Cost-utility of 20-valent pneumococcal conjugate vaccine compared to no vaccination and recommended alternative vaccines among Belgian adults.

BACKGROUND: The Belgian Superior Health Council (SHC) preferentially recommended the 20-valent pneumococcal conjugate vaccine (PCV20) for adults aged ≥65 years, immunocompromised patients, and patients aged ≥50 years suffering from conditions that increase their risk for pneumococcal infections. The objective of this paper is to present the cost-utility of PCV20 compared to no vaccination and the alternative sequence of PCV15 followed by the 23-valent pneumococcal polysaccharide vaccine (PPV23) in this population. RESEARCH DESIGN AND METHODS: The analysis employed a static Markov model capturing lifetime risk of pneumococcal infections, associated disutility, mortality, and costs from different healthcare payer perspectives. RESULTS: Results indicated use of PCV20 among Belgian older and at-risk adults is highly cost-effective compared to no vaccination, with an incremental cost per quality-adjusted life-year (QALY) of €4,164. Compared to the sequential regimen (PCV15+PPV23), PCV20 vaccination is a cost-saving strategy. Subgroup analysis indicated PCV20 vaccination of at-risk adults aged 65-84 years would also be cost-saving from the national healthcare perspective. CONCLUSION: Based on current knowledge, this analysis suggests that access to PCV20 should be proposed in all adults recommended for vaccination by the SHC as PCV20 prevents additional hospitalizations and deaths caused by pneumococcal infection at an affordable cost.

Pneumococcal infections cause a high burden on infected patients and society. Vaccination of patients at risk of severe infection has been recommended for decades, but uptake of pneumococcal vaccines in adults has historically been low in Belgium, where patients have borne the vaccine costs and the recommended vaccination schedule required the sequential administration of two vaccines. A single PCV20 dose is recommended as the preferred vaccine for adults at risk due to age or other factors in Belgium as it is expected to provide lasting protection against more types of disease-causing pneumococcal bacteria as well as being simpler to administer than alternatives requiring multiple injections. Uptake is expected to improve with the recent reimbursement of the new PCV20 vaccine, though reimbursement covers only a portion of the recommended population. This paper presents a detailed analysis of the PCV20 cost-effectiveness in all adults at increased risk of severe pneumococcal disease, including immunocompromised adults younger than 65 years. Our analysis captures and compares the lifetime risk of pneumococcal disease and associated healthcare costs in an unvaccinated cohort, a cohort vaccinated with the alternative recommendation of PCV15 and PPV23 vaccines and a cohort vaccinated with PCV20. This cost-effectiveness analysis indicates that use of PCV20 will help decrease the number of pneumococcal disease cases, hospitalizations, and premature deaths at an affordable healthcare cost: PCV20 is a cost-effective option compared to no vaccination and a cost-saving option compared to the sequential regimen PCV15 followed by PPV23 in the Belgian adult population recommended for pneumococcal vaccination.

Validation of a Novel Forecasting Method for Estimating the Impact of Switching Pneumococcal Conjugate Programs: Evidence from Belgium.

INTRODUCTION: Since 2010, 10-valent (PCV10) and 13-valent pneumococcal conjugate vaccines (PCV13) have been available as part of infant national immunization programs. Belgium is as one of the few countries that implemented PCV13 (2007-2015), switched to PCV10 (2015-2018) and then switched back to PCV13 (2018-present) after observing increases in disease. We assessed the impacts of both historical and prospective PCV choice in the context of the Belgian health care system and used this experience to validate previously developed economic models. METHODS: Using historical incidence (2007-2018) of pneumococcal disease for Belgian children aged < 16 years, observed invasive pneumococcal disease (IPD) trends from surveillance data were used to estimate future disease in a given PCV13- or PCV10-based program. We compared observed incidence data with two modeled scenarios: (1) the 2015 switch to PCV10 and (2) a hypothetical continuation of PCV13 in 2015. Finally, we explored the potential impact of PCV choice from 2019 to 2023 by comparing three scenarios: (3) continued use of PCV10; (4) a switch back to PCV13; (5) a hypothetical scenario in which Belgium never switched from PCV13. RESULTS: Model predictions underestimated observed data from 2015 to 2018 by 100 IPD cases among ages < 16 years. Comparing observed data with scenario 2 suggests that PCV13 would have prevented 105 IPD cases from 2015 to 2018 compared with PCV10. Switching to PCV13 in 2019 would avert 625 IPD cases through 2023 compared with continuing PCV10. Scenario never switching from PCV13 would have resulted in a reduction of 204 cases from 2016 to 2023 compared with switching to PCV10 and switching back to PCV13. CONCLUSION: The findings from this study suggest that previously published modeling results of PCV13 versus PCV10 in other countries may have underestimated the benefit of PCV13. These results highlight the importance of continually protecting against vaccine-preventable pneumococcal serotypes.

Cost-effectiveness of PCV13 vaccination in Belgian adults aged 65-84 years at elevated risk of pneumococcal infection.

BACKGROUND: The Belgian Superior Health Council (SHC) recently added a 13-valent pneumococcal conjugate vaccine (PCV13) to its recommendations for adult pneumococcal vaccination. This study addresses the policy question regarding whether a single dose of PCV13 should be reimbursed among Belgian adults aged 65-84 years with chronic comorbidities ("moderate-risk") or immunosuppression ("high-risk"). METHODS: A cohort model was developed to project lifetime risks, consequences, and costs of invasive pneumococcal disease (IPD) and pneumococcal community-acquired pneumonia (CAP). Parameter values were estimated using published literature and available databases, and were reviewed by Belgian experts. PCV13 effectiveness was assumed to be durable during the first 5 years following receipt, and to progressively decline thereafter with 15 years protection. The Belgian National Health Insurance perspective was employed. RESULTS: Use of PCV13 (vs. no vaccine) in moderate/high-risk persons aged 65-84 years (n = 861,467; 58% vaccination coverage) would be expected to prevent 527 cases of IPD, 1,744 cases of pneumococcal CAP and 176 pneumococcal-related deaths, and reduce medical care costs by €20.1 million. Vaccination costs, however, would increase by €36.9 million and thus total overall costs would increase by €16.8 million. Cost per QALY gained was €17,126. In probabilistic sensitivity analyses, use of PCV13 was cost-effective in 97% of 1,000 simulations. CONCLUSIONS: Reimbursement of PCV13 in moderate/high-risk Belgian adults aged 65-84 years would be cost-effective from the Belgian healthcare perspective.

Correction: Capture-Recapture Estimators in Epidemiology with Applications to Pertussis and Pneumococcal Invasive Disease Surveillance.

[This corrects the article DOI: 10.1371/journal.pone.0159832.].

Capture-Recapture Estimators in Epidemiology with Applications to Pertussis and Pneumococcal Invasive Disease Surveillance.

INTRODUCTION: Surveillance networks are often not exhaustive nor completely complementary. In such situations, capture-recapture methods can be used for incidence estimation. The choice of estimator and their robustness with respect to the homogeneity and independence assumptions are however not well documented. METHODS: We investigated the performance of five different capture-recapture estimators in a simulation study. Eight different scenarios were used to detect and combine case-information. The scenarios increasingly violated assumptions of independence of samples and homogeneity of detection probabilities. Belgian datasets on invasive pneumococcal disease (IPD) and pertussis provided motivating examples. RESULTS: No estimator was unbiased in all scenarios. Performance of the parametric estimators depended on how much of the dependency and heterogeneity were correctly modelled. Model building was limited by parameter estimability, availability of additional information (e.g. covariates) and the possibilities inherent to the method. In the most complex scenario, methods that allowed for detection probabilities conditional on previous detections estimated the total population size within a 20-30% error-range. Parametric estimators remained stable if individual data sources lost up to 50% of their data. The investigated non-parametric methods were more susceptible to data loss and their performance was linked to the dependence between samples; overestimating in scenarios with little dependence, underestimating in others. Issues with parameter estimability made it impossible to model all suggested relations between samples for the IPD and pertussis datasets. For IPD, the estimates for the Belgian incidence for cases aged 50 years and older ranged from 44 to58/100,000 in 2010. The estimates for pertussis (all ages, Belgium, 2014) ranged from 24.2 to30.8/100,000. CONCLUSION: We encourage the use of capture-recapture methods, but epidemiologists should preferably include datasets for which the underlying dependency structure is not too complex, a priori investigate this structure, compensate for it within the model and interpret the results with the remaining unmodelled heterogeneity in mind.

Pneumococcal lower respiratory tract infections in adults: an observational case-control study in primary care in Belgium.

BACKGROUND: Serious lower respiratory tract infections (SLRTIs), especially Streptococcus pneumoniae (SP)-related pneumonia cause considerable morbidity and mortality. Chest imaging, sputum and blood culture are not routinely obtained by general practitioners (GPs). Antibiotic therapy is usually started empirically. The BinaxNOW® and Urine Antigen Detection (UAD) assays have been developed respectively to detect a common antigen from all pneumococcal strains and the 13 pneumococcal serotypes present in the vaccine Prevenar 13® (PCV13). METHODS: OPUS-B was a multicentre, prospective, case-control, observational study of patients with SLRTI in primary care in Belgium, conducted during two winter seasons (2011-2013). A urine sample was collected at baseline for the urine assays. GPs were blinded to the results. All patients with a positive BinaxNOW® test and twice as much randomly selected BinaxNOW® negative patients were followed up. Recorded data included: socio-demographics, medical history, vaccination history, clinical symptoms, CRB-65 score, treatments, hospitalization, blood cultures, healthcare use, EQ-5D score. The objectives were to evaluate the percentage of SP SLRTI within the total number of SLRTIs, to assess the percentage of SP serotypes and to compare the burden of disease between pneumococcal and non-pneumococcal SLRTIs. RESULTS: There were 26 patients with a BinaxNOW® positive test and 518 patients with a BinaxNOW® negative test. The proportion of pneumococcal SLRTI was 4.8 % (95 % CI: 3.1 %-7.2 %). Sixty-eight percent of positive cases showed serotypes represented in PCV13. In the BinaxNOW-positive patients, women were more numerous, there was less exposure to young children, seasonal influenza vaccination was less frequent, COPD was more frequent, the body temperature and the number of breaths per minute were higher, the systolic blood pressure was lower, the frequency of sputum, infiltrate, chest pain, muscle ache, confusion/disorientation, diarrhoea, pneumonia and exacerbations of COPD was more frequent, EQ-5D index and VAS scale were lower, the number of visits to the GP, of working days lost and of days patients needed assistance were higher. CONCLUSIONS: SP was responsible for approximately 5 % of SLRTIs observed in primary care in Belgium. Pneumococcal infection was associated with a significant increase in morbidity. Sixty-eight percent of serotypes causing SLRTI were potentially preventable by PCV13.

Prevalence and clinical characteristics of remission during treatment in generalized anxiety.

OBJECTIVE: Although the remission criteria for generalized anxiety are well defined, there is not much data available on the point prevalence of remission. The Measuring Impact of Remission in Anxiety Disorders in Belgium (MIRABEL) study is a naturalistic study designed to document the point prevalence of remission in patients treated for general anxiety and potential factors affecting this prevalence. METHODS: The study population consisted of 618 adult outpatients being treated for generalized anxiety. The sample is defined by the key symptoms of generalized anxiety disorder rather than by fulfilling the exact DSM-IV-TR diagnostic criteria. Remission was defined as a Hamilton Anxiety Scale (HAM-A) score of less than or equal to 7. To reduce the interrater reliability, the HAM-A was assessed by the attending physicians who had no specific training. Factors investigated as possibly related to remission included sociodemographic, disease and treatment characteristics. RESULTS: The point prevalence of remission in the study population was estimated at 13.3%. Remission prevalence varied with occupational status and severity of the current anxiety episode. Remission prevalence was lower in the presence of comorbidity and was proportional to the number of comorbid symptoms. Remitters took fewer medications but were treated longer. Remission prevalence was higher in patients who were taking antidepressants, but was lower in patients who were taking sedatives. CONCLUSIONS: These findings underline the poor prognosis of generalized anxiety.

Objective: remission of depression in primary care The Oreon Study.

OBJECTIVE: Treatment of depression should result in the absence of symptoms, i.e. remission, in order to restore the functional status of the patient and reduce the risk for relapse. The study assessed the current remission rates in primary care and determined the influencing factors. METHODS: 10 consecutive depressive patients treated by antidepressants for at least 3 months and not more than 12 months were screened by each investigator. Remission rates were defined using the Hamilton-Depression scale 7 items (score of 3 or less) as well as the Carroll self rating scale (score of 7 or less). In addition, patients completed the Sheehan Disability Scale (SDS). Initial severity of depression, type of treatment and socio-economic factors were collected. RESULTS: 292 general practitioners screened a total of 2630 patients. Results indicated low remission rates: 28.3% according to the clinician and 17.1% according to the patient. Absence of remission was associated with higher impairment in work, social and family life. The most frequently reported residual symptoms in nonremitters were general somatic symptoms (92%), depressed mood (92%), psychic anxiety (91%) and impaired work and activities (89%). No differences were observed in remission rates between men and women. Remission rates were significantly lower in patients living alone as compared to those living in couple or family (25.1% vs 30.2%, p=0.03), in patients with lower education (21.3% vs 32.3%, p<0.001), in patients speaking French as compared to Dutch (24.0% vs 34.0% p<0.001), and unemployed patients compared to patients having an occupation (17.1% vs 39.0%, p<0.001). Higher initial severity and number of previous episodes decreased remission rates (p<0.001). CONCLUSION: This study shows low remission rates in depressed patients treated in general practice. The absence of remission is associated with impairment in work, social and family life. Special attention should be given to identify patients who do not reach remission.

Socioeconomic correlates of generalized anxiety disorder and major depression in primary care: the GADIS II study (Generalized Anxiety and Depression Impact Survey II).

A previous Generalized Anxiety Disorder Impact Survey (GADIS I) performed on 15,399 Belgian patients consulting their primary care physicians, revealed high prevalences of generalized anxiety disorder (GAD) and major depression (MD) with important regional differences. The objective of this study (GADIS II) was to replicate previous findings and to evaluate the role of socioeconomic factors in the diagnoses of GAD and MD. A large-scale cross-sectional survey was conducted in a random sample of 377 general practitioners distributed geographically over Belgium and Luxemburg. Each physician was asked to screen 40 consecutive patients at predefined time periods for the presence of GAD and MD using sections of the Mini International Neuropsychiatric Interview (MINI). Socioeconomic parameters were collected. The level of impairment was assessed using the Sheehan Disability Scale. In a sample of 13,699 patients, point prevalences of GAD and of MD were found to be 13.4 and 11.0%, respectively. Overall, 17.8% of the population was positive for GAD and/or MD. Both disorders were significantly more frequent in women than in men. Marked regional differences were observed with prevalences for GAD and/or MD of 24.2% in Brussels, 22.7% in Wallonia, 13.6% in Luxemburg and 12.9% in Flanders. Several socioeconomic factors were significantly associated with positive diagnoses: living alone, a low level of education and unemployment. However, regional differences remained significant even after controlling for socioeconomic factors. The study confirms the high prevalence of GAD and MD in primary care and the role of several socioeconomic and regional factors in the illnesses.

Prevalence and impact of generalized anxiety disorder and major depression in primary care in Belgium and Luxemburg: the GADIS study.

PURPOSE: GADIS aims at determining the prevalence of generalized anxiety disorder (GAD) and major depression (MD) in primary care and their impact on the patient's functioning in Belgium and Luxemburg. METHOD: A large scale screening program was conducted at the consultation of general practitioners to detect patients with GAD and MD according to DSM-IV criteria. We collected additional data regarding the use of hypnotic, tranquilizer, antidepressant and analgesic medications. Impact on the patient was assessed with the Sheehan disability scale. RESULTS: Three hundred GP's in Belgium and Luxemburg were asked to screen 50 consecutive patients. Of the 13,677 analyzed patients, 8.3% were diagnosed to have GAD and 6.3% MD. Comorbidity was observed in 4.2% of patients. The prevalence was much higher in the French-speaking part of Belgium. GAD and MD were associated with impairment in social, familial and professional functioning. Only a minority of patients with GAD and/or MD was treated with an antidepressant and almost half of subjects with GAD and/or MD were treated with a tranquilizer. CONCLUSION: Prevalence rates of GAD and MD in primary care in Belgium are comparable to other countries. GAD and MD are disabling conditions. Antidepressants are still used only in a minority of subjects with GAD and/or MD in primary care in Belgium and Luxemburg. The prevalence of GAD and MD appears to be much higher in French-speaking parts of Belgium.

Venlafaxine compared with fluoxetine in outpatients with depression and concomitant anxiety.

The aim of this double-blind study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of patients with depression and anxiety. A total of 146 moderately depressed patients with associated anxiety were randomized to receive 75 mg/d venlafaxine or 20 mg/d fluoxetine for 12 wk. Dose increases were permitted after 2 wk of treatment, to 150 mg/d venlafaxine and 40 mg/d fluoxetine, to optimize response. At the final visit, a statistically significantly greater efficacy of venlafaxine over fluoxetine was observed on depressive symptoms and concomitant anxiety, and 75.0 and 50.7% of patients administered venlafaxine and fluoxetine, respectively, showed an overall response. A sustained response (for at least 2 wk), present at the end of the study was achieved in 57.8 and 43.3% of patients in the venlafaxine and fluoxetine groups, respectively, and at the final visit, 59.4 and 40.3% of patients, respectively, were in remission (virtually asymptomatic). Dose increases were required by a greater percentage of patients in the fluoxetine group (52.9%), than in the venlafaxine group (37.1%), and in those patients whose dose was increased, a higher efficacy was again observed with venlafaxine. Venlafaxine and fluoxetine were well tolerated, with the most frequently experienced adverse events being nausea and headache. Fewer patients in the venlafaxine group than in the fluoxetine group reported at least one adverse event (55.7 and 67.1% patients, respectively). Venlafaxine therefore proved to be significantly more effective than fluoxetine in improving depressive symptoms and concomitant anxiety.