Economic Evaluation Associated With Clinical-Grade Mobile App-Based Digital Therapeutic Interventions: Systematic Review.

BACKGROUND: Digital therapeutics (DTx), a class of software-based clinical interventions, are promising new technologies that can potentially prevent, manage, or treat a spectrum of medical disorders and diseases as well as deliver unprecedented portability for patients and scalability for health care providers. Their adoption and implementation were accelerated by the need for remote care during the COVID-19 pandemic, and awareness about their utility has rapidly grown among providers, payers, and regulators. Despite this, relatively little is known about the capacity of DTx to provide economic value in care. OBJECTIVE: This study aimed to systematically review and summarize the published evidence regarding the cost-effectiveness of clinical-grade mobile app-based DTx and explore the factors affecting such evaluations. METHODS: A systematic review of economic evaluations of clinical-grade mobile app-based DTx was conducted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines. Major electronic databases, including PubMed, Cochrane Library, and Web of Science, were searched for eligible studies published from inception to October 28, 2022. Two independent reviewers evaluated the eligibility of all the retrieved articles for inclusion in the review. Methodological quality and risk of bias were assessed for each included study. RESULTS: A total of 18 studies were included in this review. Of the 18 studies, 7 (39%) were nonrandomized study-based economic evaluations, 6 (33%) were model-based evaluations, and 5 (28%) were randomized clinical trial-based evaluations. The DTx intervention subject to assessment was found to be cost-effective in 12 (67%) studies, cost saving in 5 (28%) studies, and cost-effective in 1 (6%) study in only 1 of the 3 countries where it was being deployed in the final study. Qualitative deficiencies in methodology and substantial potential for bias, including risks of performance bias and selection bias in participant recruitment, were identified in several included studies. CONCLUSIONS: This systematic review supports the thesis that DTx interventions offer potential economic benefits. However, DTx economic analyses conducted to date exhibit important methodological shortcomings that must be addressed in future evaluations to reduce the uncertainty surrounding the widespread adoption of DTx interventions. TRIAL REGISTRATION: PROSPERO International Prospective Register of Systematic Reviews CRD42022358616; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022358616.

Tonsillectomy in children and in adults: changes in practice following the opening of a day-surgery unit with dedicated operating room.

OBJECTIVES: To study the impact of the opening of a day-surgery unit on the practice of tonsillectomy in adults and children in the light of the experience of our department, and to compare complications between day-surgery and conventional admission. MATERIAL AND METHODS: A retrospective review was conducted of all tonsillectomies performed since the opening of a dedicated day-surgery room, using the ENT and emergency department data-bases. RESULTS: Between October 2013 and December 2014, 179 tonsillectomies were performed (51 in adults, 128 in children), including 108 day-surgeries. Between 2012 and 2014, the number of tonsillectomies increased by 12.7%, with an 18.27% increase in children and stable adult rate. Within 1 year, day-surgery became predominant for children (73.19%) and equaled conventional admission for adults (47.22%). For almost all patients without same-day discharge, the reasons were organizational or due to malorientation (comorbidity, or unsuitable home environment). Day-case tonsillectomy in children showed a 30-day complications rate comparable to those reported in the literature (8.3% postoperative hemorrhage), with a higher rate in adults (35.3%). Onset of complications was at a mean 6 days in adults and 9 days in children; only 2 patients developed complications between 6 and 24hours postoperatively. CONCLUSION: The present study showed that opening a day-surgery unit led to changes in practice, with most tonsillectomies now performed on an outpatient basis, without increased complications, and notably immediate complications. Outpatient tonsillectomy thus seems to be a solution of choice compared to conventional admission, in terms of cost saving and of patient comfort, without sacrificing safety. The dedicated operating room facilitates scheduling and thereby increasing turnover by reducing wait time.

Effect of a lysine depletion-repletion protocol on the compensatory growth of growing-finishing pigs.

The effect of Lys restriction followed by a repletion period on the performance of growing pigs was studied during 3 feeding phases, each lasting 28 d. A total of 47 castrated male pigs (G Performer 8.0 × Fertilis 25 pigs; Genetiporc Inc., Saint-Bernard, QC, Canada; initial BW of 26.7 ± 2.7 kg) were given each d 70% or 100% of their Lys requirements according to 1 of the following 5 sequences: 70-70-70, 70-70-100, 70-100-70, 70-100-100, or 100-100-100 (for each sequence, numbers indicate the Lys supply percentage in phase 1, 2, and 3, respectively). Individual Lys requirements were estimated daily on the basis of each pig's actual BW and feed intake and BW gain patterns obtained by regression using each pig's historical data. At the end of phase 1, the pigs given 100% of their Lys requirements had higher ADFI ( = 0.01), ADG ( < 0.01), and average daily protein deposition ( < 0.01) than did the pigs given 70% of their requirements. Similar results were observed during phases 2 and 3. At the end of phase 2, the pigs in the 70-100 sequence did not display any compensatory response, given that their ADFI, ADG, and average daily protein deposition did not differ from those of the pigs in the 100-100 sequence. Similar results were observed during phase 3. Although no compensatory growth was observed during the growing phases, the fact that the pigs in the 70-100-100 treatment were able to catch up in terms of BW and body protein mass to the pigs in the 100-100-100 sequence could indicate that a small degree of compensation did occur; these research results cannot ascertain that any compensatory growth occurred.

Fibula free flap in the treatment of mandibular osteoradionecrosis.

INTRODUCTION: Mandibular osteoradionecrosis (mORN) is one of the major complications of radiation therapy in head and neck cancer. It is responsible for intractable pain and functional problems. Radical treatment, required in case of failure of conservative management, consists in wide resection of the necrotic tissue followed by reconstruction, notably by free flaps. The present study assessed the efficacy of reconstructive surgery by fibula free flap (FFF) in terms of pain, suppuration and functional results. MATERIAL AND METHODS: A retrospective study recruited 5 cases of mORN treated surgically with FFF reconstruction between 2005 and 2012. For each patient, pain, resolution of suppuration, articulation, mastication and swallowing functions and recovery of oral feeding were assessed. RESULTS: The flaps had good vitality in 4 of the 5 patients. Infection and pain resolved in all patients. Functional results were satisfactory in 4 of the 5 cases (80%). There was no recurrence of mORN. CONCLUSIONS: Micro-anastomosed FFF seems to be the method of choice for mandibular reconstruction in advanced mORN. Delayed treatment, however, seems to reduce the chances of good functional results. The precise indications for radical surgery and its timing remain to be defined, but it appears wise to decide on ever earlier radical surgery in the hope of obtaining better functional results.

Criteria for admission of odontogenic infections at high risk of deep neck space infection.

OBJECTIVES: Many patients with odontogenic infections are hospitalised because of the risk of deep neck space infection. The objective of this study was to identify risk factors allowing more reliable selection of patients requiring hospitalisation for both specialists and emergency physicians. MATERIAL AND METHODS: This retrospective study was based on a cohort of 97 patients hospitalised for odontogenic infection in the Department of Otorhinolaryngology and Head and Neck Surgery of Centre hospitalier Sud Francilien, Île-de-France, from January 2008 to June 2012. RESULTS: The majority of patients presented with dental abscess (66 patients; 68%). Nineteen patients (20%) presented with deep neck space infection. The frequency of deep neck space infection was significantly higher in patients with mandibular odontogenic infection (16/55 patients (29%) than in those with maxillary odontogenic infection (3/42 (7%); P ≤ 0.009). The incidence of deep neck space infection was significantly higher in patients with dental abscess (17/66, (26%) than in those without dental abscess (2/31 (6%); P ≤ 0.03). CONCLUSION: In addition to the well-known classical criteria (fever, neck swelling, dyspnoea, dysphagia, trismus, leukocytosis, elevated C reactive protein (CRP)), the criteria for admission for odontogenic infection should include mandibular odontogenic infection and/or the presence of dental abscess.

Costing bias in economic evaluations.

Determining the cost-effectiveness of healthcare interventions is key to the decision-making process in healthcare. Cost comparisons are used to demonstrate the economic value of treatment options, to evaluate the impact on the insurer budget, and are often used as a key criterion in treatment comparison and comparative effectiveness; however, little guidance is available to researchers for establishing the costing of clinical events and resource utilization. Different costing methods exist, and the choice of underlying assumptions appears to have a significant impact on the results of the costing analysis. This editorial describes the importance of the choice of the costing technique and it's potential impact on the relative cost of treatment options. This editorial also calls for a more efficient approach to healthcare intervention costing in order to ensure the use of consistent costing in the decision-making process.

Evaluation of a method estimating real-time individual lysine requirements in two lines of growing-finishing pigs.

The implementation of precision feeding in growing-finishing facilities requires accurate estimates of the animals' nutrient requirements. The objectives of the current study was to validate a method for estimating the real-time individual standardized ileal digestible (SID) lysine (Lys) requirements of growing-finishing pigs and the ability of this method to estimate the Lys requirements of pigs with different feed intake and growth patterns. Seventy-five pigs from a terminal cross and 72 pigs from a maternal cross were used in two 28-day experimental phases beginning at 25.8 (±2.5) and 73.3 (±5.2) kg BW, respectively. Treatments were randomly assigned to pigs within each experimental phase according to a 2×4 factorial design in which the two genetic lines and four dietary SID Lys levels (70%, 85%, 100% and 115% of the requirements estimated by the factorial method developed for precision feeding) were the main factors. Individual pigs' Lys requirements were estimated daily using a factorial approach based on their feed intake, BW and weight gain patterns. From 25 to 50 kg BW, this method slightly underestimated the pigs' SID Lys requirements, given that maximum protein deposition and weight gain were achieved at 115% of SID Lys requirements. However, the best gain-to-feed ratio (G : F) was obtained at a level of 85% or more of the estimated Lys requirement. From 70 to 100 kg, the method adequately estimated the pigs' individual requirements, given that maximum performance was achieved at 100% of Lys requirements. Terminal line pigs ate more (P=0.04) during the first experimental phase and tended to eat more (P=0.10) during the second phase than the maternal line pigs but both genetic lines had similar ADG and protein deposition rates during the two phases. The factorial method used in this study to estimate individual daily SID Lys requirements was able to accommodate the small genetic differences in feed intake, and it was concluded that this method can be used in precision feeding systems without adjustments. However, the method's ability to accommodate large genetic differences in feed intake and protein deposition patterns needs to be studied further.

Health inequalities associated with neighbourhood deprivation in the Quebec population with hypertension in primary prevention of cardiovascular disease.

INTRODUCTION: Although a number of studies look at prevalence, incidence, treatment, mortality and morbidity in relation to hypertension, few have taken into account the effect of residential neighbourhood on these health indicators in the population diagnosed with hypertension. OBJECTIVES: The objective of this study was to measure and compare prevalence, mortality, morbidity, use of medical resources and treatments in relation to the level of material and social deprivation of the area of residence, in a population with a diagnosis of hypertension in primary prevention for cardiovascular disease (CVD) in Quebec in 2006-2007. METHODS: This study is based on a secondary analysis of the medical administrative data of the Quebec health insurance board, the Régie de l'assurance maladie du Québec, for a cohort of 276 793 patients aged 30 years or older who had been diagnosed with hypertension in 2006 or 2007, but who did not have a known diagnosis of CVD. The health indicators adjusted for age and sex are prevalence, death, a cardiovascular event, physician visits, emergency department visits and use of antihypertensives. Twenty-five types of areas of residence were obtained by crossing the material and social deprivation quintiles. RESULTS: Compared with patients living in materially and socially advantaged areas, those living in deprived areas were at 46% higher risk of a cardiovascular event, 47% higher risk of being frequent emergency department visitors and 31% higher risk of being frequent users of a general practitioner's services, but 25% lower risk of being frequent users of medical specialists' services. Little or no variation was observed in the use of antihypertensives. CONCLUSION: This study reveals the existence, in a CVD primary prevention context, of large variations in a number of health indicators among hypertensive patients owing to the material and social deprivation of residential neighbourhood. It is therefore important to take the socioeconomic context into account when planning interventions to prevent CVDs and their consequences.

TITRE: Inégalités de santé associées à la défavorisation du secteur de résidence au sein de la population du Québec ayant reçu un diagnostic d'hypertension artérielle en prévention primaire des maladies cardiovasculaires. INTRODUCTION: Bien que plusieurs études traitent de la prévalence, de l'incidence, du traitement, de la mortalité et de la morbidité en lien avec l'hypertension artérielle (HTA), peu d'entre elles tiennent compte de l'influence des secteurs de résidence sur ces indicateurs de santé au sein de la population ayant reçu un diagnostic d'HTA. OBJECTIFS: L'objectif de cette étude était de mesurer et comparer la prévalence, la mortalité, la morbidité, l'utilisation des ressources médicales et les traitements selon le niveau de défavorisation matérielle et sociale du secteur de résidence au sein de la population ayant reçu un diagnostic d'HTA en prévention primaire des maladies cardiovasculaires (MCV) au Québec en 2006-2007. MÉTHODOLOGIE: Cette étude repose sur une analyse secondaire des données médico- administratives de la Régie de l'assurance maladie du Québec pour une cohorte de 276 793 patients de 30 ans et plus ayant reçu un diagnostic d'HTA en 2006 ou en 2007 mais sans diagnostic connu de MCV. Les indicateurs de santé ajustés pour l'âge et le sexe sont la prévalence, le décès, un événement cardiovasculaire, les consultations médicales, les consultations à l'urgence ainsi que l'utilisation d'antihypertenseurs. Vingt-cinq types de secteurs de résidence ont été obtenus par croisement des quintiles de défavorisation matérielle et sociale. RÉSULTATS: Par rapport aux patients vivant dans des secteurs favorisés matériellement et socialement, ceux vivant dans des secteurs défavorisés avaient 46 % plus de risque d'événement cardiovasculaire, 47 % plus de risque d'être de grands utilisateurs de l'urgence, 31 % plus de risque d'être de grands utilisateurs des services d'un omnipraticien, mais 25 % moins de risque d'être de grands utilisateurs des services de médecins spécialistes. Peu ou pas de variation n'a été observée quant à l'utilisation d'antihypertenseurs. CONCLUSION: Cette étude révèle l'existence, dans le cadre de la prévention primaire des MCV, d'importantes variations pour plusieurs indicateurs de santé chez des patients hypertendus en raison de la défavorisation matérielle et sociale de leur secteur de résidence. Il est donc important de tenir compte du contexte socioéconomique lors de la planification d'interventions visant à prévenir les maladies cardiovasculaires et leurs conséquences.

Pollination ecology and reproductive success in Jack-in-the-pulpit (Arisaema triphyllum) in Québec (Canada).

Pollination ecology and reproductive success of Jack-in-the-pulpit (Arisaema triphyllum) were studied in two natural populations in Québec, Canada. Individual A. triphyllum plants can be of three types: male, female or bisexual. In both populations studied, the presence of bisexual inflorescences was not negligible (13%), where 'female' and 'male' bisexual plants were categorised according to the relative number of stamens and ovaries. 'Male bisexual' plants produce only pollen and 'female bisexual' plants produce only fruit. Hence, A. triphyllum is a true dioecious plant, as each plant only reproduces through either the male or the female function. 'Female bisexual' plants were equivalent to female plants in terms of visitation rate by insects, fructification rate and production of berries and seeds. Neither agamospermy in female plants nor self-pollination in 'female bisexual' plants was found, thus A. triphyllum relies on insects for cross-pollination. Despite the long flowering cycle, a low visitation rate was documented: only 20-40% of inflorescences were visited, according to gender, by a mean of 1.5 insects. In this study, Mycetophilidae represented the most generically diversified and abundant family, as well as the most efficient insect pollinator, especially the genera Docosia and Mycetophila.

Needed: system dynamics for the drug discovery process.

A system dynamics structure to characterize the link between technology and critical management decisions in the drug discovery process (DDP) is needed. The DDP includes many interacting feedback loops that impact decisions executed in early stages and that influence performance in later development stages. The complexity of the DDP and the absence of systemic perspective, contributes imprecision to decision-makers' own mental models, and limits their ability to generate decisions that provoke genuine process improvements. Hence, the emergence and use of new integrated technology- and knowledge-based approaches bridge to R&D concern at least early attrition rates, critical high-content chemical lead value identification and time delay reduction for the early phase DDP.

Bayesian versus Frequentist statistical modeling: a debate for hit selection from HTS campaigns.

The existing literature suggests the Bayesian-Frequentist debate could soon be involved in the prioritization of hits from HTS campaigns. The Bayesian-Frequentist debate reflects two archetypical attitudes regarding the process of conducting scientific and technological research. This review article covers recent advances in statistical analyses, currently in use, for hit selection in the drug discovery process. The impact of decisions (e.g. attrition) executed at early stages in the drug discovery process influences HTS performance in later development stages. It shows that, as the high content value of the information from HTS campaigns increases over time, the two statistical approaches aim to provide similar answers, but they might not succeed.

Non-uniform strain distribution within rat cartilaginous growth plate under uniaxial compression.

Growth plates are highly inhomogeneous in morphology and composition. Mechanical loading can modulate longitudinal bone growth, though the mechanisms underlying this mechanobiology are poorly understood. The proximal tibial growth plates of six rats were tested in vitro under uniaxial compression to 5% strain, and confocal microscopy was used to track and capture images of fluorescently labeled cell nuclei with increasing applied strains. The local strain patterns through the growth plate thickness were quantified using texture correlation analysis. The technique of texture correlation analysis was first validated by comparing theoretical simulated strain maps generated from numerically distorted images. The texture correlation algorithm was sensitive to the grid size superimposed on the original image, but remained insensitive to parameters related to the size of the final image mask, which was searched by the correlation algorithm for each grid point of the original image. Within the growth plate, experimental strain distributions were non-uniform in all six specimens. Growth plates were mostly under compression strains. The strain distributions differed among the histomorphological zones of the growth plate, which was most obvious in specimens with regular growth plate shape: higher compressive strains (4-8 times higher than the applied 5% strain) were located mainly in regions overlapping the reserve and hypertrophic zones with lower compressive strains in the proliferative zone. This study documents the non-uniform mechanical behavior of growth plate across its three histological zones when exposed to compression. Further investigation is required to establish the significance of non-uniform strain fields during growth in vivo.

Needed: models of biotechnology intellectual property.

Although never uncontroversial, intellectual property rights in biotechnological innovation are once more the focus of intense debate. The debate has yet to reach any result, largely because of several important errors in the way that various disciplines approach it. These errors include making assumptions without empirical basis and conflating various intellectual property regimes. What is needed is a transdisciplinary integrated method to correct these errors. Such a method can be implemented through the construction of alternative models of intellectual property protection designed to balance the various social, ethical and economic constraints that affect biotechnology.

Hemodynamic and biochemical characteristics of the aorta in the WKY, SHR, WKHT, and WKHA rat strains.

This study was designed to characterize the hemodynamic and biochemical properties of the abdominal aorta in four genetically related inbred rat strains that express genetic hypertension and hyperactive behavior in varying combinations. These include (1) the spontaneously hypertensive rat (SHR), which is hypertensive, hyperactive, and hyperreactive to stress; (2) Wistar-Kyoto (WKY) rats, which express none of these traits; (3) WKHT rats, which are hypertensive but not hyperactive; and (4) WKHA rats, which are hyperactive and hyperreactive to stress, but normotensive. Together, these four strains allowed us to examine the structural and functional changes in the aorta in the hypertensive SHR, the most widely used animal model of genetic hypertension, while controlling for the variables of hyperactivity and hyperreactivity that are also expressed in the SHR. Four groups of animals of both sexes were studied: (1) WKY, n = 101, (2) WKHA, n = 33, (3) WKHT, n = 91, and (4) SHR, n = 28. Blood pressure (BP) was determined by tail plethysmography as well as direct intraarterial monitoring under anesthesia. Fixed specimens were prepared for histologic analysis and the wall thickness determined morphometrically. Quantification of soluble tissue protein, elastin, and collagen in the aortic tissue was determined by measuring leucine (leu), hydroxyproline (HP/leu), and desmosine (DES/leu). The hypertensive strains (SHR and WKHT) had significantly higher tail BP than the normotensive strains (WKY and WKHA)-WKY: 128.7 +/- 22.3; WKHA: 126.7 +/- 14.6; WKHT: 162.8 +/- 21.2; SHR: 164.2 +/- 36.1 (p < 0.0001). Additionally, intraaortic diastolic BP and mean BP were higher in SHR rats than in WKHT. Morphometric studies showed the media thickness in the SHR rats was significantly greater than in the WKY and WKHA rats and no different than in the WKHT rats. Significantly less of the aortic wall protein was present as elastin in the hypertensive rats (SHR and WKHT), as well as the hyperactive rats (WKHA), compared to rats that had neither trait (WKY). These studies provide new information regarding aortic structure and function in genetic hypertension using inbred strains to control for the hyperactivity/hyperreactivity traits that coexist with hypertension in the SHR. They reveal that hypertensive aortas have altered matrix proteins that cannot be explained simply on the basis of blood pressure alone.

Intravenous leiomyomatosis with intracardiac extension.

Intravenous leiomyomatosis is a benign smooth muscle tumor of uterine origin characterized by grossly visible masses of smooth muscle cells growing within venous channels. A case of leiomyomatosis arising in the uterine veins with extension into the right iliac veins, vena cava, right atrium, right ventricle and into the pulmonary outflow tract is described. The tumor was completely and successfully removed by a staged approach with median sternotomy followed by laparotomy several days later. A brief review of the literature and a discussion of the operative approach are presented.