Trial Period Research Articles

Tinnitus reduction in patients with single-sided deafness: the effect of cochlear implantation, bone conduction devices, and contralateral routing of sound hearing aids investigated in a randomized controlled trial.

Single-sided deafness (SSD) is often accompanied by tinnitus, resulting in a decreased quality of life. Currently, there is a lack of high level of evidence studies comparing different treatment options for SSD regarding tinnitus reduction. This randomized controlled trial (RCT) evaluated the effect of a cochlear implant (CI), bone conduction device (BCD), contralateral routing of sound (CROS), and no treatment on tinnitus outcomes in SSD patients, with follow-up extending to 24 months. A total of 120 adult SSD patients were randomized to three groups: CI, a trial period with first a BCD on a headband, then a CROS, or vice versa. After the trial periods, patients opted for a BCD, CROS, or no treatment. At the start of follow-up, 28 patients were implanted with a CI, 25 patients with a BCD, 34 patients had a CROS, and 26 patients chose no treatment. The Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ), the Visual Analog Scale (VAS), and the Hospital Anxiety and Depression Scale (HADS) were completed at baseline and at 3, 6, 12, and 24 months of follow-up. The CI and BCD groups showed significantly decreased tinnitus impact scores. The CI group showed the largest decrease, which was already observed at 3 months of follow-up. Compared to the baseline, the median THI score decreased by 23 points, the TQ score by 17 points, and the VAS score by 60 points at 24 months. In the BCD group, the TQ score decreased by 9 points, and the VAS decreased by 25 points at 24 months. The HADS anxiety and depression subscale showed no indication for anxiety or depression at baseline, nor at 24 months, for all groups. In this RCT, SSD patients treated with a CI or BCD showed an overall decrease in tinnitus impact scores up to 24 months compared to baseline. The CI group reported a stable and the largest reduction. Cochlear implants appear to be superior to BCD and CROS, and no treatment for achieving partial or complete resolution of tinnitus in patients with SSD. Netherlands Trial Register, www.onderzoekmetmensen.nl/nl/trial/26952, NTR4457, CINGLE trial.

Characteristics of older adults receiving enteral feeding at a geriatric medical center

BackgroundMalnutrition is a prevalent and hard-to-treat condition in older adults. enteral feeding is common in acute and long-term care. Data regarding the prognosis of patients receiving enteral feeding in geriatric medical settings is lacking. Such data is important for decision-making and preliminary instructions for patients, caregivers, and physicians. This study aimed to evaluate the prognosis and risk factors for mortality among older adults admitted to a geriatric medical center receiving or starting enteral nutrition (EN).MethodsA cohort retrospective study, conducted from 2019 to 2021. Patients admitted to our geriatric medical center who received EN were included. Data was collected from electronic medical records including demographic, clinical, and blood tests, duration of enteral feeding, Norton scale, and Short Nutritional Assessment Questionnaire score. Mortality was assessed during and after hospitalization. Data were compared between survivors and non-survivors. Multivariate logistic regressions were performed to identify the variables most significantly associated with in-hospital mortality.ResultsOf 9169 patients admitted, 124 (1.35%) received enteral feeding tubes. More than half of the patients (50.8%) had polypharmacy (over 8 medications), 62% suffered from more than 10 chronic illnesses and the majority of patients (122/124) had a Norton scale under 14. Most of the patients had a nasogastric tube (NGT) (95/124) and 29 had percutaneous endoscopic gastrostomies (PEGs). Ninety patients (72%) died during the trial period with a median follow-up of 12.7 months (0.1–62.9 months) and one-year mortality was 16% (20/124). Associations to mortality were found for marital status, oxygen use, and Red Cell Distribution Width (RDW). Age and poly-morbidity were not associated with mortality.ConclusionIn patients receiving EN at a geriatric medical center mortality was lower than in a general hospital. The prognosis remained grim with high mortality rates and low quality of life. This data should aid decision-making and promote preliminary instructions.

Sacral neuromodulation for voiding dysfunction and urinary retention

Voiding dysfunction and non-obstructive urinary retention are common conditions with debilitating patient symptoms. Treatment of these conditions can be challenging with limited conservative options available. Sacral Neuromodulation is a minimally invasive treatment which has been demonstrated to deliver good success rates in this patient population. It provides patients with a trial period to establish the likelihood of treatment success prior to implantation of a full system and can be reversed should the need arise.This review looks at the potential mechanisms of action of Sacral Neuromodulation in patients with voiding dysfunction or non-obstructive urinary retention, along with the literature evaluating success rates both in the short and long term. It aims to examine any possible predictive factors that may play a role in guiding patient selection and improving patient counselling. It also addresses gaps in the literature and areas where further research is needed.

Car or Cargo Bike? Determinants for the Use of a Small Vehicle Type in Urban Logistics: A Stated Preference Survey Among Commercial Transport Operators

To address the adverse effects of urban freight, downshifting to smaller vehicles, such as cargo bikes, has been indicated as a viable solution. Existing literature on freight mode choice rarely considers vehicles smaller than truck size. We aimed to fill this research gap by quantifying how vehicular, operational, trip-based, contextual, and individual determinants influenced the decision between cargo bikes and cars in urban logistics. To that end, a stated preference survey was conducted among 537 German organizations after they had been familiarized with cargo bikes through a 3-month vehicle trial period. Participants then took part in a survey in which they had to choose between the modes cargo bike, car, or neither of these two alternatives. The survey data were analyzed using a mixed logit model with 4,833 observations. The model estimations demonstrated that the values and signs of parameters were in accordance with both our expectations and the literature. The results indicated that cargo bikes were an attractive alternative to cars for delivery and service trips of short duration in fair weather. The probability of choosing a cargo bike over a car could be further increased by improving bike infrastructure or imposing parking limitations. The preference for cargo bike could be observed for respondents in dense urban centers and low-density parts of the country alike. Around 3 out of 10 respondents decided to buy their own cargo bike after the study, demonstrating the effectiveness of low-threshold testing programs in changing habits toward more sustainable mobility solutions.

Attenuation of Delayed Onset Muscle Soreness with Acute Consumption of Essential Amino Acids

Introduction: Prior studies of the acute benefits of protein supplementation have determined a benefit in improving post-exercise muscle anabolism and aiding the recovery of muscle function and performance. Previous acute protein supplement studies in post-exercise protein synthesis and anabolic intracellular signaling reported no attenuation in muscle damage or elevated muscle function. The aim of this study is to implement a specific content of essential amino acids with resistance and aerobic exercises to quantify the difference in strength, endurance, and flexibility during the delayed onset muscle soreness common with a new exercise protocol. Methods: We enrolled 42 participants (22 EAA and 20 Controls) completed an hour-long aerobic and resistance exercise protocol including flexibility, resistance, and aerobic exercises for three consecutive days. The study participants were randomly assigned to the EAA (6.6g) per day (EAA + Gatorade) group or the control (Gatorade) group. The data was analyzed in a double-blinded format. Results: Both groups improved the initial flexibility respectively throughout the three exercise days but were not significantly different (p=0.32) in the sit and reach. For the resistance/power activities, the EAA group improved in the repetitions for push-ups (p=0.014 vs 0.21) and dips (0.0002 vs 0.59) compared to the controls. The EAA group was faster although not statistically significant in the 20-meter sprint and improved in the 1.5-mile run during the third day (P=0.002 vs 0.48) compared to the control group. Conclusions: The data in the results supports that acute ingestion of the essential amino acid supplements provides increased physical performance and decreases the DOMS symptoms in sedentary participants over the three-day trial period of exercise.

Effects of L-Methionine and DL-Methionine on Growth Performance, Methionine-Metabolizing Enzyme Activities, Feather Traits, and Intestinal Morphology of Medium-Growing, Yellow-Feathered Chickens between 1 and 30 Days of Age.

This experiment investigated the effects of L-Methionine (L-Met) on growth performance, Met-metabolizing enzyme activity, feather traits, and small intestinal morphological characteristics, and compared these with DL-Methionine (DL-Met) for medium-growing, yellow-feathered broilers during the starter phase. Furthermore, the aim was to provide recommendations for the appropriate dietary Met levels in feed. A total of 1584 1-d broilers were randomly divided into 11 treatment groups with six replicates of 24 birds each: basal diet (CON, Met 0.28%), basal diet + L-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%), and basal diet + DL-Met (0.04%, 0.08%, 0.12%, 0.16%, 0.20%). The total trial period was 30 days. Compared with broilers fed the basal diet, those fed 0.04 to 0.20% supplemental Met had higher final body weight (FBW), average daily feed intake (ADFI), average daily gain (ADG), and lower feed-to-gain ratio (F: G) (p < 0.05). Compared with DL-Met groups, the L-Met group had higher FBW and ADG (p < 0.05). The relative bioavailability (RBV) of L-Met in ADG of 1-30 d was 142.5%. Chicks fed diets supplemented with L-Met had longer fourth primary feather lengths compared to birds fed the control and diets supplemented with DL-Met (p < 0.05). Compared to the control, birds supplemented with DL-Met or L-Met had an increased moulting score (p ≤ 0.05). Chicks fed diets supplemented with L-Met had lower activities of methionine adenosyl transferase (MAT) compared to those fed the basal diet or supplemented with DL-Met (p < 0.05). Chicks supplemented with either DL-Met or L-Met had higher activities of cystathionine β-synthase (CBS) than those fed the basal diet (p < 0.05). Compared with the control, chicks fed diets supplemented with either DL-Met or L-Met had an enhanced level of albumin in plasma (p < 0.05). There were no obvious differences in the plasma content of uric acid and total protein among the treatments (p > 0.05). Chicks fed diets supplemented with either DL-Met or L-Met had higher villus height and V/C in the duodenal than chicks fed the basal diet (p < 0.05). The jejunum morphology was not affected by either L-Met or DL-Met supplementation (p > 0.05). Therefore, dietary supplementation with DL-Met or L-Met improved the growth performance, feather traits, and intestinal morphological characteristics of medium-growing, yellow-feathered broiler chickens aged 1 to 30 d by decreasing the enzyme activities of Met methylation (MAT) and increasing the enzyme activities of the sulfur transfer pathway (CBS), and supplementation with L-Met showed a better improvement compared with DL-Met. The relative efficacy of L-Met to DL-Met was 142.5% for ADG of yellow-feathered broilers. The appropriate Met levels for medium-growing, yellow-feathered broilers are between 0.36~0.38% (supplementation with DL-Met) or 0.32~0.33% (supplementation with L-Met) when based on ADG and feed-to-gain ratio.

Early epidural lead migration in spinal cord stimulator trials: A case series

BackgroundSpinal cord stimulation (SCS) devices are routinely trialed to assess pain and functional improvement before permanent lead implantation. Lead migration is a common complication that may cause a loss of therapeutic effect in patients who may otherwise benefit from SCS. The timing of lead migration during the trial period is currently unknown. ObjectivesWe hypothesize that significant lead migration may occur early in the SCS trial period, such as postoperative day 1 or 2, which may allow for contact stimulation adjustment to prevent false negative trial results. As such, in this study, we aim to evaluate the incidence and distance of lead migration in early thoracic SCS trial period. MethodsWe performed a case series of 27 patients ≥19 years of age who received differential target multiplexed thoracic SCS trials for chronic neuropathic pain from July 1, 2020 to July 1, 2023. Patients with a neuropathic pain diagnosis failing medical treatment, without structural pathology limiting epidural access, and with psychiatric clearance for suitability are eligible for SCS trials at our center. Pre- and post-flexion radiographs taken immediately after implantation and on postoperative day 1 or 2 were examined to assess the distance of lead migration. Clinically significant lead migration was pre-defined as ≥ 10 mm. ResultsThe mean (SD) distances of epidural lead migration on postoperative day 1 or 2 were 18.2 (12.9) mm and 19.1 (13.3) mm for the cephalic and caudal leads, respectively. All migrations were caudad except for one trial. Clinically significant lead migration occurred in 20/27 (74 %) patients. ConclusionClinically significant epidural lead migration occurs in the early SCS trial period.

Effects of potassium diformate on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora in Cherry Valley ducks

This study was performed to investigate the effects of potassium diformate (KDF) on growth performance, apparent digestibility of nutrients, serum biochemical indices, and intestinal microflora of Cherry Valley ducks. In total, 144 female healthy 1-day-old Cherry Valley ducks were divided into 3 groups with 6 replicates per group and 8 ducks per replicate according to the principle of similar body weight. The control group was fed a basic diet. In the 2 experimental groups, 0.8% and 1.2% KDF was added to the basic diet, respectively. The trial period was 6 wk and the pretrial period was 3 wk. The final weight and ADG were significantly higher in the 0.8% KDF group than in the control group (P < 0.05). The feed-to-gain ratio was significantly lower in both KDF groups than in the control group (P < 0.05). The apparent digestibility of CP was significantly higher in both KDF groups than in the control group (P < 0.05). The apparent digestibility of calcium was also significantly higher in the 0.8% KDF group (P < 0.05). The serum levels of alkaline phosphatase, cholesterol, and total protein were significantly lower in the 0.8% KDF group than in the control group (P < 0.05), the IgM content was significantly higher (P < 0.05), the low-density lipoprotein cholesterol, triglyceride, and urea levels were significantly lower (P < 0.01), and the glucose level was significantly higher (P < 0.01). The serum total protein level was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of Firmicutes and Patescibacteria in the gut of ducks was significantly higher in the 0.8% KDF group than in the control group (P < 0.05), the relative abundance of unclassified Erysipelotrichaceae and Lactobacillus was significantly higher (P < 0.01), and the relative abundance of Fusobacteriota was significantly lower (P < 0.05). However, the relative abundance of Firmicutes in the gut of ducks was significantly higher in the 1.2% KDF group than in the control group (P < 0.05). The relative abundance of unclassified Erysipelotrichaceae and Clostridium sensu stricto 1 was significantly higher (P < 0.01), as was the relative abundance of Fusobacteriota and Proteobacteria (P < 0.05). These findings indicate that the addition of 0.8% KDF to the diet can improve the growth performance of Cherry Valley ducks, promote the absorption of nutrients, change the structure of the microflora in the cecum, and increase the relative abundance of dominant bacteria. It was also shown that there was a significant difference between the 0.8% and 1.2% KDF levels which suggest that the safety margin for overdosing is quite low.

Daily Supplementation with Bifidobacterium longum KACC91563 Alleviates Allergic Contact Dermatitis in an Animal Model.

Allergic contact dermatitis (ACD) is the most common chronic inflammatory skin disease (or immune-mediated disease), causing disruption to our psychological condition and life quality. In this study, the therapeutic properties of probiotic Bifidobacterium longum (B. longum) was investigated by using an ACD-induced animal model. For ACD induction, BALB/c mice ear and dorsal skin were sensitized with 240 µL of 1% (w/v) 2,4-dinitrochlorobenzene (DNCB) twice (3-day intervals). After a week of the first induction, the mice were re-sensitized by painting on their dorsal skin and ear with 0.4% (w/v) DNCB for a further three times (once per week). Before the ACD induction of 2 weeks and throughout the trial period, the BALB/c mice were supplemented daily with 1 mL of 1.0 × 109 CFU or 5.0 × 109 CFU B. longum using an intragastric gavage method. The ACD-induced mice without B. longum supplementation were used as a control. Results show that B. longum supplementation significantly alleviated ACD symptoms (e.g., ear swelling, epidermal damage) and immune response (e.g., reduced immune cell recruitment, serum IgE level, and cytokine production). The therapeutic efficiency of B. longum increased as the supplementation dose increased. Thus, daily supplementation with 5.0 × 109 CFU probiotic B. longum could be an effective method for the prevention and treatment of ACD.

Evaluation of tumor-suppressive properties and apoptotic functions of Mad Honey and Vincristine applications in a rat model of breast cancer

In this study, the suppressive effects of vincristine and Turkish mad honey alone and in co-applications were biochemically, hematologically, and histopathologically investigated in a mammary tumor model induced with 7,12-dimethylbenz[a]anthracene (DMBA) in rats. A total of 72 rats, 43-49 days old, were divided into 6 groups of 12 rats each. The control group (CG) consisted of healthy rats. The vehicle group (VG) received only vehicle substance and the cancer control group (CCG) was given only DMBA. DMBA and the honey group (HG) given group. DMBA and the vincristine (VinG) given group, and DMBA, the vincristine-honey group (VHG) received both Turkish mad honey and vincristine. Turkish mad honey and/or vincristine was given in the last 4 weeks of the 13-week trial period. White blood cell and lymphocyte counts differed significantly in the CCG and VG groups. Alanine transaminase and total protein levels were higher in the CCG and VinG groups. Aspartate transaminase was higher in the CCG, HG and VG groups. Caspase-3 and Bax protein levels were in the HG and VHG groups significantly higher than CCG. In caspase-8 protein level VHG significantly higher than other groups. Caspase -9 protein level was in CG and VG groups significantly lower than other groups. Bcl-xL increased more in the CCG group. Anaplasia was reduced in the HG and VinG groups, although apoptosis and other cellular damages increased. It was concluded that mad honey and vincristine could be considered together as effective therapeutic agents in this model of DMBA-induced breast cancer.

Registration of ‘Coral’ pink bean

Abstract‘Coral’ (Reg. no. CV‐359, PI 705151) pink bean (Phaseolus vulgaris L.), developed by Michigan State University AgBioResearch was released in 2022 as a midseason, disease‐resistant, upright short vine bean cultivar with uniform dry down. Coral was developed with the pedigree breeding method to the F4 generation followed by pure line selection for disease, agronomic, and quality traits. Coral combines high yield potential with midseason maturity in a pink bean seed type. Over the span of 6 years of field trials, Coral produced an average yield of 3228 kg ha−1, flowered at 46 days, and matured in 97 days. Plants averaged 48 cm in height, with a lodging resistance score of 1.4, and seed size of 42 g 100 seed−1. Notably, Coral has outperformed ‘Rosetta’ by 8% across the 6‐year trial period and reached maturity 1 day earlier. It is well adapted to the intensively managed, narrow‐row, direct‐harvested production systems where beans are typically grown in Michigan and the Upper Midwest. Coral exhibits resistance to Bean common mosaic virus, is susceptible to anthracnose, has shown tolerance to common bacterial blight, and white mold. Additionally, it demonstrated tolerance to root rot caused by Rhizoctonia solani similar to Rosetta. Seed size of Coral (42 g 100 seed−1) is larger than Rosetta (37 g 100 seed−1). Seed of Coral meets industry standards for packaging and canning quality in the pink bean seed class.

Dehydrated and live black soldier fly larvae as environmental enrichment in indigenous slow-growing chickens: performance, gut health, and chitinolytic enzyme activity

The demand for sustainable and ethically farmed animal products is on the rise as consumers become more environmentally and animal welfare conscious. The need to diminish the consumption of soybean meal is urgent, and companies are looking for ways to respond to this necessity by looking for alternatives to soybean meal. This study assessed the impact of introducing whole dehydrated and live black soldier fly larvae (BSFL) into the diet of an indigenous chicken breed as environmental enrichment. A total of 144 39-day-old male Bianca di Saluzzo chickens were distributed among 18 pens and assigned to three different experimental groups. The control group received a diet where soybean meal was entirely replaced by alternative ingredients. The two experimental groups were given the same diet supplemented with 5% of the expected daily feed intake of whole dehydrated BSFL or whole live BSFL. Throughout the trial period (from the bird age of 39–174 days of age), live weight was recorded every 21 days, and the average daily gain, daily feed intake, and feed conversion ratio were calculated. The time required for the birds to consume the larvae was recorded three times a week. At age 147 and 174 days, 12 birds per treatment were selected based on mean live weight and slaughtered. Measurements included hot and chilled carcass weights, organ weights (spleen, liver, heart, stomach), breast and thigh muscle weights, and the corresponding yields were calculated. Acid protease activity was measured in proventriculus extract, and chitinase and chitosanase activity was calculated based on the release of reducing sugars from chitin or chitosan. The results showed little improvement in final live weights and daily feed intakes of the animals fed the insect larvae compared with control birds. Larva supplementation had no negative impact on the overall well-being of the animals assessed by blood analysis and histopathological assessment of the intestinal tract, spleen, and liver. No differences were found between the dehydrated vs live insect larvae consumption times, with all larvae being eaten up very rapidly (< 3 min). The birds fed BSFL showed an increase in chitinase activity. These findings support the potential use of whole BSFL as a form of environmental enrichment, particularly in their dehydrated form, being more convenient to use and store, which would also encourage the uptake of this practice by farmers.

578 Optimising Emergency Theatre Efficiency with the Use of a Pre-Anaesthetic Holding Bay, a Quality Improvement Project

Abstract Aim An efficient emergency theatre depends on the coordination of multiple surgical specialties, anaesthetists, and theatre staff. The serial nature of an operating list leads to downtime between cases. We sought to reduce delays between emergency cases by implementing a pre-anaesthetic holding bay. Method Anonymised data was collected from a prospectively maintained mandatory database of theatre activity. Exclusion criteria were non-surgical procedures, first case, out-of-hours procedures, and critical care admissions. Suitability was determined from a period pre-implementation and a pre-defined trial period to ensure safe rollout. Pre-, trial, and post-implementation were compared. Results 349 emergency procedures were performed in three months post-implementation. After exclusion criteria 110 were suitable for pre-anaesthetic holding bay use, and in 35 (31.8%) it was utilised. Most cases were general surgery (61%), vascular surgery (15%), and gynaecology (12%). Holding bay use decreased time without a patient in the anaesthetic room from 50 to 5 minutes (p&amp;lt;.001) and the time between procedures from 86 to 43 minutes (p&amp;lt;.001). There was no difference in anaesthetic time between the groups (36 vs 38 minutes, p=.40). Over the three months 40 more in-hours cases were completed in 48 days with no difference in procedures across the periods. Conclusions Pre-anaesthetic holding bay use reduced theatre downtime by 90%, allowing more procedures to be performed in-hours. All specialties engaged with the holding bay but to varying extent, and ensuring investment from surgeons, anaesthetists, and theatre staff is essential. This intervention, implemented with no extra resources, has increased efficiency and improved safety in the emergency theatre list.

Individualised Lifestyle Intervention in Polycystic Ovarian Syndrome Women Who Desire Fertility: A Feasibility Study

Background: Polycystic ovarian syndrome (PCOS) is one of the common causes of anovulatory infertility among women in the reproductive age group. Women with PCOS and obesity often have difficulty in conceiving, and they are more prone for developing metabolic syndrome. Lifestyle modification plays a key role in women with PCOS, who are overweight or obese and is recommended as a first line management option. The earlier trials evaluating the role of lifestyle intervention in infertile PCOS women had methodological issues, smaller sample size and high dropout rates and none of these trials reported live birth as their outcome. Aim: The current study was planned to explore the feasibility of conducting large adequately powered multicentric trial in future in South Asian women with PCOS who desire fertility. Setting and Design: The study was done in the Department of Reproductive Medicine and Surgery &amp; the Department of Endocrinology and Metabolism at a university level tertiary care hospital. The study is an open label, single center, randomized controlled trial. Materials and Methods: A total of 60 PCOS women aged between 18-40 years with body mass index of &gt; 23 kg/m2 who desire fertility, were randomized to individualized lifestyle intervention and usual care. The primary outcome was the dropout rate, and the secondary outcomes were change in body weight, anthropometric parameters, clinical pregnancy rates and the quality of life specific to PCOS after the trial period. All the participants were followed up for 6 months and the outcomes were assessed. Statistical Analysis: Comparison between the intervention and control groups was done using statistical tests using the SPSS and R software. Results: The dropout rates were significantly higher in the individualized lifestyle intervention arm compared to usual care control arm (19/30, 63% vs 9/30, 30%, P=0.019). We did not find any statistically significant difference in anthropometric measurements, pregnancy rates (P=0.57) and clinical pregnancy rates (P=0.21) and quality of life specific to PCOS compared with sixth month visit from baseline visit. Conclusion: The current feasibility study showed significantly higher dropout rates in individualized lifestyle intervention arm compared to usual care control arm. The knowledge gained from the feasibility study has been used to design an adequately powered trial to evaluate effectiveness of individualized lifestyle intervention in women with PCOS who wish to conceive.

Nemolizumab with concomitant topical therapy in adolescents and adults with moderate-to-severe atopic dermatitis (ARCADIA 1 and ARCADIA 2): results from two replicate, double-blind, randomised controlled phase 3 trials

Nemolizumab, an interleukin (IL)-31 receptor subunit α antagonist, inhibits the IL-31 pathway of itch and skin inflammation in atopic dermatitis. Two international phase 3 studies were done to assess the efficacy and safety of nemolizumab in atopic dermatitis. In this Article we report results for the 16-week initial treatment period of both trials. ARCADIA 1 and ARCADIA 2 were identical 48-week randomised, double-blind, placebo-controlled phase 3 trials in adult and adolescent participants (aged ≥12 years) with moderate-to-severe atopic dermatitis, associated pruritus, and inadequate response to topical steroids. Participants were enrolled from 281 clinics, hospitals, and academic centres in 22 countries across both trials, and were randomly assigned (2:1) to receive nemolizumab 30 mg subcutaneously (baseline loading dose 60 mg) or matching placebo once every 4 weeks with background topical corticosteroids (TCS) with or without topical calcineurin inhibitors (TCI; ie, TCS-TCI background treatment). Randomisation was done via interactive response technology and stratified by baseline disease and pruritus severity. Study staff and participants were masked throughout the study, with outcome assessors masked until database lock. Coprimary endpoints at week 16 post-baseline were Investigator's Global Assessment (IGA) success (score of 0 [clear skin] or 1 [almost clear skin] with a ≥2-point improvement from baseline) and at least 75% improvement in Eczema Area and Severity Index score from baseline (EASI-75 response). Outcome rates were compared between groups with the Cochran-Mantel-Haenszel test adjusting for randomisation strata. The key secondary endpoints were the proportion of participants with Peak Pruritus Numerical Rating Scale (PP-NRS) score improvement of at least 4 points at weeks 1, 2, 4, and 16; PP-NRS score below 2 at weeks 4 and 16; Sleep Disturbance Numerical Rating Scale score improvement of at least 4 points at week 16; EASI-75 response plus PP-NRS score improvement of at least 4 points at week 16; and IGA success plus PP-NRS score improvement of at least 4 points at week 16. Efficacy analyses were done on an intention-to-treat basis; safety analyses included all participants who received one dose of nemolizumab or placebo. Both studies are completed (ClinicalTrials.gov: ARCADIA 1, NCT03985943 and ARCADIA 2, NCT03989349). Between Aug 9, 2019, and Nov 2, 2022, 1728 participants were enrolled across both trials: 1142 were allocated to nemolizumab plus TCS-TCI (620 in ARCADIA 1 and 522 in ARCADIA 2) and 586 to placebo plus TCS-TCI (321 in ARCADIA 1 and 265 in ARCADIA 2). ARCADIA 1 included 500 (53%) male participants and 441 (47%) female participants, and ARCADIA 2 included 381 (48%) male participants and 406 (52%) female participants. Mean age ranged from 33·3 (SD 15·6) years to 35·2 (17·0) years across the treatment groups. Both trials met the coprimary endpoints; at week 16, a greater proportion of participants receiving nemolizumab plus TCS-TCI versus placebo plus TCS-TCI had IGA success (ARCADIA 1: 221 [36%] of 620 vs 79 [25%] of 321, adjusted percentage difference 11·5% [97·5% CI 4·7-18·3], p=0·0003; ARCADIA 2: 197 [38%] of 522 vs 69 [26%] of 265, adjusted difference 12·2% [4·6-19·8], p=0·0006) and an EASI-75 response (ARCADIA 1: 270 [44%] vs 93 [29%], adjusted difference 14·9% [7·8-22·0], p<0·0001; ARCADIA 2: 220 [42%] vs 80 [30%], adjusted difference 12·5% [4·6-20·3], p=0·0006). Significant benefits were observed with nemolizumab for all key secondary endpoints including improvement in itch, as early as week 1, and sleep improvement by week 16. The safety profile was similar between nemolizumab plus TCS-TCI and placebo plus TCS-TCI. In the safety sets, 306 (50%) of 616 participants (ARCADIA 1) and 215 (41%) of 519 participants (ARCADIA 2) who received nemolizumab plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in six [1%] and 13 [3%], respectively); and 146 (45%) of 321 (ARCADIA 1) and 117 (44%) of 263 (ARCADIA 2) who received placebo plus TCS-TCI had at least one treatment-emergent adverse event (serious treatment-emergent adverse events in four [1%] and three [1%], respectively). Ten serious treatment-emergent adverse events possibly related to nemolizumab were reported in five (1%) participants in ARCADIA 2. No deaths occurred. Nemolizumab plus TCS-TCI was efficacious and showed statistically and clinically significant improvements in inflammation and itch in adults and adolescents with moderate-to-severe atopic dermatitis. Nemolizumab might offer a valuable extension of current therapies if approved. Galderma.

Enhancing Muscovy Duck Meat Quality and Growth Development Through Oregano Extract Supplementation: A Study in Agricultural Innovation

This study investigated the effects of oregano extract (OE) supplementation on the growth and meat quality of Muscovy ducks, aiming to optimize meat quality and explore sustainable dietary interventions in poultry production. Twenty-five male Muscovy ducks were meticulously allocated to five treatment groups, each comprising five replications, employing a Completely Randomized Design (CRD). Ducks were exposed to varying levels of oregano extract supplementation with five dietary treatments: T0 (control), T1 (25% OE), T2 (50% OE), T3 ( 75% OE), and T4 (100% OE). Throughout the 4-week trial period, individual ducks were accommodated in designated pens to facilitate precise monitoring. The investigation examined several growth parameters, including feed intake (FI, the amount of feed consumed by each duck), feed cost (FC, the expense associated with feeding each duck), weight gain (WG, the increase in body weight of each duck over the specified time period), and feed conversion ratio (FCR, the ratio of feed consumed to weight gained), assessed at weekly intervals. Results showed that OE supplementation did not significantly affect feed intake or weight gain, except for weeks 1 and 2 where T3, supplemented with 75% OE, exhibited the highest weight gain. However, OE supplementation significantly improved FCR, with T3 showing the lowest FCR, indicating enhanced nutrient utilization. Additionally, T3 displayed the highest fasted live weight, dressed weight, and dressing percentage, suggesting improved meat production and quality. Sensory analysis revealed that T3 consistently exhibited favorable meat quality attributes. Overall, T3 demonstrated the highest general acceptability among consumers, based on criteria such as taste, texture, and overall satisfaction. The study highlights the potential of OE supplementation to optimize feed efficiency and enhance meat quality in Muscovy ducks.

An exploratory randomised trial investigating feasibility, potential impact and cost effectiveness of link workers for people living with multimorbidity attending general practices in deprived urban communities

BackgroundSocial prescribing link workers are non-health or social care professionals who connect people with psychosocial needs to non-clinical community supports. They are being implemented widely, but there is limited evidence for appropriate target populations or cost effectiveness.This study aimed to explore the feasibility, potential impact on health outcomes and cost effectiveness of practice-based link workers for people with multimorbidity living in deprived urban communities.MethodsA pragmatic exploratory randomised trial with wait-list usual care control and blinding at analysis was conducted during the COVID 19 pandemic (July 2020 to January 2021). Participants had two or more ongoing health conditions, attended a general practitioner (GP) serving a deprived urban community who felt they may benefit from a one-month practice-based social prescribing link worker intervention.. Feasibility measures were recruitment and retention of participants, practices and link workers, and completion of outcome data. Primary outcomes at one month were health-related quality of life (EQ-5D-5L) and mental health (HADS). Potential cost effectiveness from the health service perspective was evaluated using quality adjusted life years (QALYs), based on conversion of the EQ-5D-5L and ICECAP-A capability index to utility scoring.ResultsFrom a target of 600, 251 patients were recruited across 13 general practices. Randomisation to intervention (n = 123) and control (n = 117) was after baseline data collection. Participant retention at one month was 80%. All practices and link workers (n = 10) were retained for the trial period. Data completion for primary outcomes was 75%. There were no significant differences identified using mixed effects regression analysis in EQ-5D-5L (MD 0.01, 95% CI -0.07 to 0.09) or HADS (MD 0.05, 95% CI -0.63 to 0.73), and no cost effectiveness advantages. A sensitivity analysis that considered link workers operating at full capacity in a non-pandemic setting, indicated the probability of effectiveness at the €45,000 ICER threshold value for Ireland was 0.787 using the ICECAP-A capability index.ConclusionsWhile the trial under-recruited participants mainly due to COVID-19 restrictions, it demonstrates that robust evaluations and cost utility analyses are possible. Further evaluations are required to establish cost effectiveness and should consider using the ICE-CAP-A wellbeing measure for cost utility analysis.RegistrationThis trial is registered on ISRCTN.Title: Use of link workers to provide social prescribing and health and social care coordination for people with complex multimorbidity in socially deprived areas.Trial ID: ISRCTN10287737.Date registered 10/12/2019.Link: https://www.isrctn.com/ISRCTN10287737

Comprehensive assessment of combined inorganic and organic fertilization strategies on cotton cultivation: implications for sustainable agriculture.

The integration of inorganic and organic fertilizers is increasingly being recommended to address the demand for sustainable cotton cultivation and to mitigate the ecological impacts of reliance on inorganic fertilizers. However, the nuanced effects of this combined fertilization approach on soil quality, cotton growth, yield, and their interaction mechanisms, remain unclear. To elucidate this, a 2-year field trial (2022-2023) was conducted, incorporating five fertilization treatments: low inorganic fertilizer (BI1), high inorganic fertilizer (BI2), organic fertilizer (BO), combined low inorganic and organic fertilizer (BIO1), and combined high inorganic and organic fertilizer (BIO2). This study aimed to evaluate the influence of these treatments on soil quality, cotton growth, and yield. The results indicate that the BO treatment significantly enhanced plant height growth rate, and BIO1 treatment increased leaf area index and dry matter accumulation growth rate. Critical soil parameters such as alkali-hydrolyzed nitrogen and available potassium emerged as pivotal determinants of soil quality over the trial period, corresponding to soil quality index (SQI) values of 0.482 and 0.478, and yields of 7506.19 kg ha-1 and 6788.02 kg ha-1, respectively. Water productivity reached optimum levels at SQI values of 0.461 and 0.462, with corresponding efficiencies of 13.31 kg (ha mm)-1 and 12.16 kg (ha mm)-1. Partial least squares path modeling revealed that integrating organic fertilizer with reduced inorganic fertilizer usage significantly boosts cotton yield by enhancing soil quality (path coefficient: 0.842). In conclusion, this integrated fertilization strategy not only improves soil health but also increases agricultural productivity. It presents a promising approach for optimizing crop yields while fostering sustainable agricultural practices. © 2024 Society of Chemical Industry.

Mortality and Associated Risk Factors Among People Living With HIV With Kaposi Sarcoma: A5263/AMC066 and A5264/AMC067.

AIDS-related Kaposi sarcoma (AIDS-KS) remains a leading cause of morbidity and mortality among people living with HIV in Africa. Mortality among people with AIDS-KS on antiretroviral therapy remains high compared with people on antiretroviral therapy who do not have AIDS-KS. People living with HIV with Kaposi sarcoma (KS) who participated in 2 randomized trials (A5263/AMC066 [advanced stage] and A5264/AMC067 [mild-to-moderate stage]) conducted by AIDS Clinical Trials Group/AIDS Malignancy Consortium in low- and middle-income countries. We estimated mortality rates over the trial period. Cox proportional hazards regressions were used to identify baseline characteristics associated with mortality and compared mortality rates between participants who had KS progression within 12 weeks of treatment initiation (early progression of KS [KS-PD]) and those who did not. Of the 329 and 189 eligible participants in A5263/AMC066 and A5264/AMC067, 71 (21.6%) and 24 (12.7%) died, respectively. In both trials, hypoalbuminemia was associated with increased hazards of death compared with normal albumin; A5263/AMC066: mild hypoalbuminemia (adjusted hazard ratio [aHR] = 3.01; 95% CI: 1.42 to 6.29), moderate hypoalbuminemia (aHR = 5.11; 95% CI: 2.54 to 10.29), and severe hypoalbuminemia (aHR = 14.58; 95% CI: 6.32 to 35.60), and A5264/AMC067: mild hypoalbuminemia (aHR = 5.66; 95% CI: 1.90 to 16.93) and moderate hypoalbuminemia (aHR = 7.02; 95% CI: 2.57 to 19.15). The rate of death was higher among participants who had early KS-PD than those without early KS-PD in A5263/AMC066 (HR = 5.09; 95% CI: 1.71 to 15.19) but not in A5264/AMC067 (HR = 1.74; 95% CI: 0.66 to 4.62). Albumin measurements may be used to identify individuals at higher risk of death after initiating KS treatment and for evaluation of interventions that can reduce AIDS-KS mortality.

Cortico-cancellous osseointegration into additively manufactured titanium implants using a load-bearing femoral ovine model.

Introduction: Titanium-based implants can be used to fill voids in bone reconstruction surgery. Through additive manufacturing (AM), it is possible to produce titanium implants with osteoconductive properties such as high porosity and low stiffness. AM facilitates a level of design flexibility and personalization that is not feasible with traditional techniques. Methods: In this study, osseointegration into titanium alloy (Ti-6Al-4V) lattices was investigated for 12weeks post-implantation using a novel bicortical load-bearing ovine model. The objective was to assess the safety and efficacy of AM-fabricated implants using two lattice structures of contrasting stiffness spanning the full width of the femoral condyle. Results: This was achieved by evaluating implant osseointegration and bone-implant contact properties by histomorphometry, scoring local implant tissue responses via histopathology, and micro-computed tomography reconstruction. Discussion: We found that Ti-6Al-4V implants facilitated widespread and extensive osseointegration, with bone maturation ongoing at the conclusion of the trial period. Following the implantation period, no adverse clinical indications that could be directly ascribed to the presence of the implanted device were identified, as determined by macroscopic and microscopic observation.