Objective
To investigate a new therapeutic strategy, with rapid corticosteroid dose tapering and limited cyclophosphamide (CYC) exposure, for older patients with systemic necrotizing vasculitides ...(SNVs; polyarteritis nodosa PAN, granulomatosis with polyangiitis Wegnener's GPA, microscopic polyangiitis MPA, or eosinophilic GPA Churg‐Strauss EGPA).
Methods
A multicenter, open‐label, randomized controlled trial comprising patients ≥65 years old and newly diagnosed as having SNV was conducted. The experimental treatment consisted of corticosteroids for ∼9 months and a maximum of six 500‐mg fixed‐dose intravenous (IV) CYC pulses, every 2–3 weeks, then maintenance azathioprine or methotrexate. The control treatment included ∼26 months of corticosteroids for all patients, combined with 500 mg/m2 IV CYC pulses, every 2–3 weeks until remission, then maintenance for all patients with GPA or MPA and for those with EGPA or PAN with a Five‐Factors Score (FFS) of ≥1. Randomization used a 1:1 ratio computer‐generated list and was performed centrally with sealed opaque envelopes. The primary outcome measure was ≥1 serious adverse event (SAE) occurring within 3 years of followup. Secondary outcome measures included remission and relapse rates.
Results
Among the 108 patients randomized, 4 were excluded (early consent withdrawal or protocol violation). Mean ± SD age at diagnosis was 75.2 ± 6.3 years. Analysis at 3 years included 53 patients (21 GPA, 21 MPA, 8 EGPA, and 3 PAN) in the experimental arm and 51 patients (15 GPA, 23 MPA, 6 EGPA, and 7 PAN) in the conventional arm. In total, 32 (60%) versus 40 (78%) had ≥1 SAE (P = 0.04), most frequently infections; 6 (11%) versus 7 (14%) failed to achieve remission (P = 0.71); 9 (17%) versus 12 (24%) died (P = 0.41); and 20 (44%) of 45 versus 12 (29%) of 41 survivors in remission experienced a relapse (P = 0.15).
Conclusion
For older SNV patients, an induction regimen limiting corticosteroid exposure and with fixed low‐dose IV CYC pulses reduces SAEs in comparison to conventional therapy, and does not affect the remission rate. Three‐year relapse rates remain high for both arms.
Elderly people are at high risk for pneumococcal infections. However, older age is not an eligibility factor for pneumococcal vaccination in France. Adults with certain co-morbidities or ...immunocompromised states are eligible for vaccination, which leaves adults aged ≥65 years without comorbidities at-risk for pneumococcal infections. The objective of the study was to evaluate the acceptability to healthcare professionals (HCPs) of extending pneumococcal vaccination to all individuals ≥65 years. Based on themes identified in semi-structured interviews with 24 HCPs, a representative sample of 500 general practitioners and pharmacists were surveyed about their knowledge, attitudes and beliefs with respect to pneumococcal vaccination for individuals ≥65 years. Current recommendations for pneumococcal vaccination are poorly understood by participants (mean score: 5.8/10). Respondents were generally supportive of inclusion of age in vaccination recommendations (7.5/10), with 58% being very supportive. For 72% of HCPs, this would contribute to improved vaccination coverage. The strategy could be facilitated by associating pneumococcal vaccination with the influenza vaccination campaign (8.3/10). Pharmacists were favourable to participating in pneumococcal vaccination (8.5/10). In conclusion, extension of pneumococcal vaccination to all people aged ≥65 years would be welcomed by HCPs, simplifying identification of patients to be vaccinated and potentially improving vaccination coverage.
Cogan syndrome is mainly treated with steroids. We aimed to determine the place of DMARDs and biologic-targeted treatments.
We conducted a French nationwide retrospective study of patients with Cogan ...syndrome (n=40) and a literature review of cases (n=22) and analyzed the efficacy of disease-modifying anti-rheumatic drugs (DMARDs) and tumor necrosis factor α (TNF-α) antagonists.
We included 62 patients (31 females) (median age 37years range 2–76. At diagnosis, 61 patients (98%) had vestibulo-auditory symptoms, particularly bilateral hearing loss in 41% and deafness in 31%. Ocular signs were present in 57 patients (92%), with interstitial keratitis in 31 (51%). The first-line treatment consisted of steroids alone (n=43; 70%) or associated with other immunosuppressive drugs (n=18; 30%). Overall, 13/43 (30%) and 4/18 (22%) patients with steroids alone and with associated immunosuppressive drugs, respectively (p=0.8), showed vestibulo-auditory response; 32/39 (82%) and 15/19 (79%) ocular response; and 23/28 (82%) and 10/14 (71%) general response. Overall 61 patients had used a total of 126 lines of treatment, consisting of steroids alone (n=51 lines), steroids with DMARDs (n=65) and infliximab (n=10). Vestibulo-auditory response was significantly more frequent with infliximab than DMARDs or steroids alone (80% vs 39% and 35%, respectively), whereas ocular, systemic and acute-phase reactant response rates were similar. Infliximab was the only significant predictor of vestibulo-auditory improvement (odds ratio 20.7 95% confidence interval 1.65; 260, p=0.019).
Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome, but prospective studies are necessary.
•Vestibulo-auditory response was similar with DMARDs and steroids alone.•Infliximab could lead to vestibulo-auditory response in DMARDS and steroid-refractory Cogan syndrome.•The 5 and 10-years incidence of relapse increased under steroids and DMARDS, while it stayed stable with infliximab.
To evaluate the effect of adding a 10-week treatment of adalimumab to a standardised treatment with corticosteroids on the ability to taper more rapidly corticosteroid doses in patients with newly ...diagnosed giant cell arteritis (GCA).
Patients included in this double-blind, multicentre controlled trial were randomly assigned to receive a 10-week subcutaneous treatment of adalimumab 40 mg every other week or placebo in addition to a standard prednisone regimen (starting dose 0.7 mg/kg per day). The primary endpoint was the percentage of patients in remission on less than 0.1 mg/kg of prednisone at week 26. Analysis was performed by intention to treat (ITT).
Among the 70 patients enrolled (adalimumab, n=34; placebo, n=36), 10 patients did not receive the scheduled treatment, seven in the adalimumab and three in the placebo group. By ITT, the number of patients achieving the primary endpoint was 20 (58.9%) and 18 (50.0%) in the adalimumab and placebo arm, respectively (p=0.46). The decrease in prednisone dose and the proportion of patients who were relapse free did not differ between the two groups. Serious adverse events occurred in five (14.7%) patients on adalimumab and 17 (47.2%) on placebo, including serious infections in three patients on adalimumab and five on placebo. Two patients died in the placebo arm (septic shock and cancer) and one in the adalimumab group (pneumonia).
In patients with newly diagnosed GCA, adding a 10-week treatment of adalimumab to prednisone did not increase the number of patients in remission on less than 0.1 mg/kg of corticosteroids at 6 months.
NCT00305539.
Tuberculosis in the Elderly Caraux-Paz, Pauline; Diamantis, Sylvain; de Wazières, Benoit ...
Journal of clinical medicine,
12/2021, Letnik:
10, Številka:
24
Journal Article
Recenzirano
Odprti dostop
The tuberculosis (TB) epidemic is most prevalent in the elderly, and there is a progressive increase in the notification rate with age. Most cases of TB in the elderly are linked to the reactivation ...of lesions that have remained dormant. The awakening of these lesions is attributable to changes in the immune system related to senescence. The mortality rate from tuberculosis remains higher in elderly patients. Symptoms of active TB are nonspecific and less pronounced in the elderly. Diagnostic difficulties in the elderly are common in many diseases but it is important to use all possible techniques to make a microbiological diagnosis. Recognising frailty to prevent loss of independence is a major challenge in dealing with the therapeutic aspects of elderly patients. Several studies report contrasting data about poorer tolerance of TB drugs in this population. Adherence to antituberculosis treatment is a fundamental issue for the outcome of treatment. Decreased completeness of treatment was shown in older people as well as a higher risk of treatment failure.
Elderly people are at increased risk of influenza and pneumococcal diseases. Influenza increases clinical pneumococcal disease incidence. Pneumococcal vaccination could therefore be a supplement to ...influenza vaccination. This study evaluated all-cause mortality and antibiotic consumption according to elderly people's influenza and pneumococcal vaccination status. Its goal was to demonstrate that vaccination with both Influenza and pneumococcal vaccines decrease all-cause mortality and antibiotic consumption. From 2004-10-01 to 2004-12-31 (3 mo), elderly people (≥ 65 y) who lived in the Gard department (South of France) were offered both vaccinations. Among the 68,897 subjects followed-up one year after this vaccination campaign, 21,303 (30.9%) were vaccinated with both vaccines, 18,651 (27.1%) with influenza vaccine alone, 3,769 (5.5%) with pneumococcal vaccine alone; 25,174 (36.5%) subjects were unvaccinated. Mortality rate (per 1,000 inhabitants-year) adjusted on gender, age and prior underlying chronic disease was 17.9 (95% CI: 16.3-19.6), 20.8 (19.0-22.8), 22.5 (19.0-26.6) and 24.7 (22.7-26.8), respectively. It was 42.1 (38.8-45.8) in elderly people with underlying chronic disease who received both vaccines vs. 58.1 (53.7-62.9) in unvaccinated elderly people. The decrease in mortality rate was 27.0% (20.0-34.0) in subjects who received both vaccines and 16.0% (6.0-24.0) in those who received influenza vaccine. No significant reduction in mortality rate was seen with the pneumococcal vaccine alone. Influenza and/or pneumococcal vaccinations did not decrease antibiotic consumption that drastically increases during the winter period. An additive effect was observed in the prevention of all-cause mortality with influenza and pneumococcal vaccines given together in elderly people, including in those with underlying chronic disease.
The aim of this study was to identify factors predictive of nursing home admission (NHA) over a period of 1 year among elderly subjects with dementia.
The study population was drawn from the SAFES ...cohort that was formed within a national research program into the recruitment of emergency departments in 9 teaching hospitals. Subjects were to have been hospitalized in a medical ward in the same hospital as the emergency department to which they were initially admitted. Subjects who experienced NHA before emergency department admission were excluded. Those with a confirmed diagnosis of dementia were considered in the present analysis. NHA has been defined as the incident admission into either a nursing home or other long term care facility within the follow-up period. Data obtained from a Comprehensive Geriatric Assessment were used in a Cox model to predict 1-year NHA.
The 425 subjects of the study were 86 ± 6 years old, and were mainly women (63%). NHA rate was 40% (n = 172). Four factors were identified to increase NHA risk: age 85 or older (hazard ratio HR = 1.5; 95% confidence interval CI = 1.1-2.1), inability to use the toilet (HR = 2.5; 95% CI = 1.5-4.2), balance disorders (HR = 1.5; 95% CI = 1.1-2.1), and living alone (HR = 1.5; 95% CI = 1.1-2.1). Three factors decreased this risk significantly: inability to transfer (HR = 0.5; 95% CI = 0.3-0.8), increased number of children (HR = 0.88; 95% CI = 0.96-0.99), and increased initial Mini-Mental State Examination score (HR = 0.97; 95% CI = 0.8-0.9).
NHA determinants in dementia are strongly linked to the patient's own characteristics but also to his or her physical or social environment. Interventions should target both members of the dyad "patient-caregiver" because both are affected by the disease.
To assess the impact of a hygiene-encouragement program on reducing infection rates (primary end point) by 5%.
A cluster randomized study was carried out over a 5-month period.
Fifty nursing homes ...(NHs) with 4345 beds in France were randomly assigned by stratified-block randomization to either a multicomponent intervention (25 NHs) or an assessment only (25 NHs).
The multicomponent intervention was targeted to caregivers and consisted of implementing a bundle of infection prevention consensual measures. Interactive educational meetings using a slideshow were organized at the intervention NHs. The NHs were also provided with color posters emphasizing hand hygiene and a kit that included hygienic products such as alcoholic-based hand sanitizers. Knowledge surveys were performed periodically and served as reminders.
The primary end point was the total infection rate (urinary, respiratory, and gastrointestinal infections) in those infection cases classified either as definite or probable. Analyses corresponded to the underlying design and were performed according to the intention-to-treat principle. This study was registered (#NCT01069497).
Forty-seven NHs (4515 residents) were included and followed. The incidence rate of the first episode of infection was 2.11 per 1000 resident-days in the interventional group and 2.15 per 1000 resident-days in the control group; however, the difference between the groups did not reach statistical significance in either the unadjusted (Hazard Ratio HR = 1.00 95% confidence interval (CI) 0.89-1.13; P = .93) or the adjusted (HR = 0.99 95% CI 0.87-1.12; P = .86) analysis.
Disentangling the impact of this type of intervention involving behavioral change in routine practice in caregivers from the prevailing environmental and contextual determinants is often complicated and confusing to interpret the results.
Objectives: Giant cell arteritis (GCA) is associated with severe outcomes such as infections and cardiovascular diseases. We describe here the impact of GCA patients’ characteristics and treatment ...exposure on the occurrence of severe outcomes. Methods: Data were collected retrospectively from real-world GCA patients with a minimum of six-months follow-up. We recorded severe outcomes and treatment exposure. In the survival analysis, we studied the predictive factors of severe outcomes occurrence, including treatment exposure (major glucocorticoids (GCs) exposure (>10 g of the cumulative dose) and tocilizumab (TCZ) exposure), as time-dependent covariates. Results: Among the 77 included patients, 26% were overweight (BMI ≥ 25 kg/m2). The mean cumulative dose of GCs was 7977 ± 4585 mg, 18 patients (23%) had a major GCs exposure, and 40 (52%) received TCZ. Over the 48-month mean follow-up period, 114 severe outcomes occurred in 77% of the patients: infections—29%, cardiovascular diseases—18%, hypertension—15%, fractural osteoporosis—8%, and deaths—6%. Baseline diabetes and overweight were predictive factors of severe outcomes onset (HR, 2.41 1.05−5.55, p = 0.039; HR, 2.08 1.14−3.81, p = 0.018, respectively) independently of age, sex, hypertension, and treatment exposure. Conclusion: Diabetic and overweight GCA patients constitute an at-risk group requiring tailored treatment, including vaccination. The effect of TCZ exposure on the reduction of severe outcomes was not proved here.
Background and aims:
The French institute for study of geriatric infection risk (ORIG) has run a multiphase multicenter study (VESTA) to develop and implement active programs promoting healthcare ...worker (HCW) influenza vaccination. The present article reports results after implementation of the first active program.
Method:
A cluster-randomized controlled trial was conducted from December 1 to December 15, 2005, and a total of 43 geriatric wards (3646 HCWs) were randomly assigned to two clusters. The program cluster (24 wards; 1918 HCWs) received the active program whereas no action was taken in the control cluster (19 wards; 1728 HCWs). The program was educational; its objective was to convince HCWs to be vaccinated by giving them topdown scientific information and developing a sense of altruism. Data from 1201 HCWs (63%) from the program cluster and 1144 HCWs (66%) from the control cluster were collected.
Results:
The program failed to increase the HCW influenza vaccination rate (program: 34%; control: 32%; p>0.05), but won the faithfulness of vaccinated HCWs (5% vs 8% HCWs quitted vaccination;
p
<0.05).
Conclusions:
Resistance to active influenza vaccination programs was found. Future active programs will have to restore a climate of confidence between sources of knowledge and HCWs and promote “self-protection” in contrast with the protection of elderly people.
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