Phenylketonuria (PKU) is an inborn error of metabolism. When diagnosed late, it causes developmental delay or severe irreversible intellectual disability. This study aimed at evaluating the health ...status and healthcare consumption of late-diagnosed PKU patients in France.
This retrospective observational study used health insurance claims data from the French SNDS (Système National des Données de Santé) database, which contains data from over 66 million French inhabitants. Patients with PKU were identified between 2006 and 2018 by ICD-10 diagnosis codes E70.0 / E70.1 documented as a chronic condition (affection de longue durée – ALD) or in the inpatient setting. Patients with PKU were matched to controls by age, sex, and region. Patients with late-diagnosed PKU were defined as patients born before the nationwide implementation of newborn screening in France in 1972. Outcomes were analyzed for the year 2018.
In total, 3549 patients with PKU were identified in the database on January 1st, 2018. Of those, 3469 patients could be matched to 17,170 controls without PKU. Of these, 2175 patients were at least 16 years old of whom 647 patients were categorized as late-diagnosed. The late-diagnosed PKU patients suffered significantly more often from hypertension (60.9% vs. 50.4%, p < 0.0001), hypercholesterolemia (41.7% vs. 26.9%, p < 0.0001), diabetes (24.4% vs. 14.1%, p < 0.0001), depression (20.6% vs. 13.8%, p < 0.0001), ischemic heart disease (16.1% vs. 6.6%, p < 0.0001), obesity (7.9% vs. 2.5%, inpatient diagnoses only, p < 0.0001), and chronic kidney disease (5.2% vs. 1.3%, inpatient diagnoses only, p < 0.0001) compared with their non-PKU controls. Consequently, significantly more patients with late-diagnosed PKU received medication to treat comorbidities associated with the nervous (82.6% vs 77.0%; p = 0.0021) and cardiovascular system (69.5% vs 58.0%; p < 0.0001). Overall, only 3.4% of patients with late-diagnosed PKU received dietary amino-acid supplements and 0.7% received sapropterin.
The results indicate that PKU is associated with a significantly higher risk of comorbidities along with increased pharmaceutical prescriptions in patients with late-diagnosed PKU, compared with non-PKU controls. The increased risk of comorbidities was more pronounced than in patients with early-diagnosed PKU, as shown in previous research, but these patients are older than those with early-diagnosed PKU. Only few late-diagnosed patients were treated specifically for PKU. Patients with late-diagnosed PKU should be referred to specialized centers to prevent and manage comordities and introduce PKU-specific treatment when it is possible.
•Analysis of clinical impact of late-diagnosed PKU in adults in French SNDS database•Comorbidity burden was higher with late-diagnosed PKU compared to non-PKU controls•Rates of age-related comorbidities as well as depression and obesity were increased•Only few late-diagnosed PKU patients received PKU-specific medication•PKU-specific treatment, prevention and management of comorbidities are needed
Data on health care consumption and costs of asthma in the French population are scarce.
The study objective was to describe the burden of asthma according to GINA treatment steps in the CONSTANCES ...cohort.
Data from 162,725 participants included between 2012 and 2019 were extracted. Participants were considered as current asthmatics if asthma was reported at inclusion and asthma symptoms and/or treatments were reported in 2019. Participants were classified in three categories according to GINA treatment steps. The results were compared to non-asthmatic participants matched with a propensity score calculated on age, sex, region of residence, precariousness score and year of inclusion.
Among 162,725 participants aged 18–69 years, 6783 asthmatics (1566 not treated for asthma, 2444 + 251 GINA steps 1 + 2, 1054 + 1315 GINA steps 3 + 4, and 153 GINA step 5) were matched with 6783 controls. Average annual ambulatory cost and average annual hospitalization cost were respectively €1925 and €719 for asthmatics versus €1376 and €511 for participants without asthma (p < 0,0001). Cardiovascular risk factors, co-morbidities, visits and hospitalizations were higher for asthma participants as compared to controls and increased with GINA steps, as well as inpatient and outpatient costs. However, for cardiovascular risk factors and co-morbidities, differences were non-significant in multivariate analyses. Pharmacy costs were ten times higher for GINA step 5 participants than for GINA steps 1–2 participants: €3187 versus €393 (p < 0,0001).
mean cost of asthma was estimated at €757 per patient/year and increased with GINA treatment step.
•Data on the economic burden of asthma in France are rare and old.•An actual and precise estimate of the cost of asthma in France and its burden in terms of symptoms and comorbidities.•We provide estimations of the impact of clinical care and health programs on costs, which can inform decision-makers.
As people living with HIV (PLHIV) age, the burden of non-HIV related comorbidities increases resulting in additional healthcare costs. The present study aimed to describe the profile, the prevalence ...and the incremental costs of non-HIV related comorbidities in PLHIV compared to non-HIV matched controls (1:2 ratio) in France.
The French permanent sample of health beneficiaries (Echantillon généraliste de bénéficiaires EGB), a claims database representative of the national population, was used to assess comorbidities in PLHIV which were identified by the ICD-10 diagnosis codes of hospitalization, full healthcare coverage, and drug reimbursements between 2011 and 2014. The control group was matched by year of birth, gender, region of residence, and economic status. Total costs of outpatient care and hospitalizations were analysed from a societal perspective. A general linear model was used to assess the incremental cost per patient in PLHIV.
A total of 1,091 PLHIV and 2,181 matched controls were identified with a mean ± standard deviation age of 46.7 ± 11.5 years. The prevalence of alcohol abuse (5.8% vs 3.1%; p<0.001), chronic renal disease (1.2% vs 0.3%; p = 0.003), cardiovascular disease (7.4% vs 5.1%; p = 0.009), dyslipidaemia (22% vs 15.9%; p<0.001), hepatitis B (3.8% vs 0.1%; p<0.001) and hepatitis C (12.5% vs 0.6%; p<0.001) was significantly higher in PLHIV compared with non-HIV controls. Other comorbidities such as anaemia, malnutrition, psychiatric diseases, and neoplasms were also more prevalent in PLHIV. Hospitalizations were significantly increased in PLHIV compared to controls (33.2% vs 16%; p<0.001). Mean total cost was 6 times higher for PLHIV compared to controls and 4 times higher after excluding antiretroviral drugs (9,952€ vs. 2,593€; p<0.001). Higher costs per person in PLHIV were significantly associated to aging (42€ per patient/year), chronic cardiovascular disease (3,003€), hepatitis C (6,705€), metastatic carcinoma (6,880€) and moderate or severe liver disease (6,299€).
Our results demonstrated an increase in non-HIV related comorbidities among PLHIV compared to matched controls. This study contributes to raise awareness on the burden of chronic comorbidities.
Human immunodeficiency virus (HIV) remains a significant cause of morbidity and mortality worldwide. The aim of this study was to describe the mortality rate and associated comorbidities in a ...nationwide population-based cohort of persons living with HIV (PLWHIV) and to compare it with mortality in an age and gender-matched cohort of non-HIV individuals in France.
Using data from the French national health data system, we identified and included 173 712 PLWHIV (66.5% men) and 173 712 non-HIV participants (66.5% men) matched for age and gender. PLHIV were identified based on ICD-10 HIV diagnoses, HIV-specific laboratory tests, and/or prescriptions for antiretroviral therapy specific to HIV. Hazard ratios (HRs) of mortality were assessed using multiple Cox regression models.
During the 13 years of follow-up (2006-18), we observed 20 018 deaths among PLWHIV compared with 6262 deaths among non-HIV participants (11.52% vs. 3.60%, P < 0.001). The over-mortality of PLWHIV was expressed by univariable HR = 2.135 (2.072-2.199), which remained significant after adjustment for region, Complementary Universal Health Insurance and AME, with multivariable HR = 2.182 (2.118-2.248). The results remained significant after adjusting for comorbidities, including infectious diseases HR = 1.587 (1.538-1.638). Notably, PLWHIV were more importantly associated with mortality in women HR = 2.966 (2.767-3.180), compared in men HR = 1.961 (1.898-2.027).
Although the life expectancy of PLWHIV has globally increased, the causes of death should be prioritized in prevention policies and care management. Gender-specific policies should be highlighted, as we observed a higher impact of HIV mortality in women.
Little is known about the characteristics and prognosis of patients with peripheral arterial disease (PAD) and related real-life health costs in France.
A cohort of patients diagnosed with PAD ...between 2007 and 2011 was extracted from the French Echantillon Généraliste des Bénéficiaires (EGB) claims database. The patients were followed up from the date of PAD diagnosis. Their characteristics, incidence of death and other events, treatments, and costs were analyzed by comparison with age- and gender-matched PAD-free controls.
There were 5889 patients with PAD identified. Mean age was 70.8 years, and 68.1% of patients were male. Diabetes was present in 28.9% of patients (13.2% of controls), hypercholesterolemia in 52.9% (28.7%), and hypertension in 46.6% (12.3%); 4.9% of patients had a history of unstable angina or myocardial infarction (0.5%), and 6.0% had a history of stroke or transient ischemic attack (1.4%). At inclusion, 69.3% of patients were receiving antiplatelet drugs (17.3%), 52.3% statins (21.9%), 26.7% angiotensin-converting enzyme inhibitors (13.7%), and 24.2% angiotensin receptor blockers (16.6%). Cumulative mortality rates were 13.2% at 1 year and 19.4% at 2 years (3.2% and 6.5% in controls). Cumulative incidence rates of death and major cardiovascular events (myocardial infarction and ischemic stroke) were 15.7% (95% confidence interval CI, 14.8%-16.6%) at 1 year and 22.9% (95% CI, 21.9%-24.0%) at 2 years vs 3.9% (95% CI, 3.4%-4.4%) and 7.8% (95% CI, 7.1%-8.5%) in controls. All differences were statistically significant (P < .05). Total annual management costs were €14,949 in the PAD group and €3812 in the control group.
Mortality is elevated and cardiovascular events are frequent among French PAD patients. PAD drug treatment guidelines are not fully implemented in France.
Objectives
Invasive meningococcal disease (IMD) is an uncommon disease known for its acute phase mortality and long-term sequelae. The objective was to assess the impact of IMD on post-discharge ...mortality risk and dependence on the French state for financial aid.
Methods
A 6-year retrospective analysis in the national insurance database (SNIIRAM) assessed mortality in IMD cases (both during acute phase and post-discharge) and matched controls as well as benefit claims (i.e., for salary loss compensation SLC, long-term sickness ALD and complementary health insurance CMUc). Observed survival data were extrapolated to estimate lifetime life expectancy following IMD.
Results
Between 2012 and 2017, 3532 incident IMD cases were hospitalised in France (peak in < 2 years and 15–24 year olds), of which 23.3% developed sequelae. With an average follow-up of 2.8 years, 12.9% of cases vs. 3.2% of controls died (
p
< 0.0001), with significantly more cases than controls dying both during the acute phase and post-discharge. Around a third of these deaths occurred post-discharge. Extrapolation to lifetime life expectancy estimated that having IMD at any age significantly reduces life expectancy in survivors of the acute disease phase, e.g., by around 16 years for cases aged 0–50 years. IMD cases in France were significantly more likely to receive state-funded SLC (relative risk RR 3.9, 95% confidence interval 95% CI 2.3–6.4) and ALD benefits (RR 1.85, 95% CI 1.71–2.00).
Conclusions
IMD has a significant impact on mortality post-discharge, expected to persist over a lifetime. In addition to long-term sequelae, the financial burden extends beyond the healthcare sector. These results highlight the importance of IMD prevention (e.g., vaccination).
Plain Language Summary
Invasive meningococcal disease (IMD) is an uncommon disease mainly affecting children, with severe consequences such as a risk of dying within hours of symptoms and a risk of developing long-term conditions affecting health, learning and ability to work. Little is known of the risk of dying in survivors after discharge from hospital or of survivors’ financial support needs. The French national insurance claims database (SNIIRAM) was reviewed for data on IMD patients hospitalised between 2012 and 2017 and matched controls without IMD. Data, available following IMD hospitalisation for an average of around 3 years, were extrapolated to estimate the lifelong impact of the disease. Among 3532 hospitalised IMD cases, the study found that nearly 13% died, of which a third of deaths occurred post-discharge. The cases who survived the acute disease phase were also more likely to require government funds because of loss of salary or to cover long-term healthcare costs. In addition to the well-known acute phase burden of IMD, this study has shown that there is a long-term effect on risk of dying and on need for government support. This demonstrates the importance of prevention, for example, by vaccination.
Abstract Background Mortality and complications of acute myocardial infarction (AMI) in France have declined over the last twenty years, but still remain high. Practice guidelines recommend secondary ...prevention measures to reduce these. Insurance claims databases can be used to assess the management of post MI and other cardiovascular outcomes in everyday practice. Methods A cohort study was performed in a 1/97 representative sample of the French nationwide claims and hospitalisation database (EGB database). All adults with a documented hospitalisation for MI between 2007 and 2011 were included, and followed for three years. Data was extracted on demographics, the index admission, reimbursed medication, comorbidities, post-MI events and death. Results During the study period, 1977 individuals hospitalised for an MI were identified, with a mean (± SD) age of 63.8 (± 14.3) years, 65.8% were men, 82.4% had hypertension and 37.6% hypercholesterolaemia. The mean duration of hospitalisation was seven days and 8.3% of patients died during hospitalisation. After discharge, the majority of patients received secondary prevention with statins (92.2%), anti-platelet drugs (95.6%), beta-blockers (86.0%) and angiotensin converting enzyme inhibitors (71.4%). After three years of follow-up post-discharge, cumulative mortality was 20.5% 18.4%;22.5% and the cumulative incidence of reinfarction and stroke/TIA were 4.7% 95% CI: 3.7%;5.7% and 4.1% 3.1%;5.0%, respectively. Conclusions Despite high use of secondary prevention at discharge, mortality and incidence of serious cardiovascular events following MI remain high. This underscores the need to improve secondary prevention.
We aimed to assess the effectiveness and cost of patients with first line tyrosine kinase inhibitors (TKIs) sequence of first (1G) and second generation (2G) followed by osimertinib.
Using the French ...nationwide claims and hospitalization database, we analyzed non-small-cell lung cancer patients who had been treated with osimertinib between April 2015 and December 2017, after a first line treatment with a TKI-1G/2G.
The median time on treatment for sequential TKI-1G/2G followed by osimertinib was 34 months (95% CI: 31-46); 13 and 12months, respectively for TKI 1G or 2G and TKI 3G, respectively. The median overall survival for sequential TKI 1G or 2G followed by osimertinib was 37 months (95% CI: 34-42). The mean monthly costs per patient was €5162.
These results, in line with those observed during clinical trials, confirm the effectiveness of the sequence TKI-1G/2G followed by osimertinib in
-mutated non-small-cell lung cancer.
The objective of this analysis is to perform an indirect comparison of elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by ...using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).
An indirect comparison was performed by using a generalization of Bucher's methodology to calculate risk differences. Two phase III clinical trials (GS-US-236-0102 and SINGLE-described above) were used.
Results of the indirect comparison showed no statistically significant risk difference of the efficacy endpoint of achieving HIV RNA < 50 copies/mL between E/C/F/TDF and ABC/3TC + DTG for the ITT population at weeks 48, 96 and 144: respectively -3.7% (CI95% = -10.8%; 3.4%), -5.2% (CI95% = -13.2%; 2.8%) and -3.1% (CI95% = -12.0%; 5.7%). There was no statistically significant differences in the risk difference for serious adverse events (5.7% (CI95% = -2.2%; 12.3%)), drug related adverse event (2.7% (CI95% = -7.0%;12.4%)), drug related serious adverse event (0.8% (CI95% = -1.6%;3.2%)) and death (0.5% (CI95% = -0.8%;1.8%)), respectively, between E/C/F/TDF and ABC/3TC + DTG. A significant difference was found for discontinuation due to adverse events with a higher rate for E/C/F/TDF (difference = 8.6% (CI95% = 3.3%; 13.9%)). There was also no statistically significant risk difference of the viral resistance of 1.2% (CI95% = -1.2; 3.7) between E/C/F/TDF and ABC/3TC + DTG at week 48, 1.7% at week 96 (CI95% = -1.1; 4.5) and 2.2% (CI95% = -1.0; 5.4) at week 144.
Considerable variations in diagnosis and therapeutic practices are reported for hyperthyroidism (HT) between countries.
A clinical study was conducted among a representative sample of 263 ...endocrinologists in France. All consecutive patients seen for HT during the study period were included. Diagnosis and treatment modalities were recorded from hyperthyroid patients with Graves disease (GD,
= 802), multinodular goiter (MNG,
= 121), and toxic adenoma (TA,
= 69).
Antithyroid antibodies were measured in half of the population (anti-TPO in 48.5% and anti-TSH receptor in 57.8%). Patients had thyroid ultrasonography and scintigraphy in 93.8 and 40.3%, respectively. Therapeutic management depended on the etiology: for the first episode of GD, antithyroid drugs (ATDs) were the first-line treatment in 91% of the patients, combined with surgery in 6.1% and with radioiodine in 2.9%. Surgery was preferred to radioiodine in MNG (52.6 vs. 22.4%) and TA (59.1 vs. 24.2%). Euthyroid status was achieved after 3 months in 64.4% of GD. A "block and replace" protocol was used in 41.2% of patients. After 3 months, 73% of patients were euthyroid in the "block and replace" group compared to 56.2% in the group with ATDs alone (
= 0.009). For MNG and TA, more than 75% of patients were euthyroid at the 3-month follow-up.
Large discrepancies remain between clinical practice and international guidelines. These results should boost efforts to improve adherence to these guidelines.
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