Measurements of dune erosion processes during the RealDune/REFLEX experiments.

Nearshore hydro- and morphodynamic data were collected during a field experiment under calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime. The experiment was conducted on the Sand Engine near Kijkduin, the Netherlands, from October 18, 2021, to January 7, 2022. Two artificial unvegetated dunes were constructed just above the high water line to measure storm erosion and dune impacts from higher water levels and waves. During the experiment, three storms occurred that resulted in significant erosion of both dunes. The collected hydrodynamic data include pressure sensor and velocimeter data along two cross-shore transects. The collected morphodynamic data include bathymetry and topography surveys, optical backscatter sensor data in the inner surf zone, and a continuous cross-shore line-scanning lidar data set of the dune face. This comprehensive data set can be used to (1) study relevant nearshore hydrodynamic and morphodynamic processes that occur during calm conditions, moderate conditions, and storm conditions with dune erosion in the collision regime, and (2) validate existing dune erosion models.

Development of a Conceptual Model for the Patient Experience of Immunoglobulin A Nephropathy (IgAN): A Qualitative Literature Review.

INTRODUCTION: Immunoglobulin A nephropathy (IgAN) is a kidney disorder that can lead to progressive kidney disease. Currently, there lacks a comprehensive overview of the symptoms and impacts experienced by those living with IgAN that would help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in clinical trials. The aim of this study was to develop a conceptual model of the adult and pediatric patient experience of IgAN, including disease signs and symptoms, treatment side effects, and impact on functioning and well-being. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and children diagnosed with IgAN. Data sources were identified through an electronic database search of journal articles (MEDLINE, Embase, PsycINFO; June 2021), hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from articles. Extracted data were qualitatively analyzed, aided by ATLAS.ti v7. Codes were applied to data; concepts (i.e., symptoms) were identified, named, and refined. A conceptual model was developed by grouping related concepts into domains. RESULTS: In total, five sources were identified for analysis: two journal articles, two online anthologies of patient stories, and one patient organization-sponsored "Voice of the Patient" meeting report. Conceptual model symptom domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight gain, sleep problems, urinary problems, and gastrointestinal problems. Impact domains included emotional/psychological well-being, physical functioning/activities of daily living, social functioning, work/school, and relationships. CONCLUSIONS: Secondary analysis of published qualitative literature permitted development of a novel conceptual model depicting the patient experience of IgAN; however, its depth is limited by a lack of available literature. Further qualitative research is recommended to refine and/or confirm the concepts and domains, determine any relationships between them, and explore the outcomes that are most meaningful to patients. The refined model will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future IgAN clinical trials.

Development of a Conceptual Model for the Patient Experience of Focal Segmental Glomerulosclerosis (FSGS): A Qualitative Targeted Literature Review.

INTRODUCTION: Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease and can progress to end stage kidney disease (ESKD). An overview of symptoms and impacts of the disease experienced will help inform the selection or development of fit-for-purpose clinical outcome assessments (COA) to be used in FSGS clinical trials. This study aimed to develop a conceptual model (CM) of the adult and pediatric patient experience of FSGS including disease signs/symptoms, treatment side-effects, and impact on functioning and wellbeing. METHODS: This study comprised a systematic review and thematic analysis of qualitative studies with adults and pediatric patients diagnosed with FSGS. Data sources were identified through an electronic database search of journal articles (Medline, Embase, PsycINFO; June 2021) and hand-searching of conference proceedings, patient advocacy group websites, and gray literature. Non-English articles were excluded. Identified data (patient/caregiver quotes, author summaries, and interpretations of patient experiences) were extracted from the articles. Extracted data were qualitatively analyzed aided by ATLAS.ti v7. Codes were applied to data and concepts (symptoms/impacts) were identified, named, and refined. A CM was developed by grouping related concepts into domains. RESULTS: In total, 12 sources were identified for analysis: 6 journal articles and 6 series of patient testimonials. Salient sign/symptom/side-effect domains included swelling/puffiness (edema), pain/aches/discomfort, fatigue, weight changes, skin problems, respiratory problems, and sleep problems. Salient impact domains included emotional/psychological wellbeing, physical functioning/activities of daily living, social functioning, and work/school. CONCLUSION: Secondary analysis of published qualitative literature permitted development of a CM describing the adult and pediatric experience of FSGS. Concept elicitation interviews are recommended to refine the CM, confirm the salient/most bothersome concepts, and confirm the extent of impact on daily life. The refined CM will provide a useful tool to inform the selection, development, and/or amendment of COAs for use in future FSGS clinical trials.

Experiences of nurses and midwives with disabilities: A scoping review.

AIM: To identify the extent and type of evidence exploring the workplace experiences of nurses and midwives with disabilities. DESIGN: Scoping Review. DATA SOURCES: Four electronic databases were systematically searched in February 2022 to identify studies discussing the experiences of nurses and midwives with disabilities, published between 2012 and 2022. Google Scholar and Theses Global were also searched. REVIEW METHODS: All search results, irrespective of their format, were uploaded to Covidence to assist with the selection of evidence. Studies discussing the experiences of nurses and midwives with disabilities were included. Two reviewers conducted screening and data extraction independently, and a third reviewer resolved conflicts. RESULTS: Searches identified 130 studies. After screening for title and abstract, full-text review identified 23 studies for data extraction and analysis. Data were summarized and presented in tabular form under two categories (1) workplace experiences and (2) impact in the workplace. Results were presented in a descriptive, narrative form with accompanying tables. CONCLUSION: The nurse or midwife can be impacted significantly by disability. Currently, little is known about the workplace experiences of nurses and midwives with disabilities. Therefore, a better understanding of the experiences of the nurse and midwives with disabilities is important to increase diversity, equity, accessibility, and inclusion. IMPACT: Shortage of nurses and midwives worldwide highlights the need to understand why nurses and midwives with disabilities decide to leave the profession. Further research exploring the experiences of nurses or midwives with disabilities will help identify support requirements, develop frameworks for reasonable adjustment accommodations, and assist with future workforce planning. The EQUATOR guidelines for PRISMA have been met. No Patient or Public Contribution.

Efficacy of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate for the prevention of heartworm disease in dogs.

Dirofilaria immitis, the mosquito-borne agent of dirofilariosis, a chronic and sometimes fatal cardiopulmonary canine disease, is endemic in most warm and temperate regions in the world. The efficacy of an oral endectoparasiticide product (test product or TP) combining moxidectin, afoxolaner, and pyrantel pamoate was evaluated for the prevention of heartworm disease in dogs, in two laboratory and one field studies. In each laboratory study, 20 D. immitis-naïve beagle dogs were experimentally infected with D. immitis. Ten control dogs were sham-treated, and ten dogs were administered the TP targeting the minimum effective dose, six times monthly and starting 30 days post infection. At necropsy seven months after inoculations, no heartworms were found in any of the TP treated dog, whereas 19 to 42 live heartworms were found in the control dogs. In each study, treatment efficacy was 100% and the difference between treated and untreated groups was highly significant (p < 0.0001). A field study was conducted through the full transmission season in several heartworm-endemic regions of the United States. One hundred and twenty client-owned dogs that were negative for D. immitis at enrollment were administered twelve monthly oral doses of the TP at label dose. Blood tests for D. immitis antigen and modified Knott's tests for microfilariae remained negative through the full duration of the study, demonstrating that all dogs were protected from heartworm infection during the full transmission season. These studies demonstrated that TP administered monthly for at least six doses is effective at preventing dirofilariosis.

Key measurement concepts and appropriate clinical outcome assessments in pediatric achondroplasia clinical trials.

BACKGROUND: This study aimed to identify fit-for-purpose clinical outcome assessments (COAs) to evaluate physical function, as well as social and emotional well-being in clinical trials enrolling a pediatric population with achondroplasia. Qualitative interviews lasting up to 90 min were conducted in the US with children/adolescents with achondroplasia and/or their caregivers. Interviews utilized concept elicitation methodology to explore experiences and priorities for treatment outcomes. Cognitive debriefing methodology explored relevance and understanding of selected COAs. RESULTS: Interviews (N = 36) were conducted with caregivers of children age 0-2 years (n = 8) and 3-7 years (n = 7) and child/caregiver dyads with children age 8-11 years (n = 15) and 12-17 years (n = 6). Children/caregivers identified pain, short stature, impacts on physical functioning, and impacts on well-being (e.g. negative attention/comments) as key bothersome aspects of achondroplasia. Caregivers considered an increase in height (n = 9/14, 64%) and an improvement in limb proportion (n = 11/14, 71%) as successful treatment outcomes. The Childhood Health Assessment Questionnaire (CHAQ) and Quality of Life in Short Stature Youth (QoLISSY-Brief) were cognitively debriefed. CHAQ items evaluating activities, reaching, and hygiene were most relevant. QoLISSY-Brief items evaluating reaching, height bother, being treated differently, and height preventing doing things others could were most relevant. The CHAQ and QoLISSY-Brief instructions, item wording, response scales/options and recall period were well understood by caregivers and adolescents age 12-17. Some children aged 8-11 had difficulty reading, understanding, or required caregiver input. Feedback informed minor amendments to the CHAQ and the addition of a 7-day recall period to the QoLISSY-Brief. These amendments were subsequently reviewed and confirmed in N = 12 interviews with caregivers of children age 0-11 (n = 9) and adolescents age 12-17 (n = 3). CONCLUSIONS: Achondroplasia impacts physical functioning and emotional/social well-being. An increase in height and improvement in limb proportion are considered to be important treatment outcomes, but children/adolescents and their caregivers expect that a successful treatment should also improve important functional outcomes such as reach. The CHAQ (adapted for achondroplasia) and QoLISSY-Brief are relevant and appropriate measures of physical function and emotional/social well-being for pediatric achondroplasia trials; patient-report is recommended for age 12-17 years and caregiver-report is recommended for age 0-11 years.

Validation of patient-reported vaso-occlusive crisis day as an endpoint in sickle cell disease studies.

Individuals with sickle cell disease (SCD) experience vaso-occlusive crises (VOC). Historically, VOC episodes have been assessed through medical utilization, thereby excluding events managed at home. In order to validate a daily patient-reported outcome for patients with SCD to accurately report their VOC status and experience of a pain crisis, a SCD Diary was included in Evaluation of Longitudinal Pain Study in Sickle Cell Disease (ELIPSIS), a longitudinal, six-month, non-interventional study. The daily patient-completed diary included a description of SCD pain crisis, followed by questions on: pain crisis in the past 24 h (VOC Day question; respective response yes or no), worst pain, tiredness, and functioning. Thirty-five patients with SCD participated in ELIPSIS. Analyses were performed to validate the patient-reported VOC Day. Mean symptoms and functioning scores on the first or last VOC Day of a VOC Event were compared using t-tests with the mean of the three non-VOC Days before and after the event. Mean severity of symptoms and functioning scores on all VOC Days compared to all non-VOC Days were higher, with statistically significant mean differences between first/last VOC Days and respective three non-VOC Days (p's < .01). A subset of patients (n = 15) and caregivers (n = 9) were interviewed to evaluate their understanding of the SCD Diary questions. Nearly all confirmed that the pain crisis description accurately described the VOC experience, and participants expressed confidence differentiating SCD crisis pain from everyday pain. These results demonstrate patients can reliably report their experiences with VOC-related pain crises using the SCD Diary.

A Retrospective Study of Clinical and Economic Burden of Focal Segmental Glomerulosclerosis (FSGS) in the United States.

INTRODUCTION: Information on the economic burden of focal segmental glomerulosclerosis (FSGS) is sparse. This study characterized health care resource utilization (HCRU) and costs in patients with FSGS, and evaluated the impact of nephrotic range proteinuria on these outcomes. METHODS: This retrospective, observational cohort study used administrative claims data from the Optum Clinformatics Data Mart Database from October 2015 to December 2019. Patients with FSGS (n = 844; first claim = index event) between April 2016 and December 2018 were matched on index date, age, sex, and race to non-FSGS controls (n = 1688). FSGS nephrotic range (urine protein/creatinine ratio >3000 mg/g or albumin/creatinine ratio >2000 mg/g) and non-nephrotic subpopulations were identified. Baseline comorbidities, 12-month post-index all-cause HCRU and costs (per patient per year [PPPY]), and immunosuppressant prescriptions were compared between matched cohorts and between FSGS subpopulations. RESULTS: Comorbidity burden was higher in FSGS. Of 308 patients with available urine protein/creatinine ratio/albumin/creatinine ratio results, 36.4% were in nephrotic range. All-cause HCRU was higher in FSGS across resource categories (all P < 0.0001); 50.6% of FSGS and 23.3% of controls were prescribed glucocorticoids (P < 0.0001). Mean total medical costs were higher in FSGS ($59,753 vs. $8431 PPPY; P < 0.0001), driven by outpatient costs. Nephrotic range proteinuria was associated with higher all-cause inpatient, outpatient, and prescription costs versus nonnephrotic patients (all P < 0.0001), resulting in higher total costs ($70,481 vs. $36,099 PPPY; P < 0.0001). CONCLUSIONS: FSGS is associated with significant clinical and economic burdens; the presence of nephrotic range proteinuria increased the economic burden. New treatment modalities are needed to reduce proteinuria, help improve patient outcomes, and reduce HCRU and associated costs.

Target animal safety evaluation of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for cats.

The safety profile of NexGard® Combo, a novel topical product for cats combining esafoxolaner, eprinomectin and praziquantel, for the treatment and prevention of internal and external parasites, was evaluated in kittens, in two margin-of-safety studies (Studies #1 and #2), and in an oral tolerance study (Study #3). In the margin of safety studies, kittens were dosed several times topically with multiples of the maximum exposure dose (1×): in Study #1, 3× and 5× doses four times at 2-week intervals; in Study #2, 1×, 3× and 5× doses six times at 4-week intervals. In Study #3, kittens were dosed orally once with a 1× dose. Furthermore, in Study #1, another group of kittens was dosed topically twice at a 4-week interval with a formulation of esafoxolaner as the sole active ingredient dosed at 23×. Physical examinations and clinical pathology analyses were performed throughout the studies, followed by necropsy and detailed histopathological evaluation in Studies #1 and #2. No significant treatment related effects were observed in the three studies, except for one occurrence of reversible neurological signs attributed to eprinomectin in one cat after the third 5× dose in Study #2, with clinical signs observed nine hours after dosing, pronounced for a few hours, significantly improved the next day, and absent 2 days after dosing. In conclusion, NexGard® Combo was demonstrated safe in kittens following repeated topical administrations and following oral ingestion, and very high topical doses of esafoxolaner were well tolerated.

TITLE: Évaluation de la sécurité des animaux cibles d'une nouvelle combinaison topique d'esafoxolaner, d'éprinomectine et de praziquantel pour les chats. ABSTRACT: Le profil de sécurité de NexGard® Combo, un nouveau produit topique destiné aux chats associant l'esafoxolaner, l'éprinomectine et le praziquantel, pour le traitement et la prévention des parasites internes et externes, a été évalué chez les chatons, dans deux études de marge de sécurité (études n° 1 et n° 2) et dans une étude de tolérance orale (étude n° 3). Dans les études de marge de sécurité, les chatons ont reçu plusieurs doses topiques avec des multiples de la dose maximale d'exposition (1×) : dans l'étude n° 1, des doses 3× et 5×, quatre fois, à des intervalles de 2 semaines ; dans l'étude n° 2, des doses 1×, 3× et 5×, six fois, à des intervalles de 4 semaines. Dans l'étude n° 3, les chatons ont reçu une dose orale une fois avec une dose 1×. De plus, dans l'étude n° 1, un autre groupe de chatons a reçu une dose topique deux fois à 4 semaines d'intervalle avec une formulation d'esafoxolaner comme seul ingrédient actif dosé à 23×. Des examens physiques et des analyses de pathologie clinique ont été effectués tout au long des études, suivis d'une autopsie et d'une évaluation histopathologique détaillée dans les études n° 1 et n° 2. Aucun effet significatif lié au traitement n'a été observé dans les trois études, à l'exception d'une occurrence de signes neurologiques réversibles attribués à l'éprinomectine chez un chat après la troisième dose 5× dans l'étude n° 2, avec des signes cliniques observés neuf heures après l'administration, prononcés pour quelques heures, considérablement améliorée le lendemain et absent 2 jours après l'administration. En conclusion, NexGard® Combo s'est avéré sûr chez les chatons après des administrations topiques répétées et après une ingestion orale, et des doses topiques très élevées d'esafoxolaner ont été bien tolérées.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel against Amblyomma americanum in cats.

Esafoxolaner, a purified enantiomer of afoxolaner with insecticidal and acaricidal properties, is combined with eprinomectin and praziquantel in NexGard® Combo, a novel topical endectoparasiticide product for cats. The efficacy of this novel formulation was assessed in two experimental studies against induced infestations with Amblyomma americanum, a tick species of major importance, highly prevalent in a large southeastern quarter of the United States. In each study, 10 cats were randomly allocated to a placebo control group and 10 cats to a novel formulation treated group. Infested cats were treated topically once at the minimum recommended dose. Both studies were designed to test curative efficacy on existing infestation, 72 h after treatment, and to test preventive efficacy, 72 h after subsequent weekly (Study #1) or fortnightly (Study #2) infestations for one month. For each infestation, all cats were infested with 50 unfed adult A. americanum. At each tick count, in both studies, at least 8 in 10 placebo control cats were infested with 13 (26%) or more live ticks, demonstrating adequate infestation throughout the studies. Curative efficacy of the novel formulation was 99% in both studies; preventive efficacy was 92% and 100% for at least one month.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre Amblyomma americanum chez le chat. ABSTRACT: L'esafoxolaner, un énantiomère purifié d'afoxolaner aux propriétés insecticides et acaricides, est associé à l'éprinomectine et au praziquantel dans NexGard® Combo, un nouvel endectoparasiticide topique pour chats. L'efficacité de cette nouvelle formulation a été évaluée dans deux études expérimentales contre les infestations induites par Amblyomma americanum, une espèce de tique d'importance majeure, très répandue dans un grand quart sud-est des États-Unis. Dans chaque étude, dix chats ont été répartis au hasard dans un groupe témoin placebo et dix chats dans un groupe traité par une nouvelle formulation. Les chats infestés ont été traités une fois par voie topique à la dose minimale recommandée. Les deux études ont été conçues pour tester l'efficacité curative sur une infestation existante, 72 heures après le traitement, et pour tester l'efficacité préventive, 72 heures après des infestations hebdomadaires (étude n° 1) ou bimensuelles (étude n° 2) pendant un mois. Pour chaque infestation, tous les chats étaient infestés par 50 A. americanum adultes non nourris. À chaque décompte de tiques, dans les deux études, au moins 8 chats sur 10 du groupe témoin placebo étaient infestés de 13 (26 %) ou plus tiques vivantes, ce qui démontre une infestation adéquate tout au long des études. L'efficacité curative de la nouvelle formulation était de 99 % dans les deux études, l'efficacité préventive était de 92 % et 100 % pendant au moins un mois.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel in cats against Toxocara cati and Dipylidium caninum.

NexGard® Combo, a novel topical antiparasitic product for cats, combines the insecticide/acaricide esafoxolaner with the nematocide eprinomectin and cestodicide praziquantel. The efficacy of this combination product was evaluated against two common endoparasites of global occurrence in cats, the nematode Toxocara cati and the cestode Dipylidium caninum, in five controlled studies using naturally or experimentally infected cats with parasites of North American, South African or European origin. Cats evaluated in these studies harbored patent infection of the target parasite confirmed through a pre-treatment fecal examination. In each study, cats were allocated randomly to two groups of equal size (8 or 10 cats per group per study), one group treated with a placebo (mineral oil) and the other with NexGard® Combo. Both treatments were administered once as a spot-on at 0.12 mL per kg body weight to deliver the minimum label dosage (1.44 mg/kg esafoxolaner, 0.48 mg/kg eprinomectin, and 10.0 mg/kg praziquantel) to the NexGard® Combo-treated cats. To determine efficacy, geometric mean parasite counts seven to 12 days after treatment of placebo-treated (control) cats and NexGard® Combo-treated cats were compared. The efficacy of NexGard® Combo was 98.8% and 100% against adult T. cati in two studies; and 98.0%, 98.3% and 93.2% against D. caninum in three studies. No adverse events related to treatment were observed throughout the studies. These studies demonstrate high efficacy against these major feline endoparasites and excellent acceptability of the novel topical antiparasitic combination of esafoxolaner, eprinomectin and praziquantel.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel chez le chat contre Toxocara cati et Dipylidium caninum. ABSTRACT: NexGard® Combo, un nouveau produit antiparasitaire topique pour chats combine l'insecticide/acaricide esafoxolaner avec le nématocide éprinomectine et le cestodicide praziquantel. L'efficacité de ce produit d'association a été évaluée contre deux endoparasites communs d'occurrence mondiale chez le chat, le nématode Toxocara cati et le cestode Dipylidium caninum, dans cinq études contrôlées utilisant des chats naturellement ou expérimentalement infectés par des parasites d'origine nord-américaine, sud-africaine ou européenne. Les chats évalués dans ces études présentaient une infection patente du parasite cible confirmée par un examen fécal avant le traitement. Dans chaque étude, les chats ont été répartis au hasard en deux groupes de taille égale (8 ou 10 chats par groupe et par étude), un groupe traité avec un placebo (huile minérale) et l'autre avec NexGard® Combo. Les deux traitements ont été administrés une fois par spot-on à 0,12 mL par kg de poids corporel pour délivrer la dose minimale indiquée sur l'étiquette (1,44 mg/kg d'esafoxolaner, 0,48 mg/kg d'éprinomectine et 10,0 mg/kg de praziquantel) pour les chats du groupe traité par NexGard® Combo. Pour déterminer l'efficacité, les nombres moyens géométriques de parasites sept à 12 jours après le traitement des chats traités par placebo (témoins) et des chats traités par NexGard® Combo ont été comparés. L'efficacité de NexGard® Combo était de 98,8 % et de 100 % contre T. cati adulte dans deux études, et de 98,0 %, 98,3 % et 93,2 % contre D. caninum dans trois études. Aucun événement indésirable lié au traitement n'a été observé tout au long des études. Ces études démontrent la grande efficacité contre ces principaux endoparasites félins et l'excellente acceptabilité de la nouvelle combinaison antiparasitaire topique d'esafoxolaner, d'éprinomectine et de praziquantel.

Efficacy of a novel topical combination of esafoxolaner, eprinomectin and praziquantel for the prevention of heartworm disease in cats.

NexGard® Combo is a novel topical endectoparasiticide formulation for cats combining the insecticide/acaricide esafoxolaner, the nematodicide eprinomectin and the cestodicide praziquantel. The efficacy of this novel formulation for the prevention of heartworm disease in cats was tested in two experimental studies using an induced infection model and a randomized, blinded, placebo-controlled study design, and two USA isolates of Dirofilaria immitis. In each study, 20 naïve cats were each inoculated sub-cutaneously with 100 third-stage larvae of D. immitis 30 days before treatment. Following randomization to two treatment groups of ten cats, each cat was treated topically once, either with the minimum recommended dose of the novel formulation, or with an identical volume of placebo. Five months after treatment (6 months after infections), the cats were humanely euthanized for parasite recovery and count. Efficacy was calculated by comparison of the numbers of adult D. immitis recovered in the control and in the novel formulation groups. In the control groups of each study, D. immitis were recovered in seven and nine cats (respective worm counts ranges 1-7 and 1-16, respective geometric means 1.6 and 5.1). In both studies, none of the treated cats harbored any D. immitis at necropsy and the calculated efficacy of the novel formulation was 100%. There were no adverse reactions related to treatment with the novel formulation. The results of these two studies demonstrate that a topical NexGard® Combo application at the minimum label dose is well-tolerated and efficacious in preventing heartworm disease in cats.

TITLE: Efficacité d'une nouvelle association topique d'esafoxolaner, d'éprinomectine et de praziquantel pour la prévention de la dirofilariose chez les chats. ABSTRACT: NexGard® Combo est une nouvelle formulation d'endectoparasiticide topique pour chats combinant l'insecticide/acaricide esafoxolaner, le nématodicide éprinomectine et le cestodicide praziquantel. L'efficacité de cette nouvelle formulation pour la prévention de la maladie du ver du cœur (dirofilariose) chez les chats a été testée dans deux études expérimentales utilisant un modèle d'infection induite et une conception d'étude randomisée, en aveugle et contrôlée par placebo, et deux isolats américains de Dirofilaria immitis. Dans chaque étude, vingt chats naïfs ont chacun été inoculés par voie sous-cutanée avec 100 larves de troisième stade de D. immitis 30 jours avant le traitement. Après randomisation dans deux groupes de traitement de dix chats, chaque chat a été traité par voie topique une fois, soit avec la dose minimale recommandée de la nouvelle formulation, soit avec un volume identique de placebo. Cinq mois après le traitement (6 mois après les infections), les chats ont été euthanasiés sans cruauté pour la récupération et le dénombrement des parasites. L'efficacité a été calculée en comparant les nombres de D. immitis adultes collectés dans le groupe contrôle et dans le groupe ayant reçu la nouvelle formulation. Dans les groupes témoins de chaque étude, D. immitis a été trouvé chez sept et neuf chats (les nombres de vers respectifs variaient de 1 à 7 et de 1 à 16, les moyennes géométriques respectives étaient 1,6 et 5,1). Dans les deux études, aucun des chats traités ne présentait de D. immitis lors de l'autopsie et l'efficacité calculée de la nouvelle formulation était de 100%. Il n'y a eu aucun effet indésirable lié au traitement avec la nouvelle formulation. Les résultats de ces deux études démontrent qu'une application topique de NexGard® Combo à la dose minimale indiquée sur l'étiquette est bien tolérée et efficace pour prévenir la dirofilariose chez les chats.

Weak evidence of country- and institution-related status bias in the peer review of abstracts.

Research suggests that scientists based at prestigious institutions receive more credit for their work than scientists based at less prestigious institutions, as do scientists working in certain countries. We examined the extent to which country- and institution-related status signals drive such differences in scientific recognition. In a preregistered survey experiment, we asked 4,147 scientists from six disciplines (astronomy, cardiology, materials science, political science, psychology and public health) to rate abstracts that varied on two factors: (i) author country (high status vs lower status in science); (ii) author institution (high status vs lower status university). We found only weak evidence of country- or institution-related status bias, and mixed regression models with discipline as random-effect parameter indicated that any plausible bias not detected by our study must be small in size.

Validity of The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS): a daily activity criterion checklist for infants and toddlers.

BACKGROUND: The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) is a 50-item, criterion-specified questionnaire that assesses a child's adaptive skills in everyday context and can be used in high-risk follow-up settings to identify risk for adverse neurodevelopmental outcome. Our aim was to validate the WIDEA-FS by comparing a sample of typically developing children to children with special health needs and to compare results to the Capute Scales, which include domains of including both the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). METHODS: Six hundred and sixty children (typically developing and having special healthcare needs) aged 0-36 months completed the WIDEA-FS, the CAT, and the CLAMS assessments. RESULTS: Children with special health needs scored significantly lower on the WIDEA than those with typical development. WIDEA-FS subscales were significantly associated with the CAT (WIDEA-FS self-care 0.87, social cognition 0.89) and the CLAMS (WIDEA-FS communication 0.96, social cognition 0.92) tests. CONCLUSIONS: The WIDEA-FS has concurrent validity with the CAT and CLAMS and construct validity in that children with special health needs have significantly poorer performance on the WIDEA-FS than children with typical development. IMPACT: The WIDEA-FS demonstrated both construct validity and concurrent validity with the Capute Scales, including the Cognitive Adaptive Test (CAT) and the Clinical Linguistic and Auditory Milestone Scale (CLAMS). This is the first study to validate the use of the WIDEA-FS in children with typical development and children with special healthcare needs. The WIDEA-FS is a quick and valid checklist that can be used to assess neurodevelopmental functioning during daily activities in typically developing children and those at risk for neurodevelopmental differences.

Classification of Opioid Usage Through Semi-Supervised Learning for Total Joint Replacement Patients.

Opioid misuse and overdose have become a public health hazard and caused drug addiction and death in the United States due to rapid increase in prescribed and non-prescribed opioid usage. The misuse and overdose are highly related to opioid over-prescription for chronic and acute pain treatment, where a one-size-fits-all prescription plan is often adopted but can lead to substantial leftovers for patients who only consume a few. To reduce over-prescription and opioid overdose, each patient's opioid usage pattern should be taken into account. As opioids are often prescribed for patients after total joint replacement surgeries, this study introduces a machine learning model to predict each patient's opioid usage level in the first 2 weeks after discharge. Specifically, the electronic health records, patient prescription history, and consumption survey data are collected to investigate the level of short-term opioid usage after joint replacement surgeries. However, there are a considerable number of answers missing in the surveys, which degrades data quality. To overcome this difficulty, a semi-supervised learning model that assigns pseudo labels via Bayesian regression is proposed. Using this model, the missing survey answers of opioids amount taken by the patients are predicted first. Then, based on the prediction, pseudo labels are assigned to those patients to improve classification performance. Extensive experiments indicate that such a semi-supervised learning model has shown a better performance in the resulting patients classification. It is expected that by using such a model the providers can adjust the amount of prescribed opioids to meet each patient's actual need, which can benefit the management of opioid prescription and pain intervention.

Minimally Invasive SPML Surgery for Children with Cerebral Palsy: Program Development.

Improvements in surgical and rehabilitation care are critical to lessen the burden of cerebral palsy (CP), the most common cause of severe physical disability in childhood. The selective percutaneous myofascial lengthening (SPML) surgical procedure is a minimally invasive method designed to improve ambulation by lengthening contracted musculoskeletal tissues. Information on surgical procedures, efficacy, and safety of SPML for children with CP is lacking. Phase 1 of our research is a "proof-of-principle" study for multisite SPML to improve functional mobility of children with CP, and Phase 2 assesses safety, reoperation rates, and efficacy over time in subsequent patient series. Phase 1 was a repeated measurement case series study of 17 children (mean age 7.6 years). One physical therapist, blinded to the surgeon's measurements, measured bilateral knee and ankle motion before and after SPML procedures, using video recordings of a standardized gait path. Functional Mobility Scale (FMS) 5, 50, and 500 outcomes were taken pre- and postoperatively and via telephone follow-up. In Phase 2, multisite SPLM surgeries were implemented in larger successive cohorts from 2006 to 2017. Complications, reoperation rates, and efficacy were retrospectively analyzed. Phase 1 results showed improvement in the children's knee and ankle motion while ambulating and improved FMS 5, 50, and 500 outcomes postoperatively (mean, 6.3 months). At second follow-up (mean 33.3 months), FMS 500 scores continued improvement, while FMS 5 and FMS 50 scores maintained. During Phase 2, the complication rate was 2.4%, and reoperation rates (including reoperations due to maturation) were between 8% and 13%. Improvements to correct ankle equinus were recorded in 498 cases. In conclusion, in a specialized center, single-event, multilevel SPML surgeries of children with CP safely improved ambulatory knee and ankle angle motion and daily mobility outcomes. Future educational studies of training needs for surgeons new to the approach are needed.

Comparison of readmissions among hospitalized nonvalvular atrial fibrillation patients treated with oral anticoagulants in the United States.

Objectives: To compare the risks of 1-month all-cause, major bleeding (MB)-related and stroke-related readmissions and the associated hospital resource use and costs among patients previously hospitalized for nonvalvular atrial fibrillation (NVAF) and treated with warfarin, rivaroxaban, and dabigatran vs apixaban. Methods: Adult patients hospitalized with NVAF (any discharge diagnosis position) who received apixaban, warfarin, rivaroxaban, or dabigatran during hospitalization were identified from the Premier database (1 January 2013-30 June 2017) and grouped into respective cohorts. Propensity score matching was used to generate cohorts with similar characteristics. In regression analyses the risk of readmissions that occurred within 1 month of discharge were evaluated and the associated length of stay (LOS) and costs compared. Results: NVAF patients treated with warfarin vs apixaban had significantly greater risk of all-cause (odds ratio [OR] = 1.05; confidence interval [CI] = 1.02-1.08; p < .001), MB-related (OR: 1.28; CI: 1.16-1.42; p < .001), and stroke-related (OR: 1.33; CI: 1.11-1.58; p = .002) readmissions; for all readmission categories, average LOS was significantly longer and costs significantly higher for warfarin treated patients. NVAF patients treated with rivaroxaban versus apixaban had significantly greater risk of all-cause (OR: 1.06; CI: 1.02-1.09; p = .001) and MB-related (OR = 1.62; CI = 1.44-1.83; p < .001) readmissions, but not stroke-related readmission; for MB-related readmissions average LOS and costs were higher for rivaroxaban treated patients. Significant differences in risks of all-cause, MB-related, and stroke-related readmissions were not observed between the apixaban and dabigatran cohorts. Conclusion: In this retrospective real-world analysis of NVAF patients, apixaban treatment was associated with better clinical outcomes than warfarin or rivaroxaban and lower hospital resource burden.

Exploring the acceptability of implantable defibrillators in patients with cardiac dystrophinopathy and carers.

Objective: Unlike for patients with other forms of cardiomyopathies, those with severe ventricular dysfunction due to Duchenne muscular dystrophy (DMD) are not offered implantable cardioverter-defibrillator (ICD) therapy routinely. This prospective study aimed to determine the views of DMD-patients and their carers about discussing sudden death risk and their acceptance of ICDs. Design and setting: Adults with DMD (n=9) and parents/carers (n=9) participated in audio-recorded, 60-90 min focus group sessions (patients 2; parents/carers 2) conducted through either a face-to-face session at a neutral venue or a videoconference. Sessions were facilitated by a clinical psychologist, experienced in conducting focus group research. All participants understood the rationale for the study and the nature of ICD therapy. The same predefined themes were explored with each group. Recordings were transcribed, analysed thematically by two researchers, working independently and then agreed. Differences in responses between patient and carer groups were also studied and compared. Participants all provided informed written consent and the study had ethical approval. Results: Three main themes emerged: (1) access to/quality of information provided by professionals and patient engagement with them; (2) decision-making about ICDs; (3) individuals' own 'lived experience' of DMD. Conclusions: The main findings were: (1) patients with DMD want to have their risk of sudden arrhythmic death discussed, when relevant and (2) if ICD therapy were established as beneficial, they would welcome an individualised discussion about its appropriateness for them.

Validation of obesity coding among newly treated nonvalvular atrial fibrillation patients using an integrated electronic medical record and claims database.

Objective: To evaluate the validity of diagnosis codes for identifying obesity and morbid obesity among newly treated nonvalvular atrial fibrillation (NVAF) patients.Methods: An integrated electronic medical record (EMR) and claims database (1 January 2013-31 March 2018) was used. Adult patients with ≥1 claim for an oral anticoagulant (OAC) from 1 January 2014-30 September 2017 were identified (index date). Patients were required to have ≥1 atrial fibrillation diagnosis, no OAC use or valvular disease during the 12 months before index date, ≥12 months of continuous enrollment before and ≥6 months after index date, and ≥1 BMI measurement 6 months before or after index date. Patients with BMI ≥30 kg/m2 and BMI ≥40 kg/m2 were classified as obese and morbidly obese, respectively. Sensitivity, specificity and positive predictive value (PPV) were calculated to assess the validity of diagnosis codes for obesity and morbid obesity.Results: A total of 7501 patients met all selection criteria. Forty-six percent of patients had BMI ≥ 30 kg/m2, of whom about one-quarter had a BMI ≥ 40 kg/m2. Twenty-five percent and 10% of patients had a diagnosis code for obesity or morbid obesity, respectively. Sensitivity, specificity and PPV for obesity diagnosis codes were 48.67% (95% CI: 47.00%-50.35%), 95.24% (94.54%-95.88%) and 89.78% (88.32%-91.12%), respectively, and 62.75% (59.30%-66.11%), 96.46% (95.99%-96.89%) and 67.93% (64.43%-71.29%) for morbid obesity diagnosis codes, respectively.Conclusion: Among newly treated NVAF patients, obesity diagnosis codes had high PPV, high specificity and modest sensitivity. Morbid obesity diagnosis codes also had high specificity, but modest PPV and sensitivity. These findings have implications for case selection and control for obesity as a confounder in studies using a claims database.