Defining minimum volume thresholds to increase quality of care: a new patient-oriented approach using mixed integer programming

A positive relationship between treatment volume and outcome quality has been demonstrated in the literature and is thus evident for a variety of procedures. Consequently, policy makers have tried to translate this so-called volume–outcome relationship into minimum volume regulation (MVR) to increase the quality of care—yet with limited success. Until today, the effect of strict MVR application remains unclear as outcome quality gains cannot be estimated adequately and restrictions to application such as patient travel time and utilization of remaining hospital capacity are not considered sufficiently. Accordingly, when defining MVR, its effectiveness cannot be assessed. Thus, we developed a mixed integer programming model to define minimum volume thresholds balancing utility in terms of outcome quality gain and feasibility in terms of restricted patient travel time and utilization of hospital capacity. We applied our model to the German hospital sector and to four surgical procedures. Results showed that effective MVR needs a minimum volume threshold of 125 treatments for cholecystectomy, of 45 and 25 treatments for colon and rectum resection, respectively, of 32 treatments for radical prostatectomy and of 60 treatments for total knee arthroplasty. Depending on procedure type and incidence as well as the procedure’s complication rate, outcome quality gain ranged between 287 (radical prostatectomy) and 977 (colon resection) avoidable complications (11.7% and 11.9% of all complications). Ultimately, policy makers can use our model to leverage MVR’s intended benefit: concentrating treatment delivery to improve the quality of care.

     

Approximation of diffuse attenuation,Kd, for MODIS high-resolution bands

A high resolution depth attenuation product (K_d^hires) was developed using MODIS 500 m and 250 m spectral bands. The K_d^hires was compared with Wang’s operational K_d for the Chesapeake Bay. Minimal differences were observed between the two methods, with greatest deviation occurring in areas of high turbidity in the tributaries. After tuning the new K_d^hires, the mean absolute error and bias between the two algorithms was 0.22 m^?1 and 0.026 m^?1, indicating good agreement. Higher spatial resolution provides for improved retrievals along the coast and into the narrow sections of the tributaries, coinciding with areas of concern to estuarine health and coastal management applications.     

Impact of COVID-19 on U.S. and Canadian neurologists’ therapeutic approach to multiple sclerosis: a survey of knowledge,attitudes, and practices

Journal of Neurology - To report the understanding and decision-making of neuroimmunologists and their treatment of patients with multiple sclerosis (MS) during the early stages of the SARS-CoV-2...     

An inducible mouse model for microvillus inclusion disease reveals a role for myosin Vb in apical and basolateral trafficking

Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with an onset within a few days to months after birth, resulting in persistent watery diarrhea. Mutations in the myosin Vb gene (MYO5B) have been identified in the majority of MVID patients. However, the exact pathophysiology of MVID still remains unclear. To address the specific role of MYO5B in the intestine, we generated an intestine-specific conditional Myo5b-deficient (Myo5b^fl/fl;Vil-CreERT2) mouse model. We analyzed intestinal tissues and cultured organoids of Myo5b^fl/fl;Vil-CreERT2 mice by electron microscopy, immunofluorescence, and immunohistochemistry. Our data showed that Myo5b^fl/fl;Vil-CreERT2 mice developed severe diarrhea within 4 d after tamoxifen induction. Periodic Acid Schiff and alkaline phosphatase staining revealed subapical accumulation of intracellular vesicles in villus enterocytes. Analysis by electron microscopy confirmed an almost complete absence of apical microvilli, the appearance of microvillus inclusions, and enlarged intercellular spaces in induced Myo5b^fl/fl;Vil-CreERT2 intestines. In addition, we determined that MYO5B is involved not only in apical but also basolateral trafficking of proteins. The analysis of the intestine during the early onset of the disease revealed that subapical accumulation of secretory granules precedes occurrence of microvillus inclusions, indicating involvement of MYO5B in early differentiation of epithelial cells. By comparing our data with a novel MVID patient, we conclude that our mouse model completely recapitulates the intestinal phenotype of human MVID. This includes severe diarrhea, loss of microvilli, occurrence of microvillus inclusions, and subapical secretory granules. Thus, loss of MYO5B disturbs both apical and basolateral trafficking of proteins and causes MVID in mice.Microvillus inclusion disease (MVID) is a rare intestinal enteropathy with autosomal recessive inheritance, which was first described in 1978 (1). MVID patients cannot take up any nutrients and are often completely dependent on parenteral nutrition. The disease is characterized by villus atrophy, (partial) loss of microvilli on the apical plasma membrane of intestinal epithelial cells, and accumulation of intracellular vesicles/vacuoles, containing apical proteins and microvilli (2, 3). In addition, some studies also show mislocalization of apical and basolateral proteins, occasional crypt hyperplasia, and villus fusion (4–6).In the great majority of patients, MVID is caused by mutations in MYO5B, encoding the motorprotein, myosin Vb (5). In two patients, mutations in syntaxin 3 (STX3) caused a variant form of MVID (7). More than 41 unique mutations along the different regions in MYO5B have been identified in MVID patients, including deletions and nonsense, missense, and splice-site mutations (8–10). MYO5B is coding for the actin-based myosin 5b motor protein, which regulates apical membrane trafficking (5, 11). MYO5B functions as a homodimer and has three functional domains: an N-terminal motor domain, a calmodulin-binding domain, and a C-terminal tail, which binds cargo through association with the small GTPases RAB8A and/or RAB11A (12, 13). Altered expression of myosin Vb affects the apical membrane trafficking mechanism in epithelial cells, causing mislocalization of apical brush border proteins, such as villin (vil), CD10, or alkaline phosphatase (ALP) in the cytoplasm of duodenal enterocytes (2, 3, 5), and an increased apical localization of transferrin receptor (5, 14).Although mouse models mimicking certain features of MVID have previously been described, such as Rab8 (15), Cdc42 (16, 17), and Rab11a knockout (KO) mice (18, 19), no mutations in the coding regions of those genes have been reported in human MVID patients. Current in vitro models to study apical trafficking and polarization-associated diseases such as MVID are the parental Caco2 cell line, Caco-BBE, and LS174 W4 cells, in which polarization can be induced in vitro (4, 8, 12, 20). Although valuable knowledge about the function of MYO5B in polarization was gained in these models, the direct relevance of the colon cancer cell lines for the disease is questionable, and diverging results have been obtained with knockdown of MYO5B in the parental Caco2 cells compared with the more polarized Caco-BBE cells (8, 12, 20). As such, we here present an inducible MVID mouse model that recapitulates the genetic defects in man, which allows analysis of the role of MYO5B in a physiological setting and the sequence of events in MVID pathophysiology.     

Occupational Characteristics of Adults with Pediatric-Onset Spinal Cord Injury

Background:

Employment rates among individuals with spinal cord injury (SCI) are lower than in the general population and little is known about the specific occupations in which they are employed.

Objectives:

To describe specific occupations of adults with pediatric-onset SCI using the 2010 Standard Occupational Classification (SOC) system and to determine associations between SOC occupations and demographic factors.

Methods:

Cross-sectional data specific to education and employment were collected from the last interviews of a larger longitudinal study. Occupations were categorized according to the 2010 SOC system. SOC groups were compared within gender level of injury and final education.

Results:

Of the 461 total participants 219 (47.5%) were employed and specific occupations were available for 179. Among the SOC groups Education Law Community Service Arts and Media Occupations were most prevalent (30.2%) followed by Management Business and Finance Occupations (21.1%) Computer Engineering and Science Occupations (10.6%) Administrative and Office Support Occupations (10.0%) Service Occupations (7.3%) Healthcare Practitioners and Technical Occupations (3.9%) and Production Occupations (3.4%). Differences were found in the distribution of SOC groups between gender levels of injury and final education groups.

Conclusion:

A wide variety of occupations were reported in adults with pediatric-onset SCI generally in concordance with final education and functional ability levels.     

Neonatal blue light phototherapy increases café-au-lait macules in preschool children

Neonatal blue light phototherapy (NBLP) is an effective treatment for hyperbilirubinaemia. Concerning the influence on melanocytic nevi, conflicting studies have been published. To assess the role of NBLP according to the incidence of melanocytic nevi in preschool children, a cohort of 104 5- to 6-year-old children were included. The case group consisted of 52 NBLP-exposed children, while the control group (n?=?52) never had NBLP and was matched regarding age, gender, gestational age and skin phototype. Six dizygotic twins were included with one twin having received NBLP, respectively. The following parameters were recorded: nevi count, presence of freckles, café-au-lait macules, skin phototype and previous history of sun exposure. There was no significant association between nevi count and exposure to NBLP (median nevi count 17.0 compared to 18.5 in controls). No significant difference was also found in the dizygotic twin pairs with a median nevi count of 10.0 (with NBLP) compared to 14.5 (without NBLP). However, a significantly higher prevalence of café-au-lait macules was found in children with NBLP (mean count 0.5) than in children without NBLP (mean count 0.2; p?=?0.001). Significant predictors for the number of melanocytic nevi included skin phototype, sun exposure and vacations in the South. Conclusion: In this study, NBLP had no significant influence on the development of melanocytic nevi, but on café-au-lait macules which was a new finding. Differences with comparable studies regarding age, differentiation between nevi and other pigmented lesions as well as dose and type of NBLP need to be taken into account for further investigations.     

The plunging ranula. Pathogenesis, diagnosis and management

Ranulas are cysts resulting from retention, or extravasation of saliva from the sublingual gland. Two varieties are described: a superficial or oral ranula and a cervical or plunging ranula. The plunging ranula is located below the mylohyoid muscle and may present as a swelling in the upper part of the neck. Four cases are described to illustrate that this condition can be the cause of a neck swelling. Aetiology, differential diagnosis and surgical management are also discussed. Recurrences are mainly due to unfamiliarity with this phenomenon and ignorance of its aetiology. Successful treatment of the plunging ranula consists of excision of the ipsilateral sublingual salivary gland, which is the source of this disorder, and intra-oral evacuation of the pseudocyst of the neck swelling. There is no need for an extensive neck dissection of the cervical extension.