Prospective, Observational, Multicenter, Real-World Study of the Efficacy, Safety, and Pattern of Use of the Dexamethasone Intravitreal Implant in Diabetic Macular Edema in France: Short-Term Outcomes of LOUVRE 3.

INTRODUCTION: To evaluate real-world efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in diabetic macular edema (DME) in France. METHODS: In this prospective, multicenter, observational, noncomparative, post-reimbursement study, consecutively enrolled patients with DME had a baseline evaluation on day 0. Those treated with DEX on day 0 were to be reevaluated at week 6 and months 6, 12, 18, and 24. DEX retreatment and/or alternative therapies were allowed during follow-up. The primary outcome measure was the maximum best corrected visual acuity (BCVA) gain from baseline during follow-up. Secondary outcome measures included time to maximum BCVA gain, patients (%) with prespecified BCVA gains from baseline at each visit, maximum central retinal thickness (CRT) reduction from baseline, patients (%) with CRT reduction ≥ 20% from baseline at each visit, patients (%) with DME resolution (per investigator judgement), and adverse events (AEs). RESULTS: Of 112 patients/eyes with DME for 3.5 years (mean) at baseline, 80 (including 86.1% previously treated) received DEX on day 0 and were analyzed for efficacy. Early study termination precluded collection of ≥ 12-month efficacy data. Patients received 1.4 DEX injections over 8.3 months (averages). The maximum BCVA gain from baseline was 3.6 letters, reached after 77.2 days (averages); 24.6% (week 6) and 15.0% (month 6) of patients experienced ≥ 10-letter BCVA gains from baseline. The mean maximum CRT reduction from baseline was -146.4 µm; 61.4% (week 6) and 36.0% (month 6) of patients had CRT reductions ≥ 20% from baseline, and 68.1% reported DME resolution at least once during follow-up. Ocular hypertension (n = 8, 12.1%) was the most frequent treatment-related AE. CONCLUSIONS: LOUVRE 3 confirmed that DEX improves BCVA and CRT, even in a patient population that had predominantly received DEX before enrollment in the study, and showed that DME resolution was observed during follow-up. DEX tolerability was consistent with published data, supporting treatment benefits in DME. GOV IDENTIFIER: NCT03003416.

Real-Life Efficacy, Safety, and Use of Dexamethasone Intravitreal Implant in Posterior Segment Inflammation Due to Non-infectious Uveitis (LOUVRE 2 Study).

INTRODUCTION: To evaluate real-life efficacy, safety, and treatment patterns with the dexamethasone intravitreal implant (DEX) in posterior segment inflammation due to non-infectious uveitis (treatment-naïve or not) in French clinics. METHODS: In this prospective, multicenter, observational, non-comparative, post-reimbursement study, consecutive patients with posterior segment inflammation due to non-infectious uveitis were enrolled and evaluated at baseline (day 0). Those who received DEX on day 0 were re-evaluated at months 2, 6, and 18. Retreatment with DEX and/or alternative therapies was allowed during follow-up. PRIMARY OUTCOME: patients (%) with at least a 15-letter gain in best corrected visual acuity (BCVA) at 2 months. Secondary outcomes included patients (%) with at least 15-letter BCVA gains at 6 and 18 months; mean BCVA change from baseline at 2, 6, and 18 months; and patients (%) retreated, mean central retinal thickness (CRT), and adverse events (AEs) at all post-baseline visits. RESULTS: Ninety-seven of 245 enrolled patients with posterior segment inflammation due to non-infectious uveitis (80% previously treated) and disease duration of 5 years (average) received DEX on day 0 and were included in efficacy analyses. At month 2 (n = 91), 20.5% of patients (95% CI 12.0-28.9) gained at least 15 letters from a baseline mean of 60.9 letters; the mean gain was 6.2 letters (95% CI 3.5-8.9). At month 6, 50.0% (n = 38/76) of patients did not receive alternative treatment or DEX retreatment, mostly because inflammation had sufficiently subsided (n = 27/38, 71.1%). Although early study termination prevented efficacy analysis at 18 months (n = 12), CRT reductions persisted throughout follow-up. From baseline to month 18, 21/245 (8.6%) patients had DEX-related AEs; 17/245 (6.9%) had ocular hypertension (most common AE). CONCLUSION: LOUVRE 2 confirms DEX efficacy on visual acuity and CRT in predominantly DEX-pretreated patients with relatively old/stabilized uveitis. DEX tolerability was consistent with known/published data, confirming treatment benefits in posterior segment inflammation due to non-infectious uveitis. GOV IDENTIFIER: NCT02951975.

Two-year, prospective, multicenter study of the use of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in the clinical setting in France.

PURPOSE: To evaluate patterns of use and long-term efficacy and safety of dexamethasone intravitreal implant (DEX implant) in the treatment of macular edema secondary to branch or central retinal vein occlusion (BRVO, CRVO) in French clinical practice. METHODS: A 24-month, prospective, multicenter, longitudinal, observational study (LOUVRE) conducted at 48 randomly selected sites in metropolitan France enrolled consecutive adult patients with macular edema following retinal vein occlusion (RVO) who were treated with DEX implant at baseline. Re-treatment with DEX implant and use of other RVO treatments was at the physician's discretion. The primary endpoint was the change in best-corrected visual acuity (BCVA) from baseline to month 6. Secondary endpoints included change in BCVA, intraocular pressure (IOP), adverse events, and RVO treatments administered through month 24. RESULTS: The analysis population of 375 patients (53.9 % BRVO, 46.1 % CRVO) received a mean of 2.6 DEX implant injections over 2 years; mean time between injections was 6.6 months. Mean (SD) change in BCVA from baseline was 5.1 (19.0) letters at month 6 (p < 0.001) and 4.6 (22.3) letters at month 24 (p < 0.001). During the study, 208 patients (55.5 %) received treatment other than DEX implant for RVO, usually laser or ranibizumab therapy, with first use of other therapy occurring at a mean of 8.7 months. Mean change from baseline BCVA at month 6 was 5.5 letters (p < 0.001, N = 254) in patients who had received only DEX implant and 4.2 letters (p = 0.006, N = 121) in patients who had received additional other RVO treatment during the first 6 months. At month 24, mean change from baseline BCVA was +20.7 letters in patients treated with a single DEX implant only (p < 0.001), +4.9 letters in patients treated with ≥2 DEX implants only (p = 0.029), and +2.3 letters in patients treated with DEX implant and other RVO treatment (p = 0.143). The most common adverse events (incidence) were cataract progression (39.7 %) and increased IOP (34.4 %). No glaucoma incisional surgeries were required. CONCLUSIONS: Efficacy and safety of DEX implant in the treatment of RVO-associated macular edema were demonstrated in the French clinical setting. Patients who switched from DEX implant to other RVO treatments did not have improved outcomes. The study is registered at ClinicalTrials.gov with the identifier NCT01618266.

Similar herpes zoster incidence across Europe: results from a systematic literature review.

BACKGROUND: Herpes zoster (HZ) is caused by reactivation of the varicella-zoster virus (VZV) and mainly affects individuals aged ≥50 years. The forthcoming European launch of a vaccine against HZ (Zostavax®) prompts the need for a better understanding of the epidemiology of HZ in Europe. Therefore the aim of this systematic review was to summarize the available data on HZ incidence in Europe and to describe age-specific incidence. METHODS: The Medline database of the National Library of Medicine was used to conduct a comprehensive literature search of population-based studies of HZ incidence published between 1960 and 2010 carried out in the 27 member countries of the European Union, Iceland, Norway and Switzerland. The identified articles were reviewed and scored according to a reading grid including various quality criteria, and HZ incidence data were extracted and presented by country. RESULTS: The search identified 21 studies, and revealed a similar annual HZ incidence throughout Europe, varying by country from 2.0 to 4.6/1 000 person-years with no clearly observed geographic trend. Despite the fact that age groups differed from one study to another, age-specific HZ incidence rates seemed to hold steady during the review period, at around 1/1 000 children <10 years, around 2/1 000 adults aged <40 years, and around 1-4/1 000 adults aged 40-50 years. They then increased rapidly after age 50 years to around 7-8/1 000, up to 10/1 000 after 80 years of age. Our review confirms that in Europe HZ incidence increases with age, and quite drastically after 50 years of age. In all of the 21 studies included in the present review, incidence rates were higher among women than men, and this difference increased with age. This review also highlights the need to identify standardized surveillance methods to improve the comparability of data within European Union Member States and to monitor the impact of VZV immunization on the epidemiology of HZ. CONCLUSIONS: Available data in Europe have shortcomings which make an accurate assessment of HZ incidence and change over time impossible. However, data are indicative that HZ incidence is comparable, and increases with age in the same proportion across Europe.

Does monastic life predispose to the risk of Saint Anthony's fire (herpes zoster)?

BACKGROUND: The consequences of the epidemiology of varicella for zoster epidemiology are still debated. We therefore compared the frequency of herpes zoster in an adult population with virtually no varicella zoster virus (VZV) exposure with that in the general population (GP). METHODS: We performed a national, multicenter, observational, exposed versus nonexposed, comparative study. The nonexposed population consisted of members of contemplative monastic orders (CMO) of the Roman Catholic Church living in 40 isolated monasteries in France. The exposed population consisted of a sample of the GP representative of the French population in terms of age group, sex, socio-occupational categories, and regions. RESULTS: The primary analysis population comprised 920 members of CMO (41.5% nuns; mean age, 64.2 years) and 1533 members of the GP (51.9% women; mean age, 64.6 years). The reported frequency of zoster was 16.2% among CMO and 15.1% in the GP (P = .27, adjusted for sex and age). The reported mean age of onset of zoster was 54.8 and 48.6 years, respectively (P = .06). CONCLUSIONS: This study failed to demonstrate an increased risk or earlier onset of zoster in members of CMO not exposed to VZV, compared with that in the GP. Although adults highly exposed to VZV could have a reduced risk of zoster, compared with the GP, our results suggest that the opposite is not true: adults not exposed to VZV are not at increased risk of zoster when compared with the GP, challenging the relevance of the assumptions and forecasts of current epidemiological models.

[Assessment of 24 years of infant growth monitoring in a rural area of Senegal (1969-1992)]. / Bilan de 24 années de suivi pondéral de nourrissons d'une zone rurale au Sénégal (1969-1992).

UNLABELLED: Undernutrition in young children in developing countries is associated with an increased risk of death. But in several studies, a decrease in mortality was not associated with any decrease in the prevalence of undernutrition. STUDY AREA: A rural population of Casamance (Senegal) has been under yearly demographic surveillance by The French National Institute of Demographic Studies (INED) since 1985. Between 1960-1964 and 1990-1994, under-5 and child (1-4 years) mortality rates dropped from 312 to 127 and from 201 to 68 per 1,000, respectively. Since 1961, French Catholic nuns who are also professional nurses have been in charge of a private village dispensary located in a rural area of Casamance. This dispensary delivers permanent, high quality service and is widely attended. GROWTH MONITORING PROGRAMME: A growth-monitoring programme, supported by Cathwell, was initiated in 1969 for 0-5-year-old children (0-3 from 1985). Children were weighed wearing light clothes to the nearest 10g. Weights were recorded in a register that also contained information concerning identity (name, sex, date of birth) and address. All weights were plotted on growth charts kept by the mothers. During the sessions, the nurses provided nutrition education messages (i.e., preparation of high-energy and nutrient-dense infant gruels using local foods), advice on illness management (oral rehydration during diarrhoea) and hygiene (well and water-jar disinfection, construction of pit-latrines), importance of vaccination. From 1975, they also distributed free chloroquine during the malaria transmission season (May-November) for prevention and early presumptive treatment. Most likely thanks to this programme, infant and child mortality reached a low level at the end of the 1980s. In 1990, plasmodium resistance to chloroquine appeared, increasing malaria mortality. METHODS: All weight measurements taken in 1969-1994 were entered into a database. This paper presents an analysis of weight measurements taken at 3-23 months of age from 1969-1992. A total of 4,636 infants were weighed at least once, but only 3,912 infants (1,983 boys and 1,929 girls) were available for the analysis, 724 being excluded due to missing data. RESULTS: The average coverage of the programme during the month of February was 88% for infants aged 3-23 months. Mean weight was examined at three target ages: 5, 11 and 15 months. Not only did the nutritional status not improve between 1969 and 1989, it even deteriorated in some years for all three age-cohorts. The nutritional status of infants in this community did not differ significantly from that of 12-23 month-old Senegalese children in the 1992-1993 Demographic and Health Survey (DHS). Seasonal differences in mean weight and the prevalence of underweight became significant in the rainy season since 1975. Underweight for the 15-month-old children increased over time during the rainy season. These findings were unexpected, since malaria morbidity is thought to be at least partially responsible for seasonal variations in the nutritional status of young children, and despite the fact that the nurses began a malaria control programme in 1975. CONCLUSION: The rapid transition towards lower childhood mortality observed in this rural area of Casamance (Senegal), was not concomitant with any improvement in infants' nutritional status from 1969 through 1992. Focused public health interventions such as vaccinations and malaria prevention probably did not improve the nutritional status. Paradoxically, growth monitoring may have been more helpful in improving health than growth. Targeted specific nutritional interventions are needed to significantly improve growth of children in this community.

Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon, France.

This study gives, for the first time, an estimate of the incidence and the cost of rotavirus infection in day care centers in Lyon, France.

Risk factors for acellular and whole-cell pertussis vaccine failure in Senegalese children.

Although use of acellular pertussis vaccine was associated with a higher rate of vaccine failure than that of whole-cell vaccine in the Senegal Pertussis Trial conducted in 1990-1994 on 4189 children, risk factors for vaccine failure regarding exposure and susceptibility to pertussis have not been studied so far. Pertussis occurred in 346 vaccinated children. Three factors were found to be associated with vaccine failure, independently of the vaccine type, namely the degree of exposure, birth rank, and time since weaning. In the whole-cell vaccine group, the risk of failure increased with birth rank [RR = 2.95 (1.51-5.75)] and was higher in non stunted children [RR = 1.43 (1.05-1.94)]. In the acellular vaccine group, the risk of failure increased with age at exposure to B. pertussis [RR = 2.24 (1.21-4.12) after 18 months of age] and the degree of exposure [RR = 2.14 (1.17-3.93) when the child shared the hut of an index case]. These results highlight the influence of environmental factors on the success of pertussis vaccination. However, they do not explain the shorter duration of protection provided by the acellular vaccine compared to the whole-cell vaccine which persist after controlling and thus might be related to the nature of the vaccine.

No improvement in weight-for-age of young children in southern Senegal, 1969-1992, despite a drastic reduction in mortality. Evidence from a growth monitoring programme.

BACKGROUND: Undernutrition is associated with an increased risk of death among young children in developing countries. Infant and child nutritional status and mortality were monitored in a rural area of Casamance, Senegal. METHODS: Analysis of weight measurements taken at 3-24 months of age during routine growth monitoring in the community's private dispensary 1969-1992 (3912 children, 4642 child-years) and of mortality rates of children estimated from maternal recall for 1960-1985 and yearly census 1985-1995. RESULTS: Between 1960-1964 and 1990-1994, under-5 and child (1-4 years) mortality rates decreased from 312 to 127 and from 201 to 68 per 1000, respectively. About 90% of resident children attended growth monitoring in 1985-1992. Mean weight-for-age was at a minimum at 15 months of age (-1.60 z-scores [SD: 0.95]); the prevalence of underweight was 33.2% (95% CI: 31.5, 34.9). The latter increased significantly over time, both when comparing all years of follow-up (P for trend <0.01) and over three pre-defined time periods (28.6, 34.6, and 35.0% in 1969-1974, 1975-1984, and 1985-1992, respectively, P for trend <0.05). Mean weight-for-age decreased over time in infancy and in the second year of life. CONCLUSION: No improvement in nutritional status was found among young children 1969-1992 despite a drastic decrease in mortality. Focused public health interventions such as vaccinations and malaria prevention probably did not enhance weight-for-age. Paradoxically, growth monitoring may have been more helpful in improving health than growth.

Sex steroids and age-related macular degeneration in older French women: the POLA study.

PURPOSE: Postmenopausal women are reported to be at higher risk of eye diseases than men. The purpose of our study is to determine the relationships between endocrine status, specially plasma sex hormones levels, and the severity of age-related macular degeneration (AMD) in a large community-based sample of older French women. METHODS: The POLA (Pathologies Oculaires Liées à l'Age) Study is a population-based study on age-related eye diseases and their risk factors. The study enrolled 2584 residents of Southern France, among whom 1451 women aged 60 years or older were recruited between June 1995 and July 1997. A standardized international classification and grading system for AMD was used. Circulating sex hormones levels were measured from fasting blood samples. RESULTS: No association of hormone replacement therapy (HRT), hysterectomy, or oophorectomy was found with soft drusen, pigmentary abnormalities, or late AMD. After multivariate adjustment, higher plasma levels of dehydroepiandrosterone sulfate (DHEAS) were associated with a higher prevalence of soft drusen (OR = 1.21; 95% CI = 1.01-1.44). CONCLUSION: These results may indicate no beneficial effect of HRT on AMD. The positive association of DHEAS with AMD requires further investigation.

Relationships between hormonal status and cataract in french postmenopausal women: the POLA study.

PURPOSE: Prevalence rate of cataract is higher in women than in men. Sex hormones have been hypothesized to be linked with this gender difference. Our aim is to study the relationships between hormonal status and cataract in postmenopausal women. METHODS: The Pathologies Oculaires Liées à l'Age (POLA) study is a population-based study on age-related eye diseases and their risk factors, in 2584 residents of Sète (France). Cataract classification was based on a standardized lens examination, according to Lens Opacities Classification System III. Biological measurements were performed from fasting blood samples. We conducted a cross-sectional study in the female participants (n=1451) aged over 60 years. RESULTS: No association of hormone replacement therapy (HRT) with any type of cataract was found, but an increased risk of cataract surgery was observed in women with a long duration of hormone therapy >/=5 years) (multivariate-adjusted odds ratio (OR)=3.80; 95% CI: 1.45-9.94). Globally, the risk for cataract (any type) was not associated with a long duration of HRT use (OR=1.06; 95% CI: 0.64-1.74). After multivariate adjustment, oophorectomy was associated with a reduced risk of cataract (OR=0.60; 95% CI=0.38-0.94). In the multivariate model, no association was found between estradiol, total testosterone or sex-hormone-binding globulin and cataract. However, high levels of dehydroepiandrosterone sulfate (DHEAS) were associated with a reduced risk of cataract (OR=0.79; 95% CI: 0.63-0.99). CONCLUSION: HRT use was not associated with cataract. A reduced risk of cataract was found in oophorectomized women and in women with high DHEAS levels.