Lockdowns lose one third of their impact on mobility in a month

As the novel coronavirus (COVID‐19) pandemic spread across the world over the past year, many countries imposed lockdowns in the form of stay at home requirements on their citizens to mitigate its spread. We analyze mobility data from 93 countries implementing lockdowns to investigate their immediate impact on mobility and the subsequent evolution of mobility. We find that at the start of a lockdown, median mobility is reduced to 36% below the baseline, and by another 18% in the subsequent 2 weeks. 70 countries had lockdowns lasting beyond 4 weeks and showed a significant reduction in mobility compared to that prior to the lockdown. Mobility was at its minimum 18 days into the lockdown for the median country. Comparing this minimum mobility to the average mobility 2 weeks before the lockdown, we observe a median reduction of 50 percentage points, evidencing that lockdowns reduce mobility. For 59 of these 70 countries, lockdowns lasted at least 4 weeks after reaching minimum mobility and most observed a significant rebound in mobility during the lockdown period. For the median country, 30.1% of the mobility reduction achieved is lost within 4 weeks, and lockdowns lose all their impact on mobility in 112.1 days. Overall, our findings show that while lockdowns significantly reduce mobility, this impact is also subject to fatigue as the lockdown period extends longer. The magnitude of mobility reductions achieved and fatigues reported in this research can help policy makers anticipate the likely impact of their lockdown policies.

Ataxia and mobility in children following surgical resection of posterior fossa tumour: A longitudinal cohort study

Purpose To report the course of ataxia in children up to 2 years post-operatively, following surgical resection of a posterior fossa tumour (PFT). Methods Thirty-five children, (median age 9 years, range 4–15) having resection of PFT, were assessed using the Scale for the Assessment and Rating of Ataxia (SARA), Brief Ataxia Rating Scale (BARS) and the mobility domain of the Paediatric Evaluation of Disability Index (PEDI-m) at initial post-operative period (baseline), 3 months, 1 year and 2 years post-operatively. Results Baseline median scores of the SARA and BARS were 8.5 (range 0–35.5), and 7 (0–25) respectively. Ataxia improved at 3 months (median SARA and BARS reduction 3.5 and 4, respectively). Additional gradual improvements in SARA were recorded at 1 (median reduction 2) and 2 years post-operatively (median reduction 0.5). Median baseline PEDI-m was 54.75 (range 15.2–100) with improvement at 3 months (median increase 36.95) and small improvement at 1 year (median increase 2.5) and 2 years (median increase 5.8). Children with medulloblastoma and midline tumours (median baseline SARA 10 and 11, respectively) demonstrated more severe ataxia than children with low-grade gliomas and unilateral tumours (median baseline SARA 7.5 and 6.5, respectively). Conclusion The largest improvement in ataxia scores and functional mobility scores is demonstrated within the first 3 months post-operatively, but ongoing gradual improvement is observed at 2 years. Children with medulloblastoma and midline tumour demonstrated higher ataxia scores long term.

Mass mask-wearing notably reduces COVID-19 transmission

Mask-wearing has been a controversial measure to control the COVID-19 pandemic. While masks are known to substantially reduce disease transmission in healthcare settings (Howard et al 2021), studies in community settings report inconsistent results (Brainard et al 2020). Investigating the inconsistency within epidemiological studies, we find that a commonly used proxy, government mask mandates, does not correlate with large increases in mask-wearing in our window of analysis. We thus analyse the effect of mask-wearing on transmission instead, drawing on several datasets covering 92 regions on 6 continents, including the largest survey of individual-level wearing behaviour (n=20 million) (Kreuter et al 2020). Using a hierarchical Bayesian model, we estimate the effect of both mask-wearing and mask-mandates on transmission by linking wearing levels (or mandates) to reported cases in each region, adjusting for mobility and non-pharmaceutical interventions. We assess the robustness of our results in 123 experiments across 22 sensitivity analyses. Across these analyses, we find that an entire population wearing masks in public leads to a median reduction in the reproduction number R of 25.8%, with 95% of the medians between 22.2% and 30.9%. In our window of analysis, the median reduction in $R$ associated with the wearing level observed in each region was 20.4% [2.0%, 23.3%]. We do not find evidence that mandating mask-wearing reduces transmission. Our results suggest that mask-wearing is strongly affected by factors other than mandates. We establish the effectiveness of mass mask-wearing, and highlight that wearing data, not mandate data, are necessary to infer this effect.

Enhanced Recovery After Surgery can Improve Patient Outcomes and Reduce Hospital Cost of Gastrectomy for Cancer in the West: A Propensity-Score-Based Analysis

Background Data on ERAS for gastrectomy are scarce, and the majority of the studies come from Eastern countries. Patients in the West are older and suffer from more advanced tumors that impair their clinical condition and often require neoadjuvant treatment. This retrospective study assessed the feasibility and safety of an Enhanced Recovery After Surgery (ERAS) protocol for gastrectomy in a Western center. Methods We conducted a single-center study of 351 patients operated for gastric cancer: 103, operated from January 2015 to December 2016, followed the standard pathway, while 248, operated from January 2017 to December 2019, followed the ERAS program. The primary outcomes considered were length of hospital stay (LOS) and direct costs. Secondary outcomes were 90-day morbidity and mortality, readmission rate, and compliance with ERAS items. A propensity score (PS) was built on confounding variables. Results Compliance with ERAS items after the program was ≥ 70%. Univariable analysis evidenced a 2-day median reduction in LOS and a median cost reduction of €826 per patient in the ERAS group. PS-based multivariable analysis confirmed a significant, 2-day decrease in median LOS and a €1097 saving after ERAS introduction. Ninety-day mortality decreased slightly in ERAS group, while complications and readmissions did not change significantly. When complications were included in the multivariable analysis, ERAS retained its significance, although the effects on LOS and cost were blunted to a median reduction of 1 day and €775, respectively. Conclusions ERAS for gastrectomy improved patients’ recovery and reduced hospital costs without changes in morbidity, mortality, or readmission.

MO253A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED DOSE-RANGING STUDY (LUMINA-1 STUDY) TO EVALUATE THE SAFETY AND EFFICACY OF CCX140 IN SUBJECTS WITH FOCAL SEGMENTAL GLOMERULOSCLEROISS (FSGS)*

Background and Aims Primary Focal Segmental Glomerulosclerosis (FSGS) is the most common primary glomerular disease in patients with end stage renal disease in the United States. Current treatment regimens target reduction in proteinuria, but may have limited response or exhibit disease recurrence. CCX140 is an orally-administered selective small molecule inhibitor of the C-C chemokine receptor 2 (CCR2) under investigation for the treatment reduction of proteinuria in patients with FSGS. The primary objectives of this study were to evaluate the safety and efficacy of CCX140 in patients with FSGS and a urine protein to creatinine ratio (UPCR) of ≥1 g/g. Efficacy was assessed by the change in UPCR. Method Forty-six adult patients with primary or genetic FSGS were randomized into a double-blind, placebo-controlled Phase 2 dose-ranging study designed to evaluate the safety and efficacy of CCX140. Changes of urinary protein excretion estimation (UPCR) from baseline to Week 12 were measured in four blinded treatment groups (three active CCX140 doses of 5 mg once daily, 10 mg and 15 mg twice-daily (BID) vs placebo). Starting at Week 12, all subjects including those in the placebo group received the CCX140, 15 mg BID for an additional 12 weeks, and UPCR changes from Week 12 to Week 24 were assessed. There was a 4-week follow-up period from Week 24 to Week 28 where no CCX140 was administered. Results In the intent to treat (ITT) analysis of UPCR changes at Week 12 relative to baseline, the 15 mg BID CCX140 group exhibited the greatest reduction of UPCR (median reduction from baseline 0.9 g/g or approximately 30%, and approximately 25% reduction from baseline for the geometric mean), but that did not differ significantly from the placebo group (median reduction from baseline 0.45 g/g; or approximately 22%, and approximately 23% reduction from baseline for the geometric mean). Also, after crossover of the blinded portion of the trial to 15 mg BID active dosing, the previous placebo group did not appear to exhibit an additional reduction of UPCR. CCX140 at all doses was well-tolerated, with no serious adverse events (SAEs) during the blinded trial and a numerically lower rate of treatment-emergent adverse events in the CCX140 treatment groups. Conclusion In the study, CCX140 did not demonstrate a therapeutically meaningful reduction in proteinuria relative to the control group after 12 weeks of blinded treatment. The study provides insights into the natural disease progression of patients with primary or genetic FSGS as part of a clinical trial setting.

The efficacy of ultrasound-guided multifidus cervicis plane block versus greater occipital nerve block for cervicogenic headache

Introduction Traditionally, non-invasive and invasive techniques were used for the treatment of cervicogenic headache (CH). Greater occipital nerve block is the most frequent peripheral nerve block invasive technique used for the management of cervicogenic headache. The purpose of this prospective, double-blinded study was to compare the efficacy of two different techniques: multifidus cervicis plane block and greater occipital nerve block in the treatment of refractory cervicogenic headache by using ultrasound. Methods Sixty patients with cervicogenic headache were recruited and diagnosed according to the ICHD-III beta version. The patients were divided into two groups, one group was for greater occipital nerve block and the other group was for multifidus cervicis plane block with ultrasound-guided. Results Visual analog scale (VAS) was 2.09% in the multifidus cervicis plane block (MCPB) group and was 2.22% in the greater occipital nerve block (GONB) group with a median reduction of − 4.33 and − 3.048, respectively, at 2-week visits with a statistically significant difference better in the MCPB group (P < 0.001). At 4 weeks visits, VAS scale was better in the MCPB group than in the GONB group (3.79 and 4.44, respectively) with a median reduction in VAS scale (− 3.27 and − 3.095, respectively) and statistically significant differences between both groups (P = 0.020). Conclusion Both the ultrasound-guided multifidus cervicis plane block and greater occipital nerve block are effective as intervention techniques in the treatment of refractory cervicogenic headache. These techniques are simple, safe, more reliable with less side effects, and often reduce the requirements of analgesic drugs.

The effects of water immersion and walking on leg volume, ankle circumference and epifascial thickness in healthy subjects with occupational edema

Background Balneotherapy has been considered beneficial in patients with chronic venous disease due to patient-reported positive outcomes on improvement of symptoms and quality of life. Study aim: Assessing the effects of prolonged water immersion (WI) on leg edema and epifascial thickness and to compare these data with those achieved after continuous walking on ground. Material and methods On three consecutive days, 14 otherwise healthy volunteers (9 females, 5 males, mean age 53 ± 10 years) affected by occupational edema (OE), defined as the edema developing during the time period of the working day and disappearing overnight, stayed standing immobile in a swimming pool for 30 minutes (30’), continuously walking again for 30’ in the same pool and walking on ground for 30’ without interruptions in a randomized sequence. Leg volume, ankle circumference and epifascial thickness of both legs were assessed each day before and after each intervention. Results Leg volume showed a median reduction by 4.20% (IQR 5-3.6) (p = 0.0002) after 30’ of immobile standing immersion and by 6.50% (IQR 7.30-5.61) (P < 0.0001) when the patients walked in the pool. Ankle circumference showed a median reduction by 2.89% (IQR 4.23-2.03) (p = 0.02) with the subjects staying standing still in water and by 5.98% (IQR 7.47-4.14) (p = 0.0002) after 30’ walking in the pool. Epifascial thickness showed a median reduction by 24.35% (IQR 35.26-22.5) (P < 0.0001) when the volunteers remained standing still and by 32.66% (IQR 36.91-28-84) (P < 0.0001), when walking in water. Leg volumetry showed a median reduction by 0.20% (IQR-0.44-0.29) (p = 0.375) after walking on ground for 30’. Ankle circumference and epifascial thickness did not show any difference walking on ground compared to baseline situation. Conclusions This study showed that 30’ of WI, especially when associated with walking, reduced leg volume in otherwise heathy subjects with OE and that walking outside the water did not.

Establishment, contagiousness, and initial spread of SARS-CoV-2 in Canada

This study empirically quantifies dynamics of SARS-CoV-2 establishment and early spread in Canada. We developed a transmission model that was simulation tested and fitted in a Bayesian framework to timeseries of new cases per day prior to physical distancing interventions. A hierarchical version was fitted to all provinces simultaneously to obtain average estimates for Canada. Across scenarios of a latent period of 2–4 d and an infectious period of 5–9 d, the R0 estimate for Canada ranges from a minimum of 3.0 (95% CI: 2.3–3.9) to a maximum of 5.3 (95% CI: 3.9–7.1). Among provinces, the estimated commencement of community transmission ranged from 3 d before to 50 d after the first reported case and from 2 to 25 d before the first reports of community transmission. Among parameter scenarios and provinces, the median reduction in transmission needed to obtain R0 < 1 ranged from 46% (95% CI: 43%–48%) to 89% (95% CI: 88%–90%). Our results indicate that local epidemics of SARS-CoV-2 in Canada entail high levels of stochasticity, contagiousness, and observation delay, which facilitates rapid undetected spread and requires comprehensive testing and contact tracing for its containment.

A Flexible Proof Format for SAT Solver-Elaborator Communication

We introduce , a new proof format for unsatisfiable SAT problems, and its associated toolchain. Compared to , the format allows solvers to include more information in proofs to reduce the computational cost of subsequent elaboration to . The format is easy to parse forward and backward, and it is extensible to future proof methods. The provision of optional proof steps allows SAT solver developers to balance implementation effort against elaboration time, with little to no overhead on solver time. We benchmark our toolchain against a comparable toolchain and confirm >84% median reduction in elaboration time and >94% median decrease in peak memory usage.

Longitudinal patient-reported outcomes and restrictive opioid prescribing after minimally invasive gynecologic surgery

ObjectiveTo determine post-discharge patient-reported symptoms before and after implementation of restrictive opioid prescribing among women undergoing minimally invasive gynecologic surgery.MethodsWe compared clinical outcomes and symptom burden among a cohort of 389 women undergoing minimally invasive gynecologic surgery at a single institution before and after implementation of a restrictive opioid prescribing quality improvement initiative in July 2018. Post-discharge symptom burdens were collected up to 42 days after discharge using the MD Anderson Symptom Inventory and analyzed using linear mixed effects models.ResultsThe majority of women included in this study were white non-smokers and the median age was 55 (range 23–83). Most women underwent hysterectomy (64%), had surgery for malignancy (71%), and were discharged from the hospital on the day of surgery (65%). Women in the restrictive opioid prescribing group had a median reduction in morphine equivalent dose prescribed at discharge of 83%, corresponding to a median reduction in 25 tablets of 5 mg oxycodone per person. There was no difference between opioid prescribing groups in either the rate of refill requests (P=1) or hospital re-admission (P=1) up to 30 days after discharge. After adjustment for co-variates, there was no statistically significant difference in post-discharge symptom burden including patient-reported pain (P=0.08), sleep (P=0.30), walking interference (P=0.64), activity interference (P=0.12), or affective interference (P=0.67). There was a trend toward less reported constiptation in the restrictive opioid prescribing group that did not reach statistical significance (P=0.05).ConclusionWe found that restrictive post-operative opioid prescribing was not associated with differences in longitudinal symptom burden among women undergoing minimally invasive gynecologic surgery. These results provide the most comprehensive picture to date of post-operative symptom recovery under different opioid prescribing approaches, lending additional support for existing recommendations to reduce opioid prescribing following gynecologic surgery.