Ecological validity of a deep learning algorithm to detect gait events from real-life walking bouts in mobility-limiting diseases

Introduction: The clinical assessment of mobility, and walking specifically, is still mainly based on functional tests that lack ecological validity. Thanks to inertial measurement units (IMUs), gait analysis is shifting to unsupervised monitoring in naturalistic and unconstrained settings. However, the extraction of clinically relevant gait parameters from IMU data often depends on heuristics-based algorithms that rely on empirically determined thresholds. These were mainly validated on small cohorts in supervised settings. Methods: Here, a deep learning (DL) algorithm was developed and validated for gait event detection in a heterogeneous population of different mobility-limiting disease cohorts and a cohort of healthy adults. Participants wore pressure insoles and IMUs on both feet for 2.5 h in their habitual environment. The raw accelerometer and gyroscope data from both feet were used as input to a deep convolutional neural network, while reference timings for gait events were based on the combined IMU and pressure insoles data. Results and discussion: The results showed a high-detection performance for initial contacts (ICs) (recall: 98%, precision: 96%) and final contacts (FCs) (recall: 99%, precision: 94%) and a maximum median time error of −0.02 s for ICs and 0.03 s for FCs. Subsequently derived temporal gait parameters were in good agreement with a pressure insoles-based reference with a maximum mean difference of 0.07, −0.07, and <0.01 s for stance, swing, and stride time, respectively. Thus, the DL algorithm is considered successful in detecting gait events in ecologically valid environments across different mobility-limiting diseases

Hematopoietic stem cell transplantation for CD40 ligand deficiency: results from an EBMT/ESID-IEWP-SCETIDE-PIDTC Study

BACKGROUND: CD40 ligand (CD40L) deficiency, an X-linked primary immunodeficiency, causes recurrent sinopulmonary, Pneumocystis and Cryptosporidium infections. Long-term survival with supportive therapy is poor. Currently, the only curative treatment is hematopoietic stem cell transplantation (HSCT). OBJECTIVE: We performed an international collaborative study to improve patients' management, aiming to individualize risk factors and determine optimal HSCT characteristics. METHODS: We retrospectively collected data on 130 patients who underwent HSCT for CD40L deficiency between 1993-2015. We analyzed outcome and variables relevance with respect to survival and cure. RESULTS: Overall survival (OS), event-free survival (EFS) and disease-free survival (DFS) were 78.2%, 58.1% and 72.3% 5 years post-HSCT. Results were better in transplants performed ≥2000 and in children <10 years old at HSCT. Pre-existing organ damage negatively influenced outcome. Sclerosing cholangitis was the most important risk factor. After 2000, superior OS was achieved with matched donors. Use of myeloablative regimens and HSCT ≤2 years from diagnosis associated with higher OS and DFS. EFS was best with matched sibling donors, myeloablative conditioning (MAC) and bone marrow-derived stem cells. Most rejections occurred after reduced intensity or non-myeloablative conditioning, which associated with poor donor cell engraftment. Mortality occurred mainly early after HSCT, predominantly from infections. Among survivors who ceased immunoglobulin replacement, T-lymphocyte chimerism was ≥50% donor in 85.2%. CONCLUSION: HSCT is curative in CD40L deficiency, with improved outcome if performed before organ damage development. MAC is associated with better OS, EFS and DFS. Prospective studies are required to compare risks of HSCT with those of life-long supportive therapy

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts: an economic decision model

Objectives: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. Data sources: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. Review methods: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GPprescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. Results: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 £/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 £/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 £/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 £/% cured for OTC duct tape and 0.76 £/% cured for OTC cryotherapy to 1.12 £/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. Conclusions: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more costeffective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care

Effectiveness and cost-effectiveness of salicylic acid and cryotherapy for cutaneous warts: an economic decision model

Objectives: To estimate the costs of commonly used treatments for cutaneous warts, as well as their health benefits and risk. To create an economic decision model to evaluate the cost-effectiveness of these treatments, and, as a result, assess whether a randomised controlled trial (RCT) would be feasible and cost-effective. Data sources: Focus groups, structured interviews and observation of practice. Postal survey sent to 723 patients. A recently updated Cochrane systematic review and published cost and prescribing data. Review methods: Primary and secondary data collection methods were used to inform the development of an economic decision model. Data from the postal survey provided estimates of the effectiveness of wart treatments in a primary care setting. These estimates were compared with outcomes reported in the Cochrane review of wart treatment, which were largely obtained from RCTs conducted in secondary care. A decision model was developed including a variety of over-the-counter (OTC) and GPprescribed treatments. The model simulated 10,000 patients and adopted a societal perspective. Results: OTC treatments were used by a substantial number of patients (57%) before attending the GP surgery. By far the most commonly used OTC preparation was salicylic acid (SA). The results of the economic model suggested that of the treatments prescribed by a GP, the most cost-effective treatment was SA, with an incremental cost-effectiveness ratio (ICER) of 2.20 £/% cured. The ICERs for cryotherapy varied widely (from 1.95 to 7.06 £/% cured) depending on the frequency of applications and the mode of delivery. The most cost-effective mode of delivery was through nurse-led cryotherapy clinics (ICER = 1.95 £/% cured) and this could be a cost-effective alternative to GP-prescribed SA. Overall, the OTC therapies were the most cost-effective treatment options. ICERs ranged from 0.22 £/% cured for OTC duct tape and 0.76 £/% cured for OTC cryotherapy to 1.12 £/% cured for OTC SA. However, evidence in support of OTC duct tape and OTC cryotherapy is very limited. Side-effects were commonly reported for both SA and cryotherapy, particularly a burning sensation, pain and blistering. Conclusions: Cryotherapy delivered by a doctor is an expensive option for the treatment of warts in primary care. Alternative options such as GP-prescribed SA and nurse-led cryotherapy clinics provide more costeffective alternatives, but are still expensive compared with self-treatment. Given the minor nature of most cutaneous warts, coupled with the fact that the majority spontaneously resolve in time, it may be concluded that a shift towards self-treatment is warranted. Although both duct tape and OTC cryotherapy appear promising new self-treatment options from both a cost and an effectiveness perspective, more research is required to confirm the efficacy of these two methods of wart treatment. If these treatments are shown to be as cost-effective as or more cost-effective than conventional treatments, then a shift in service delivery away from primary care towards more OTC treatment is likely. A public\ud awareness campaign would be useful to educate patients about the self-limiting nature of warts and the possible alternative OTC treatment options available. Two future RCTs are recommended for consideration: a trial of SA compared with nurse-led cryotherapy in primary care, and a trial of home treatments. Greater understanding of the efficacy of these home treatments will give doctors a wider choice of treatment options, and may help to reduce the overall demand for cryotherapy in primary care