Mechanical Thrombectomy with Intravenous Thrombolysis versus Thrombolysis Alone for the Treatment of Stroke: A Systematic Review of Economic Evaluations.

Mechanical thrombectomy has revolutionized the management of stroke by improving the recanalization rates and reducing deleterious consequences. It is now the standard of care despite the high financial cost. A considerable number of studies have evaluated its cost effectiveness. Therefore, this study aimed to identify economic evaluations of mechanical thrombectomy with thrombolysis compared with thrombolysis alone to provide an update of existing evidence, focusing on the period after proof of effectiveness of mechanical thrombectomy. Twenty-one studies were included in the review: 18 were model-based economic evaluations to simulate long-term outcomes and costs, and 19 were conducted in high-income countries. Incremental cost-effectiveness ratios ranged from -$5,670 to $74,216 per quality-adjusted life year. Mechanical thrombectomy is cost-effective in high-income countries and in the populations selected for clinical trials. However, most of the studies used the same data. There is a lack of real-world and long-term data to analyze the cost effectiveness of mechanical thrombectomy in treating the global burden of stroke.

Validation of an algorithm identifying incident primary immune thrombocytopenia in the French national health insurance database.

OBJECTIVES: To evaluate the accuracy of an algorithm identifying newly diagnosed immune thrombocytopenia (ITP) patients in the French national health insurance database (SNIIRAM). METHODS: The source of data was the SNIIRAM of Midi-Pyrenees region (southwest of France, three million inhabitants). Data of patients with at least one ITP code (D69.3 code of the International Classification of Disease, version 10) were extracted between January 1, 2012, and December 31, 2014. We used an algorithm that identifies newly diagnosed primary ITPs. Medical charts of incident ITPs were reviewed. Positive predictive values (PPVs) of identification of true, incident, and primary ITP cases were estimated. RESULTS: Of the 168 patients selected, 161 were true ITP cases yielding a PPV of 95.8% (95% confidence interval-95% CI: 92.8-98.8). Among them, 128 were truly incident according to symptom onset date and 134 according to the diagnosis date yielding PPVs of 79.5% (95% CI: 73.2-85.7) and 83.2% (95% CI: 77.4-89.0), respectively. Median time between estimated diagnosis date by the algorithm and true diagnosis date was 0 days (interquartile range: 0 to 15). CONCLUSIONS: This study showed a very good PPV of this algorithm identifying incident primary ITP patients in the SNIIRAM.

Positive predictive values of selected hospital discharge diagnoses to identify infections responsible for hospitalization in the French national hospital database.

PURPOSE: The identification of infections in electronic health databases is a key issue for pharmacoepidemiology research. The aim of this study was to assess the positive predictive values (PPVs) of hospitalizations for infection in the Système National d'Information Inter-régimes de l'Assurance Maladie, that is the electronic database recording in-and-out hospital data for the entire French population (66 million inhabitants). METHODS: The source of data was the database of hospitalizations (Programme de Médicalisation des Systèmes d'Informations) of Toulouse University hospital, South of France (2880 beds). Among all hospital stays between September and December 2014, we randomly selected 100 stays with an International Classification of Diseases, 10th revision code of infection as primary diagnosis and 100 as related diagnosis. Medical charts were reviewed to assess the PPV of infection codes, as well as the PPV of correct coding of infection type among the true positive cases. RESULTS: The PPVs of codes of infection as reason for hospitalization were 0.97, 95% confidence interval (CI) [0.93-1.00] for primary diagnosis codes and 0.70, 95% CI [0.61-0.71] for related diagnosis codes. Among the true positive cases, the PPVs of correct coding of the type of infection were, respectively, 0.98, 95% CI [0.95-1.00] and 0.93, 95% CI [0.88-0.98]. CONCLUSIONS: Hospitalizations for infection codes have very good PPVs in the Programme de Médicalisation des Systèmes d'Informations. Copyright © 2016 John Wiley & Sons, Ltd.

Rituximab versus splenectomy in persistent or chronic adult primary immune thrombocytopenia: an adjusted comparison of mortality and morbidity.

Splenectomy and rituximab are both recommended as second-line treatment in immune thrombocytopenia (ITP), but they have never been directly compared. We compared their efficacy and serious adverse outcomes in a retrospective cohort of 105 adult primary ITP patients exposed to one or other of these treatments. Primary outcome was composite: death from hemorrhage or from infection and hospitalization for bleeding or for infection. Secondary outcomes were overall mortality, hospitalization for bleeding, hospitalization for infection, as well as response and complete response (international definitions). Analyses were adjusted on a propensity score. Patients treated with rituximab (n = 43) were older and had more comorbidities than the splenectomized patients (n = 62). Mean follow-up was, respectively, 3 and 8.4 years. After adjustment on the propensity score, there was no difference between the two groups regarding the primary and other clinical outcomes. In the multivariate analysis, only a history of mucosal bleeding (HR 3.2 95% CI [1.2-8.5]) and a Charlson score ≥1 (HR 4.2 95% CI [1.8-9.6]) were associated with the primary outcome. These two factors were also associated with hospitalization for bleeding. As expected, response, complete response and maintenance rates were higher in the splenectomy group. Splenectomy compared with rituximab was independently associated with a response at 12 months (OR 4.4, 95% CI [1.7-11.8]). Then, adjusted analyses in this real-life cohort confirmed the better results of splenectomy compared with rituximab.

Influence of deprivation on hospital care pathways and costs for people with ischaemic stroke: A trajectory modelling study.

BACKGROUND: Socioeconomic characteristics have a strong impact on the incidence of stroke. The highest levels of morbidity and mortality are associated with the lowest socioeconomic positions. Moreover, the health insurance budget for stroke is significant. OBJECTIVES: To describe typical Hospital Care Pathways (HCPs) and their costs 1 year after acute stroke and to assess the impact of individuals' socioeconomic characteristics on HCPs and costs. METHODS: This retrospective observational study used hospital data on people with primary ischaemic stroke in a region of France (Haute-Garonne). HCPs were identified by sequential analysis. Multinomial logistic regression was used to analyse the impact of socioeconomic characteristics on HCPs as measured using an ecological index of deprivation, and a gamma regression model was used to analyse costs. RESULTS: The analysis identified 4 typical HCPs. The first HCP consisted exclusively of consultations, the second was composed of consultations and hospitalisations, the third included hospitalisations during the first 2 months after stroke followed by consultations, and the fourth included long-term hospitalisations. After adjustment, deprivation was associated with HCPs and determined its costs: a high level of social disadvantage determined the type of pathway and increased the costs. CONCLUSIONS: This study is one of the first to assess the impact of social inequalities in health on post-stroke HCPs in France and their corresponding costs. Our results confirm the hypothesis that healthcare costs differ according to the level of deprivation.

Cost-effectiveness analysis of vaginal misoprostol versus dinoprostone pessary: A non-inferiority large randomized controlled trial in France.

OBJECTIVE: To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 µg) compared with a slow-release dinoprostone (PGE2) pessary (10 µg) for labor induction due to an unfavorable cervix at term. METHODS: We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS: Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION: Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

Safety of Pyrazinamide for the Treatment of Tuberculosis in Older Patients Over 75 Years of Age: A Retrospective Monocentric Cohort Study.

OBJECTIVES: Pyrazinamide (PZA) has a controversial safety profile in older patients. We aimed to assess the frequency and risk factors for adverse drug reactions (ADRs) in patients over 75 years of age treated for tuberculosis with or without PZA. METHODS: We conducted a retrospective monocentric study including patients aged over 75 years treated for active tuberculosis between 2008 and 2018. The frequency, type, seriousness, and causality assessment of ADRs to anti-tuberculosis treatment were compared between patients receiving PZA or not. Risk factors for ADRs were investigated using univariable and multivariable analyses by logistic regression. RESULTS: Among the 110 patients included, 54 (49.1%) received PZA (group 1) and 56 (50.9%) did not (group 2). ADRs to anti-tuberculosis drugs occurred in 31 patients (57.4%) in groups 1 and 15 (26.8%) in group 2 (p = 0.003). PZA-related ADRs occurred in 40.7% of exposed patients. Frequency of renal ADRs was higher in group 1 (9.3% vs 0%; p = 0.026). Rates of hepatic (18.5% vs 12.5%; p = 0.38), digestive (22.2% vs 8.9%; p = 0.054), and allergic (14.8% vs 5.4%; p = 0.12) ADRs were numerically higher in group 1 although the differences were not statistically significant. Serious ADRs occurred more frequently in group 1 (24.1% vs 8.9%; p = 0.03). The use of PZA was the only independent risk factor for ADRs to anti-tuberculosis drugs (odds ratio 3.75, 95% CI 1.5-9.6; p = 0.0056). No risk factors for PZA-related ADRs were identified. CONCLUSION: In older French patients, the use of PZA was associated with more frequent ADRs to anti-tuberculosis drugs.

Assessment of the Accuracy of Using ICD-10 Codes to Identify Systemic Sclerosis.

IMPORTANCE: With the increased use of data from electronic medical records for research, it is important to validate in-patient electronic health records/hospital electronic health records for specific diseases identification using International Classification of Diseases, Tenth Revision (ICD-10) codes. OBJECTIVE: To assess the accuracy of using ICD-10 codes to identify systemic sclerosis (SSc) in the French hospital database. DESIGN SETTING AND PARTICIPANTS: Electronic health record database analysis. The setting of the study's in-patient database was the Toulouse University Hospital, a tertiary referral center (2880 beds) that serves approximately 2.9 million inhabitants. Participants were patients with ICD-10 discharge diagnosis codes of SSc seen at Toulouse University Hospital between January 1, 2010, and December 31, 2017. MAIN OUTCOMES AND MEASURES: The main outcome was the positive predictive value (PPV) of discharge diagnosis codes for identifying SSc. The PPVs were calculated by determining the ratio of the confirmed cases found by medical record review to the total number of cases identified by ICD-10 code. RESULTS: Of the 2766 hospital stays, 216 patients were identified by an SSc discharge diagnosis code. Two hundred were confirmed as SSc after medical record review. The overall PPV was 93% (95% CI, 88-95%). The PPV for limited cutaneous SSc was 95% (95% CI, 85-98%). CONCLUSIONS AND RELEVANCE: Our results suggest that using ICD-10 codes alone to capture SSc is reliable in The French hospital database.

The Use of Transthoracic Echocardiogram to Quantify Pulmonary Vascular Resistance in Patients with Systemic Sclerosis.

OBJECTIVE: To explore the accuracy of tricuspid regurgitation velocity (TRV) to right ventricular outflow tract time-velocity integral (TVIRVOT) ratio by Doppler to determine pulmonary vascular resistance (PVR) in patients with systemic sclerosis (SSc). METHODS: Thirty-five consecutive adult patients with SSc, fulfilling the 2013 European League Against Rheumatism/American College of Rheumatology classification criteria, with sinus rhythm referred for right heart catheterization (RHC), were retrospectively included. All patients underwent a transthoracic echocardiogram (TTE) performed within 24 h of RHC. Patients with SSc were recruited regardless of disease activity, cardiac symptoms, and treatment regimen. Doppler measurements were compared to RHC measurements. A linear regression equation was generated to predict PVR by echocardiogram based on the TRV/TVIRVOT ratio. The accuracy of Doppler measurements for predicting PVR > 3 Wood units was assessed by computing the areas under the receiver-operating characteristic curves. RESULTS: There were 20 (57%) females in the study. The mean age was 65 ± 12 years. Mean and systolic pulmonary arterial pressures were 31 ± 8 and 53 ± 15 mmHg, respectively. There was a good correlation between TRV/TVIRVOT ratio assessed by Doppler and PVR measured by RHC (R = 0.743, p < 0.001). The equation generated by this analysis was the following: PVR by Doppler = 11.3 × (TRV/TVIRVOT) + 1.7. A cutoff value of 0.21 for TRV/TVIRVOT ratio provided the best sensitivity (86%) and specificity (86%) to determine PVR > 3 Wood units. CONCLUSION: Our study suggests that TTE using Doppler could be a useful and noninvasive tool for estimating PVR in patients with SSc.

Positive predictive values of peripheral arterial and venous thrombosis codes in French hospital database.

French hospital database, called Programme de Médicalisation des Systèmes d'Information (PMSI), covers all hospital stays in France (>66 million inhabitants). The aim of this study was to estimate the positive predictive values (PPVs) of primary diagnosis codes of peripheral arterial and venous thrombosis codes in the PMSI, encoded with the International Classification of Diseases, 10th revision. Data were extracted from the PMSI database of Toulouse University Hospital, south of France. We identified all the hospital stays in 2015 with a code of peripheral arterial or venous thrombosis as primary diagnosis. We randomly selected 100 stays for each category of thrombosis and reviewed the corresponding medical charts. The PPV of peripheral arterial thrombosis codes was 83.0%, 95% confidence interval (CI): 73.9-89.1, and the PPV of correct location of thrombosis was 81.0%, 95% CI: 72.2-87.5. The PPV of pulmonary embolism was 99.0%, 95% CI: 93.8-99.9. The PPV of peripheral venous thrombosis was 95.0%, 95% CI: 88.2-98.1, and the PPV of correct location of thrombosis was 85.0%, 95% CI: 76.7-90.7. Primary diagnoses of peripheral arterial and venous thrombosis demonstrated good PPVs in the PMSI.

Zoster after Cyclophosphamide for Systemic Lupus Erythematosus or Vasculitis: Incidence, Risk Factors, and Effect of Antiviral Prophylaxis.

OBJECTIVE: To assess the incidence and the risk factors for zoster in patients exposed to intravenous cyclophosphamide (CYC) for systemic vasculitis or systemic lupus erythematosus (SLE), as well as the protective effect of prophylaxis by valacyclovir (VCV). METHODS: This retrospective study included all adults treated by intravenous CYC for SLE or systemic vasculitis between 2011 and 2015 at Toulouse University Hospital, France. Zoster occurrence was recorded using medical chart review, laboratory data, and patient interviews. Univariate Cox models were computed to assess the risk factors for zoster and the protective effect of prophylaxis by VCV. RESULTS: The cohort consisted of 110 patients (81 systemic vasculitis and 29 SLE). During a mean followup of 3.4 years after CYC initiation, 10 cases of zoster occurred, leading to an overall incidence of 27.9/1000 patient-years (95% CI 15.2-50.6); it was 59.4/1000 patients (95% CI 27.5-123.6) during the year after CYC initiation. Four patients experienced persistent postherpetic neuralgia. Probable risk factors were lymphopenia < 500/µl at CYC initiation (HR 5.11, 95% CI 0.94-27.93) and female sex (HR 4.36, 95% CI 0.51-37.31). The incidence was higher in patients with SLE (HR as compared with systemic vasculitis patients = 2.68, 95% CI 0.54-13.26). None of the 19 patients exposed to VCV during the followup developed zoster. CONCLUSION: The incidence of zoster is high in systemic vasculitis and in patients with SLE exposed to intravenous CYC. CYC may favor postherpetic neuralgia. Prophylaxis by VCV should be considered, particularly in cases of lymphopenia < 500/µl at CYC initiation and during the year after.

Clinical Impact and Cost-Effectiveness of an Education Program for PD Patients: A Randomized Controlled Trial.

BACKGROUND: Parkinson's disease (PD) is characterized by its impact on quality of life, constituting a substantial economic burden on society. Education programs implicating patients more in the management of their illness and complementing medical treatment may be a beneficial adjunct in PD. This study assessed the impact of an education program on quality of life and its cost-effectiveness in PD patients. METHODS: This single-center, prospective, randomized study assessed an education program consisting of individual and group sessions over a 12-month period. A total of 120 PD patients were assigned to either the Treated by Behavioral Intervention group (TTBI) or the no TTBI group. The primary outcome criterion was quality of life assessed using PDQ39. The Unified Parkinson's Disease Rating Scale (UPDRS) and psychological status were collected. An economic evaluation was performed, including calculations of incremental cost-effectiveness ratios (ICERs). RESULTS: After 12 months of follow-up, changes recorded in the PDQ39 between the groups were not significantly different but better changes were observed in each dimension in the TTBI group compared to the no TTBI group. UPDRS I, II and total score were significantly improved in TTBI group compared to the no TTBI group. Mean annual costs did not differ significantly between the two groups. CONCLUSION: This study suggested that the education program positively impacts the perceived health of PD patients without increasing medical costs.

Association of selenium with thyroid volume and echostructure in 35- to 60-year-old French adults.

OBJECTIVE: To investigate the relationship between selenium status, thyroid Volume and gland echostructure. DESIGN: Cross-sectional. METHODS: In 792 men (45-60 Years) and 1108 women (35-60 Years) from the SU.VI.MAX study, thyroid Volume and gland echostructure were determined ultrasonographically. At baseline, thyrotropin, free thyroxine, selenium, zinc, alpha-tocopherol, beta-carotene, retinol, urinary iodine and thiocyanate concentrations were measured. Alcohol consumption, smoking, and menopausal status were assessed by a questionnaire. A stepwise linear and a logistic regression model were used, adjusting for antioxidant vitamins, trace elements status and age. RESULTS: In women, there was an inverse association between selenium status and thyroid Volume (P=0.003). A protective effect of selenium against goiter (odds ratio (OR)=0.07, 95% confidence interval (CI)=0.008-0.6) and thyroid tIssue damage (OR=0.2, 95% CI=0.06-0.7) was observed. There was no evidence of an association between menopausal status and other antioxidant elements, thyroid Volume or thyroid hypoechogenicity. Smoking, but not alcohol consumption, was associated with an increased risk of thyroid enlargement in women (OR=3.94, 95% CI=1.64-9.48). No association between thyroid Volume, thyroid structure or selenium was found in men. CONCLUSION: Our findings suggest that selenium may protect against goiter. Selenium was related to thyroid echostructure, suggesting it may also protect against autoimmune thyroid disease.

Methodological considerations in cost of illness studies on Alzheimer disease.

Cost-of-illness studies (COI) can identify and measure all the costs of a particular disease, including the direct, indirect and intangible dimensions. They are intended to provide estimates about the economic impact of costly disease. Alzheimer disease (AD) is a relevant example to review cost of illness studies because of its costliness.The aim of this study was to review relevant published cost studies of AD to analyze the method used and to identify which dimension had to be improved from a methodological perspective. First, we described the key points of cost study methodology. Secondly, cost studies relating to AD were systematically reviewed, focussing on an analysis of the different methods used. The methodological choices of the studies were analysed using an analytical grid which contains the main methodological items of COI studies. Seventeen articles were retained. Depending on the studies, annual total costs per patient vary from $2,935 to $52, 954. The methods, data sources, and estimated cost categories in each study varied widely. The review showed that cost studies adopted different approaches to estimate costs of AD, reflecting a lack of consensus on the methodology of cost studies. To increase its credibility, closer agreement among researchers on the methodological principles of cost studies would be desirable.

Effectiveness of telephone support during chemotherapy in patients with diffuse large B cell lymphoma: the Ambulatory Medical Assistance (AMA) experience.

BACKGROUND: During chemotherapy, patients experience disabling side effects or even sometimes life-threatening treatment-related complications, contributing to poor quality of life, reduced therapeutic compliance, decreased relative dose-intensity, and ultimately poorer outcomes. OBJECTIVES: The Ambulatory Medical Assistance (AMA) project, a monitoring procedure based on a standardized telephone intervention, was aimed to improve ambulatory care quality in aggressive B-cell lymphomas treated with standard front-line R-CHOP therapy. DESIGN: Non-comparative prospective study. SETTING AND PARTICIPANTS: Over a three-years period, one hundred diffuse large B cell lymphoma (DLBCL) patients were treated in a single hospital and monitored in an ambulatory setting through planned telephone interventions delivered by a single nurse under the supervision of an oncologist. METHODS: In addition to biological monitoring, patients received a bi-weekly telephone call from an oncology-certified nurse. All events were recorded on a call form, which was forwarded to a supervisor oncologist. Nurse calls resulted in one of the following: no intervention, grade 1 intervention based on a pre-established protocol managed by the nurse under oncologist supervision, or grade 2 intervention related to more severe complications, managed directly by the oncologist, and mostly resulting in secondary hospitalization. RESULTS: The AMA procedure consisted of 3592 phone calls (600 h) resulting in 989 interventions (27.5%). Grade 1 intervention represented 950 cases whereas grade 2 intervention was noted in only 39 cases (3.9%). AMA also appeared to improve medical management. Indeed, compared to the literature, we observed lower incidence in secondary hospitalization (6%), delayed treatment (6%), reduced relative dose-intensity (RDI) (no patient with RDI<80%), toxic death (0%), and red blood cell transfusion (13%). CONCLUSIONS: AMA appears to improve R-CHOP therapy management. However, comparative studies are needed to demonstrate the advantage of the AMA over standard management, in terms of therapeutic compliance, progression-free survival, and medico-economics efficacy.