International Survey to Establish Prioritized Outcomes for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: There are over 4,000 trials conducted in people with coronavirus disease 2019. However, the variability of outcomes and the omission of patient-centered outcomes may diminish the impact of these trials on decision-making. The aim of this study was to generate a consensus-based, prioritized list of outcomes for coronavirus disease 2019 trials. DESIGN: In an online survey conducted in English, Chinese, Italian, Portuguese, and Spanish languages, adults with coronavirus disease 2019, their family members, health professionals, and the general public rated the importance of outcomes using a 9-point Likert scale (7-9, critical importance) and completed a Best-Worst Scale to estimate relative importance. Participant comments were analyzed thematically. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public, and health professionals (including clinicians, policy makers, regulators, funders, and researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: In total, 9,289 participants from 111 countries (776 people with coronavirus disease 2019 or family members, 4,882 health professionals, and 3,631 members of the public) completed the survey. The four outcomes of highest priority for all three groups were: mortality, respiratory failure, pneumonia, and organ failure. Lung function, lung scarring, sepsis, shortness of breath, and oxygen level in the blood were common to the top 10 outcomes across all three groups (mean > 7.5, median ≥ 8, and > 70% of respondents rated the outcome as critically important). Patients/family members rated fatigue, anxiety, chest pain, muscle pain, gastrointestinal problems, and cardiovascular disease higher than health professionals. Four themes underpinned prioritization: fear of life-threatening, debilitating, and permanent consequences; addressing knowledge gaps; enabling preparedness and planning; and tolerable or infrequent outcomes. CONCLUSIONS: Life-threatening respiratory and other organ outcomes were consistently highly prioritized by all stakeholder groups. Patients/family members gave higher priority to many patient-reported outcomes compared with health professionals.The project is funded by the Flinders University and the National COVID-19 Clinical Evidence Taskforce, convened by the Australian Living Evidence Consortium, hosted by Cochrane Australia, School of Public Health and Preventive Medicine, Monash University supported by the Australian Government, Victorian Department of Health and Human Services, Ian Potter Foundation, Walter Cottman Endowment Fund (managed by Equity Trustees) and the Lord Mayor's Charitable Foundation). AT is supported by The University of Sydney Robinson Fellowship. ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z

Core Outcomes Set for Trials in People With Coronavirus Disease 2019.

OBJECTIVES: The outcomes reported in trials in coronavirus disease 2019 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed coronavirus disease 2019. DESIGN: Four international online multistakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed coronavirus disease 2019, informed by a survey involving 9,289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set. SETTING: International. SUBJECTS: Adults 18 years old and over with confirmed or suspected coronavirus disease 2019, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). INTERVENTIONS: None. MEASUREMENTS: None. MAIN RESULTS: Six themes were identified. "Responding to the critical and acute health crisis" reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiple organ failure. "Capturing different settings of care" highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. "Encompassing the full trajectory and severity of disease" was addressing longer term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). "Distinguishing overlap, correlation and collinearity" meant recognizing that symptoms such as shortness of breath had distinct value and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). "Recognizing adverse events" refers to the potential harms of new and evolving interventions. "Being cognizant of family and psychosocial wellbeing" reflected the pervasive impacts of coronavirus disease 2019. CONCLUSIONS: Mortality, respiratory failure, multiple organ failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in coronavirus disease 2019 trials

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

In Vitro Digestibility Assessment of Whey from Goat and Camel Milk Fermented with <i>Lactobacillus helveticus</i> for Use as a Base in Formulating Follow-On Formula

Follow-on formulas are necessary for newborns that are unable to breastfeed. Thus, the development of formulas more tailored to infants’ needs is highly important. Recently, using camel milk, goat milk, and sweet milk whey in the formulation of follow-on formulas has gained researchers’ attention. Moreover, developing postbiotic systems to create formulas that mimic human milk, are easy to digest, improve compatibility with an infant’s gut, and boost immunity is crucial. Thus, this study aimed to create and assess different formulations using fermented whey from camel and goat milks. The fermentation process involved the use of Lactobacillus helveticus as a probiotic and proteolytic lactic acid bacterium strain. The study monitored the proteolytic activity and antioxidant properties of sweet whey produced from cow, camel, and goat milks during the fermentation process with L. helveticus. Also, three different milk fat blends were recombined using edible vegetable oils (coconut oil, rice bran oil, and canola oil) and then they were used to formulate follow-on formulas with a similar fat composition to human milk. Finally, the prepared formulas were tested for their in vitro digestibility and antioxidant activity before and after digestion. The L. helveticus strain had high proteolytic activity towards whey proteins from all the types of milk used in the study. A fermentation time of 6 h produced a higher proteolytic degree and antioxidant activity than 2 and 4 h of fermentation. No significant differences were observed for proteolytic degree and antioxidant activity between 6 and 12 h of fermentation for the cow, camel, and goat whey samples. Regarding the fat blends, animal milk fat, rice bran oil, and canola oil in a fat combination were essential to provide the required amount of unsaturated fatty acids in the follow-on formulas, especially the linoleic acid–α-linolenic acid (LA:ALA) ratio. Adding coconut oil in small amounts to the follow-on formulas provided the required amounts of saturated fatty acids, especially lauric and meristic acids. The follow-on formula based on cow or goat milk whey fermented with L. helveticus released more free amino acids (mmol tyrosine equivalent mL−1) with high levels of antioxidants compared to unfermented ones. The release of free amino acids in the follow-on formula based on camel milk whey was not affected by fermentation. Our results recommend using L. helveticus in the fermentation of follow-on formulas based on camel and goat whey instead of formulas based on cow milk proteins

Dehydroepiandrosterone (DHEA) Improves the Metabolic and Haemostatic Disturbances in Rats with Male Hypogonadism

Objectives: The current work was designed to study the effect of dehydroepiandrosterone (DHEA) on glucose homeostasis, liver functions and hemostatic disturbances in a rat model of bilateral orchidectomy (ORCH). Methods: 32 male rats (n = 8) were randomly assigned into 4 groups; (i) control (sham operated) group; were normal rats in which all surgical procedures were done without ORCH, (ii) Control + DHEA group: as control group but rats were treated with DHEA for 12 weeks, (iii) orchiectomized (ORCH) group: rats had bilateral orchidectomy and (iv) ORCH + DHEA group: orchiectomized rats treated with DHEA for 12 weeks. Four weeks after ORCH, DHEA treatment began and lasted for twelve weeks. By the end of the experiment, the parameters of glucose homeostasis, lipid profile, liver enzymes, bleeding and clotting times (B.T. and C.T.), prothrombin time (P.T.), activated partial thromboplastin time (aPTT), platelet count and aggregation, von-Willebrand factor (vWF), fibrinogen, plasminogen activator inhibitor (PAI-1), fibrin degradation products (FDP), intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelin-1 were measured. Results: ORCH caused significant deteriorations in the parameters of glucose homeostasis, lipid profile, and liver functions (p p < 0.01) with significant shortening of bleeding and clotting times. DHEA replacement therapy significantly decreased glucose, insulin, PAI-1, fibrinogen, ICAM-1, and VCAM-1 when compared to ORCH rats. Conclusion: DHEA ameliorated the metabolic, hepatic, hypercoagulable, and hypofibrinolysis disturbances induced by ORCH

Antioxidative, Antidiabetic, and Hypolipidemic Properties of Probiotic-Enriched Fermented Camel Milk Combined with <i>Salvia officinalis</i> Leaves Hydroalcoholic Extract in Streptozotocin-Induced Diabetes in Rats

Antioxidative, antidiabetic, and hypolipidemic properties of probiotic-enriched fermented camel milk (FCM) combined with Salvia officinalis L. leaves hydroalcoholic extract (SOHE) in streptozotocin-induced diabetes in rats were investigated. Phytochemicals analysis and antioxidant capacity indicated that S. officinalis contained high phenolics with super antioxidant activity. Subsequently, HPLC analysis demonstrated 13 phenolic acids and 14 flavonoids in considerable amounts with ferulic acid and resveratrol as predominant, respectively. The antidiabetic and hypolipidemic properties of FCM and SOHE were examined in a designed animal model consisting of seven treated groups for four weeks. There was a negative group (G1); the positive group (G2) received a single dose (50 mg kg−1) of streptozotocin (STZ) by intraperitoneal injection (i.p.); in G3, diabetic rats (DRs) orally received 5 mL FCM kg−1 daily; in G4, DRs orally received 50 mg GAE SOHE kg−1 daily; in G5, DRs orally received 5 mL FCM contains 25 mg GAE SOHE kg−1 daily; in G6, DRs orally received 5 mL FCM contains 50 mg GAE SOHE kg−1 daily; in G7, DRs orally received 50 mg metformin kg−1 daily. Combining FCM with SOHE at 25 or 50 mg kg−1 exhibited a synergistic effect in significantly lowering random blood glucose (RBG), fasting blood glucose (FBG), and improved weight gain recovery %. The hypolipidemic effect of FCM + 50 mg GAE SOHE kg−1 was significantly higher than using FCM or SOHE individually, and attenuation in triglycerides (TG), total cholesterol (CHO), and high- and low-density lipoproteins (HDL and LDL), and very-low-density lipoproteins (VLDL) was remarked. Combining FCM with SOHE at 25 or 50 mg kg−1 ameliorated liver and kidney functions better than individual uses of FCM, SOHE, or metformin. Interestingly, FCM with 50 mg SOHE kg−1 presented significant improvement in the activity of antioxidant enzymes, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and a substantial reduction in malonaldehyde (MDA) levels with 53.75%, 89.93%, 63.06%, and 58.69% when compared to the STZ group (G2), respectively. Histopathologically, administrating FCM + 25, 50 mg SOHE kg−1 or 50 mg kg−1 metformin showed a normal histological structure of both islets of Langerhans cells and acini. In conclusion, combining FCM with SOHE presented synergistic and therapeutical efficacy. It could be beneficial and profitable for controlling diabetes mellitus complications and protecting against oxidative stress

Antioxidative, Antidiabetic, and Hypolipidemic Properties of Probiotic-Enriched Fermented Camel Milk Combined with Salvia officinalis Leaves Hydroalcoholic Extract in Streptozotocin-Induced Diabetes in Rats

Antioxidative, antidiabetic, and hypolipidemic properties of probiotic-enriched fermented camel milk (FCM) combined with Salvia officinalis L. leaves hydroalcoholic extract (SOHE) in streptozotocin-induced diabetes in rats were investigated. Phytochemicals analysis and antioxidant capacity indicated that S. officinalis contained high phenolics with super antioxidant activity. Subsequently, HPLC analysis demonstrated 13 phenolic acids and 14 flavonoids in considerable amounts with ferulic acid and resveratrol as predominant, respectively. The antidiabetic and hypolipidemic properties of FCM and SOHE were examined in a designed animal model consisting of seven treated groups for four weeks. There was a negative group (G1); the positive group (G2) received a single dose (50 mg kg&minus;1) of streptozotocin (STZ) by intraperitoneal injection (i.p.); in G3, diabetic rats (DRs) orally received 5 mL FCM kg&minus;1 daily; in G4, DRs orally received 50 mg GAE SOHE kg&minus;1 daily; in G5, DRs orally received 5 mL FCM contains 25 mg GAE SOHE kg&minus;1 daily; in G6, DRs orally received 5 mL FCM contains 50 mg GAE SOHE kg&minus;1 daily; in G7, DRs orally received 50 mg metformin kg&minus;1 daily. Combining FCM with SOHE at 25 or 50 mg kg&minus;1 exhibited a synergistic effect in significantly lowering random blood glucose (RBG), fasting blood glucose (FBG), and improved weight gain recovery %. The hypolipidemic effect of FCM + 50 mg GAE SOHE kg&minus;1 was significantly higher than using FCM or SOHE individually, and attenuation in triglycerides (TG), total cholesterol (CHO), and high- and low-density lipoproteins (HDL and LDL), and very-low-density lipoproteins (VLDL) was remarked. Combining FCM with SOHE at 25 or 50 mg kg&minus;1 ameliorated liver and kidney functions better than individual uses of FCM, SOHE, or metformin. Interestingly, FCM with 50 mg SOHE kg&minus;1 presented significant improvement in the activity of antioxidant enzymes, reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and a substantial reduction in malonaldehyde (MDA) levels with 53.75%, 89.93%, 63.06%, and 58.69% when compared to the STZ group (G2), respectively. Histopathologically, administrating FCM + 25, 50 mg SOHE kg&minus;1 or 50 mg kg&minus;1 metformin showed a normal histological structure of both islets of Langerhans cells and acini. In conclusion, combining FCM with SOHE presented synergistic and therapeutical efficacy. It could be beneficial and profitable for controlling diabetes mellitus complications and protecting against oxidative stress

Valorization of Different Dairy By-Products to Produce a Functional Dairy–Millet Beverage Fermented with <i>Lactobacillus paracasei</i> as an Adjunct Culture

Fermented dairy products not only have a long shelf-life but also have beneficial nutritional values. The products are deficient in dietary fiber and certain bioactive compounds. Adding grains to dairy products is a widespread practice to improve the nutritional and economic aspects. In this work, we studied the effect of fermented millet–milk beverages (FMBs) using pearl millet grains and three different dairy by-products (sweet whey, sweet buttermilk, and skimmed milk). A control treatment prepared with water was also manufactured for comparison. Samples were continuously prepared and fermented using a commercial yogurt starter culture (YC-381) containing L. delbrueckii subsp. bulgaricus, Streptococcus thermophilus, and a pure strain of L. paracasei subsp. Paracasei. Four FMBs (water based: WB-FMB, whey based: WHB-FMB, buttermilk based: BMB-FMB, and skimmed milk based: SMB-FMB) were analyzed during cold storage at 4 °C for up to 15 days for chemical, microbiological properties, minerals content, antioxidant properties, glycemic index, and glycemic load on days 1, 8, and 15. The sensory characteristics of the FMBs were also evaluated during cold storage (4 °C/15 days). In general, the progression of acidity was slower in SMB-FMB and WHB-FMB samples during fermentation compared to in the BMB-FMB sample. The longest fermentation time was for the SMB-FBM sample (3 h), while the shortest was for the BMB-FMB sample (1.5 h). Reflecting the good manufacturing practices, all samples were free of coliform, mold, and yeast. No bacterial growth was detected in the WB-FMB sample at days 8 and 15 of storage, while the growth of Lactobacillus spp. and S. thermophilus was significantly higher (9.97 ± 0.01 and 9.48 ± 0.06, respectively) in the BMB-FMB sample compared to in the other three FMBs. The FMBs produced using dairy by-products had more antioxidant properties. All samples were better perceived during sensory evaluation by panelists than the water-based sample, except for the BMB-FMB sample, in which a bitter taste appeared. In the BMB-FMB sample, the proteolytic degree was significantly higher (4.8 ± 0.09) after 3 h of fermentation by about 460% than in the fresh sample. All samples had a low glycemic index and glycemic load. In addition, acidity progression was slower in SMB-FMB and WHB-FMB samples during fermentation and storage compared to the WB-FMB sample. Therefore, it could be recommended that it is more beneficial to prepare fermented millet–milk beverages using dairy by-products and suitable starter cultures under optimal fermentation conditions instead of using water to maximize the nutritional and economic aspects

Core outcomes set for trials in people with COVID-19

Objective: The outcomes reported in trials in COVID-19 are extremely heterogeneous and of uncertain patient relevance, limiting their applicability for clinical decision-making. The aim of this workshop was to establish a core outcomes set for trials in people with suspected or confirmed COVID-19. Design: Four international online multi-stakeholder consensus workshops were convened to discuss proposed core outcomes for trials in people with suspected or confirmed COVID-19, informed by a survey involving 9289 respondents from 111 countries. The transcripts were analyzed thematically. The workshop recommendations were used to finalize the core outcomes set Setting: International Participants: Adults aged 18 years and over with confirmed or suspected COVID-19, their family members, members of the general public and health professionals (including clinicians, policy makers, regulators, funders, researchers). Main Results: Six themes were identified. Responding to the critical and acute health crisis reflected the immediate focus on saving lives and preventing life-threatening complications that underpinned the high prioritization of mortality, respiratory failure, and multiorgan failure. Capturing different settings of care highlighted the need to minimize the burden on hospitals and to acknowledge outcomes in community settings. Encompassing the full trajectory and severity of disease was addressing longer-term impacts and the full spectrum of illness (e.g. shortness of breath and recovery). Distinguishing overlap, correlation and collinearity meant recognizing that symptoms such as shortness of breath had distinct value, and minimizing overlap (e.g. lung function and pneumonia were on the continuum toward respiratory failure). Recognizing adverse events refers to the potential harms of new and evolving interventions. Being cognizant of family and psychosocial wellbeing reflected the pervasive impacts of COVID-19. Conclusions: Mortality, respiratory failure, multiorgan failure, shortness of breath, and recovery are critically important outcomes to be consistently reported in COVID-19 trials.The project is funded by the Flinders University and the National COVID-19 Clinical Evidence Taskforce, convened by the Australian Living Evidence Consortium, hosted by Cochrane Australia, School of Public Health and Preventive Medicine, Monash University supported by the Australian Government, Victorian Department of Health and Human Services, Ian Potter Foundation, Walter Cottman Endowment Fund (managed by Equity Trustees) and the Lord Mayor's Charitable Foundation). AT is supported by The University of Sydney Robinson Fellowship. ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z