Hydration and clinical warning signs of dengue fever in primary care: An observational prospective study.

OBJECTIVES: Dengue fever is an arbovirosis expanding worldwide, for which hydration has been reported to reduce the risk of hospitalization. Our objective was to estimate the volume of hydration in Reunionese patients with dengue. METHODS: A prospective observational study included patients presenting with a 'dengue-like' syndrome in ambulatory care. General practitioners recruited patients during consultation, and beverage consumption over the previous 24 hours was reported at two different times. Warning signs were defined according to the 2009 WHO guidelines. RESULTS: GPs included 174 patients from April to July 2019. Average oral hydration volume was 1863 mL and 1944 mL, at the 1st and 2nd medical consultations, respectively. Water was the most wide consumed liquid. Drinking at least 5 glasses of liquid was significantly associated with fewer clinical warning signs at the 1st medical consultation (p = 0.044). CONCLUSIONS: Sufficient hydration volume could prevent dengue warning signs. Further studies with standardized measurement of hydration would be needed.

MOVIE: a phase I, open-label, multicenter study to evaluate the safety and tolerability of metronomic vinorelbine combined with durvalumab plus tremelimumab in patients with advanced solid tumors.

BACKGROUND: Anti-programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) agents have only moderate antitumor activity in some advanced solid tumors (AST), including breast cancer (BC), prostate cancer (PC), cervical cancer (CC), and head and neck cancer (HNC). Combining anti-PD-L1 with anti-cytotoxic T-lymphocyte-associated protein (CTLA) and chemotherapy may significantly improve efficacy. PATIENTS AND METHODS: MOVIE is a multicohort phase I/II study examining the combination of anti-PD-L1 durvalumab (Durv; 1500 mg IV Q4W) plus anti-CTLA tremelimumab (Trem; 75 mg IV Q4W) with metronomic vinorelbine (MVino; 20-40 mg orally daily) in various AST resistant to conventional therapies. The primary objective of the phase I part was to determine the maximum tolerated dose (MTD) and recommended dose for phase II (RP2D). RESULTS: Among the 14 patients enrolled during phase I, including 13 women and 1 man, 9 had BC, 1 PC, 2 CC, and 2 miscellaneous cancers with high mutational loads. Median age was 53 years. A total of 12 patients were assessable for the dose-escalation part in which only one dose-limiting toxicity (DLT) was observed [one neutropenia without fever, grade (G) 4]. Two (14.3%), four (28.6%), and four (28.6%) patients had G ≥3 adverse events (AEs) related to MVino, Durv, and Trem, respectively. Treatment-related events included mostly clinical AEs with asthenia (eight G2; three G3), colitis (one G2, one G3), diarrhea (one G3), nausea (two G2), dry skin (two G2), maculopapular rash (one G3), and hyperthyroidism (three G2). No toxic death was reported. Preliminary data showed one patient (CC) who presented a complete response and four patients with stable disease (SD). CONCLUSIONS: MTD was not reached and dose level 2 (MVino 40 mg, Durv 1500 mg, Trem 75 mg) was selected as RP2D. The safety profile of the combination was manageable and consistent with previous reports of Trem + Durv or MVino. Phase II is currently ongoing in BC, PC, CC, HNC, and miscellaneous cohorts.

Description of Participants in the "Atout Age Mobility" Prevention Workshops at the University Hospital Center of La Réunion: A Prospective Study.

INTRODUCTION: As the population ages, loss of autonomy is becoming a priority public health issue. "Atout Age Mobility" prevention interventions for seniors aim to limit frailty, which is a predictive and reversible factor in the loss of autonomy and disability. OBJECTIVES: The objective of this study is to describe the impact of these interventions on the physical performance and quality of life of a pilot sample of participants. DESIGN: We conducted a prospective study named 5P PILOT with 3 months of follow up. SETTINGS: Subjects were recruited by convenience sampling from participants in the "Atout Age Mobility" workshops at Saint Joseph from 04/09/2017 to 29/01/2019. PARTICIPANTS: Retired people over 55 years old with no contraindications to physical activity recruited from participants in the "Atout Age Mobility" workshops in Saint Joseph. Intervention(s) (for clinical trials) or Exposure(s) (for observational studies): All participants completed 12 weeks of physical exercise called the "Atout Age Mobility" workshop, which lasted 60 minutes each week and was supervised by physical activity coaches. Main Outcome(s) and Measure(s): Physical performance was assessed by Short physical performance battery (SPPB), 10-m gait speed and grip strength measurement. Quality of life through the SF-36 test. RESULTS: Ninety-six patients were included and 55 (57.3%) completed the study. There was a significant improvement in gait speed (1.35±0.26m/s vs. 1.27±0.24m/s; p=0.008). There was no significant change in SF-36, grip strength dominant arm and SPPB at the 0.01 significance level. CONCLUSION: The "Atout Ages Mobility" workshops seem to significantly improve gait speed but not other aspects of physical performance or quality of life.

Foot ischemia related to essential thrombocytemia and atherosclerosis.

We report two cases of foot ischemia combining microvascular thrombosis related to essential thrombocytemia (ET) and a proximal ulcerating atherosclerotic plaque. This suggests that myeloproliferative neoplasms could also trigger distal embolism from an unstable atherosclerotic plaque by creating a prothrombotic status. These distal ischemic events were the first ET manifestation and therefore lead to myeloproliferative neoplasm diagnosis. In ET, thrombosis event can occur with a normal platelet count. Furthermore, hemogram should be regularly controlled among JAK2 muted patients considering the frequent evolution from isolated JAK2 mutation to ET.

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations.

Preliminary study on the effect of sex on skin cooling response during whole body cryostimulation (-110 °C): Modeling and prediction of exposure durations.

In order to determine the required duration of whole-body exposure to extreme cold (-110 °C) in males and females for achieving the same cold-induced response, a mathematical model of skin cooling kinetics was developed. This modeling is derived from the implementation of a new experimental cryotherapy protocol to obtain continuous skin temperature maps over time. Each 3-min whole-body cryostimulation session was divided into six incremental sessions of 30 s carried out over six consecutive days. Seventeen young, healthy subjects (8 males aged 22.6 ±3.0 years and 9 females aged 23.7 ±4.7 years) agreed to participate in this study. The smallest sex-related difference in temperature was found in the trunk area (2.93 °C after 3 min) while the greatest temperature drop was found in the lower limbs (5.92 °C after 3 min). The largest temperature variation was observed between the trunk and the lower limbs, and peaked at 2.67 °C in males and 6.99 °C in females. For both sexes, skin cooling kinetics showed a strong transient exponential type decrease followed by linear regression behavior. It appeared that for achieving the same cold-induced response, the required duration of cryostimulation is longer for males. For example, a trunk skin cooling of -12 °C could be achieved in 125s for females vs 170s for males (+36% longer); for the lower limbs, the same skin cooling magnitude could be reached after 87s for females vs 140s for males (+62% longer).

Affective response to whole-body cryotherapy: Influence of sex, body mass index, age, time of day, and past experience.

OBJECTIVE: Whole-Body Cryotherapy (WBC) has seen a recent surge in popularity with patients with inflammatory conditions, athletes, and even people seeking to improve general health and quality of life. WBC treatment usually requires participation in a dozen of 3-min long sessions. But compliance is considered difficult due to possible cold-induced unpleasant sensations. Based on hedonic psychology assumptions, ratings of pleasure-displeasure experienced during a taks or activity may be important to understand individual differences in attendance. METHODS: Two hundred fifty nine customers from two French cryocenters took the Feeling Scale immediately after their first WBC session. RESULTS: End affect appeared to be negatively valenced (M = -1.85, SD = 1.38, 95 % confidence interval: -2.02 to -1.68). Additional statistical analyses revealed a moderating influence of past experience, in women only. Similarly, BMI was found to be negatively associated with displeasure in women, but not in men. CONCLUSION: These findings are discussed and further research directions are suggested.

Effects of Whole-Body Cryostimulation (-90°C) on Somnolence and Psychological Well-Being in an Older Patient with Restless Legs Syndrome.

BACKGROUND: We aimed at evaluating the feasibility and effects of intense (i.e. -90°C) whole-body cryostimulation (WBC) on somnolence and psychological well-being in an older-adult patient diagnosed with restless legs syndrome (RLS). METHODS: An interrupted time series approach was used in which the efficacy of cryostimulation was evaluated by measuring self-reported fatigue, wake time sleepiness, and well-being several times prior to, during, and after exposure to treatment (i.e. daily 3-min sessions of intense WBC). RESULTS: No adverse event occurred. Reported levels of sleepiness decreased immediately following the beginning of the treatment phase. In the same time, self-reported well-being significantly increased. Effects sizes were of large magnitude. CONCLUSION: In summary, the present study demonstrated that daily exposure to extremely cold air in an enclosed space for 2 weeks was feasible and effective in promoting physical and psychological states in an older patient with sleep disturbances.

Evaluation of zeta potential of nanomaterials by electrophoretic light scattering: Fast field reversal versus Slow field reversal modes.

Zeta potential of nanomaterials designed to be used in nanomedicine is an important parameter to evaluate as it influences in vivo behaviour hence biological activity, efficacy and safety. As mentioned by the International Organization for Standardization (ISO), electrophoretic light scattering is a relevant method for evaluating zeta potential. The present work aimed to validate a new protocol based on the application of Fast Field Reversal mode and to explore its scope with nanomaterials investigated as nanomedicines. Its scope was then compared with that of an already validated protocol which uses both Fast Field Reversal and Slow Field Reversal modes. The new protocol was validated within the framework of the application of the Smoluchowski approximation. Its performances complied with the ISO standard. The protocol could be applied to evaluate mean zeta potential of soft nanomaterials including polymer-based nanoparticles and liposomes. However, it appeared unsuitable to evaluate zeta potential of dense nanomaterials including rutile titanium dioxide nanoparticles. Compared with the previously validated protocol which only applied to the determination of zeta potential of polymer nanoparticles, this new validated protocol gives access to the determination of zeta potential to a wider range of nanomedicines under conditions complying with quality control assessments.

[New strategies in specific care for benign prostatic hypertrophy in older men]. / Nouvelles stratégies dans la prise en charge de l'hypertrophie bénigne de la prostate chez le sujet âgé.

Beyond its scientific and ethical competencies, a good doctor is characterized by his communication skills. The ability to listen is fundamental. During an interview, the physician must keep in mind a bio-psycho-social approach while being able to hear the unspeakable and inaudible. Knowledge of patients and their relatives, which seems to be a specific knowledge for general practitioners, offers a lot of information. Among the main sensitive topics that the clinician must identify are: intrafamily violence, domestic violence, substance abuse and anxiety-depressive disorders. In order to improve, the practitioner can use tools such as the Calgary-Cambridge guide and techniques used in Motivational Maintenance.

Au-delà de ses compétences scientifiques et déontologiques, un bon médecin se caractérise par ses compétences communicationnelles. La capacité d'écoute est fondamentale. Durant un entretien, le médecin doit garder à l'esprit une approche bio-psycho-sociale tout en étant capable d'entendre l'indicible et l'inaudible. La connaissance des patients et de leurs proches, qui semble être une connaissance spécifique aux médecins généralistes, offre énormément d'informations. Parmi les principaux sujets sensibles que doit repérer le clinicien, se trouvent : la violence intrafamiliale, la violence conjugale, les abus de substances et les pathologies anxio-dépressives. Afin de s'améliorer, le praticien peut s'aider d'outils tels que le guide de Calgary-Cambridge ainsi que des techniques utilisées en Entretien Motivationnel.

Should whole body cryotherapy sessions be differentiated between women and men? A preliminary study on the role of the body thermal resistance.

The aim of this study was to investigate how body thermal resistance between sexes evolves over time in the recovery period after a WBC session and to show how this parameter should be considered as a key parameter in WBC protocols. Eighteen healthy participants volunteered for the study (10 males and 8 females). Temperature (core and skin) were recorded pre- and post (immediately and every 5 min until 35 min post) exposure to a single bout of WBC (30 s at -60 °C, 150 s at -110 °C). From both core and skin temperatures a bio-heat transfer model was applied which led to the analytical formulation of the body thermal resistance. An unsteady behavior presenting a similar time-evolution trend in the body insulative response is shown for both females and males, possibly due to the vasodilatation process following an intense peripheral vasoconstriction during the extreme cold. Females present a 37% higher inner thermal resistance than males when reaching an asymptotical thermal state at rest due to a higher concentration of body fat percentage. Adiposity of tissues inherent in fat mass percentage appears to be a key parameter in the body thermal resistance to be taken into account in the definition of appropriate protocols for males and females. The conclusions of this preliminary study suggest that in order to achieve the same skin effects on temperature and consequently to cool efficiency tissues in the same way, the duration of cryotherapy protocols should be shorter when considering female compared to male.

Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.

AIMS: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS: Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.

Effect of whole body cryotherapy interventions on health-related quality of life in fibromyalgia patients: A randomized controlled trial.

INTRODUCTION: Although fibromyalgia syndrome (SFM) affects 2-4 percent of adults, research has not identified a preferred therapeutic option for patients worldwide yet. Based on recent findings, it can be expected that whole body cryotherapy can improve health-reported quality of life by alleviating the symptoms of musculoskeletal pain and fatigue. OBJECTIVE: Our aim was to determine whether whole body cryotherapy only can result in improved perceived health and quality of life in fibromyalgia patients. METHODS: 24 patients with fibromyalgia diagnosis were randomized into 2 groups (n=11 in the whole body cryotherapy group, n=13 in the control group). In the whole body cryotherapy group, 10 sessions of whole body cryotherapy were performed (in addition to usual care) in a standard cryotherapy room over a duration of 8days. Subjects in the control group did not change anything in their everyday activities. Quality of life was assessed just before and one month after treatment. RESULTS: Compared with the control group, patients in the whole body cryotherapy group reported significantly improved for health-reported quality of life. These effects lasted for at least one month following intervention. CONCLUSION: Based on these findings, whole body cryotherapy can be recommended as an effective clinically adjuvant approach in the improvement of health-related quality of life in fibromyalgia patients.

[Evaluation of stone size before flexible ureteroscopy: Which measurement is best?] / Évaluation de la taille des calculs urinaires avant urétéroscopie souple : quelle mesure choisir ?

PURPOSE: To retrospectively assess the clinical utility in ureteroscopy (URS) planning of radiological parameters as predictor of stone-free status after a single flexible ureteroscopy. MATERIAL: Sixty-seven patients with renal stones treated by flexible URS were retrospectively evaluated. To assess the clinical utility of radiological parameters, relationships between stone-free (SF) status and stone burden (maximal diameter, calculated area, calculated volume, cumulative diameter, and tridimentionnal volume [V3D]) were analyzed using the area under the receiver operating characteristics curve and logistic regression. RESULTS: Maximal diameter (AUC=0.75), calculated area (AUC 0.79), calculated volume (AUC=0.79), cumulative diameter (AUC=0.80) and tridimensional volume (AUC=0.82) revealed ability to predict SF status after URS. CONCLUSION: Stone burden evaluation is critical in predicting SF status after a single URS. Planar and volumetric measurements showed equal ability to predict SF status. V3D is more accurate but diameter measurement remains easier in clinical practice. LEVEL OF EVIDENCE: 4.

[Diagnosis and treatment of nephrolithiasis and prevention of recurrences]. / Mise au point et traitement des lithiases rénales et prévention des récidives.

INTRODUCTION: despite fluctuations, the prevalence of nephrolithiasis has significantly increased during the last decades in industrialized nations worldwide (1 to 15 %), which has a significant impact on the cost of healthcare. This increased prevalence is mainly explained by diet modifications. Environmental, metabolic and genetic factors may also influence the formation of kidney stones. As a consequence, the medical management of this disease is preferentially multidisciplinary and involves urologists, nephrologists, radiologists, biologists and dietitians. Urological management : may be mandatory during any acute and/or remote phase of an episode of renal colic, in case of residual stones. Several techniques are available: insertion of double J stent, extracorporeal shock wave lithotripsy, ureteroscopy (flexible or rigid), percutaneous nephrolithotomy and more occasionally, open surgery. Nephrological management: is justified in the course of the acute episode and aims to identify the causal factor(s) of kidney stones formation. The diagnostic approach involves a thorough interrogation (personal medical and surgical history, details of the kidney stone disease and family medical history) as well as a metabolic assessment. Moreover, given the high rate of recurrence (about 50 % within 5 to 10 years), individualized secondary prevention measures are necessary. The recommendations should take into account the identified risk factors and any metabolic abnormalities.

INTRODUCTION: la néphrolithiase est une affection dont la prévalence (1 à 15 %) a beaucoup augmenté ces dernières décennies dans les pays industrialisés et a, de ce fait, un impact sur les dépenses en soins de santé. Cette augmentation de prévalence s'explique essentiellement par une modification des habitudes alimentaires. La survenue d'une néphrolithiase peut en outre, être influencée par des facteurs environnementaux, métaboliques voire génétiques. La prise en charge de cette affection est le plus souvent pluridisciplinaire, impliquant urologues, néphrologues, radiologues, biologistes et diététiciens. La prise en charge urologique peut être nécessaire en phase aiguë et/ou à distance de l'épisode de colique néphrétique, pour l'élimination éventuelle de calculs résiduels. Plusieurs techniques sont disponibles : la mise en place de sondes double J, la lithotritie extracorporelle, l'urétéroscopie (souple ou rigide) voire la néphrolithotomie percutanée et plus rarement la chirurgie ouverte. La prise en charge néphrologique est justifiée au décours de l'épisode aigu et vise à identifier la ou les cause(s) ayant conduit à la formation de calculs. La démarche diagnostique comporte un interrogatoire approfondi (antécédents personnels médicaux et chirurgicaux, histoire de la maladie lithiasique et antécédents familiaux) et un bilan métabolique. Par ailleurs, compte-tenu du taux élevé de récidive (environ 50 % dans les 5 à 10 ans), la mise en place de mesures individualisées de prévention secondaire est nécessaire. Ces recommandations doivent tenir compte des facteurs de risque identifiés et des éventuelles anomalies du bilan métabolique.

Clinical impact of NK-cell reconstitution after reduced intensity conditioned unrelated cord blood transplantation in patients with acute myeloid leukemia: analysis of a prospective phase II multicenter trial on behalf of the Société Française de Greffe de Moelle Osseuse et Thérapie Cellulaire and Eurocord.

Unrelated cord blood transplantation (UCBT) after a reduced intensity conditioning regimen (RIC) has extended the use of UCB in elderly patients and those with co-morbidities without an HLA-identical donor, although post-transplant relapse remains a concern in high-risk acute myeloid leukemia (AML) patients. HLA incompatibilities between donor and recipient might enhance the alloreactivity of natural killer (NK) cells after allogeneic hematopoietic stem-cell transplantation (HSCT). We studied the reconstitution of NK cells and KIR-L mismatch in 54 patients who underwent a RIC-UCBT for AML in CR in a prospective phase II clinical trial. After RIC-UCBT, NK cells displayed phenotypic features of both activation and immaturity. Restoration of their polyfunctional capacities depended on the timing of their acquisition of phenotypic markers of maturity. The incidence of treatment-related mortality (TRM) was correlated with low CD16 expression (P=0.043) and high HLA-DR expression (P=0.0008), whereas overall survival was associated with increased frequency of NK-cell degranulation (P=0.001). These features reflect a general impairment of the NK licensing process in HLA-mismatched HSCT and may aid the development of future strategies for selecting optimal UCB units and enhancing immune recovery.

[Efficacy and safety of available therapies in the management of idiopathic overactive bladder: A systematic review of the literature]. / Hyperactivité vésicale idiopathique : efficacité et tolérance des traitements pharmacologiques : revue de la littérature.

OBJECTIVE: Study the efficacy and adverse events of different pharmacological lines in the treatment of idiopathic overactive bladder (iOAB). METHODS: PubMed research on meta-analyses and randomized controlled trials (RCT) focused on the efficacy and adverse effects of anticholinergics, botulinum toxin and mirabegron since 2005. RESULTS: Ten meta-analyses of anticholinergics were selected; 16 randomized controlled trials (ERC) comparing botulinum toxin A to either anticholinergic or placebo and 10 ERC studying mirabegron. All the molecules studied showed efficacy compared to placebo in the treatment of iOAB. Anticholinergics remain the first-line pharmacological treatment allowing a significant reduction in the number (nb) of incontinence (-5/week) and in the number of urination (-4/week) as well as a perception of subjective improvement of the symptoms reported by 56 % of the patients treated against 41 % for the placebo group (RR: 1.39 [95 % CI: 1.28-1.51]). The most commonly reported side effect is dry mouth (30 % vs. 8 % in the placebo group). Injections of botulinum toxin A appear to be relatively comparable to anticholinergics in the first line with a decrease in urinary emergency incontinence (UTI) of 3.3/d in the toxin group versus 3.4/d in the anticholinergic group (P=0.81). There was also a higher rate of complete resolution of urinary incontinence in the toxin group (27 % vs. 13 % P=0.03) but significant adverse effects such as lower urinary tract infections (33 % vs. 13 % P>0.01). And the risk of using self-catheterization (5 % vs. 0 % P=0.01). In view of the invasive character of the toxin injections and their side effects, this treatment remains a 2nd line therapy. The same is true for mirabegron: similar efficacy (IUU number in the mirabegron group 50mg -1.74 vs. -1.53 In the solifenacin group 5mg, P>0.5) but different side effects with arterial hypertension (the oral dryness rate being comparable to that in the placebo group). The choice of use of anticholinergic or mirabegron should be based on the balance of efficacy/tolerance to be estimated for each patient. CONCLUSION: The different molecules have shown their efficacy in the treatment of iOAB with acceptable tolerance. There is a lack of direct comparisons between treatments available. Further studies are needed to evaluate the possible interest of a combination of these molecules as well as the search for predictive factors of response to these different therapies.