Long-term efficacy and safety of a hyaluronic acid dermal filler based on Tri-Hyal technology on restoration of midface volume.

INTRODUCTION: Art Filler Volume (AFV) is a hyaluronic acid (HA)-based filler formulated with "Tri-Hyal" technology, a unique combination of three sizes of HA chains. This study assessed AFV efficacy and safety over 18 months when used to restore midface volume. METHODS: During this open-label study, a maximum of 1.8 mL AFV was injected into each cheek area on Day 0 (D0). Subjects were evaluated at D21, when, if necessary, a retouch could be performed (maximum 1.2 mL per cheek). Subjects were evaluated at seven follow-up visits through to D540. The primary assessment was based on the evolution of the Medicis Midface Volume Scale (MMVS) grade on D21. Secondary outcomes were local and general adverse events, investigator- and subject-assessed Global Aesthetic Improvement Scale scores and changes in self-esteem. RESULTS: Of the 79 healthy Caucasians enrolled (mean age 54.8 years), 25 required a second injection. In the intention-to-treat population, mean overall MMVS scores improved significantly from D0 (3.2 ± 0.4) to D21 (1.8 ± 0.6) and D42 (1.7 ± 0.6) (all p < 0.0001). MMVS scores for each cheek also improved significantly, irrespective of retouch on D21: 22% of injections showed a persistent benefit at D540 without retouch. The most common adverse events were pain on palpation (19%), erythema (15%) and edema (13%); most were mild or moderate and resolved within 2 weeks. CONCLUSION: AFV produces a sustained objective and subjective midface volume restoration in female and male subjects, often without retouching, and was well tolerated.

Effectiveness of a Long-term Home-Based Exercise Training Program in Patients With COPD After Pulmonary Rehabilitation: A Multicenter Randomized Controlled Trial.

BACKGROUND: Most patients with COPD do not maintain exercise training after pulmonary rehabilitation (PR). RESEARCH QUESTION: Does a 12-month home-based, minimal-equipment strength training program after PR have an effect on dyspnea, exercise capacity, and patient-reported outcomes in patients with COPD? STUDY DESIGN AND METHODS: In a parallel-arm multicenter study across four Swiss PR clinics, patients with COPD were allocated randomly (1:1 ratio) into an intervention group (IG; home-based strength training program) or control group (CG; usual care). The primary outcome was change in Chronic Respiratory Questionnaire (CRQ) dyspnea scale score from baseline to 12 months. Secondary outcomes were change in exercise capacity (1-min sit-to-stand-test [1MSTST], 6-min walk test [6MWT]), health-related quality of life, exacerbations, and symptoms. We assessed the IG's experience by interviews at study end. Main analyses were based on the intention-to-treat approach, and adjusted linear regression models were used. RESULTS: One hundred twenty-three patients with COPD (IG, n = 61; CG, n = 62) were randomized, 61 of whom were women and whose mean ± SD age was 66.8 ± 8.1 years and mean ± SD FEV1 was 39.3 ± 15.3% predicted. One hundred four participants completed 12 months of follow-up (IG, n= 53; CG, n= 51). Of the 53 IG participants, 37 participants (70%) conducted the training until study end. We found no difference in change in CRQ dyspnea scale score over 12 months (adjusted mean difference, 0.28; 95% CI, -0.23 to 0.80; P = .27). We found moderate evidence for a difference in 1MSTST repetitions favoring the IG (adjusted mean difference, 2.6; 95% CI, 0.22-5.03; P = .033), but no evidence for an effect in other outcomes. Seventy-nine percent of the IG reported positive effects that they attributed to the training. INTERPRETATION: The home exercise program had no effect on dyspnea, but improved 1MSTST performance and patient-perceived fitness. The supported program was well accepted by patients with COPD and may facilitate continued exercise training at home. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03461887; URL: www. CLINICALTRIALS: gov.

Survival after inpatient or outpatient pulmonary rehabilitation in patients with fibrotic interstitial lung disease: a multicentre retrospective cohort study.

BACKGROUND: The impact of pulmonary rehabilitation (PR) on survival in patients with fibrotic interstitial lung disease (ILD) is unknown. Given the challenges conducting a large randomised controlled trial, we aimed to determine whether improvement in 6-minute walk distance (6MWD) was associated with better survival. METHODS: This retrospective, international cohort study included patients with fibrotic ILD participating in either inpatient or outpatient PR at 12 sites in 5 countries. Multivariable models were used to estimate the association between change in 6MWD and time to death or lung transplantation accounting for clustering by centre and other confounders. RESULTS: 701 participants (445 men and 256 women) with fibrotic ILD were included. The mean±SD ages of the 196 inpatients and 505 outpatients were 70±11 and 69±12 years, respectively. Baseline/changes in 6MWD were 262±128/55±83 m for inpatients and 358±125/34±65 m for outpatients. Improvement in 6MWD during PR was associated with lower hazard rates for death or lung transplant on adjusted analysis for both inpatient (HR per 10 m 0.94, 95% CI 0.91 to 0.97, p<0.001) and outpatient PR (HR 0.97, 95% CI 0.95 to 1.00, p=0.042). Participation in ≥80% of planned outpatient PR sessions was associated with a 33% lower risk of death (95% CI 0.49% to 0.92%). CONCLUSIONS: Patients with fibrotic ILD who improved physical performance during PR had better survival compared with those who did not improve performance. Confirmation of these hypothesis-generating findings in a randomised controlled trial would be required to definitely change clinical practice, and would further support efforts to improve availability of PR for patients with fibrotic ILD.

European Multicenter Prospective Study Evaluating Long-Term Safety and Efficacy of the Polycaprolactone-Based Dermal Filler in Nasolabial Fold Correction.

BACKGROUND: Age-related changes affecting facial areas can be corrected using minimally invasive dermal fillers. The use of polycaprolactone-dermal filler (PCL-filler) in aesthetics is increasing. OBJECTIVE: To evaluate the long-term safety and efficacy of the PCL-filler, in a European, multicenter, prospective study. MATERIALS AND METHODS: Subjects (n = 90) with moderate/severe nasolabial folds (Wrinkle Severity Rating Scale [WSRS]: 3 to 4) were treated on Day 0 with a single injection of similar volume on each side; safety and efficacy assessments were performed over an 18-month period. In 1 of the 3 study centers, safety was evaluated at 30 months. RESULTS: At Month 12 (M12; primary endpoint), 84% of subjects showed a ≥1-point improvement on the WSRS (M6: 92%; M18: 64%). From the investigator/subject's evaluation, from Day 7 to M12, Global Aesthetic Improvement was reported for >90% of subjects, with the effect maintained for up to 18 months in >80% of patients. Subjects/investigators reported high satisfaction and skin quality improvement. Most of the immediate injection-site reactions disappeared after 2 to 4 days. No severe or unexpected adverse events were reported. CONCLUSION: This study demonstrated the long-term safety and efficacy of the PCL-filler, with safety confirmed for up to 30 months.

Diagnosis, Prevention and Treatment of Stable COPD and Acute Exacerbations of COPD: The Swiss Recommendations 2018.

The Swiss National Guidelines 2013 for chronic obstructive pulmonary disease have been revised in order to acknowledge recent progress in diagnosis and management of this disease. The resulting new Swiss recommendations are based on best evidence from the literature, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2018 report and other published national guidelines. Misdiagnosis of chronic obstructive pulmonary disease is common and means that patients do not always receive optimal treatment. To improve the management of patients with chronic obstructive pulmonary disease in Switzerland, these recommendations encourage a more comprehensive assessment of patients, based on the combined assessment of symptoms, degree of airflow limitation, risk of exacerbation and the presence of comorbidities. Recommendations for evidence-based preventive measures, as well as pharmacological and non-pharmacological strategies for the management of both stable and acute exacerbations of chronic obstructive pulmonary disease are provided in this update.

Treatment of COPD Exacerbation in Switzerland: Results and Recommendations of the European COPD Audit.

BACKGROUND: The European COPD Audit initiated by the European Respiratory Society (ERS) evaluated the management of hospital admissions due to exacerbation of chronic obstructive pulmonary disease (COPD) in several European countries. Data on the treatment of severe acute exacerbations of COPD (AECOPDs) in Switzerland are scarce. OBJECTIVES: In light of the GOLD 2010 guidelines, this work aims to examine the quality of care for AECOPD and to provide specific recommendations for the management of severe AECOPD in Switzerland. METHODS: A total of 295 patients requiring hospital admission to 19 Swiss hospitals due to exacerbation of COPD during a predefined 60 days in 2011 were included in the study. We compared the Swiss data to the official GOLD 2010 recommendations and to the results of the other European countries. RESULTS: Approximately 43% of the Swiss patients with severe AECOPD were current smokers at hospital admission, compared to 33% of the patients in other European countries (p < 0.001). In Switzerland and in Europe, spirometry data were not available for most patients at hospital admission (65 and 60%, respectively; p = 0.08). In comparison to other European countries, antibiotics were prescribed 14% less often in Switzerland (p < 0.001). Only 79% of the patients in the Swiss cohort received treatment with a short-acting bronchodilator at admission. CONCLUSIONS: Considering the overall high standard of health care in Switzerland, in light of the GOLD 2010 guidelines we are able to make 7 recommendations to improve and standardize the management of severe AECOPD for patients treated in Switzerland.

The Emervel French survey: a prospective real-practice descriptive study of 1,822 patients treated for facial rejuvenation with a new hyaluronic acid filler.

BACKGROUND: Emervel consists of a range of 5 hyaluronic acid (HA) fillers (Touch, Classic, Lips, Deep, and Volume), with a fixed HA concentration (20 mg/mL), and various degrees of cross-linking and calibration. OBJECTIVES: To describe the current use of Emervel fillers in France. METHODS: Prospective multicenter, cross-sectional, real-practice, descriptive survey, including 1,822 patients injected with Emervel fillers for face rejuvenation by 58 French physicians between September 2010 and July 2011. The injection modalities were left to the respective physician's discretion. RESULTS: The physicians were dermatologists (52.3%), surgeons (43.8%), or general practitioners (14.1%). Nasolabial folds (NLF) with a mean severity 2.4 were mainly injected with Emervel Deep (51.0%) and Emervel Classic (36.0%) (mean volume: 1.0 mL), and primarily with the linear retrograde (LR) technique (89.3%). Marionette lines (ML), with a mean severity 2.6 were mainly injected with Emervel Deep (52.5%) and Emervel Classic (34.6%) (mean volume: 0.8 mL), and mainly with the LR technique (79.5%). More than 90% of patients had scores of 0 or 1 for erythema, bruising, edema, and pain. No serious adverse events were reported up to 15 months after the injection. CONCLUSION: These data could contribute to upcoming international consensus on optimal injection modalities of the Emervel range of HA fillers.

Humidified high flow nasal oxygen during respiratory failure in the emergency department: feasibility and efficacy.

OBJECTIVE: Heated and humidified high flow nasal cannula oxygen therapy (HFNC) represents a new alternative to conventional oxygen therapy that has not been evaluated in the emergency department (ED). We aimed to study its feasibility and efficacy in patients exhibiting acute respiratory failure presenting to the ED. METHODS: Prospective, observational study in a university hospital's ED. Patients with acute respiratory failure requiring > 9 L/min oxygen or with ongoing clinical signs of respiratory distress despite oxygen therapy were included. The device of oxygen administration was then switched from non-rebreathing mask to HFNC. Dyspnea, rated by the Borg scale and a visual analog scale, respiratory rate, and S(pO(2)) were collected before and 15, 30, and 60 min after beginning HFNC. Feasibility was assessed through caregivers' acceptance of the device in terms of practicality and perceived effect on the subjects, evaluated by questionnaire. RESULTS: Seventeen subjects, median age 64 y (46-84.7 y), were studied. Pneumonia was the most common reason for oxygen therapy (n = 9). HFNC was associated with a significant decrease in both dyspnea scores: Borg scale from 6 (5-7) to 3 (2-4) (P < .001), and visual analog scale from 7 (5-8) to 3 (1-5) (P < .01). Respiratory rate decreased from 28 breaths/min (25-32 breaths/min) to 25 breaths/min (21-28 breaths/min) (P < .001), and S(pO(2)) increased from 90% (88.5-94%) to 97% (92.5-100%) (P < .001). Fewer subjects exhibited clinical signs of respiratory distress (10/17 vs 3/17, P = .03). HFNC was well tolerated and no adverse event was noted. Altogether, 76% of healthcare givers declared preferring HFNC, as compared to conventional oxygen therapy. CONCLUSIONS: HFNC is possible in the ED, and it alleviated dyspnea and improved respiratory parameters in subjects with acute hypoxemic respiratory failure.

Efficacy and safety of a new hyaluronic acid dermal filler in the treatment of severe nasolabial lines - 6-month interim results of a randomized, evaluator-blinded, intra-individual comparison study.

BACKGROUND: Hyaluronic acid (HA) fillers are frequently used for the correction of facial soft tissue defects. AIM: To compare the efficacy and safety of a novel HA filler, HA(E) (Emervel Deep), with those of HA(P) (Restylane Perlane) in the treatment of severe nasolabial folds (NLF). PATIENTS/METHODS: A split-face, randomized and evaluator-blinded comparison study. Subjects were randomized to receive injection of HA(E) or HA(P) on their left or right NLF. Efficacy was evaluated based on the change in Wrinkle Severity Rating Scale (WSRS) from baseline. Local tolerability was assessed based on subject diary during the first 3 weeks after injection. Adverse events were also evaluated. RESULTS: At both weeks 12 and 24, the mean improvement in WSRS from baseline was significantly greater for HA(E) than for HA(P) (1.58±0.89 vs. 1.33±0.82 at week 24; P=0.002). Similar volume of both products was injected at baseline and touch-up. Both fillers were well tolerated, with similar worst score distribution and mean score for erythema, edema/swelling, bruising, and pruritus. Significantly less severe pain/tenderness was reported with HA(E) than with HA(P) (P<0.05). CONCLUSIONS: The new HA filler HA(E) provides better efficacy and similar local tolerability compared with HA(P) 6 months after the treatment of severe NLF.

Is mid-regional pro-atrial natriuretic peptide (MRproANP) an accurate marker of bacteremia in pyelonephritis?

INTRODUCTION: Mid-regional pro-atrial natriuretic peptide (MRproANP) increases during systemic infections and could possibly correlate with bacteremia. METHODS: We determined the characteristics of MRproANP for accuracy to detect positive blood culture. RESULTS: Bacteremia was positive in 58 (15%) of 347 patients. MRproANP levels increased in patients with bacteremia (98.4 pmol/L [interquartile range (IQR) 68.2-153.1] vs. 66.4 pmol/L [IQR 51.0-90.3], p <0.01). Performance of MRproANP to predict bacteremia [AUC = 0.69, 95%CI: 0.61-0.77] was equivalent to C-reactive protein (0.66 [95%CI: 0.59-0.74], p = 0.53) but less accurate than procalcitonin (0.78 [95%CI: 0.72-0.84], p <0.001). CONCLUSION: Although MRproANP increased in bacteremic patients with acute pyelonephritis, results of likelihood ratios discarded its use at bedside to predict bacteremia.

[Primary epiploic appendagitis: a nonsurgical and often misdiagnosed pathology]. / Appendagite épiploïque primitive: un diagnostic non chirurgical souvent méconnu.

INTRODUCTION: Primary epiploic appendagitis (PEA) is characterized by the association of localized abdominal pain with guarding. Depending on its localization, it may simulate acute appendicitis or diverticular sigmoiditis. Symptoms correspond to necrosis of the epiploic appendix due the torsion and vascular occlusion of the main epiploic pedicle. OBSERVATION: A 34-year-old man (BMI=29.38) was examined for persistent localized abdominal pain of the left lower quadrant three days after receiving systemic antibiotic therapy for what was diagnosed as mild diverticular sigmoiditis. Abdominal examination showed localized guarding in the left lower quadrant, with no fever, vomiting or diarrhea. Laboratory results showed no inflammatory response. Abdominal ultrasound showed no evidence of left hydronephrosis. Helical CT showed a localized zone of necrosis of the epiploic appendix of the sigmoid colon and thus confirmed the diagnosis without surgical exploration. Symptoms regressed after a week of analgesic treatment. DISCUSSION: PEA is a rare disease. It often occurs in mildly overweight adult men (around 35 years of age). The combination of acute abdomen with localized abdominal guarding and no evidence of fever or inflammation is the typical presentation. Surgical exploration (laparoscopy) can be avoided for diagnosis if helical CT shows a localized fatty zone situated outside the colon wall with a high attenuating dot point that corresponds to central necrosis of the epiploic appendix.

Contribution of a common single-nucleotide polymorphism to the genetic predisposition for erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited disorder of heme biosynthesis that results from a partial deficiency of ferrochelatase (FECH). Recently, we have shown that the inheritance of the common hypomorphic IVS3-48C allele trans to a deleterious mutation reduces FECH activity to below a critical threshold and accounts for the photosensitivity seen in patients. Rare cases of autosomal recessive inheritance have been reported. We studied a cohort of 173 white French EPP families and a group of 360 unrelated healthy subjects from four ethnic groups. The prevalences of the recessive and dominant autosomal forms of EPP are 4% (95% confidence interval 1-8) and 95% (95% confidence interval 91-99), respectively. In 97.9% of dominant cases, an IVS3-48C allele is co-inherited with the deleterious mutation. The frequency of the IVS3-48C allele differs widely in the Japanese (43%), southeast Asian (31%), white French (11%), North African (2.7%), and black West African (<1%) populations. These differences can be related to the prevalence of EPP in these populations and could account for the absence of EPP in black subjects. The phylogenic origin of the IVS3-48C haplotypes strongly suggests that the IVS3-48C allele arose from a single recent mutational event. Estimation of the age of the IVS3-48C allele from haplotype data in white and Asian populations yields an estimated age three to four times younger in the Japanese than in the white population, and this difference may be attributable either to differing demographic histories or to positive selection for the IVS3-48C allele in the Asian population. Finally, by calculating the KA/KS ratio in humans and chimpanzees, we show that the FECH protein sequence is subject to strong negative pressure. Overall, EPP looks like a Mendelian disorder, in which the prevalence of overt disease depends mainly on the frequency of a single common single-nucleotide polymorphism resulting from a unique mutational event that occurred 60,000 years ago.

[Prescription of retinoids in psoriasis]. / Prescrire les rétinoïdes dans le psoriasis.

Systemic retinoids inhibit keratinisation and have anti-inflammatory properties. In 30 years, they have revolutionised numerous aspects of dermatological practice, particularly in the management of psoriasis. In the management strategy of severe psoriasis, acitretin has first place of the medications currently available. It is the on-going treatment par excellence. It is even more effective and better tolerated when doses are progressively increased in steps to reach the optimal effective dose that corresponds to the maximum tolerated dose. The dose is adjusted according to this tolerance and not to standardise doses. With this precondition, the secondary effects are benign, sometimes bothersome with an increasing fragility of the mucous membranes of the epithelia and the phaneres, bearing witness to the medication impregnation of tissues and the interference with the natural retinoids. Due to their teratogenic risk, the only restriction concerns women of childbearing age in whom all prescription of retinoids is subject to some legal considerations that are indispensable to respect.