Top-Funded Digital Health Companies Offering Services for Type-1 Diabetes Patients: Business Models and Scalability Considerations

This paper aims to assess how the top-funded digital health companies in T1DM can create value for customers and which implications this has in terms of scalability. Med tech companies, academia, and policymakers should be able to make better strategic decisions based on the findings provided. Companies were identified using a leading venture capital database, PitchBook. Our analysis revealed that 50% of the thirty top-funded companies pursue a Layer Player strategy to generate value for T1DM patients. We recommend that companies in T1DM focus more on automated services such as conversational agents to improve scalability. In terms of scalability, many companies have room for improvement by increasingly relying on automated services, among other things

Soil organic carbon cycling in a long-term agricultural experiment,Switzerland

Soils are one of the largest organic carbon pools and changes in the carbon release from soils has considerable impact on the composition of atmospheric CO2. Alongside the accelerated carbon release from soils by anthro-pogenic warming (Crowther et al., 2016), agricultural use strongly affects soil organic carbon (SOC) (Johnstonet al., 2009). Conversion from conventional to organic farming has been suggested a valuable contribution to sequester SOC providing a great mitigation potential within agricultural practices (Smith et al., 2008).Here we present SOC contents and 14C activity under two different farming practices in the long-termagricultural DOK trial at Therwil, Switzerland (Mäder et al., 2002). In this long-lasting agricultural experiment, we compare biodynamic farming (biodyn), which receives manure and biodynamic preparations, with conventional farming (conmin), which receives only mineral fertilizers. We analyzed functional SOC fractions from both farming practices for SOC concentration and radiocarbon (∆14C) in two soil layers (0-20 cm and 20-50 cm).Three SOC fractions were obtained by density and particle size fractionation: particular organic matter (POM,labile pool), mineral-associated organic matter 20μm (MOM >20μm, labile pool).Our results clearly show higher SOC concentrations for biodyn compared to conmin in all SOC fractions in the upper soil layer (0-20 cm). In the subsoil (20-50 cm) we found a negligible influence of farming practices with depth. High ∆14C values in the POM and >20μm fraction indicated that they are a more labile and fastcycling carbon pool, whereas lower∆14C values in the 20μm fraction, with higher ∆14C values in the biodyn system suggesting greater input of fresh plant material with a faster turnover

Assessing cortisol from hair samples in a large observational cohort: The Whitehall II study

Hair cortisol concentrations (HCC) have been suggested to reflect long-term integrated cortisol levels, but most evidence of associations with co-variates is from small samples of healthy volunteers. The objective of this study was to describe the collection of hair samples in a large cohort study and report associations of demographic and health measures with HCC. We examined HCC measured from the 3 cm hair segment near the scalp in 3507 participants (aged 59–83 y) from The Whitehall II occupational cohort study of British civil servants. Hair samples were analysed using a column switching LC–APCI–MS/MS assay. Findings from mutually adjusted linear regression analyses revealed lower HCC in participants who reported use of hair dye [% difference (95%CI); −12.5 (−22.0, −1.9), p value = 0.022] and evidence suggestive of differences by length of sample storage and seasonal variation. With regard to demographic variables, HCC was lower in women compared to men [−17.0 (−24.8, −8.4), p value <0.001] and higher in Black compared to other ethnic groups. Prevalent diabetes, use of systemic corticosteroids and cardiovascular medication were independently associated with higher HCC. With regard to health, depressive symptoms were associated with higher HCC [20.0 (8.1, 33.3), p value = 0.001] following adjustment for physical disease and medication. We conclude that hair steroid analysis presents significant opportunities for assessing cortisol in large scale cohorts. Demographic factors, sample storage, season of collection and hair characteristics should be considered in future analyses. Health status, both mental and physical, is linked to HCC

Spinal cord tethering and syringomyelia after trauma: impact of age and surgical outcome

Posttraumatic spinal cord tethering and syringomyelia frequently lead to progressive neurological loss. Although several studies demonstrated favourable outcome following spinal cord detethering with/without shunting, additional research is required as no clear consensus exists over the ideal treatment strategy and knowledge about prognostic demographic determinants is currently limited. In this investigation, we retrospectively investigated 67 patients (56 men, 11 women) who were surgically treated and followed for symptomatic spinal cord tethering and syringomyelia from 2012 to 2022 at our center. Age (B-coefficient 0.396) and severity of trauma to the spinal cord (B-coefficient − 0.462) have been identified as independent predictors for the rate of development of symptomatic spinal cord tethering and syringomyelia (p < 0.001). Following untethering surgery including expansion duraplasty with/without shunting, 65.9% of patients demonstrated an improvement of neurological loss (p < 0.001) whereas 50.0% of patients displayed amelioration of spasticity and/or neuropathic pain (p < 0.001). Conclusively, active screening for symptomatic spinal cord tethering and syringomyelia, particularly in younger patients with severe spinal trauma, is crucial as surgical untethering with/without shunting is able to achieve favourable clinical outcomes. This knowledge may enable clinicians to tailor treatment strategies in spinal cord injury patients suffering from progressive neurological loss towards a more optimal and personalized patient care

Correspondence between hair cortisol concentrations and 30-day integrated daily salivary and weekly urinary cortisol measures

Characterization of cortisol production, regulation and function is of considerable interest and relevance given its ubiquitous role in virtually all aspects of physiology, health and disease risk. The quantification of cortisol concentration in hair has been proposed as a promising approach for the retrospective assessment of integrated, long-term cortisol production. However, human research is still needed to directly test and validate current assumptions about which aspects of cortisol production and regulation are reflected in hair cortisol concentrations (HCC). Here, we report findings from a validation study in a sample of 17 healthy adults (mean ± SD age: 34 ± 8.6 yrs). To determine the extent to which HCC captures cumulative cortisol production, we examined the correspondence of HCC, obtained from the first 1cm scalp-near hair segment, assumed to retrospectively reflect 1-month integrated cortisol secretion, with 30-day average salivary cortisol area-under-the curve (AUC) based on 3 samples collected per day (on awakening, +30 min, at bedtime) and the average of 4 weekly 24-hr urinary free cortisol (UFC) assessments. To further address which aspects of cortisol production and regulation are best reflected in the HCC measure, we also examined components of the salivary measures that represent: 1) production in response to the challenge of awakening (using the cortisol awakening response [CAR]), and 2) chronobiological regulation of cortisol production (using diurnal slope). Finally, we evaluated the test-retest stability of each cortisol measure. Results indicate that HCC was most strongly associated with the prior 30-day integrated cortisol production measure (average salivary cortisol AUC) (r = 0.61, p = 0.01). There were no significant associations between HCC and the 30-day summary measures using CAR or diurnal slope. The relationship between 1-month integrated 24-hr UFC and HCC did not reach statistical significance (r = 0.30, p = 0.28). Lastly, of all cortisol measures, test-retest correlations of serial measures were highest for HCC (month-to-month: r = 0.84, p < 0.001), followed by 24-hr UFC (week-to-week: r’s between 0.59 and 0.68, ps < 0.05) and then integrated salivary cortisol concentrations (week-to-week: r’s between 0.38 and 0.61, p’s between 0.13 and 0.01). These findings support the contention that HCC provides a reliable estimate of long-term integrated free cortisol production that is aligned with integrated salivary cortisol production measured over a corresponding one-month period

Prediction of in-hospital bleeding in acutely ill medical patients: External validation of the IMPROVE bleeding risk score.

INTRODUCTION Pharmacological thromboprophylaxis slightly increases bleeding risk. The only risk assessment model to predict bleeding in medical inpatients, the IMPROVE bleeding risk score, has never been validated using prospectively collected outcome data. METHODS We validated the IMPROVE bleeding risk score in a prospective multicenter cohort of medical inpatients. Primary outcome was in-hospital clinically relevant bleeding (CRB) within 14 days of admission, a secondary outcome was major bleeding (MB). We classified patients according to the score in high or low bleeding risk. We assessed the score's predictive performance by calculating subhazard ratios (sHRs) adjusted for thromboprophylaxis use, positive and negative predictive values (PPV, NPV), and the area under the receiver operating characteristic curves (AUC). RESULTS Of 1155 patients, 8 % were classified as high bleeding risk. CRB and MB within 14 days occurred in 0.94 % and 0.47 % of low-risk and in 5.6 % and 3.4 % of high-risk patients, respectively. Adjusted for thromboprophylaxis, classification in the high-risk group was associated with an increased risk of 14-day CRB (sHR 4.7, 95 % confidence interval [CI] 1.5-14.5) and MB (sHR 4.9, 95%CI 1.0-23.4). PPV was 5.6 % and 3.4 %, while NPV was 99.1 % and 99.5 % for CRB and MB, respectively. The AUC was 0.68 (95%CI 0.66-0.71) for CRB and 0.73 (95%CI 0.71-0.76) for MB. CONCLUSION The IMPROVE bleeding risk score showed moderate to good discriminatory power to predict bleeding in medical inpatients. The score may help identify patients at high risk of in-hospital bleeding, in whom careful assessment of the risk-benefit ratio of pharmacological thromboprophylaxis is warranted

Contemplative mental training reduces hair glucocorticoid levels in a randomized clinical trial

Objective To investigate the effect of regular contemplative mental training on endocrine and psychological indices of long-term stress. Methods An open-label efficacy trial that comprised three distinct 3-month modules targeting attention and interoception, socio-affective or socio-cognitive abilities through dyadic exercises and secularised meditation practices was conducted with healthy adults. Participants underwent the training for three months, nine months, or were assigned to a retest control cohort. Chronic stress indices were assayed at four timepoints: pre-training and after three, six and nine months. The main outcome measures were cortisol (HC) and cortisone (HE) concentrations in hair and self-reported long-term stress. Results Of 362 initially randomized individuals, 30 dropped out before study initiation (N = 332; mean age-40. 7 ± SD = 9.2 years; 197 women). Hair-based glucocorticoid assays were available from n = 227, and questionnaire data from n = 326. Results from three separate training cohorts (TCs) revealed consistent decreases in HC and HE levels over the first three (TC3) to six months (TC1 and TC2) of training, with no further reduction at the final 9-month mark (baseline to end-of-training, HC: TC1, t(355) = 2.59, p = .010; est.:0.35[0.14]; TC2, t(363) = 4.06, p < .001; est.:0.48[0.12]; TC3: t(368) = 3.18, p = .002; est.:0.41[0.13]; HE: TC1, t(435) = 3.23, p = .001; est.:0.45[0.14]; TC2: t(442) = 2.60, p = .010; est.:0.33[0.13]; TC3: t(446) = 4.18, p < .001; est.:0.57[0.14]). Training effects on HC increased with practice frequency, and effects on both HC and HE were independent of training content and unrelated to change in self-reported chronic stress. Self-reported stress, and cortisol to dehydroepiandrosterone ratios as an exploratory endpoint, were also reduced, albeit less consistently. Conclusions Our results point to the reduction of long-term cortisol exposure as a mechanism through which contemplative mental training may exert positive effects on practitioners' health. Trial registration: ClinicalTrials.gov identifier: NCT0183310

Aplastic anemia and concomitant autoimmune diseases

The association of aplastic anemia (AA) with other autoimmune diseases (AID) has been described but so far not systematically evaluated. We assessed the incidence and the outcome of concomitant AID in a retrospective, single-center study of 243 patients with severe AA treated between 1974 and 2006 with either immunosuppression (186) or hematopoietic stem cell transplantation (57) and a median follow-up time of 9.3years (0-33). Clinically manifest AID were observed in 24 out of 243 (10 ± 3.7%) patients. Age at diagnosis of AA was significantly younger in patients without AID compared to patients with AID (median, 20 versus 52years; P < 0.001). In 12 patients where the diagnosis of AID was done before AA therapy, response to antithymocyte globulin was good for AA (ten out of 12) but not for AID (2 out of 12). In 13 patients in which AID occurred after first-line therapy, the median time to the AID was 7years (range 3months-27.5years

Circumcision does not alter long-term glucocorticoids accumulation or psychological effects associated with trauma- and stressor-related disorders

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Male infants and boys through early adolescence can undergo circumcision either for the sake of upholding religious traditions or for medical reasons. According to both, Jewish as well as Islamic tenets, circumcision is a religious rite symbolizing the bond with God. The World Health Organization (WHO), the United Nations Council (UNC) as well as the American Academy of Pediatrics (AAP), and the Centers for Disease Control and Prevention (CDC) strongly recommend circumcision to promote hygiene and prevent disease. This procedure has frequently been criticized by various communities claiming that circumcision in infancy and early adolescence were psychologically traumatizing with medical implications up into old age. Due to the lack of evidence concerning an alleged increase in vulnerability, we measured objective and subjective stress and trauma markers, including glucocorticoids from hair samples, in circumcised and non-circumcised males. We found no differences in long-term limbic–hypothalamic–pituitary–adrenal axis activity, subjective stress perception, anxiety, depressiveness, physical complaints, sense of coherence and resilience. Rather, an increase in the glucocorticoid levels indicated a healthy lifestyle and appropriate functioning. Thus, our findings provide evidence that male circumcision does not promote psychological trauma. Moreover, a qualitative approach, the ambivalence construct, was used for the discussion, aiming at a discourse devoid of biases