesity and overweight in a sample of the Swiss population using measured BMI and waist circumference (WC) and explored the association with nutritional factors and living in different linguistic-cultural regions. METHODS: Data of 1,505 participants of a cross-sectional population-based survey in the three linguistic regions of Switzerland were analyzed. BMI and WC were measured, and a 24-h urine collection was performed to evaluate dietary sodium, potassium and protein intake. RESULTS: The prevalence of overweight, obesity and abdominal obesity was 32.2, 14.2 and 33.6%, respectively. Significant differences were observed in the regional distribution, with a lower prevalence in the Italian-speaking population. Low educational level, current smoking, scarce physical activity and being migrant were associated with an higher prevalence of obesity. Sodium, potassium and protein intake increased significantly across BMI categories. CONCLUSIONS: Obesity and overweight affect almost half of the Swiss adolescents and adults, and the prevalence appears to increase. Using BMI and WC to define obesity led to different prevalences. Differences were furthermore observed across Swiss linguistic-cultural regions, despite a common socio-economic and governmental framework. We found a positive association between obesity and salt intake, with a potential deleterious synergistic effect on cardiovascular risk.

Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.

BACKGROUND: In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients. METHODS: The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference. RESULTS: No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa. CONCLUSIONS: The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01666301.

Estimation of glomerular filtration rate in hospitalised patients: are we overestimating renal function?

UNLABELLED: QUESTIONS UNDER STUDY AND PRINCIPLES: Estimating glomerular filtration rate (GFR) in hospitalised patients with chronic kidney disease (CKD) is important for drug prescription but it remains a difficult task. The purpose of this study was to investigate the reliability of selected algorithms based on serum creatinine, cystatin C and beta-trace protein to estimate GFR and the potential added advantage of measuring muscle mass by bioimpedance. METHODS: In a prospective unselected group of patients hospitalised in a general internal medicine ward with CKD, GFR was evaluated using inulin clearance as the gold standard and the algorithms of Cockcroft, MDRD, Larsson (cystatin C), White (beta-trace) and MacDonald (creatinine and muscle mass by bioimpedance). RESULTS: 69 patients were included in the study. Median age (interquartile range) was 80 years (73-83); weight 74.7 kg (67.0-85.6), appendicular lean mass 19.1 kg (14.9-22.3), serum creatinine 126 µmol/l (100-149), cystatin C 1.45 mg/l (1.19-1.90), beta-trace protein 1.17 mg/l (0.99-1.53) and GFR measured by inulin 30.9 ml/min (22.0-43.3). The errors in the estimation of GFR and the area under the ROC curves (95% confidence interval) relative to inulin were respectively: Cockcroft 14.3 ml/min (5.55-23.2) and 0.68 (0.55-0.81), MDRD 16.3 ml/min (6.4-27.5) and 0.76 (0.64-0.87), Larsson 12.8 ml/min (4.50-25.3) and 0.82 (0.72-0.92), White 17.6 ml/min (11.5-31.5) and 0.75 (0.63-0.87), MacDonald 32.2 ml/min (13.9-45.4) and 0.65 (0.52-0.78). CONCLUSIONS: Currently used algorithms overestimate GFR in hospitalised patients with CKD. As a consequence eGFR targeted prescriptions of renal-cleared drugs, might expose patients to overdosing. The best results were obtained with the Larsson algorithm. The determination of muscle mass by bioimpedance did not provide significant contributions.

Pharmacokinetics of N-acetylcysteine following repeated intravenous infusion in haemodialysed patients.

OBJECTIVE: N-acetylcysteine (NAC) is a mucolytic agent with anti-oxidant properties. It might have potential positive effects in renal patients and, therefore, its pharmacokinetics and safety in haemodialysis was investigated. METHODS: Twelve dialysis patients received 2 g NAC (10 ml NAC 20% solution i.v.) mixed with 500 ml saline during the first 3 h of the session for six dialysis sessions. A bolus of heparin was injected intravenously as LWH-heparin. In six patients, one session was repeated with NAC mixed with heparin and infused through the heparin pump. RESULTS: Baseline NAC was on average 454 ng ml(-1); its concentration increased to 9,253 ng ml(-1) at the second infusion and attained a steady state between 14,000 ng ml(-1) and 17,000 ng ml(-1) at the fourth dose. We observed a C (max) of 53,458 ng ml(-1) with a t (max) of 3.0 h. Plasma clearance was 1.25 l h(-1) and dialytic clearance 5.52 l h(-1). No side effects were observed. CONCLUSION: In the case of repeated doses, the NAC pre-dose concentration after repeated infusion of 2 g of the drug during the first 3 h of a dialysis session reached the steady state at the fourth infusion, without further accumulation. The dialytic clearance is effective, the total body clearance being reduced to 1.25 l h(-1). In dialysis patients, 2 g NAC given intravenously over 3 h is a safe dosage, with no short-term side effects.

Does cystatin C improve the precision of Cockcroft and Gault's creatinine clearance estimation?

BACKGROUND: Cystatin C is increasingly used to estimate renal function, but its large intraindividual variability limits its practical value. This study aimed at verifying whether the clinical practice of associating cystatin C determination with serum creatinine (Cr) improved the ability of the Cockcroft and Gault formula to estimate creatinine clearance (CrCl). METHODS: It was an observational cross-sectional study of 134 in-patients with mildly impaired renal function. Using the Hoek et al formula (glomerular filtration rate (GFR)/1.73m2 = - 4.32 + 80.35/cystatin C mg/L), multivariate linear regressions (LREG) and artificial neural networks (ANN), we integrated cystatin C in the Cockcroft and Gault formula and analyzed the potential superiority of this procedure by comparing its performance with that of the two algorithms taken separately. RESULTS: The inclusion of cystatin C in the Cockcroft and Gault formula using the data of an LREG (CrCl = 0.371 x (Hoek et al) + 0.589 x Cockcroft and Gault), a simple mean between the two algorithms or ANN ameliorated the CrCl estimation precision allowing an absolute error reduction of approximately 4, 4 and 6%, respectively (relative values 12, 12 and 17%). CONCLUSIONS: Although the combination of the Hoek et al and Cockcroft and Gault formulae using both linear and non-linear mathematical methods allowed a statistically significant reduction in the estimation error generated by Cockcroft and Gault, considering the small impact on the estimation precision and the large intraindividual variation of both cystatin C and Cr, this procedure probably has no clinical relevance.