Final analysis of phase II results with cemiplimab in metastatic basal cell carcinoma after hedgehog pathway inhibitors.

BACKGROUND: Metastatic basal cell carcinoma (mBCC) is a rare condition with no effective second-line treatment options. Cemiplimab is an immune checkpoint inhibitor that blocks the binding of programmed cell death-1 (PD-1) to its ligands, programmed death-ligand 1 (PD-L1) and programmed death-ligand 2 (PD-L2). Here, we present the final analysis of cemiplimab in patients with mBCC after first-line hedgehog pathway inhibitor (HHI) treatment (NCT03132636). PATIENTS AND METHODS: In this open-label, single-arm, phase II study, adults with mBCC and Eastern Cooperative Oncology Group performance status ≤1, post-HHI treatment, received cemiplimab 350 mg intravenously every 3 weeks for ≤93 weeks or until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) by independent central review (ICR). Duration of response (DOR) was a key secondary endpoint. Other secondary endpoints were ORR per investigator assessment, progression-free survival (PFS), overall survival (OS), complete response rate, safety, and tolerability. RESULTS: Fifty-four patients were enrolled: 70% were male and the median age of patients was 64 [interquartile range (IQR) 57.0-73.0] years. The median duration of follow-up was 8 months (IQR 4-21 months). The ORR per ICR was 22% [95% confidence interval (CI) 12% to 36%], with 2 complete responses and 10 partial responses. Among responders, the median time to response per ICR was 3 months (IQR 2-7 months). The estimated median DOR per ICR was not reached [95% CI 10 months-not evaluable (NE)]. The disease control rate was 63% (95% CI 49% to 76%) per ICR and 70% (95% CI 56% to 82%) per investigator assessment. The median PFS per ICR was 10 months (95% CI 4-16 months); the median OS was 50 months (95% CI 28 months-NE). The most common treatment-emergent adverse events were fatigue [23 (43%)] and diarrhoea [20 (37%)]. There were no treatment-related deaths. CONCLUSIONS: Cemiplimab demonstrated clinically meaningful antitumour activity, including durable responses, and an acceptable safety profile in patients with mBCC who had disease progression on or intolerance to HHI therapy.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Age-Dependent Electroencephalogram Features in Infants Under Spinal Anesthesia Appear to Mirror Physiologic Sleep in the Developing Brain: A Prospective Observational Study.

BACKGROUND: Infants under spinal anesthesia appear to be sedated despite the absence of systemic sedative medications. In this prospective observational study, we investigated the electroencephalogram (EEG) of infants under spinal anesthesia and hypothesized that we would observe EEG features similar to those seen during sleep. METHODS: We computed the EEG power spectra and spectrograms of 34 infants undergoing infraumbilical surgeries under spinal anesthesia (median age 11.5 weeks postmenstrual age, range 38-65 weeks postmenstrual age). Spectrograms were visually scored for episodes of EEG discontinuity or spindle activity. We characterized the relationship between EEG discontinuity or spindles and gestational age, postmenstrual age, or chronological age using logistic regression analyses. RESULTS: The predominant EEG patterns observed in infants under spinal anesthesia were slow oscillations, spindles, and EEG discontinuities. The presence of spindles, observed starting at about 49 weeks postmenstrual age, was best described by postmenstrual age ( P =.002) and was more likely with increasing postmenstrual age. The presence of EEG discontinuities, best described by gestational age ( P = .015), was more likely with decreasing gestational age. These age-related changes in the presence of spindles and EEG discontinuities in infants under spinal anesthesia generally corresponded to developmental changes in the sleep EEG. CONCLUSIONS: This work illustrates 2 separate key age-dependent transitions in EEG dynamics during infant spinal anesthesia that may reflect the maturation of underlying brain circuits: (1) diminishing discontinuities with increasing gestational age and (2) the appearance of spindles with increasing postmenstrual age. The similarity of these age-dependent transitions under spinal anesthesia with transitions in the developing brain during physiological sleep supports a sleep-related mechanism for the apparent sedation observed during infant spinal anesthesia.

Application of machine learning algorithms to predict osteoporosis in postmenopausal women with type 2 diabetes mellitus.

PURPOSE: The screening and diagnosis of osteoporosis in patients with type 2 diabetes mellitus (T2DM) based on bone mineral density remains challenging because of the limited availability and accessibility of dual-energy X-ray absorptiometry. We aimed to develop and validate models to predict the risk of osteoporosis in postmenopausal women with T2DM based on machine learning (ML) algorithms. METHODS: This retrospective study included 303 postmenopausal women with T2DM. To develop prediction models for osteoporosis, we applied nine ML algorithms combined with demographic, clinical, and laboratory data. The least absolute shrinkage and selection operator were used to perform feature selection. We used the bootstrap resampling technique for model training and validation. To test the performance of the models, we calculated indices including the area under the receiver operating characteristic curve (AUROC), accuracy, sensitivity, specificity, positive predictive value, negative predictive value, F1 score, calibration curve, and decision curve analysis. Furthermore, we conducted fivefold cross-validation for parameter optimization and model validation. Feature importance was assessed using the SHapley additive explanation (SHAP). RESULTS: We identified 10 independent predictors as the most valuable features. An AUROC of 0.616-1.000 was observed for nine ML algorithms. The extreme gradient boosting (XGBoost) model exhibited the best performance, outperforming conventional risk assessment tools and registering 0.993 in the training set, 0.798 in the validation set, and 0.786 in the test set for fivefold cross-validation. Using SHAP, we found that the explanatory variables contributed to the model and their relationship with osteoporosis occurrence. Furthermore, we developed a user-friendly tool for calculating the risk of osteoporosis. CONCLUSIONS: With the integration of demographic and clinical risk factors, ML algorithms can accurately predict osteoporosis. The XGBoost model showed ideal performance. With the incorporation of these models in the clinic, patients may benefit from early osteoporosis diagnosis and treatment.

Novel role of estrogen receptor-α on regulating chondrocyte phenotype and response to mechanical loading.

OBJECTIVE: In knee cartilage from patients with osteoarthritis (OA), both preserved cartilage and damaged cartilage are observed. In this study, we aim to compare preserved with damaged cartilage to identify the molecule(s) that may be responsible for the mechanical loading-induced differences within cartilage degradation. METHODS: Preserved and damaged cartilage were harvested from the same OA knee joint. RNA Sequencing was performed to examine the transcriptomic differences between preserved and damaged cartilage cells. Estrogen receptor-α (ERα) was identified, and its function of was tested through gene knockin and knockout. The role of ERα in mediating chondrocyte response to mechanical loading was examined via compression of chondrocyte-laded hydrogel in a strain-controlled manner. Findings from the studies on human samples were verified in animal models. RESULTS: Level of estrogen receptor α (ERα) was significantly reduced in damaged cartilage compared to preserved cartilage, which were observed in both human and mice samples. Knockdown of ESR1, the gene encoding ERα, resulted in an upregulation of senescence- and OA-relevant markers in chondrocytes. Conversely, knockin of ESR1 partially reversed the osteoarthritic and senescent phenotype of OA chondrocytes. Using a three-dimensional (3D) culture model, we demonstrated that mechanical overload significantly suppressed ERα level in chondrocytes with concomitant upregulation of osteoarthritic phenotype. When ESR1 expression was suppressed, mechanical loading enhanced hypertrophic and osteogenic transition. CONCLUSION: Our study demonstrates a new estrogen-independent role of ERα in mediating chondrocyte phenotype and its response to mechanical loading, and suggests that enhancing ERα level may represent a new method to treat osteoarthritis.

Characterization of dermatological diagnoses among hospitalized patients experiencing homelessness.

While previous studies have characterized the types of dermatological disease among people experiencing homelessness (PEH) in the outpatient setting, dermatological disease among hospitalized PEH has never been evaluated. Therefore, we performed a cross-sectional analysis of hospitalized patients who received dermatology consultations at two San Francisco hospitals between March 2018 and March 2020 and compared the odds of diagnostic categories between PEH and patients with stable housing. In both unadjusted and adjusted analyses, PEH had significantly higher odds of bacterial skin infections [adjusted odds ratio (aOR) = 2.29, 95% CI 1.46-3.61], ectoparasitic disease (aOR = 9.43, 95% CI 3.79-23.47), psoriasis or seborrhoeic dermatitis (aOR = 2.50, 95% CI 1.43-4.36) and venous stasis or lymphoedema (aOR = 2.54, 95% CI 1.23-5.27) and significantly lower odds of drug reactions (aOR = 0.34, 95% CI 0.18-0.67). Overall, these findings highlight the unique dermatological challenges among hospitalized PEH and suggest potential strategies to facilitate equitable dermatology care delivery.

A pre-admission triaging tool to predict severe COVID-19 cases: ABCD score.

INTRODUCTION: Isolation of SARS-CoV-2-infected individuals is an important COVID-19 pandemic control measure. While most cases have uncomplicated infection, a small proportion of them has developed life-threatening disease. We set up a retrospective study to determine preadmission triaging tool to predict the development of severe COVID-19. MATERIALS AND METHODS: A retrospective study was conducted from 1 October 2020 to 31 January 2021 with enrolment of all SARS-CoV-2 PCR-confirmed persons aged ≥13 years. The disease severity was assessed on admission and daily throughout the hospitalisation. Test-positive individuals were considered as having "severe COVID-19" if they had ≥1 of the following: room air oxygen saturation 30 breaths/minute, signs of severe respiratory distress, or received mechanical ventilation and/or vasopressor therapy. Uni- and multi-variate analyses using SPSS Statistics Ver. 26 were performed. RESULTS: We showed that age ≥ 60 years, BMI ≥ 30.0, presentation on days 7-12 of illness, and ≥1 comorbidity were associated with development of severe COVID-19. A scoring system based on the four variables is a useful COVID-19 risk assessment tool. A total score ≥2 had a sensitivity of 60.9%, specificity of 88.2%, positive predictive value of 37.8% and negative predictive value of 95.0%. CONCLUSION: Development of preadmission triaging tool can help health care providers (HCPs) decide on the placement of test-positive individuals to appropriate isolation facilities according to the risk of developing severe COVID-19.

Predictors of Anesthetic Exposure in Pediatric MRI.

BACKGROUND. Anesthetic exposure in children may impact long-term neurocognitive outcomes. Therefore, minimizing pediatric MRI scan time in children under anesthesia and the associated anesthetic exposure is necessary. OBJECTIVE. The purpose of this study was to evaluate pediatric MRI scan time as a predictor of total propofol dose, considering imaging and clinical characteristics as covariates. METHODS. Electronic health records were retrospectively searched to identify MRI examinations performed from 2016 to 2019 in patients 0-18 years old who received propofol anesthetic. Brain; brain and spine; brain and abdomen; and brain, head, and neck MRI examinations were included. Demographic, clinical, and imaging data were extracted for each examination, including anesthesia maintenance phase time, MRI scan time, and normalized propofol dose. MRI scan time and propofol dose were compared between groups using a t test. A multiple linear regression with backward selection (threshold, p < .05) was used to evaluate MRI scan time as a predictor of total propofol dose, adjusting for sex, age, time between scan and study end, body part, American Society of Anesthesiologists (ASA) classification, diagnosis, magnet strength, and IV contrast medium administration as covariates. RESULTS. A total of 501 examinations performed in 426 patients (172 girls, 254 boys; mean age, 6.55 ± 4.59 [SD] years) were included. Single body part examinations were shorter than multiple body part examinations (mean, 52.7 ± 18.4 vs 89.3 ± 26.4 minutes) and required less propofol (mean, 17.7 ± 5.7 vs 26.1 ± 7.7 mg/kg; all p < .001). Among single body part examinations, a higher ASA classification, oncologic diagnosis, 1.5-T magnet, and IV contrast medium administration were associated with longer MRI scan times (all p ≤ .009) and higher propofol exposure (all p ≤ .005). In multivariable analysis, greater propofol exposure was predicted by MRI scan time (mean dose per minute of examination, 0.178 mg/kg; 95% CI, 0.155-0.200; p < .001), multiple body part examination (p = .04), and IV contrast medium administration (p = .048); lower exposure was predicted by 3-T magnet (p = .04). CONCLUSION. Anesthetic exposure during pediatric MRI can be quantified and predicted based on imaging and clinical variables. CLINICAL IMPACT. This study serves as a valuable baseline for future efforts to reduce anesthetic doses and scan times in pediatric MRI.

Solvent-Induced Luminescence and Structural Transformation of a Dinuclear Gold(I) (Aza-18-crown-6)dithiocarbamate Compound.

The reaction of AuCl(SMe2) with equimolar NaO5NCS2 [O5NCS2 = (aza-18-crown-6)dithiocarbamate] in CH3CN gave [Au2(O5NCS2)2]·2CH3CN (2·2CH3CN), where six other 2·solvates (solvates = 2DMF, 2DMSO, 2THF, 2acetone, 1.5toluene, and 1.5anisole) can be successfully isolated from different crystal-growing processes (i.e., ether diffusion, layer method, or evaporation in air) by dissolving the dry powder samples of 2·2CH3CN in the respective solvents, and their crystal structures are all determined by X-ray diffraction as well. It is noted that there are different intermolecular Au(I)···Au(I) contacts in combination with various luminescences for 2·solvates and indeed there is a close relationship between intermolecular Au(I)···Au(I) contacts [i.e., 2.8254(7)-2.9420(5) Å] and luminescence energies (i.e., 554-604 nm), including three examples of 2·2CH3CN, 2·0.5m-xylene, and 2·tert-butylbenzene·H2O reported in our previous work. In 2·solvates, the toluene and tert-butylbenzene solvates have the shortest [2.8254(7)-2.8289(7) Å] and longest [2.9420(5) Å] intermolecular Au(I)···Au(I) contacts, respectively, and consequently they show the respective lowest (604 nm) and highest (554 nm) luminescence energies. Indeed, 2·solvates exhibit different types of time-dependent luminescence upon solvate loss in air. Furthermore, B3LYP/LanL2DZ calculation results can help to clarify the relationship between intermolecular Au(I)···Au(I) contacts and luminescence energies for 2·solvates.

Current assessment of parental and health professional perception of the colour of neonatal vomiting: Results of a scoping survey.

PURPOSE: To determine current perceptions of doctors, nurses and parents for the colour of a neonatal vomit which should prompt an urgent surgical review. METHODS: A voluntary scoping survey of parents/guardians of patients and non-surgical healthcare professionals was conducted with respondents asked to choose from 8 different selections in a colour swatch from pale yellow to dark green. A control group consisted of 13 paediatric surgeons. Data were analysed using the paired t test, Fishers exact test. A p value of < 0.05 was considered to be significant. RESULTS: 365 participants responded: 36% (131/365) parents, 18% (64/365) nurses and 46% (166/365) doctors. 4/365 (1%) did not state their role. 343 participants completed all questions and responses were analysed using total responses for each question. 82% (121/148) of doctors and 78% (50/64) of nurses had more than 3 years of post-graduate experience. Overall, 63% (227/361) of participants (100% paediatric surgeons, 78% other doctors, 75% nurses/midwives & 30% parents) considered dark and light green vomits to be a sign of intestinal obstruction. 67% (242/361) of participants (100% paediatric surgeons, 72% other doctors, 56% nurses/midwives and 62% parents) believed dark and light green vomiting needed an urgent surgical referral. There were significant differences between the control group and other groups in terms of whether the neonate could wait until the next day for a review; nursing staff (p = 0.0002), postnatal/midwifery (p = < 0.0001), emergency medicine (p = 0.04), general practice (p = 0.002), neonatal (p = 0.0001) and paediatricians (p = 0.005). Only the neonatologists (p = 0.04), nursing staff (p = 0.001) and postnatal/midwifery (p = 0.004) believed that the neonate could have safe observation. CONCLUSION: Although the perception that green vomiting is potentially serious is acknowledged by the majority of healthcare professionals surveyed, there is still a requirement for more targeted educational practices in nursing, midwifery and medical staff.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Proportion and associated factors of meeting the 2018 Physical Activity Guidelines for Americans in adults with or at risk for knee osteoarthritis.

OBJECTIVES: Evaluate the prevalence of meeting the updated 2018 Physical Activity Guidelines for Americans (150 unbouted minutes in moderate-to-vigorous intensity physical activity [MVPA]) and determine cross-sectional factors associated with Guideline attainment in a community-based cohort of adults with or at elevated risk for knee osteoarthritis (OA). METHODS: Physical activity was monitored for 1 week in a subset of Osteoarthritis Initiative (OAI) participants with or at increased risk for knee OA. Accelerometer-measured weekly MVPA minutes were calculated; sociodemographic (age, sex, race, education, and working status) and health-related (body mass index [BMI], comorbidity, depressive symptoms, radiographic knee OA, and frequent knee symptoms) factors were assessed. We evaluated the prevalence of meeting 2018 Guidelines and used multivariate partial proportional odds model to identify factors associated with Guideline attainment, controlling for other factors in the model. RESULTS: Among 1922 participants (age 65.1 [standard deviation 9.1] years, BMI 28.4 [4.8] kg/m2, 55.2% women), 44.1% men and 22.2% women met the 2018 PA Guidelines. Adjusted cross-sectional factors associated with not-meeting 2018 Guidelines were: women, older age, higher BMI, non-Whites, depressive symptoms, not working, and frequent knee symptoms. CONCLUSION: In community-recruited adults with or at high risk for knee OA, more than 50% of men and nearly 80% of women failed to achieve the 2018 recommended level of at least 150 weekly unbouted minutes of MVPA. Study findings support gender and racial disparity in Guideline attainment and suggest addressing potentially modifiable factors (e.g., BMI, depressive symptoms, and frequent knee symptoms) to optimize benefits in PA-promoting interventions.

Long-term efficacy and safety of sonidegib in patients with advanced basal cell carcinoma: 42-month analysis of the phase II randomized, double-blind BOLT study.

BACKGROUND: Basal cell carcinomas (BCCs) exhibit aberrant activation of the hedgehog pathway. Sonidegib is a hedgehog pathway inhibitor approved for the treatment of locally advanced BCC (laBCC) and metastatic BCC (mBCC) based on primary results of the BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. OBJECTIVES: This is the final 42-month analysis of the BOLT study, evaluating the efficacy and safety of sonidegib. METHODS: Adults with no prior hedgehog pathway inhibitor therapy were randomized in a 1 : 2 ratio to sonidegib 200 mg or 800 mg once daily. Treatment continued for up to 42 months or until disease progression, unacceptable toxicity, death, study termination or withdrawal of consent. The primary efficacy end point was the objective response rate (ORR) by central review, assessed at baseline; weeks 5, 9 and 17; then subsequently every 8 or 12 weeks during years 1 or 2, respectively. Safety end points included adverse event monitoring and reporting. RESULTS: The study enrolled 230 patients, 79 and 151 in the 200-mg and 800-mg groups, respectively, of whom 8% and 3.3% remained on treatment by the 42-month cutoff, respectively. The ORRs by central review were 56% [95% confidence interval (CI) 43-68] for laBCC and 8% (95% CI 0·2-36) for mBCC in the 200-mg group and 46·1% (95% CI 37·2-55·1) for laBCC and 17% (95% CI 5-39) for mBCC in the 800-mg group. No new safety concerns emerged. CONCLUSIONS: Sonidegib demonstrated sustained efficacy and a manageable safety profile. The final BOLT results support sonidegib as a viable treatment option for laBCC and mBCC. What's already known about this topic? Basal cell carcinoma (BCC) is usually treatable with surgery or radiation therapy, but there are limited treatment options for patients with advanced BCC. Sonidegib, a hedgehog pathway inhibitor approved for the treatment of advanced BCC, demonstrated clinically relevant efficacy and manageable safety in prior analyses of the phase II randomized, double-blind BOLT study [Basal Cell Carcinoma Outcomes with LDE225 (sonidegib) Treatment]. What does this study add? This final 42-month analysis of BOLT is the longest follow-up available for a hedgehog pathway inhibitor. Clinically relevant efficacy results were sustained from prior analyses, with objective response rates by central review of the approved 200-mg daily dose of 56% in locally advanced BCC and 8% in metastatic BCC. No new safety concerns were raised. The results confirmed sonidegib as a viable long-term treatment option for patients with advanced BCC.

The 2020 International Alliance for the Control of Scabies Consensus Criteria for the Diagnosis of Scabies.

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.

Energy and protein utilisation by broiler chickens fed diets containing cottonseed meal and supplemented with a composite enzyme product.

1. The present study examined the potential of new-generation microbial enzymes to improve the utilisation of energy and protein of cottonseed meal (CSM)-containing diets, with the aim of increasing its inclusion level in broiler chickens diets. 2. Four hundred and eighty, one-day-old Ross 308 male broilers were used to assess the utilisation of energy and protein by broiler chickens fed diets containing four graded levels of CSM - none, low (4, 8, 12%), medium (5, 10, 15%) or high (6, 12, 18%) in the starter, grower, and finisher phases, respectively, supplemented with 100 mg/kg of a composite enzyme product (xylanase and ß-glucanase). 3. Inclusion of CSM improved (P < 0.01) apparent metabolisable energy (AME), with further improvement (P < 0.001) seen in the enzyme-supplemented diets. Inclusion of CSM reduced (P = 0.002) the metabolisable energy intake (MEI), but this was increased (P < 0.05) with enzyme supplementation. 4. Enzyme addition increased (P < 0.001) the net energy of production (NEp), while heat production (HP) decreased (P < 0.001) with CSM inclusion. More energy was retained as fat (P < 0.05) and protein in birds fed diets with the enzyme, but this was reduced (P < 0.029) by CSM. 5. There was an increase (P < 0.05) in efficiencies of ME use for energy, lipid and protein retention, with higher CSM levels. The enzyme improved (P < 0.013) efficiency of ME use for lipid retention. 6. Feeding diets containing CSM to the broilers enhanced (P < 0.05) protein intake (PI) and protein efficiency ratio (PER). Positive effects (P < 0.05) of enzyme were observed on protein gain (PG) and net protein utilisation (NPU). 7. Results obtained from this study suggested that nutrient utilisation of diets containing CSM by broiler chickens can be improved by enzyme supplementation.

Replacement value of cassava for maize in broiler chicken diets supplemented with enzymes.

OBJECTIVE: Pellet durability, particle size distribution, growth response, tibia bone characteristics and energy retention were measured to evaluate cassava as an alternative energy source to replace maize in broiler diets with or without Ronozyme (A+VP) enzyme composites. METHODS: A total of 480 one-day broiler chicks were randomly assigned to 8 treatments in a 4×2 factorial arrangement. Four levels of cassava: (0%, 25%, 50%, 75%) and 2 levels of enzymes (0 and 500 g/tonne) were used. Each treatment was replicated six times, with ten birds per replicate. RESULTS: The particle size distribution in the diets showed an increasing trend of small particles with increase in cassava level. Pellet durability decreased (p<0.05) with cassava inclusion. Feed intake was highest in birds fed diets with medium cassava level at 1 to 24 d and 1 to 35 d of age. The body weight gain of birds reduced (p<0.037) as cassava level increased, but it increased (p<0.017 when enzymes were added. The feed conversion ratio was high (p<0.05) when cassava level was increased, but it reduced (p<0.05) when enzymes were added. The dressing percentage (DP), and weight of drumsticks reduced (p<0.05) with increasing cassava level. Enzyme supplementation increased (p<0.05) DP, and weight of breast, thighs and drumsticks. Ash content, weight, length, width, and bone strength decreased (p<0.05) when cassava level was increased, however, they were increased with enzyme addition. The contents of Ca, K, and Zn were raised (p<0.001) with increasing cassava level. Enzyme inclusion increased (p<0.001) all mineral contents in tibia bones. Body fat and energy retained as fat decreased (p<0.001) as cassava level increased. Enzyme inclusion increased (p<0.05) body protein content and energy retained as protein. CONCLUSION: Although broiler performance was depressed by high levels of cassava inclusion, it was not affected by low levels, which further improved by enzyme supplementation.

Influence of dietary supplementation of autolyzed whole yeast and yeast cell wall products on broiler chickens.

OBJECTIVE: This study evaluated the effect of yeast products on growth performance, visceral organ weights, endogenous enzyme activities, ileal nutrient digestibility and meat yield of broiler chickens fed diets containing autolyzed whole yeast (WY) and yeast cell walls (YCW) at varying levels of inclusion. METHODS: Nine dietary treatments consisting of WY or YCW included at 0.5, 1.0, 1.5, or 2.0 g/kg diet and a control diet without yeast supplementation was used in the experiment. Each of the nine treatments was replicated six times with nine birds per replicate. Birds were housed in cages, in climate-controlled rooms and fed starter, grower and finisher diets. RESULTS: There was an improvement (p<0.05) in body weight gain and feed conversion ratio on d 10, 24, and 35 for birds fed 1.0 to 2.0 g/kg WY or YCW diet. Small intestine weight was heavier on d 10 and 24 for birds on higher levels of WY and YCW compared to the control group. On d 10 and 24, there was a significant increase (p<0.05) in tissue protein content and pancreatic enzyme activities (trypsin and chymotrypsin) of birds on 1.5 to 2.0 g/kg WY and YCW diets compared to the control group. Compared to the control group, birds on WY (2.0 g/kg diet) and YCW (at 1.5 and 2.0 g/kg diet) had better (p<0.05) protein digestibility on d 24. On d 35, there was significant improvement (p<0.05) in percentage of carcass, absolute and relative breast weight for broiler chickens fed WY and YCW mostly at 2 g/kg diet compared to birds on the control diet. CONCLUSION: Supplementation of diets with autolyzed WY and YCW products especially at 1.5 to 2.0 g/kg diet improved broiler chicken performance and meat yield through their positive effects on ileal protein digestibility and pancreatic enzyme activities.

Hip muscle strength and protection against structural worsening and poor function and disability outcomes in knee osteoarthritis.

OBJECTIVE: Examine associations of hip abductor strength with (1) cartilage damage worsening in the tibiofemoral and patellofemoral compartments 2 years later, and (2) poor function and disability outcomes 5 years later. METHODS: Participants had knee osteoarthritis (K/L ≥ 2) in at least one knee. Hip abductor strength was measured using Biodex Dynamometry. Participants underwent 3.0T MRI of both knees at baseline and 2 years later. Baseline-to-2-year cartilage damage progression, defined as any worsening of WORMS cartilage damage score, was assessed at each tibiofemoral and patellofemoral surface. LLFDI (Late-Life Function and Disability Instrument) and Chair-Stand-Rate were recorded at baseline and 5-year follow-up; outcomes analyzed using quintiles. Poor outcomes were defined as remaining in the same low-function quintiles or being in a worse quintile at 5-year follow-up. We analyzed associations of baseline hip abductor strength with cartilage damage worsening and function and disability outcomes using multivariable log-binomial models. RESULTS: 275 knees from 164 persons [age = 63.7 (SD = 9.8) years, 79.3% women] comprised the structural outcome sample, and 187 persons [age = 64.2 (9.7), 78.6% women] the function and disability outcomes sample. Greater baseline hip abductor strength was associated with reduced risks of baseline-to-2-year medial patellofemoral and lateral tibiofemoral cartilage damage worsening [adjusted relative risks (RRs) range: 0.80-0.83) and with reduced risks of baseline-to-5-year poor outcomes for Chair-Stand-Rate and LLFDI Basic Lower-Extremity Function and Disability Limitation (adjusted RRs range: 0.91-0.94). CONCLUSION: Findings support a beneficial role of hip abductor strength for disease modification and for function and disability outcomes, and as a potential therapeutic target in managing knee osteoarthritis.

Dietary hydrolysed yeast cell wall extract is comparable to antibiotics in the control of subclinical necrotic enteritis in broiler chickens.

1. The aim of this study was to examine the effect of yeast cell wall (YCW) on performance and physiological responses of broiler chickens under subclinical necrotic enteritis challenge.2. Six treatments in a 2 × 3 factorial arrangement (non-challenged or challenged plus no supplement, YCW or antibiotics (AB)) was used. Each treatment was replicated eight times with 12 birds per replicate. The treatments included: (1) Positive control (PC; no additive, not challenged); (2) Negative control (NC; no additive, with challenge); (3) YCWN = yeast cell wall (2.0 g/kg diet, not challenged; (4) YCWC = yeast cell wall (2.0 g/kg diet, challenged); (5) ABN = zinc bacitracin 50 ppm + Salinomycin 60 ppm, not challenged); (6) ABC = zinc bacitracin 50 ppm + Salinomycin 60 ppm, challenged).3. Eimeria challenge at 9 d of age did not affect feed intake (FI), body weight gain (BWG), FCR or liveability at 10 d. The BWG and FCR at 10 d were greater (P < 0.05) in birds fed YCW or AB (AB) diets relative to the PC or NC groups. On 24 and 35 d, FI, BWG, FCR and flock uniformity (28 d) were greater (P < 0.05) in the challenged groups fed YCW or AB diets compared to NC group.4. Supplementation with YCW ameliorated the negative effects of NE on liver, spleen and bursa weight of birds.5. Necrotic enteritis challenge decreased (P < 0.05) caecal Lactobacillus and Bifidobacterium spp. counts, and increased ileum lesion score and caecal Clostridium perfirngens counts. This was reversed by the addition of either YCW or AB.6. Supplementation with YCW and AB resulted to a greater (P < 0.05) dressing percentage and meat yield (35 d).7. The results indicated that YCW plays a vital role in improving the physiological response and performance of broiler chickens under subclinical necrotic enteritis challenge.

Reallocating time spent in sleep, sedentary behavior and physical activity and its association with pain: a pilot sleep study from the Osteoarthritis Initiative.

OBJECTIVE: Being physically active has broad health benefits for people with osteoarthritis (OA), including pain relief. Increasing physical activity (PA) requires reducing time in other behaviors within a fixed 24-h day. We examined the potential benefits in relation to pain from trading time in one type of wake or sleep behavior for another. METHOD: In this cross-sectional study, we used isotemporal logistic regression models to examine the estimated effect on pain from replacing time in one behavior with equal time in another, controlling for sociodemographic and health factors. Stratified analysis was conducted by the report of restless sleep. Sleep and wake behaviors [sedentary behavior (SB), light PA, moderate PA] were monitored by accelerometer in a pilot study of 185 Osteoarthritis Initiative (OAI) participants. Outcomes were bodily pain interference and knee pain. RESULTS: Moderate PA substituted for an equivalent time in sleep or other types of wake behaviors was most strongly associated with lower odds of pain (bodily pain interference odds reduced 21-25%, knee pain odds reduced 17-20% per 10-min exchange). These beneficial associations were particularly pronounced in individuals without restless sleep, but not in those with restless sleep, especially for bodily pain interference. CONCLUSION: Interventions promoting moderate physical activities may be most beneficial to address pain among people with or at high risk for knee OA. In addition to encouraging moderate-intensity PA, pain management strategies may also include the identification and treatment of sleep problems.