Alzheimer's disease and related syndromes and hospitalization: a nationwide 5-year longitudinal study.

BACKGROUND AND PURPOSE: To study the association between Alzheimer's disease and related syndromes (ADRS) and the incidence of short-stay hospitalizations from the year before (Y-1 ) to 4 years after (Y1 -Y4 ) ADRS identification in the healthcare system. METHODS: Among all beneficiaries of the French health insurance general scheme aged 40 years or more, those with an incident ADRS in 2011, identified through long-term disease registry, hospitalization diagnoses or ADRS-specific drug delivery, were matched with beneficiaries without ADRS of the same age, gender and residence area. The annual incidence rates of all-cause hospitalizations (excluding those with a diagnosis code of ADRS) were compared between individuals with or without ADRS using incidence ratios (IRs) globally and by age, gender, deprivation index and modified Charlson score. We also studied cause-specific hospitalizations using patients' diagnoses and procedure codes. RESULTS: A total of 90 871 subjects with and 90 871 subjects without ADRS were included (mean age 79.6 years, 66% females). From Y-1 to Y4 , incidence rates were significantly higher in subjects with ADRS than in those without for all-cause hospitalization [IR(Y-1 ) = 1.73; 95% confidence intervals, 1.71-1.75; IR(Y4 ) = 1.37; 95% confidence intervals, 1.35-1.39], hospitalizations for social reasons [IR(Y-1 ) = 4.28; IR(Y4 ) = 2.70], fall [IR(Y-1 ) = 5.36; IR(Y4 ) = 2.59], injury [IR(Y-1 ) = 2.71; IR(Y4 ) = 2.09] and infection [IR(Y-1 ) = 2.04; IR(Y4 ) = 2.07]. The inverse was observed for hospitalizations for cataract surgery [IR(Y-1 )=0.73; IR(Y4 ) = 0.51] or total hip prosthesis after 2 years [IR(Y4 ) = 0.72]. CONCLUSIONS: Incident ADRS cases were associated with a higher incidence of hospitalization, but these subjects underwent some common non-emergency surgeries less frequently. Future studies need to assess the clinical impact of these differences.

Identification of a group with high risk of postoperative complications after deep bowel endometriosis surgery: a retrospective study on 164 patients.

PURPOSE: Identify a group with a high risk of postoperative complications after deep bowel endometriosis surgery. METHODS: We conducted a retrospective study on patients treated from 2012 to 2018 in two departments of gynecological surgery at the Toulouse University Hospital, France. The postoperative complications were evaluated in relation to the surgical management, associated with or without non-digestive surgical procedures, initial disease and patient's characteristics. RESULTS: 164 patients were included. A postoperative complication occurred in 37.8% (n = 62) of the cases and required a secondary surgery in 18.3% (n = 30) of the cases. In the univariate analysis, the risk of postoperative complications increased significantly in the presence of segmental resection, disease progression, and associated urinary tract procedure or vaginal incision. In the multivariate analysis, the risk of overall postoperative complications was associated with the surgical management (p = 0.013 and 0.017) and particularly in the presence of segmental resection [Odds Ratio (OR): 20.87; CI 95% (1.96-221.79)]. The risk of rectovaginal fistula increased in the presence of segmental resection [OR: 22.71; CI 95% (2.74-188.01)] as well as in vaginal incision [OR: 19.67; CI 95% (2.43-159.18); p = 0.005]. CONCLUSION: The risk of overall postoperative complications and rectovaginal fistula in particular increases significantly in the presence of vaginal incision, segmental resection and urinary tract procedures after deep bowel endometriosis surgery.

Comparison of needle aspiration versus incision and drainage under local anaesthesia for the initial treatment of peritonsillar abscess.

PURPOSE: The treatment of peritonsillar abscess (PTA) is still controversial regarding the best method of drainage to perform. This study aims to compare effectiveness and safety of needle aspiration versus incision and drainage under local anaesthesia for the initial treatment of PTA. METHODS: A retrospective review of patients (age > 15 years) admitted in two tertiary medical centres for a PTA between November 2010 and October 2016 was performed. Patients were divided into two groups according to the type of drainage: needle aspiration or incision and drainage, under local anaesthesia. The primary outcome was the length of hospital stay; the need to repeat the procedure or to go to the operating room was also assessed. Complications or adverse events were listed in each group to assess safety. RESULTS: Over a 6-year period, 182 patients were admitted for a PTA and included in the analysis, with 82 patients in the aspiration group and 100 patients in the incision group. Mean age was 36.3 years, with a sex ratio of 1.33. The length of hospital stay ranged from 1 to 7 days (mean 2.7 days, median 2 days) with a median length of stay of 3.0 days (interquartile range 2-4) in the aspiration group versus 2.0 days (IQR 2-3) in patients who underwent incision and drainage (p = 0.009). A repetition of the needle aspiration was made for 46.3% of patients versus 10% of repetition of the procedure in the incision group (p = 0.0001). 12 patients (14%) of the aspiration group and 4 patients (4%) of the incision group required an additional drainage under general anaesthesia (p < 0.001). We found no differences regarding safety in both groups. CONCLUSION: Our study showed a significant decrease in the length of hospital stay in patients admitted for a PTA who underwent an initial incision and drainage under local anaesthesia, compared to needle aspiration, as well as a lower risk of repeating the procedure. A well-designed prospective and randomized study on a larger sample of patients is required to support these findings.

[Identification of neurodegenerative diseases in administrative databases in France: A systematic review of the literature]. / Identification des maladies neurodégénératives dans les bases de données médicoadministratives en France : revue systématique de la littérature.

BACKGROUND: Given the health, social and economic burden of neurodegenerative diseases (ND), the development of epidemiologic studies is required. Administrative databases, such as the French national health insurance database (SNIIRAM) could represent an opportunity for researchers. ND could be presumed from drug reimbursement data, hospital stays or registration of a chronic condition. The aim of this study was to describe, in French administrative databases, algorithms used to identify Alzheimer's disease and associated disorders (ADAD), Parkinson's disease and associated disorders (PDAD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS). METHODS: A systematic literature review was performed in Medline and gray literature through December 31th, 2015. French studies focusing on ADAD, PDAD, MS or ALS as a primary health outcome, conducted among one of the SNIIRAM data sources (outpatient reimbursements, chronic condition registration, hospital discharge) were included. RESULTS: Thirty-four studies were included (ADAD, n=18, PDAD, n=9, MS, n=4, ALS, n=3), leading to 36 algorithms. For each studied ND, there was an important variability in the algorithms, concerning (i) the type of criteria used (administrative database versus multi-source systems); (ii) the number of criteria used; (iii) the definition used for each criteria. The extent and level of drug exposure highly varied. Identification through hospitalizations showed variations in terms of type of stay (short stay, long-term stay, psychiatric ward…), extent of diagnosis codes used, diagnosis type (principal, related, associated diagnosis) and period used. A validation study was conducted for 2 out of 36 algorithms (PDAD), and criteria completeness was estimated for 3 algorithms (MS, ALS). CONCLUSION: Despite the increase in ND identification among French administrative databases, few algorithms have been validated. Validation studies should be encouraged.

Cognitive and functional patterns of nondemented subjects with equivocal visual amyloid PET findings.

PURPOSE: Despite good to excellent inter-reader agreement in the evaluation of amyloid load on PET scans in subjects with Alzheimer's disease, some equivocal findings have been reported in the literature. We aimed to describe the clinical characteristics of subjects with equivocal PET images. METHODS: Nondemented subjects aged 70 years or more were enrolled from the MAPT trial. Cognitive and functional assessments were conducted at baseline, at 6 months, and annually for 3 years. During the follow-up period, 271 subjects had (18)F-AV45 PET scans. Images were visually assessed by three observers and classified as positive, negative or equivocal (if one observer disagreed). After debate, equivocal images were reclassified as positive (EP+) or negative (EP-). Scans were also classified by semiautomated quantitative analysis using mean amyloid uptake of cortical regions. We evaluated agreement among the observers, and between visual and quantitative assessments using kappa coefficients, and compared the clinical characteristics of the subjects according to their PET results. RESULTS: In 158 subjects (58.30 %) the PET scan was negative for amyloid, in 77 (28.41 %) the scan was positive and in 36 (13.28 %) the scan was equivocal. Agreement among the three observers was excellent (kappa 0.80). Subjects with equivocal images were more frequently men (58 % vs. 37 %) and exhibited intermediate scores on cognitive and functional scales between those of subjects with positive and negative scans. Amyloid load differed between the EP- and negative groups and between the EP+ and positive groups after reclassification. CONCLUSION: Equivocal amyloid PET images could represent a neuroimaging entity with intermediate amyloid load but without a specific neuropsychological pattern. Clinical follow-up to assess cognitive evolution in subjects with equivocal scans is needed.

Regional variations in quinolone use in France and associated factors.

The purpose of this study was to investigate geographic variations in the use of quinolones in France and their associated factors. All reimbursement claims of antimicrobials were collected for 90 % of the French population for the year 2007. Dispensed quantities were then converted into defined daily doses (DDD) and adjusted for the age structure of the national population. Correlations between quinolone use and total antimicrobial use and some morbidity and socio-economic factors were studied using Spearman's rank correlation coefficients. On average, 2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007 in France, accounting for 10.2 % of the total antimicrobial consumption in adults. A 40 % variation was observed between the regions with the lowest (1.73 DID) and the highest use (2.44 DID). This variation was more important for anti-pneumococcal quinolones than for quinolones directed against urinary tract infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated with some regional socio-economic factors (unemployment, growth domestic product, health expenditures) and physician density, but was independent of the total antimicrobial use. After adjustment for age, large variations in quantitative and qualitative quinolone use were observed across French regions, especially for anti-pneumococcal fluoroquinolones. These results, though not controlled for potential epidemics variations, argue in favour of a possible improvement in quinolone prescribing to be achieved in some regions.

Evidence-based recommendations on topical treatment and phototherapy of psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: Although topical treatments and phototherapy are available for more than 40 years, there is a paucity of evidence-based recommendations regarding their use. OBJECTIVES: The aim of this work was to develop evidence-based recommendations on topical treatments and phototherapy in psoriasis for daily clinical use. METHODS: A scientific committee selected clinically relevant questions on efficacy and safety of topical agents and phototherapy in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2011, including 42 dermatologists. Recommendations for use of topical treatments and phototherapy were made during interactive workshops where the evidence was presented and discussed. Agreement among participants was assessed on a 10-point scale. The participants systematically assessed the impact of the recommendations on clinical practice. RESULTS: A total of 3555 references were identified, among which 312 articles were included in the systematic reviews. Three recommendations were issued on phototherapy including both PUVA and narrow-band UVB. The recommendations related to administration schedule, clearance rate and risk of side-effects. The mean agreement between participants was good varying from 8.5 to 9.5. Six recommendations were issued on topical treatments focusing on administration schedule, clearance rate, risk of side-effects, cost-effectiveness and measures to improve treatment adherence. The mean agreement between participants varied from 7.3 to 9.9. CONCLUSIONS: These recommendations for the use of topical agents and phototherapy in psoriasis are evidence-based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the opinion of physicians who were not involved in generating the recommendations.

Efficacy of psoralen UV-A therapy vs. narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and Narrowband UV-B (NB-UVB or UVB TL-01) are well established treatments for chronic plaque psoriasis but there is limited evidence regarding their respective efficacy. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of oral 8-methoxypsoralen-UV-A and Narrowband UV-B in psoriasis, a systematic review to assess respective response rates, remission duration and predictive factors of efficacy was performed. METHODS: A systematic search was carried out in PubMed, Cochrane and Embase databases, using the key words 'Psoriasis', 'UVB therapy', 'UVA therapy' for the period from 1980 to December 2010. RESULTS: The initial literature search identified 773 articles. The final selection included 29 randomized controlled trials: 18 were about the efficacy of PUVA, eight about the efficacy of NB-UVB and three directly compared PUVA vs. NB-UVB. The response rate defined by 75% or more improvement in PASI was 80% with PUVA vs. 70% with NB-UVB. The meta-analysis of the three comparative studies found a higher probability of remission at 6 months with PUVA than with NB-UVB [OR = 2.73 (95% CI 1.19-6.27), P = 0.02]. The choice of initial dose, according to skin type, the minimal erythemal dose or minimal phototoxic dose, incremental regimen and periodicity of the sessions did not appear to be predictive factors of efficacy for PUVA or NB-UVB. Despite methodological limitations in trials, the number of sessions needed for psoriasis clearance appeared to be lower with PUVA than with NB-UVB (approx. 17 vs. 25, respectively). CONCLUSION: PUVA and NB-UVB are both effective therapies in treatment of psoriasis. Our results suggest that compared with NB-UVB, PUVA tends to clear psoriasis more reliably, with fewer sessions, and provides with longer lasting clearance. However, the long-term safety of PUVA, especially its cutaneous carcinogenic risk, and the easier administration procedure often lead dermatologists to prefer NB-UVB as first line phototherapy treatment in plaque type psoriasis.

Carcinogenic risks of psoralen UV-A therapy and narrowband UV-B therapy in chronic plaque psoriasis: a systematic literature review.

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.

Topical corticosteroids in plaque psoriasis: a systematic review of efficacy and treatment modalities.

INTRODUCTION: Topical steroids are used for more than 50 years to treat mild-to-moderate plaque psoriasis. The purpose of this systematic review was to evaluate the efficacy but also the optimal modalities of administration of topical corticosteroids in psoriasis i.e. influence of steroid potency on clinical response, putative impact of topical formulation, occlusion procedure, rate of application to control the initial response and the potential interest of a maintenance treatment to prolong psoriasis clearance. MATERIAL AND METHODS: A systematic search was performed between 1980 and January 2011 in Medline, Embase and Cochrane databases (English and French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj. To analyse response across studies, three levels of response were categorized depending on the data available in studies: percentage of patients who achieved more than 50%, 75% or 90% improvement of initial psoriasis severity. RESULTS: From an initial selection of 1269 references, 1166 references were excluded on reading the title or the abstract and 32 on reading the article and 71 were finally retained and analysed. Fifty randomized controlled trials (RCT) assessing topical steroids in the initial treatment of mild-to-severe psoriasis body plaque psoriasis were retained: 40 were parallel-group studies and 10 were within-patient studies. Treatment duration was mostly 4 weeks. Sample size varied from 30 to 1 603 patients. Outcome measures to assess efficacy were highly variable. A total of 30-90% patients across parallel group studies experienced more than 50% of initial mild-to-severe psoriasis improvement while from 7% to 85% experienced more than 75% improvement and from 5% to 85% experienced at least 90% of improvement. The success rate in the within-patient studies varied from 10% to 70%. Eighteen RCT were performed in scalp psoriasis: 16 were parallel-group and two were within-patient studies, with a treatment follow-up time from 2 weeks to 6 months, enrolling 42-1417 patients. A total from 40% to 75% patients across studies experienced more than 75% of initial scalp psoriasis improvement and from 43% to 90% experienced more than 90% initial psoriasis improvement. Only three RCT studies evaluated topical steroids as a maintenance treatment for body psoriasis and one for scalp lesions. Despite heterogeneity in treatment schedule, topical steroid intermittent maintenance treatment was shown to prolong remission. The literature analysis did not provide with high evidence-based quality data on the role of formulation, topical steroid potency, number of applications per day to obtain the highest rate of success excepting occlusion dressing which provided with additional benefit. CONCLUSION: The clinical development of topical steroids in psoriasis did not follow state of the art modern methodology. Treatment success appears to be highly variable across studies. Maintenance intermittent treatment appears to be useful to prolong remission. Recommendations concerning topical steroids treatment modalities in plaque psoriasis should be mostly based on expert opinion.

Topical corticosteroids in plaque psoriasis: a systematic review of risk of adrenal axis suppression and skin atrophy.

BACKGROUND: Topical steroids have been used for more than 50 years in mild-to-moderate plaque psoriasis and carry a theoretical risk of adverse events. OBJECTIVES: The aim of this systematic literature review was to evaluate the risk of hypothalamo-pituitary-adrenal (HPA) axis suppression and the risk of skin atrophy with topical steroids in the treatment of plaque psoriasis. METHODS: A systematic search between 1980 and January 2011 in Medline, Embase and Cochrane databases (English, French language, adults), using the keywords 'psoriasis'/exp/mj AND 'corticosteroid'/exp/mj, RESULTS: Altogether 1269 references were found. Of these 1124 articles were excluded by reading the abstract and 123 by reading the article. A total of 22 randomized trials were selected. Effects on HPA axis: Thirteen studies, with a sample size varying from 7 to 341 patients, were selected. The effect on HPA axis was evaluated by the morning cortisol level (11 studies), the 24 h urine steroid levels (five studies) and/or by the Synacthen test (three studies). Reduction of morning cortisol was observed in 0-25% of patients in 10 short-term studies (two in scalp psoriasis, eight in body psoriasis) and in 48% of patients in the remaining short-term study (body psoriasis). Only four of these studies with three on body psoriasis evaluated the effect of long-term treatment defined as 6-month treatment duration or longer and did not identify HPA axis suppression by cortisol level measurement. The Synacthen test, considered as the gold standard to assess HPA axis, was always normal. There was no evidence of clinically significant HPA axis suppression due to absorption of topical steroids even when treating the scalp or in patients with extensive disease. Risk of skin atrophy: Thirteen studies with topical steroid evaluating treatment durations from 4 weeks to 1 year were analysed. The frequency of skin atrophy assessed clinically, varied from 0% to 5% of patients. CONCLUSIONS: The literature analysis on topical steroids in psoriasis is reassuring although the quality of safety studies is limited with a majority of short-term studies. Although short-term biological effects of topical steroids on the HPA axis were observed in several clinical studies, they were not associated with clinical signs. Adequately designed long-term studies would be necessary to better determine the risk of skin atrophy using modern methods of evaluation such as dermoscopy and echography.

Topical vitamin D analogues alone or in association with topical steroids for psoriasis: a systematic review.

OBJECTIVE: The objective of this systematic review was to prepare for evidence-based recommendations on the use of vitamin D analogues, and their combination with topical steroids in psoriasis. METHODS: Literature systematic review performed in May 2011. The Cochrane, PubMed and Embase databases were systematically searched with different combinations: including Psoriasis AND calcipotriol expanded to all vitamin D analogues. To assess efficacy across studies, we used two predefined criteria to account for the numerous endpoints found in the literature, 'Treatment success' corresponding to 90% improvement in severity and 'Satisfactory response' corresponding to 75% improvement. We conducted a meta-analysis comparing the efficacy of vitamin D analogues plus topical steroids (VDS) vs. vitamin D analogues alone (VD). To determine the relative cost-efficacy of the topical drugs available on the market, cost/efficacy ratios were calculated for each product according to the approved therapeutic regimen. RESULTS: 51 articles were selected. The application duration varied between three to 52 weeks across studies. VD as monotherapy had a satisfactory response rate between 22% to 96% and a treatment success rate ranging from 4% to 40%. VDS had a satisfactory response rate between 35% to 86% and a treatment success rate ranging from 27% to 53%. A meta-analysis found a probability of success twice higher with VDS than with VD in adult plaque psoriasis. The cost/efficacy ratio was evaluated as 1.2-1.8 times higher for VDS than for VD. CONCLUSION: VDS is twice more effective than VD and displays a better cost per success. Additional studies are needed to clarify maintenance treatment, impact on quality of life, treatment of non-plaque psoriasis. It will be important to harmonize outcome measures in future studies with topical agents in psoriasis to better appraise their efficacy.

Adherence to topical treatment in psoriasis: a systematic literature review.

BACKGROUND: Treatment adherence has been recognized as an important issue in the management of chronic diseases such as psoriasis. OBJECTIVE: The aim of this work was to analyse data about topical treatment adherence in psoriasis. METHODS: Systematic literature review (62 references) between 1980 and 2011 (database: PubMed, Embase and Cochrane; Mesh keywords: Patient Compliance [Mesh] OR Medication Adherence [Mesh] AND Psoriasis [Mesh]; limits: date of publication >1980, humans subjects, written in French or English, aged ≥ 19 years). Two parameters were evaluated: (i) the ratio of number of product applications performed vs. number of applications expected according to physician recommendations, (ii) the ratio of amount of product used vs. amount of product prescribed. RESULTS: A total of 22 studies were selected. Nine studies reported on the frequency of topical treatment application in a real world setting. Five studies showed a frequency of applications varying between 50% and 60% of those expected. Because of the high variability in medication adherence assessment methods, the data could not be combined. Twelve articles reported on the frequency of topical treatment application in randomized controlled trials with adherence varying between 55% and 100%. Concerning the amount of product use, four studies showed patients applied between 35% and 72% of the recommended dose during a treatment period of 14 days to 8 weeks. The most frequently mentioned reasons for non-adherence to topical treatment were low efficacy, time consumption and poor cosmetic characteristics of topical agents. Patients experiencing adherence issues were significant younger, were men, had younger age at onset of psoriasis and had a higher self-assessed severity. To improve adherence, the following strategies were suggested: to give patients information about psoriasis, to recognize social impact, to give written instructions for use such as a care plan, to explain side effects of topical therapies, to choose treatment and its cosmetic properties in agreement with the patient. CONCLUSIONS: Literature data about topical treatment adherence are heterogeneous and scarce. They confirm the limited topical treatment adherence in psoriasis in real life, much lower than what is reported in randomized controlled trials. Therapeutic education and clear instructions on the use of topical agents are necessary to improve adherence. Studies are needed to identify predictors of limited adherence and to identify interventions improving adherence to topical medications in psoriasis.

Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

BACKGROUND/AIM: To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. OBJECTIVE: To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. RESULTS: Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific features amounting to 61 and 88% respectively. CONCLUSIONS: Based on expert experience, the starting dose of MTX is between 5 and 10 mg/week for the first week. Fast dose escalation is recommended in order to obtain a therapeutic target dose of 15-25 mg/week. The maximum recommended dose is 25 mg/week. A folic acid supplement is necessary. The initiation of treatment by oral administration is preferred. In cases where inadequate response is obtained or in the event of poor gastrointestinal tolerance, subcutaneous dosing can be proposed at the same dose. Published data do not confirm the incidence of hepatic fibrosis. Type 2 diabetes and obesity appear to be significant risk factors in fibrosis. A combination of FibroTests and fibroscans together with measurement of the type III serum procollagen aminopeptide seem to be ideal method for monitoring liver toxicity.

Evidence-based recommendations on conventional systemic treatments in psoriasis: systematic review and expert opinion of a panel of dermatologists.

BACKGROUND: There is a high level of heterogeneity regarding the practical use of conventional systemic treatment in psoriasis. OBJECTIVES: The aim of this study was to develop evidence-based recommendations for the use of traditional systemic treatments in psoriasis in daily clinical practice: methotrexate (MTX), cyclosporin and retinoids. METHODS: A scientific committee selected clinically relevant questions concerning the use of MTX, cyclosporin and retinoids in psoriasis. This selection was made using the Delphi method. A systematic literature search was performed in Medline, Embase and the Cochrane Library. The articles selected for analysis were reviewed and the level of evidence was appraised according to the Oxford Levels of Evidence. An Expert consensus meeting took place in June 2010, including 66 dermatologists. Recommendations for daily use of psoriasis systemic treatments were made during interactive workshops where the evidence was reviewed. Agreement among participants and the impact of the recommendations on clinical practice were systematically assessed using voting procedure in a plenary session. RESULTS: A total of 2800 references were identified, among which 122 articles were included in the systematic reviews. Three key recommendations on the use of MTX in psoriasis were formulated, including optimal dosage and route, use of folic acid, risk factors for liver fibrosis and monitoring of hepatotoxicity. The recommendations for cyclosporin in psoriasis focused on the modalities of cyclosporin prescription: dosage, scheme of treatment, optimal duration of treatment, renal toxicity monitoring and evidence for use of cyclosporin in non-plaque psoriasis (erythrodermic, pustular and ungueal). Recommendations were also made concerning the efficacy and safety of retinoids (mainly acitretin) in plaque and non-plaque psoriasis. CONCLUSIONS: These recommendations for the use of traditional systemic therapies in psoriasis are evidence based and supported by a panel of dermatologists. The next step will be to disseminate these recommendations and assess the agreement of physicians who were not involved in generating the recommendations.

Oral cyclosporin in psoriasis: a systematic review on treatment modalities, risk of kidney toxicity and evidence for use in non-plaque psoriasis.

BACKGROUND: Although cyclosporin (CyA) has been in use in psoriasis for more than 20 years, there is still controversy regarding treatment strategy, monitoring of kidney function and utility in non-plaque psoriasis. OBJECTIVES: To prepare for evidence-based recommendations concerning the practical use of CyA in psoriasis, we performed a systematic review to better define treatment strategy, risk of kidney toxicity and evidence for use in non-plaque psoriasis. METHODS: A systematic search was performed on PubMed, Cochrane and Embase databases, using the key-words 'psoriasis', 'CyA', 'nephrotoxicity' during the period from 1980 to June 2010. RESULTS: The initial literature search identified 428 articles. The final selection included 16 randomized controlled trials (RCT) for treatment strategy, 25 articles (histological studies and RCT) for risk of kidney toxicity and 10 articles (RCT, prospective studies and case series) for use in non-plaque psoriasis. Higher doses of CyA of 5 mg/kg produced Psoriasis Area Severity Index (PASI) 75 response in between 50 and 97% of patients, whereas lower doses of 2.5 mg/kg yielded PASI 75 in between 28 and 85%. CyA could maintain remission at doses of at least 3 mg/kg/day. Low calory diet in obese patients was shown to improve CyA efficacy. More than 50% of the patients treated with CyA may have an increase in serum creatinin value over 30% of baseline if treatment is prolonged for 2 years. CyA at a dose of 2.5 mg/kg/day was effective for 89% of patients with palmoplantar pustulosis. More than 50% of the patients with erythrodermic psoriasis obtained a significant improvement at doses between 3 and 5 mg/kg/day at 2-4 months. CyA was more effective than etretinate on nail psoriasis. CONCLUSION: Oral CyA is indicated for patients with plaque psoriasis, pustular psoriasis or erythrodermic psoriasis. The starting dose of 5 mg/kg is associated with a higher degree of clearance. The benefit-risk appears to be better for patients without risk factors for nephrotoxicity: non-obese patients without hypertension and aged below 60. Although CyA is ideally suited for crisis intervention, continuous maintenance treatment with CyA may be envisaged in some patients provided serum creatinin is regularly monitored and the cumulative treatment duration is preferably limited to 2 years or less.

Efficacy and safety of oral retinoids in different psoriasis subtypes: a systematic literature review.

BACKGROUND: There is limited evidence regarding the efficacy and safety of retinoids in different psoriasis subtypes. OBJECTIVE: To systematically review the available literature on: (i) modalities of administration and prescription of oral retinoids as single agent or combined therapy for the treatment of plaque-type psoriasis (PV), nail psoriasis and localized and generalized pustular psoriasis : initial and optimal dosage; (ii) skeletal toxicity of retinoid for the treatment of psoriasis. METHODS: A systematic literature search was carried out in MEDLINE, EMBASE, and Cochrane Library databases from 1975 to 2010 searching for randomized controlled trials and observational studies evaluating 1) various dosages of retinoid in psoriasis and 2) skeletal toxicity of retinoid in psoriasis. Articles were limited to human subjects and English/French languages. RESULTS: Efficacy of retinoids in psoriasis. Among 1348 identified references, 44 published studies were included. Starting daily dosages between 10 and 25 mg and stepwise escalation were associated with higher clinical efficacy and lower incidence of adverse events in comparison with higher doses and regimens rapidly reaching optimal dose. Retinoids as single agent therapy appeared to show limited efficacy in PV, while the good clinical efficacy reported in pustular forms should be cautiously considered, given the spontaneously remitting course of the disease. Combining retinoids with phototherapy appeared to be highly effective in patients with PV. Potential skeletal toxicity of retinoids. 15 published studies out of 105 identified references were included. There is no strong evidence of an increased risk of skeletal abnormalities in psoriasis patients treated with retinoids. CONCLUSION: Acitretin appears to provide better efficacy in pustular psoriasis than in PV as a single agent treatment. There is no evidence for skeletal toxicity of retinoids in the setting of psoriasis, and accordingly monitoring this risk through X-ray is not warranted.

Influence of fluoroquinolone consumption in inpatients and outpatients on ciprofloxacin-resistant Escherichia coli in a university hospital.

BACKGROUND: The increase in fluoroquinolone-resistant Escherichia coli has raised the issue of treatment failure in common infections. Few studies have investigated the possible relationship between outpatient fluoroquinolone consumption and resistance in hospital. OBJECTIVE: To investigate the relationship between inpatient and outpatient fluoroquinolone use and ciprofloxacin-resistant E. coli in a teaching hospital. METHODS: An ecological study was conducted in Toulouse University Hospital and its surrounding area, the Midi-Pyrénées region (south-western France), in 2004-07. Dynamic regression models were built to study how the hospital resistance rate was linearly related to current and past values of fluoroquinolone consumption. Resistance forecasts for 2008 were then calculated and compared with actual rates for the first 5 months of the year. RESULTS: Mean resistance rate was 13.7% and mean fluoroquinolone use was 89.9 defined daily doses (DDDs)/1000 inpatient days in hospital and 2.6 DDDs/1000 inhabitants/day in the region. Taking into account past values of fluoroquinolone consumption in hospital and in outpatients, only levofloxacin use in the community remained significantly associated with resistance in hospital, with a lag of 12 months. This model explained 50% of the resistance variability. CONCLUSIONS: This ecological analysis, conducted on a teaching hospital scale, suggests that ciprofloxacin resistance in E. coli in hospital is linked to consumption of fluoroquinolones within the hospital and its surrounding community. Among all fluoroquinolones, levofloxacin use was found to be the most important factor. Consumption in outpatients appears to be a relevant determinant to consider in designing interventions to reduce resistance in hospitals.

Red Blood Cell Omega-3 Fatty Acid Composition and Psychotropic Drug Use in Older Adults: Results from the MAPT Study.

Low docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) concentration has been associated with the development of some psychiatric disorders. OBJECTIVES: to assess the association between red blood cell (RBC) DHA-EPA concentration and psychotropic drug use in older adults and between the 1-year change in RBC DHA-EPA and psychotropic drug use at 12 months. DESIGN: secondary analysis of multicenter, randomized controlled trial testing multidomain intervention and/or n-3 PUFA supplement on cognitive function (MAPT study). SETTING: France, 2008-2014. PARTICIPANTS: 1680 participants ≥70 years, community-dwelling were included. MEASUREMENTS: Psychotropic drug use was self-reported during medical interviews and assessments. RBC n-3 PUFA concentration was defined by % of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) among total fatty acids. Logistic regressions models controlling for age, sex, education, depression risk and intervention group were used. RESULTS: 1594 participants had baseline DHA-EPA concentration available (mean age=75.5±4.5 years, 65% females). At baseline, participants with DHA-EPA ≤4.82% (lowest quartile) reported higher prevalence of use of overall psychotropic drugs (34.0% vs 24.4%; aOR=1.33, 95%CI=[1.03-1.72]), anxiolytic/hypnotic drugs (25.0% vs 18.2%; aOR=1.42, 95%CI=[1.07-1.89]), and antidepressants (18.3% vs 13.5%; aOR=1.25, 95%CI=[0.93-1.72]) than participants with higher DHA-EPA. Participants who experienced an increase in DHA-EPA from baseline were less likely to use a psychotropic drug at 12 months than participants with no change or a decrease (aOR=0.72, 95%CI=[0.55-0.96]). CONCLUSION: Low RBC DHA-EPA concentration was independently associated with psychotropic drug use. Future studies are needed to assess whether low RBC DHA-EPA is a risk marker for psychotropic drug use in older adults and to better understand underlying pathophysiological mechanisms. Registration number: ClinicalTrials.gov database (NCT00672685).

[Evaluation of the nurse triage at the ophtalmology emergency department of Pierre-Paul-Riquet Hospital]. / Évaluation du questionnaire de tri infirmier aux urgences ophtalmologiques de l'hôpital Pierre-Paul-Riquet au CHU de Toulouse.

INTRODUCTION: The steady increase in the number of visits to the various emergency services combined with the decrease in medical demographics, make it necessary to optimize triage of patients to improve their care. The purpose of this study was to evaluate the pertinence of our triage questionnaire in the classification of ophthalmologic emergencies by severity. METHODS: We used a monocentric cross-sectional study. From September 5 through September 25 2017, 858 patients who had all been seen in the ophthalmology emergency department of Pierre Paul Riquet Hospital of Toulouse university medical center and had responded to the triage nurse questionnaire were included. According to the symptoms presented or not by the patient, a color code was attributed (GREEN, ORANGE or RED) in order of increasing level of emergency. For each patient, we compared the severity of the final diagnosis by Base Score with the level of emergency established by our questionnaire. RESULTS: There were 118 "GREEN" patients, 606 "ORANGE" patients and 134 "RED." We were able to analyze 822 patients. 21.65% of patients were correctly classified, 73.36% were overestimated (of which 87.06% by one level and 12.94% by two levels of severity), and 4.99% were underestimated (of which 90.24% by one level and 9.76% by two levels). CONCLUSION: Our current triage questionnaire is not sufficiently discriminating for effective triage of ophthalmologic emergencies. It often overestimates minor emergencies, causing a delay in treating other emergencies. We propose a new questionnaire modified according to the results obtained during our study.