The Needs of Patients with Psoriasis and Benefits of Apremilast in French Clinical Practice: Results from the Observational REALIZE Study.

INTRODUCTION: Real-world data on the needs of patients with psoriasis and patient-perceived benefits of apremilast are limited. We report such data from France. METHODS: The multicenter, observational REALIZE study was conducted in real-life clinical practice in France and enrolled patients with moderate-to-severe plaque psoriasis who had initiated apremilast per French reimbursement criteria in the 4 weeks preceding enrollment (September 2018-June 2020). Physician assessments and patient-reported outcomes (PROs) were collected at enrollment, 6 months, and 12 months. PROs included the Patient Benefit Index for skin diseases (PBI-S), Dermatology Life Quality Index (DLQI), and 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9). The primary outcome was PBI-S ≥ 1 (minimum clinically relevant benefit) at month 6. RESULTS: Of 379 enrolled patients who received ≥ 1 dose of apremilast, most [n = 270 (71.2%)] remained on apremilast at 6 months and over half [n = 200 (52.8%)] persisted at 12 months. Patients reported the following treatment goals as most important (≥ 70% reported goal as "very important" in the Patient Needs Questionnaire): get better skin quickly, regain disease control, be healed of skin alterations, and have confidence in the therapy. Most patients persisting on apremilast achieved a PBI-S ≥ 1 at months 6 and 12 (91.6% and 93.8%, respectively). Mean (SD) DLQI decreased from 11.75 (6.69) at enrollment to 5.17 (5.35) and 4.18 (4.39) at months 6 and 12, respectively. Most patients (72.3%) reported moderate-to-severe pruritus at enrollment and no/mild pruritus at months 6 and 12 (78.8% and 85.9%, respectively). Mean (SD) TSQM-9 Global Satisfaction scores were 68.4 (23.3) and 71.7 (21.5) at months 6 and 12, respectively. Apremilast was well tolerated; no new safety signals were identified. CONCLUSIONS: REALIZE provides insights regarding the needs of patients with psoriasis and the patient-perceived benefits of apremilast. Patients who persisted on apremilast reported improvements in quality of life, high treatment satisfaction, and clinically relevant benefits. TRIAL REGISTRATION: NCT03757013.

Psoriasis is a chronic disease and can have a large impact on patients' quality of life. Patients often discontinue psoriasis treatments for a number of reasons, including side effects, ineffectiveness, and inconvenience. Apremilast (Otezla) is a twice-daily oral tablet for the treatment of moderate-to-severe plaque psoriasis. Data on the needs of patients with psoriasis and the patient-perceived benefits of psoriasis treatments, including apremilast, are limited. The REALIZE (Real Life Data for OTEZLA Evidence) study collected data from 379 patients with moderate-to-severe psoriasis receiving apremilast for up to 12 months in clinical practice across France. Patients completed questionnaires regarding their treatment goals, how well apremilast treatment met these goals, their quality of life, and their satisfaction with apremilast treatment. At the beginning of the study, patients reported getting better skin quickly, regaining control of their psoriasis, being healed of psoriatic lesions on their skin, and having confidence in their psoriasis treatment as their most important treatment goals. Over half of the patients continued apremilast for 12 months, with most reporting that apremilast successfully met their treatment needs. Patients also reported high satisfaction with apremilast and improved quality of life. The adverse events reported in the REALIZE study were similar to the known safety profile of apremilast. Our data show that apremilast is an effective, convenient, and well-tolerated treatment that improves the symptoms of psoriasis and meets patients' needs and expectations.

Methodological quality of systematic reviews of the local management of anogenital warts: a systematic review using AMSTAR II, ROBIS and PRISMA.

INTRODUCTION: Anogenital warts (AGWs) are among the most common STDs. Many therapy options are available but are not codified. Systematic reviews (SRs) and meta-analyses (MAs) are helpful to elaborate recommendations on the management of AGWs. The objective of our study was to assess the quality and consistency of SRs for the local management of AGWs using three international tools. METHODS: Seven electronic databases were searched from inception to 10 January 2022 for this SR. The intervention of interest was any local treatment of AGWs. There was no restriction on language and population. The methodological quality, reporting quality and risk of bias (ROB) of the included SRs for the local treatments of AGWs were assessed independently by two investigators with A Measurement Tool to Assess systematic Reviews version II (AMSTAR II), Risk of Bias in Systematic Reviews (ROBIS) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: Twenty-two SRs/MAs met all inclusion criteria. According to the results of the AMSTAR II, nine included reviews were rated critically as being of low quality, and only five were of high quality. Based on the ROBIS tool, only nine SRs/MAs had a low ROB. The domain-assessed 'study eligibility criteria' were mostly rated at a low ROB, unlike the other domains. With PRISMA, the reporting checklist was relatively complete for ten SRs/MAs, but some reporting weaknesses remained in the topics of the abstract, protocol and registration, ROB and funding. DISCUSSION: Several therapy options are available for the local management of AGWs and are widely studied. However, due to the many ROB and low quality of these SRs/MAs, only a few of them have the sufficient methodological quality to support guidelines. PROSPERO REGISTRATION NUMBER: CRD42021265175.

Achromobacter spp. Surgical Site Infections: A Systematic Review of Case Reports and Case Series.

Achromobacter species are isolated from rare but severe healthcare-associated infections, including surgical site infections. They are considered to preferentially infect immunocompromised patients but so far with limited evidence. We conducted a systematic review on Achromobacter spp. surgical site infections (SSIs) to determine if such infections were indeed more commonly associated with immunocompromised patients. The secondary objective was to describe the characteristics of infected patients. Eligible articles had to be published before 30 September 2020 and to report Achromobacter spp. SSIs across all surgical specialties excluding ophthalmology. Analyses were performed on individual data without meta-analysis. Cases were divided into 2 subgroups: one group which had either prosthesis or implant and the other group which did not. A first selection led to a review of 94 articles, of which 37 were analyzed. All were case reports or case series and corresponded to 49 infected patients. Most of the patients were under 65 years of age and had undergone a heart or digestive surgery followed by deep infection with no co-infecting pathogens. Nine out of the 49 cases were immunocompromised, with similar distribution between the two subgroups (16.6% and 20%, respectively). This review suggests that Achromobacter spp. SSIs do not preferentially target immunocompromised patients.

Local Management of Anogenital Warts in Non-Immunocompromised Adults: A Network Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: No hierarchy of first-line treatments for anogenital warts (AGWs) is provided in international guidelines. This study aimed to determine the efficacy of topical treatments and ablative procedures for the management of AGWs. METHODS: Twelve electronic databases were systematically searched from inception to August 2018. All randomized controlled trials (RCTs) comparing immunocompetent adults with AGWs who received at least 1 provider-administered or patient-administered treatment in at least 1 parallel group were included. Risk of bias assessment followed the Cochrane Handbook. The study endpoint was complete lesion response after clearance and recurrence assessment. A network meta-analysis was performed. RESULTS: A network geometry was constructed based on 49 of the 70 RCTs included in our systematic review. All but 4 RCTs had a high risk of bias. The most efficacious treatments compared to placebo were surgery (RR 10.54; CI 95% 4.53-24.52), ablative therapy + imiquimod (RR 7.52; CI 95% 4.53-24.52), and electrosurgery (RR 7.10; CI 95% 3.47-14.53). SUCRA values confirmed the superiority of surgery (90.9%), ablative therapy + imiquimod (79.8%), and electrosurgery (77.1%). The most efficacious patient-administered treatments were podophyllotoxin 0.5% solution (63.5%) and podophyllotoxin 0.5% cream (62.2%). CONCLUSIONS: With low-level evidence of most included RCTs, surgery and electrosurgery were superior to other treatments after clearance and recurrence assessment. Podophyllotoxin 0.5% was the most efficacious patient-administered treatment. Combined therapies should be evaluated in future RCTs in view of their identified effectiveness. The results of future RCTs should systematically include clinical type, number and location of AGWs, and sex of the patient, to refine therapeutic indications. PROTOCOL REGISTRATION: PROSPERO-CRD42015025827.

Achromobacter xylosoxidans in hospital environments: still waters run deep!

BACKGROUND: Hospital reservoirs of Achromobacter xylosoxidans, responsible for nosocomial infections, are poorly known. METHODS: We examined the growth, survival and biofilm formation of five A. xylosoxidans strains for up to 2 y in distilled, dialysis or microfiltered water. Each strain was inoculated at 102 CFU/ml without adding nutrients. RESULTS: All strains grew at a level of 3x103 to 1.5x107 CFU/ml; each strain showed a preferred water type. Strains isolated from quaternary ammoniums showed the highest ability to grow and form biofilms in nutrient-poor waters. CONCLUSION: Medical waters and notably sterile distilled water bottles appear to be long-lasting reservoirs of A. xylosoxidans.

Local Management of Anogenital Warts in Non-immunocompromised Adults: A Systematic Review and Meta-analyses of Randomized Controlled Trials.

INTRODUCTION: Several therapeutic options are available to manage anogenital warts (AGWs). However, no hierarchy of treatments is provided in the latest European and American recommendations. This study aimed to determine the efficacy and safety of local treatments for the management of AGWs. METHODS: A search was conducted through 12 databases from inception to August 2018. All randomized controlled trials (RCTs) in which at least one parallel treatment group composed of immunocompetent adults with AGWs received at least one provider-administered or patient-administered treatment were included. Risk of bias assessment and meta-analyses of aggregated study data were performed on the basis of the Cochrane Handbook, and quality of evidence evaluation followed the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Primary endpoints were complete clearance and recurrence at 3 months. RESULTS: Seventy RCTs (9931 patients) were included. All but four RCTs had a high risk of bias. CO2 laser was slightly more efficacious than cryotherapy [risk ratio (RR) 2.05; 95% confidence interval (CI) 1.61-2.62], with fewer recurrences at 3 months (RR 0.28; 95% CI 0.09-0.89). Electrosurgery was slightly more efficacious than cryotherapy. No differences in efficacy or side effects were found between cryotherapy and imiquimod or trichloroacetic acid. Podophyllotoxin gel was slightly more efficacious than podophyllotoxin cream. 5-Fluorouracil (5-FU) was slightly more efficacious and caused less erosion than CO2 laser (RR 1.37; 95% CI 1.11-1.70). CONCLUSION: The vast majority of included RCTs had a low level of evidence, thereby preventing the establishment of a hierarchy of treatments. Nevertheless, our results provide an overview of the main AGW treatments available for general practitioners and specialists. While provider-administered treatments are superior, patient-administered treatments (e.g., imiquimod, podophyllotoxin) are useful solutions for compliant patients. PROTOCOL REGISTRATION: PROSPERO-CRD42015025827.

Achromobacter spp. healthcare associated infections in the French West Indies: a longitudinal study from 2006 to 2016.

BACKGROUND: Bacteria of the Achromobacter genus, more particularly xylosoxidans species, are responsible for various healthcare associated infections (HAI) which are increasingly described since the last decade. Cystic fibrosis (CF) patients are considered as potential reservoirs in hospitals. We performed a retrospective study to estimate the frequencies of Achromobacter spp. HAI among patients from French West Indies, to determine characteristics of infected patients and establish a possible link between CF and infections. METHODS: All adults with at least one Achromobacter spp. positive sample and infection criteria in accordance with European official definitions of HAI, hospitalized in University Hospital of Martinique from 2006 to 2016 for more than 48 h, were included. Patient clinical features, immune status and underlying diseases were obtained from medical files. A list of CF patients was given by clinicians. Antibiotic-susceptibility profiles of the strains were determined using an automated method. RESULTS: Mean incidence density was 0.038/1000 days of hospitalization. Achromobacter spp. HAI evolved as an endemic situation with a low but pretty much stable incidence rate over the 11-year observation period. An epidemic peak was noticed in 2013. Among the 66 included patients, 56.1% were immunocompetent and no one had CF. Pneumonia and bacteraemia were the two main HAI. Among the 79 isolated strains, 92.4% were resistant to at least 1 major antibiotic and 16.4% met the definition of multidrug-resistant bacteria. CONCLUSIONS: This microorganism, little known in our country because of the scarcity of CF patients, represents a threat for both immunosuppressed and immunocompetent patients and a therapeutic challenge because of its high resistance.

One NF1 Mutation may Conceal Another.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disease with complete penetrance but high variable expressivity. NF1 is caused by loss-of-function mutations in the NF1 gene, a negative regulator of the RAS-MAPK pathway. The NF1 gene has one of the highest mutation rates in human disorders, which may explain the outbreak of independent de novo variants in the same family. Here, we report the co-occurrence of pathogenic variants in the NF1 and SPRED1 genes in six families with NF1 and Legius syndrome, using next-generation sequencing. In five of these families, we observed the co-occurrence of two independent NF1 variants. All NF1 variants were classified as pathogenic, according to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) guidelines. In the sixth family, one sibling inherited a complete deletion of the NF1 gene from her mother and carried a variant of unknown significance in the SPRED1 gene. This variant was also present in her brother, who was diagnosed with Legius syndrome, a differential diagnosis of NF1. This work illustrates the complexity of molecular diagnosis in a not-so-rare genetic disease.

Management of acute-stage chikungunya disease: Contribution of ultrasonographic joint examination.

OBJECTIVE: Chikungunya (CHIKV) is an arbovirus that causes acute, debilitating polyarthritis. Its diagnosis can be difficult for clinicians not used to managing joint diseases or detecting synovitis. Joint Doppler ultrasonography (DUS) is a simple, non-invasive examination, able to visualize synovitis. Its diagnostic and prognostic value in rheumatoid arthritis is well-established. METHODS: Patients with serologically proven acute arbovirosis where included. Clinical examination and joint count were performed (DAS score). Ultrasound examination was performed by another clinician - experienced in joint DUS - who also performed ultrasound joint score. Joints were examined by DUS in B-mode looking for: subcutaneous infiltration, effusion, tenosynovitis, erosion and Doppler signal. RESULTS: In our experience, joint DUS is able to detect effusions in 92.8% of painful joints, with 28.3% of the effusions emitting a high-power Doppler signal. No erosion was observed. Subcutaneous inflammatory infiltration of the ankles (aseptic cellulitis) was found in 28.6% of patients. CONCLUSION: Joint DUS is able to detect objective signs responsible for joint pain, which can be useful for practitioners not accustomed to this type of pathology. It also makes possible distinction between articular and periarticular manifestations.

Achromobacter xylosoxidans resistance to antiseptics and disinfectants is far from obvious.

BACKGROUND: Achromobacter xylosoxidans is described as being resistant to antiseptics and disinfectants. We studied in vitro the ability of five strains to survive and grow in such solutions, with and without starvation. METHODS: Bacterial suspensions in rich media and in distilled water were inoculated into eight antiseptics or disinfectants under conditions of use. RESULTS: All strains from cultures in distilled water survived in aqueous chlorhexidine and only environmental strains survived in a quaternary ammonium-based disinfectant. Survival did not exceed 30 min and no growth was observed. CONCLUSIONS: This study highlights a relationship between starvation and survival in antiseptics and disinfectants.

Prevalence of Anxiety and Depression Symptomatology in Adolescents Faced With the Hospitalization of a Loved One in the ICU.

OBJECTIVE: ICU experience is linked to anxiety and depression symptomatology in family members of patients. Minors may be forbidden from visiting. To bring practices in line with evidence, we determined the prevalence of anxiety and depression symptomatology in adolescents visiting a relative in the ICU. DESIGN: One-year prospective observational monocenter study. SETTING: Medical-surgical ICU, University Hospital of Martinique. PATIENTS: Forty-one patients intubated for more than 2 days; 53 adolescents (12-17 yr) first- to third-degree relatives in regular contact (minimum once a month) with patient before hospitalization. INTERVENTIONS: Adolescents with unrestricted ICU access completed a satisfaction survey, anxiety history questionnaire, and psychometric evaluation (Hospital Anxiety and Depression Scale) before the patient's 15th day of hospitalization and extubation. MEASUREMENTS AND MAIN RESULTS: Forty adolescents (75.5%) visited their relative. Possible and probable anxiety and depression symptomatology prevalence was 35.9% and 18.9%, respectively, with no significant difference according to ICU visiting status. Most (80%) reported a lack of information, 40% insufficient consideration, and 27.5% misunderstood the reason for hospitalization. Two (5%) regretted visiting. Probable anxiety and depression symptomatology was associated with first-degree relationship (odds ratio, 9.1 [95% CI, 1.1-78.9]; p = 0.045), past exposure to a traumatic event (odds ratio, 8.7 [1.1-69.0]; p = 0.040) and past sense of threat (odds ratio, 10.4 [1.1-94.5]; p = 0.038). CONCLUSIONS: Anxiety and depression symptomatology is common in adolescent family members of ICU patients. An open visiting policy for adolescents is recommended, with visit planning, information meetings, and individual support from ICU staff.

Pyoderma gangrenosum after orthopaedic or traumatologic surgery: a systematic revue of the literature.

INTRODUCTION: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterised by a painful ulceration mimicking infection of the operative site. To this day, there is still no general agreement on the medical and surgical treatment of PG. This systematic review of the literature aims to summarise recent studies about post-operative PG in orthopaedic surgery to improve its medical and surgical management. METHOD: In April 2017, we carried out an exhaustive review of the literature in MEDLINE, PubMed and Cochrane databases. Key words were pyoderma gangrenosum, orthopaedic surgery, and surgical wound infection. We identified 183 articles. After excluding articles reporting idiopathic PG, cases secondary to non-orthopaedic surgery, and cases about other subtypes of dermatosis, 30 studies were identified. We only included articles reporting PG after orthopaedic or trauma surgery. RESULTS: Thirty-one cases of PG have been reported, 58% (18) of which were in women, whose mean age was 56.5 years. Clinical signs were constant, the most frequently affected site was lower limbs [77.4% (24)] and delay of symptom onset was two to 17 days. Systemic corticosteroid therapy was systematic, polyvalent immunoglobulins were used in two cases and immunosuppressive drugs in one. Negative pressure therapy was used in seven cases and hyperbaric oxygen in three. DISCUSSION: Delayed diagnosis leads to one or more surgical revisions, which could have been avoided by using early and adapted medical treatment. Early onset of a painful and infected ulcer at the operating site in a patient at risk of PG is an indicator that dermatologist advice is recommended before surgical debridement. Surgical revision, outside the inflammatory phase and/or covered by a systemic corticosteroid therapy, does not lead to PG relapse. LEVEL OF EVIDENCE: IV: Systematic revue of the literature.

Cryotherapy to treat anogenital warts in nonimmunocompromised adults: Systematic review and meta-analysis.

BACKGROUND: Cryotherapy is one of the most commonly used therapeutic modalities to treat anogenital warts (AGWs), but this treatment was not clearly established in the recent international recommendations. OBJECTIVE: To compare the efficacy and safety of cryotherapy versus other AGW treatments. METHODS: Through a systematic search of 12 electronic databases, we identified 11 randomized controlled trials, screened from database inception through October 2016, that met the inclusion criteria (including immunocompetent adults with AGWs receiving cryotherapy in 1 of the comparison groups). Primary endpoint was complete clearance of AGW. Risk-for-bias assessment was based on Cochrane Handbook recommendations. Meta-analyses used Review Manager v5.3 software. RESULTS: Cryotherapy efficacy did not appear to differ from that of trichloroacetic acid, podophyllin, or imiquimod. Electrosurgery was weakly associated with better AGW clearance than cryotherapy (risk ratio [RR] 0.80, 95% confidence interval [CI] 0.65-0.99). Cryotherapy was associated with more immediate low-level adverse events (erythema, stinging, or irritation; RR 3.02, 95% CI 1.38-6.61) and immediate pain requiring oral analgesics (RR 2.11, 95% CI 1.07-4.17) but fewer erosions (RR 0.57, 95% CI 0.36-0.90). LIMITATIONS: All but 1 randomized-controlled trial had a high risk for bias. CONCLUSION: With low-level quality of the evidence, cryotherapy is an acceptable first-line therapy to treat AGWs.

Kite-surfers' sun risk in the tropics.

A preliminary inquiry, conducted on Martinique Island, sought to determine kite-surfers' sun-protection knowledge and behaviours. Results revealed good levels of knowledge and behaviours, but very frequent sunburns (74% had at least one sunburn during the last 6 months), with particularly severe sunburns exclusively among vacationers. These results argue for the double need to focus sunburn-prevention programs on vacationers and technically adapt sun-protection means to a tropical maritime environment.