Effects Of Different Regimens Research Articles

Intra-articular Therapies for Hand Osteoarthritis: a Systematic Review and Network Meta-analysis

Abstract Objective Intra-articular injection therapy for hand osteoarthritis has inconclusive evidence regarding the effectiveness of different regimens. A systematic review and network meta-analysis of randomized controlled trials (RCTs) was conducted to examine the effectiveness of different injectants. Design The PubMed, Cochrane Library, Embase, ClinicalKey, and Scopus databases were searched for studies from inception to July 15, 2023. RCTs that applied intra-articular injection to hand osteoarthritis patients were included, and the outcomes of pain scores and functional scales were assessed. Results 14 RCTs with 674 patients met the inclusion criteria; 11 RCTs were included in the network meta-analysis. Intra-articular injected platelet-rich plasma (PRP) and dextrose significantly improved pain scores (mean difference [MD] = −4.03, 95% confidence interval [CI] = −6.51 to −1.56 for PRP; MD = −1.06, 95% CI = −2.1 to −0.02 for dextrose) and hand function (standard mean difference [SMD] = −0.93, 95% CI = −1.81 to −0.05 for PRP; SMD = −0.84, 95% CI = −1.58 to −0.09 for dextrose) in the long-term (≥6 months after treatment completion). The ranking probabilities revealed the highest effectiveness of PRP, followed by dextrose. No major adverse effects were reported. Conclusion Intra-articular injected PRP and dextrose can be recommended for treating hand osteoarthritis.

Pharmacoeconomic evaluation of Shaoma Zhijing Granules in treatment of tic disorders in children

This study conducted a pharmacoeconomic evaluation of Shaoma Zhijing Granules in the treatment of tic disorder(TD) in children. Firstly, from the perspective of the healthcare system, cost-effectiveness analysis was used to evaluate the economic efficiency of Shaoma Zhijing Granules compared with Changma Xifeng Tablets and Jiuwei Xifeng Granules in the treatment of TD in children. Then, through network Meta-analysis, the overall effectiveness of different regimens was calculated, combined with the total cost of the regimens, to calculate the incremental cost-effectiveness ratio(ICER). Finally, sensitivity analysis was performed to verify the stability of the study results and the credibility of the conclusions. This study included 17 articles, including 9 articles on Chinese patent medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 4 on Changma Xifeng Tablets), for the treatment of TD in children, and 8 articles on Chinese patent medicines combined with conventional western medicines(3 on Shaoma Zhijing Granules, 2 on Jiuwei Xifeng Granules, and 3 on Changma Xifeng Tablets). In the Chinese patent medicine group, the total cost of Shaoma Zhijing Granules for treating TD was CNY 4 410.00, with clinical total effective rate of 77.53%; the total cost of Jiuwei Xifeng Granules for treating TD was CNY 5 192.70, with clinical total effective rate of 82.13%. The ICER of Jiuwei Xifeng Granules vs Shaoma Zhijing Granules was 169.95, higher than the willingness-to-pay(WTP, cost of increasing efficiency by 1% is CNY 85.70). Therefore, Jiuwei Xifeng Granules did not have a cost-effectiveness advantage over Shaoma Zhijing Granules. The total cost of Changma Xifeng Tablets for treating TD was CNY 1 282.50, with clinical total effective rate of 80.60%. The total cost of Changma Xifeng Tablets was lower and clinical total effective rate was higher than that of Shaoma Zhijing Granules. Overall, Shaoma Zhijing Granules did not have a cost-effectiveness advantage. In the Chinese patent medicine combined with conventional western medicine group, the total cost of Shaoma Zhijing Granules for treating TD + conventional western medicines was CNY 6 768.52/6 778.48, with clinical total effective rate of 96.18%. The total cost of Jiuwei Xifeng Granules + conventional western medicines for treating TD was CNY 6 522.56, with clinical total effective rate of 88.30%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Jiuwei Xifeng Granules + conventional western medicines was 31.20, lower than WTP. Therefore, Shaoma Zhijing Granules + conventional western medicines had a cost-effectiveness advantage over Jiuwei Xifeng Granules + conventional western medicines. The total cost of Changma Xifeng Tablets + conventional western medicines for treating TD was CNY 1 706.12, with clinical total effective rate of 95.39%. The ICER of Shaoma Zhijing Granules + conventional western medicines vs Changma Xifeng Tablets + conventional western medicines was 6 334.06, higher than WTP. Therefore, although Shaoma Zhijing Granules + conventional western medicines had higher clinical total effective rate compared with Changma Xifeng Tablets + conventional western medicines, it did not have a cost-effectiveness advantage. Overall, for different medication regimens(Chinese patent medicines monotherapy or in combination with conventional western medicines), Shaoma Zhijing Granules and Jiuwei Xifeng Granules both had a cost-effectiveness advantage, but compared with Changma Xifeng Tablets, neither had a cost-effectiveness advantage. For Chinese patent medicines in combination with conventional western medicines, clinical total effective rate of Shaoma Zhijing Granules in combination with conventional western medicines for the treatment of TD in children was the highest.

Acute, chronic and conditioned effects of intranasal oxytocin in the mu-opioid receptor knockout mouse model of autism: Social context matters

Autism Spectrum Disorders (ASD) are neurodevelopmental disorders whose diagnosis relies on deficient social interaction and communication together with repetitive behaviours. Multiple studies have highlighted the potential of oxytocin (OT) to ameliorate behavioural abnormalities in animal models and subjects with ASD. Clinical trials, however, yielded disappointing results. Our study aimed at assessing the behavioural effects of different regimens of OT administration in the Oprm1 null mouse model of ASD. We assessed the effects of intranasal OT injected once at different doses (0.15, 0.3, and 0.6 IU) and time points (5, 15, and 30 min) following administration, or chronically, on ASD-related behaviours (social interaction and preference, stereotypies, anxiety, nociception) in Oprm1+/+and Oprm1-/- mice. We then tested whether pairing intranasal OT injection with social experience would influence its outcome on ASD-like symptoms, and measured gene expression in the reward/social circuit. Acute intranasal OT at 0.3 IU improved social behaviour in Oprm1-/- mice 5 min after administration, with limited effects on non-social behaviours. Chronic (8–17 days) OT maintained rescuing effects in Oprm1 null mice but was deleterious in wild-type mice. Finally, improvements in the social behaviour of Oprm1-/- mice were greater and longer lasting when OT was administered in a social context. Under these conditions, the expression of OT and vasopressin receptor genes, as well as marker genes of striatal projection neurons, was suppressed. We detected no sex difference in OT effects. Our results highlight the importance of considering dosage and social context when evaluating the effects of OT treatment in ASD.

Randomized controlled trial of enteral vitamin D supplementation (ViDES) in infants

BackgroundVitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks’ gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear.MethodsRandomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks’ postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22–26 months’ corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability.DiscussionOur study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results.Trial registrationClinicalTrials.gov NCT05459298. Registered on July 14, 2022.

Randomized Controlled Trial of Enteral Vitamin D Supplementation (ViDES) in Infants

Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear. Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 grams birth weight at a large academic center in the United States.Infants are stratified by birth weight and randomized within 96 hours after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth.We hypothesize that the higher and early vitamin D dose (800 IU/d with early feeding) compared to placebo plus routine dose (400 IU/d with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at one month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes) and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes.The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability. Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterminfants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results. ClinicalTrials.gov registered on July 14, 2022 (NCT05459298).

Alimentary Treatment with Trehalose in a Pharmacological Model of Alzheimer's Disease in Mice: Effects of Different Dosages and Treatment Regimens.

In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-β (Aβ) 25-35-induced murine model of Alzheimer's disease (AD). Aβ-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aβ load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.

Different dosages of vonoprazan for gastroesophageal reflux disease: study protocol for a pragmatic, crossover-cluster, randomized controlled trial with patient preference arms

BackgroundVonoprazan results in more potent acid suppression for gastroesophageal reflux disease (GERD) than proton pump inhibitors. It has only been approved for treating erosive esophagitis in China, but 30–40% of GERD patients cannot achieve the goal of treatment with vonoprazan 20 mg daily. This study aims to investigate whether vonoprazan could relieve the symptoms of Chinese patients with non-erosive reflux disease (NERD) and whether increased dosage or different times of dosing could increase the response rate of GERD.MethodsThis study is a pragmatic, open-label, crossover-cluster, randomized controlled trial with patient preference arms. Two thousand eight hundred eighty patients with GERD from 48 hospitals in China will be enrolled. These hospitals will be divided into a compulsory randomization cluster (24 hospitals) and a patient preference cluster (24 hospitals). Patients in the compulsory randomization cluster will be randomized to three regimens according to the crossover-cluster randomization. Patients in the patient preference cluster may choose to receive any regimen if they have a preference; otherwise, patients will be randomly assigned. The three treatment regimens will last 4 weeks, including (1) vonoprazan 20 mg p.o. after breakfast, (2) vonoprazan 20 mg p.o. after dinner, and (3) vonoprazan 20 mg p.o. after breakfast and after dinner. Patients will attend a baseline visit, a 4-week e-diary, a fourth-week visit, and a sixth-month visit online. The primary outcome is the symptom relief rate of all patients after 4-week therapy. Secondary outcomes include the healing rate of EE patients, the severity of symptoms, compliance with the therapy at the fourth-week follow-up visit, recurrent symptoms, and the frequency of self-conscious doctor visits at the sixth-month follow-up visit.DiscussionThis trial will explore the effectiveness of different regimens of vonoprazan that will be implemented with GERD patients in China. The randomization with patient preferences considered and the crossover-cluster component may improve the robustness and extrapolation of study conclusions.Trial registrationhttps://www.chictr.org.cn ChiCTR2300069857. Registered on 28 March 2023. Protocol version: February 18, 2023, Version 2.

Physical Activity and Type 2 Diabetes: In Search of a Personalized Approach to Improving β-Cell Function.

Type 2 diabetes mellitus (T2DM) is one of the most widespread diseases worldwide. Lifestyle interventions, including diet and physical activity (PA), are fundamental non-pharmacological components of T2DM therapy. Exercise interventions are strongly recommended for people with or at risk of developing or already with overt diabetes, but adherence to PA guidelines in this population is still challenging. Furthermore, the heterogeneity of T2DM patients, driven by differing residual β-cell functionality, as well as the possibility of practicing different types and intensities of PA, has led to the need to develop tailored exercise and training plans. Investigations on blood glucose variation in response to exercise could help to clarify why individuals do not respond in the same way to PA, and to guide the prescription of personalized treatments. The aim of this review is to offer an updated overview of the current evidence on the effects of different regimens and modalities of PA regarding glucose sensing and β-cell secretory dynamics in individuals with prediabetes or T2DM, with a special focus on β-cell function.

Effect of chemotherapy and different chemotherapy regimens on bone health among Chinese breast cancer women in different menstrual status: a self-control study.

Although the therapy-related bone loss attracts increasing attention nowadays, the differences in chemotherapy-induced bone loss and bone metabolism indexes change among breast cancer (BC) women with different menstrual statuses or chemotherapy regimens are unknown. The aim of the study is to explore the effects of different regimens of chemotherapy on bone health. The self-control study enrolled 118 initially diagnosed BC women without distant metastasis who underwent dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) screening and (or) bone metabolism index monitoring during chemotherapy at Chongqing Breast Cancer Center. Mann-Whitney U test, Cochran's Q test, and Wilcoxon sign rank test were performed. After chemotherapy, the BMD in the lumbar 1-4 and whole lumbar statistically decreased (- 1.8%/per 6 months), leading to a significantly increased proportion of osteoporosis (27.1% vs. 20.5%, P < 0.05), which were mainly seen in the premenopausal group (- 7.0%/per 6 months). Of the chemotherapeutic regimens of EC (epirubicin + cyclophosphamide), TC (docetaxel + cyclophosphamide), TEC (docetaxel + epirubicin + cyclophosphamide), and EC-T(H) [epirubicin + cyclophosphamide-docetaxel and/or trastuzumab], EC regimen had the least adverse impact on BMD, while the EC-TH regimen reduced BMD most (P < 0.05) inspite of the non-statistical difference between EC-T regimen, which was mainly seen in the postmenopausal group. Chemotherapy-induced amenorrhea (estradiol 94 pg/ml vs, 22 pg/ml; FSH 9.33 mIU/ml vs. 61.27 mIU/ml) was proved in premenopausal subgroup (P < 0.001). Except the postmenopausal population with calcium/VitD supplement, the albumin-adjusted calcium increased significantly (2.21 mmol/l vs. 2.33 mmol/l, P < 0.05) after chemotherapy. In postmenopausal group with calcium/VitD supplement, β-CTX decreased significantly (0.56 ng/ml vs. 0.39 ng/ml, P < 0.05) and BMD were not affected by chemotherapy (P > 0. 05). In premenopausal group with calcium/VitD supplement, PTH decreased significantly (52.90 pg/ml vs. 28.80 pg/ml, P = 0. 008) and hip BMD increased after chemotherapy (0.845 g/m2 vs. 0.952 g/m2, P = 0. 006). As for both postmenopausal and premenopausal group without calcium/VitD supplement, there was a significant decrease in bone mass in hip and lumbar vertebrae after chemotherapy (0.831 g/m2 vs. 0.776 g/m2; 0.895 g/m2 vs. 0.870 g/m2, P < 0.05). Chemotherapy might induce lumbar vertebrae BMD loss and spine osteoporosis with regimen differences among Chinese BC patients. Calcium/VitD supplementation could improve bone turnover markers, bone metabolism indicators, and bone mineral density. Early interventions on bone health are needed for BC patients during chemotherapy.

Systemic opioid regimens for postoperative pain in neonates.

Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration. Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry. We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration. According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies. In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.

Systemic opioid regimens for postoperative pain in neonates.

Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration. Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry. We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration. According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies. In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.

Association between fasting plasma glucose variability and maternal and infant outcomes in patients with hyperglycemia during pregnancy: a retrospective cohort study.

Blood glucose variability (GV) is believed to be closely related to the occurrence of adverse obstetric outcomes. However, few studies have investigated how the change in fasting plasma glucose (FPG) influenced on the adverse obstetric outcomes. This study mainly evaluated the relationship between FPG coefficient of variation (FPG-CV) and adverse outcomes in patients with gestational hyperglycemia and determine the ideal FPG-CV threshold for predicting maternal and infant outcomes. We retrospective analyzed the data of 608 pregnant hyperglycemic patients in the Obstetrics Department of Shengjing Hospital Affiliated to China Medical University between June 2019 and December 2021 and followed up inpatients through the Hospital Information System (HIS). We collected the venous FPG from 24-28 weeks of pregnancy to delivery. Maternal and infant outcomes were based on the latest definitions. The chi-square test and logistic regression analysis were performed to evaluate the correlation between FPG-CV and adverse outcomes. Two multivariate binary logistic regression models were used to adjust for confounding factors. Stratified analysis was performed according to hemoglobin A1c (HbA1c) levels (<5.9% and ≥5.9%) and insulin injection (not used and used) in the third trimester of pregnancy. The receiver operating characteristic (ROC) curve was used to evaluate the prediction of FPG-CV on adverse outcomes. All patients were divided into four groups based on the quartile of FPG-CV. The proportion of FPG-SD and insulin injections differed among the groups (P<0.05). Among the outcomes, the highest incidence rate was 26.3% for large for gestational age (LGA), 8.7% for premature delivery. FPG-CV remains independently associated with low birth weight [odds ratio (OR) =1.086, P=0.007], preterm birth (OR =1.069, P=0.012), and preeclampsia (OR =1.180, P<0.001). FPG-CV can predict preeclampsia, with an area under the curve (AUC) of 0.725. Our results suggest that patients with gestational hyperglycemia should undergo routine FPG monitoring from diagnosis to delivery. Also, the impact of blood glucose fluctuations on adverse outcomes should be considered in the clinical treatment. The rational application of hypoglycemic treatment can stabilize blood glucose levels, however, the effects of different regimens on GV and outcomes should be studied further.

Effects of different regimens of sedation on mechanically ventilated patients

Background: Up to one-third of intensive care unit (ICU) patients worldwide undergo mechanical ventilation. These patients frequently require analgesics and sedatives-potent medications with clear benefits and significant side effects. Objective: The current study intended to assess the effects of application of different regimens of sedation on mechanically ventilated patients regarding the length of ventilator days, length of hospital stay, multiple organ dysfunctions, ventilator-associated pneumonia (VAP), and mortality. Methods: One hundred adult patients who are intubated for any cause and attached to mechanical ventilation for more than 24 h will be included in this study. Drugs used for sedation were propofol and midazolam. Patients underwent history taking, clinical examination, laboratory investigations, chest X-ray, and electrocardiogram on admission. Results: At the end of this study, it was found that there was a significant increase in the sedation holiday group (Group II) over the no sedation group (Group I) regarding multiple organ dysfunction score, VAP, ventilator days, ICU stay, and hospital stay but there was no significant difference between both groups regarding mortality, spontaneous breathing trials, Glasgow Coma Scale, and complete blood count. Conclusions: Our results demonstrate that the use of sedatives can cause prolongation in the duration of mechanical ventilation, length of stay in the ICU, and total length of hospital stay. In addition, there is an increased risk of morbidity and mortality. It is possible to use a strategy of no sedation for critically ill patients undergoing mechanical ventilation without fears of failure.

Effects of Different Regimens of Insulin on Body Mass Index Commonly Used in Type 2 Diabetes Mellitus

Background: Weight gain is an ongoing challenge when initiating insulin therapy in patients with Type 2 diabetes mellitus. The aim of this study is to observe and compare the effect of commonly used regimens of insulin on body mass index (BMI) among Type 2 diabetes patients. Methods: An observational study was conducted in two diabetic centers in Dhaka starting from July 2018 to June 2019. During the 12 weeks of the data collection period, a total of 100 patients were included according to selection criteria and then divided into two equal groups. Patients who were prescribed with premixed (conventional or analog) 30/70 insulin twice daily with or without oral Antidiabetic drugs were included in Group I (n = 50) and the patients who were prescribed with insulin glargine once daily with a bolus insulin (conventional or analog) three times before large meals with or without oral Antidiabetic drugs were included in Group II (n = 50). BMI was calculated from the height and weight of the patients initially as baseline data and again after 12 weeks of treatment in both groups. Fiber Bragg grating, 2 h ABF, and hemoglobin A1C (HbA1c) change were also observed among the patients of both insulin groups from diagnostic reports during the study period. Results: After 12 weeks of treatment, mean body weight (±standard deviation [SD]) was increased significantly from 59.82 ± 12.33 kg to 60.40 ± 13.38 kg in Group I (P = 0.01) and from 59.00 ± 12.36 kg to 60.33 ± 12.97 kg in Group II (P = 0.02). Mean BMI (±SD) increased significantly from 23.71 ± 4.69 kg/m2 to 24.10 ± 4.17 kg/m2 in Group I (P = 0.01) and from 24.00 ± 4.30 kg/m2 to 24.43 ± 4.59 kg/m2 in Group II (P = 0.02) during the study period. The mean BMI compared between two study groups (24.10 ± 4.17 vs. 24.43 ± 4.59) kg/m2 m+ after 12 weeks of treatment was not statistically significant (P = 0.816). About 64.0% of patients in Group I and 68.0% in Group II have shown weight gain and BMI change after 12 weeks. Mean HbA1c (±standard deviation [SD]) reduced significantly from 10.40% ± 2.17% to 7.76% ± 1.41% in Group I and from 10.41% ± 1.80% to 7.63% ± 1.37% in Group II. About 48.0% of patients in Group I and 56.0% of patients in Group II achieved glycemic target &lt;7%. About 28.0% of patients in Group I and 20.0% of patients in Group II had hypoglycemia. Conclusion: From the current study, it can be concluded that both insulin regimens significantly cause weight gain, BMI change and also significantly effective in glycemic control. However, in comparison between the two groups, there was no significant difference. Hence, both premixed and glargine-based basal-bolus regimen can be prescribed as per patient need. This result may provide some preliminary information for further investigation

Comparative study to evaluate the role of Letrozole and low dose human menopausal gonadotrophin on ovulation induction in polycystic ovarian syndrome patients

Background: Polycystic ovarian syndrome (PCOS) is a multifaceted syndrome that affects multipleorgan systems with significant metabolic and reproductive manifestations. Treatment must be individualized on the basis of patient’s presentation, and desire for the pregnancy. Objective: To study the role of letrozole (LE) and low dose human menopausal gonadotrophen (HMG) on ovulation induction in the polycystic ovarian syndrome patients. Material &amp; Methods: The present hospital based double blind clinical trial, recruited total 105 patients’ of age 21 to 35 years women with PCOS among those attending the gynecology outpatient’s clinic in Hind Institute of Medical Sciences Safedabad Barabanki in the period from Sept 2018 to Sept 2021 were enrolled. Observation: Endometrial thickness, and number of the mature follicles of the LE+HMG group were higher significantly than other two groups (P&lt;0.001). Effects of different regimens on pregnancy. Pregnancy rate of LE+HMG group was 54.3%, which was insignificantly higher than LE group (31.4%) and HMG group (34.3%) (P&gt;0.05). There were also no statistically significant differences in rate of abortion, and rates of multiple pregnancy among the three groups. All the three groups suffered from OHSS, but the incidences rates were comparable.

Evaluation of Effectiveness of Different Regimens of Centrifugation for a Single-spin Method of Pure Platelet-containing Plasma Preparation

Aims: The aim of the study is to determine the optimal parameters of single centrifugation for the preparation of platelet-containing plasma (PCP) with maximum reduction of other cellular elements of the blood.&#x0D; Materials and Methods: 30 conditionally healthy persons aged 18 to 60 years (36.9±11.2 years) were included in the study. A total of 12 centrifugation modes were studied: 110g × 5 min, 110g × 10 min, 110g × 15 min, 140g × 5 min, 140g × 10 min, 140g × 15 min, 160g × 5 min, 160g × 10 min, 160g × 15 min, 190g × 5 min, 190g × 10 min, 190g × 15 min. To evaluate the effectiveness of different centrifugation modes, in addition to the number of basic cellular elements, such indicators as platelet capture efficiency, platelet enrichment factor, erythrocyte-reducing efficiencies and leukocyte-reducing efficiencies were studied.&#x0D; Results: When examining the volumes of the obtained plasma containing platelets, it was found that almost all centrifugation modes allow obtaining significantly different volumes of the investigated blood fraction from the others (p&lt;0.001). For clarity, the regimens were sorted according to the volume of platelet-containing plasma obtained, from the smallest to the largest. There was a progressive decrease in the numerical values of the concentration of platelets, erythrocytes and leukocytes in plasma samples. Also there was a progressive decrease in the numerical values of the coefficient of platelet enrichment.&#x0D; Conclusions: With a single centrifugation for the preparation of plasma containing platelets, the most effective mode is 160g × 10 min, which allows achieving a platelet enrichment factor of about 1.71 at a platelet concentration of 483.6 ± 45.4 × 109/l, a platelet capture efficiency of 85, 7 ± 0.1% and reductions of erythrocytes and leukocytes 98.76 ± 0.09% and 98.46 ± 0.14%, respectively.

Local and systemic therapy may be safely de-escalated in elderly breast cancer patients in China: A retrospective cohort study.

BackgroundFor elderly patients with breast cancer, the treatment strategy is still controversial. In China, preoperative axillary lymph node needle biopsy is not widely used, resulting in many patients receiving axillary lymph node dissection (ALND) directly. Our study aims to determine whether local and systemic therapy can be safely de-escalated in elderly breast cancer.MethodsPatients aged ≥70 years were retrospectively enrolled from our institution’s medical records between May 2013 and July 2021. Groups were assigned according to local and systemic treatment regimens, and stratified analysis was performed by molecular subtypes. Univariate and multivariate survival analyses were used to compare the effects of different regimens on relapse-free survival (RFS).ResultsA total of 653 patients were enrolled for preliminary data analysis, and 563 patients were screened for survival analysis. The mean follow-up was 19 months (range, 1–82 months). Axillary lymph node metastases were pathologically confirmed in only 2.1% of cN0 cases and up to 97.1% of cN+ cases. In the aspect of breast surgery, RFS showed no significant difference between mastectomy and BCS group (p = 0.3078). As for axillary surgery, patients in the ALND group showed significantly better RFS than those in the sentinel lymph node biopsy (SLNB) group among pN0 patients (p = 0.0128). Among these cases, the proportion of cN+ in ALND was significantly higher than that in SLNB (6.4% vs. 0.4%, p = 0.002), which meant axillary lymph nodes (ALNs) of ALND patients were larger in imaging and more likely to be misdiagnosed as metastatic. With regard to adjuvant therapy, univariate and multivariate analyses showed that RFS in different comprehensive adjuvant regimens were similar especially among hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)− subgroup where patients who did not receive any adjuvant therapy accounted for 15.7% (p > 0.05).ConclusionsIt is feasible to reduce some unnecessary local or systemic treatments for elderly breast cancer patients, especially in HR+/HER2− subtype. Multiple patient-related factors should be considered when making treatment plans.

Does Tocilizumab Influence the Outcome of Patients with COVID-19 Pneumonia Compared to the Standard Therapy? Retrospective Analysis of Data Obtained during Phase I COVID Pandemic

BACKGROUND: No gold standard therapy was approved globally for COVID-19 pneumonia to the date of this study. The pathophysiology of SARS-CoV-2 infection displayed the predominance of hyperinflammation and immune dysregulation in inducing multiorgan damage. Therefore, the potential benefits of both immune modulation and suppression in COVID-19 have been extensively discussed as a modality to control cytokine release syndrome (CRS). Abnormally high levels of interleukin-6 (IL-6) are a common finding in COVID-19 patients with pneumonia and acute respiratory distress syndrome, so the use of IL-6 antagonist was tested as a therapeutic option in controlling the disease. Tocilizumab is a recombinant humanized anti-human IL-6 receptor monoclonal antibody that can specifically bind the membrane-bound IL-6 receptor and soluble IL-6 receptor, thereby inhibiting signal transduction. Tocilizumab is currently FDA approved for the management of rheumatoid arthritis, giant cell arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. This study is a retrospective analysis of data polled during Phase I of COVID pandemic, adopted by the isolation hospital of Kasr Al-Ainy Medical School, Cairo University, during the period from May to September 2020. AIM: The aim of this study is to evaluate tocilizumab influence in the outcome; in terms of reducing the hospital stay, risk and duration of mechanical ventilation (invasive and noninvasive), mortality, and the incidence of complications related to drugs use (secondary bacterial infection and GIT bleeding) in patients with moderate-to-severe COVID-19. METHODS: This retrospective, observational cohort study included adults (between 18 and 80 years) with moderate-to-severe COVID-19 pneumonia, who were admitted to isolation hospital of Kasr Al-Ainy Medical School, Cairo University, between May and September 2020. We segregated the patients into two groups: Group A: In addition to the standard care protocol according to the local guidelines of the Egyptian Ministry of Health and Population in that period (supplemental oxygen, steroids in a dose of 1–2 mg/kg methylprednisolone for 5–10 days, broad-spectrum antibiotics, vitamins, and prophylactic dose of anticoagulation with low-molecular-weight heparin, proton-pump inhibitor, and poly-vitamins), they received tocilizumab intravenously in a dose of 8 mg/kg bodyweight (up to a maximum of 800 mg per dose), divided in two shots 12–24 h apart. Group B: Those received the standard care protocol alone, noting that guidelines were adjusted later on according to the updated scientific publications and WHO recommendations. The primary endpoint was to evaluate the effect of different regimens in controlling the disease, the need for mechanical ventilation and its duration (either invasive or non-invasive), length of ICU stay, hospital stay, and in-hospital mortality. Comparisons between quantitative variables were done using the non-parametric Mann–Whitney U-test. For comparison of serial measurements within each patient, the non-parametric Wilcoxon signed-rank test was used. For comparing categorical data, Chi-square (2) test was performed. Exact test was used instead when the expected frequency was &lt;5. Correlations between quantitative variables were done using Spearman correlation coefficient. RESULTS: During this period, 166 patients were admitted to ICU, suffering from severe hypoxemia with moderate to severe COVID-19 pneumonia, 10 of them were excluded (three were over 80 years old, other three had advanced stages of malignancy, two were on steroids therapy and non-invasive home ventilation due to chronic chest condition, and two were presented with MODs and deceased in &lt;48 h from admission), thus, 156 were included in the study. Group A: Seventy-six patients (49%) received tocilizumab in addition to standard therapy, Group B: Eighty patients (51%) received standard therapy only. In Group A, the mean length of ICU stay was 8.96 days with mean length of hospital stay 13.76, compared to mean length of ICU stay 9 days in Group B (p = 0.57) and mean length of hospital stay 12.46 days (p = 0.117). In Group A, 35 patients (46%) needed non-invasive mechanical ventilation (MV),12 patients of the 35 needed invasive MV in later stage, compared to 26 patients (32%) in Group B, 14 patients of the 26 needed invasive MV in later stage (p = 0.16). In Group A, 14 patients (18.4%) needed invasive mechanical ventilation, compared to 19 patients (23.7%) in Group B (p = 0.213). In Group A, 6 (7.9%) of 76 patients died, compared to 13 (16.3%) of 80 in Group B p = 0.11. The incidence of secondary bacterial infection in Group A was 16 patients (21%) compared to 21 (26%) in Group B (p = 0.44). CONCLUSION: In this study, we did not detect statistical difference in both groups of patients coming during CRS-associated COVID-19 pneumonia, regarding (ICU stay, need for and length of MV, the incidence of secondary bacterial infection, and in-hospital mortality) for COVID-19 moderate-to-severe pneumonia.

Route of postpartum oxytocin administration and maternal hemoglobin decline – A randomized controlled trial

ObjectiveOxytocin uterotonic agents are routinely administered during the third stage of labor, however, the administration route is varying, intravenously or intramuscularly. We aimed to compare the effect of different regimens of postpartum oxytocin administration on hemoglobin (Hb) and hematocrit (Hct) decline. MethodsA randomized, 3-arm study of women who delivered vaginally at term in a single tertiary medical center was conducted. Immediately following the delivery of the fetus women randomly received one of 3 oxytocin regimens: 1) intramuscular 10units (IM group); 2) intravenous 10units in 100 ml 0.9%NaCl solution over 10-15 min (IV group); or 3) combined IV + IM regimens (IV + IM group). Primary outcome was defined as the level of Hb decline between prepartum and postpartum measurements. ResultsOverall, 210 women (70 in each group) were randomized, with 171 included in the final analysis (IM group-61, IV group-57, IV + IM group-53). There was no significant difference between the groups regarding maternal age, pre-pregnancy body-mass-index (BMI), parity, operative vaginal deliveries rate, the rate of episiotomy or perineal tears or neonatal birthweight. Mean prepartum Hb and Hct level were 12.3 ± 1.1 g/dl and 36.9 ± 2.7%, respectively, with no significant difference between the groups. Mean postpartum HB and Hct decline was 1.3 ± 0.8 g/dl and 3.7 ± 2.3%, respectively, with no difference between the groups. In multivariable analysis after adjusting for parity, pre-pregnancy BMI, labor induction, episiotomy or perineal tears and neonatal birthweight, oxytocin regimen was not associated with any difference in hematological measurements. ConclusionPostpartum Hb and Hct decline was usually minor following vaginal deliveries, and was not affected by postpartum oxytocin regimen.

DEPENDENCE OF CHANGES IN THE HYGIENIC CONDITION OF THE ORAL CAVITY AND PERIODONTIUM IN CHILDREN WITH MALIGNANT TUMORS ON THE DURATION OF POLYCHEMYTHERAPY AND QUANTITIES OF CYTOSTATIC DRUGS

It is known that the course of cancer and chemotherapy adversely affect the components of homeostasis of the oral cavity, which causes stomatotoxicity. However, scientific publications have not yet provided generalized results of research on the pathogenetic mechanisms of the dental pathology formation during chemotherapy, which constitutes the relevance of this publication.&#x0D; The aim of the research was to study the effect of different regimens of the second course of chemo- therapy on the hygienic condition of the oral cavity and periodontium in children with malignant tumors of the abdominal cavity.&#x0D; The dissatisfaction with our results obtained after the first course of chemotherapy on various regimens prompted us to further research. A survey of two previously formed clinical groups was performed. All of them resumed the treatment in the oncohematology department of the Poltava Children's City Clinical Hospital following a 3-4 week break between courses. Each patient was treated according to an individual program but in the absence of dental care.&#x0D; The dental status was assessed using the Green-Vermillion, Papillary-Marginal-Alveolar (PMA), and Pa- pilla Bleeding Index.&#x0D; The study of cytograms from the surface of the gingival margin of the frontal part of the mandible was carried out taking into account the methodology developed by our department's staff. The calculation was per- formed in 10 visual fields. Statistical processing was performed according to standard conditions.&#x0D; Research results and their discussion. It should be noted that in the comparative aspect, the indexes of Green-Vermillion, PMA, and RВI at the end of the first year were 1,8, 1,3, and 1,6 times worse than in the second observation group which received more cytostatic drugs.&#x0D; At the end of the second course of chemotherapy, the dryness of the mucous membrane accompanied by a decrease in oral fluid, which became viscous, was observed in 14 children (70,0%) of the first and 18 of the second group (85.7%). In addition, 15 people in the first group (75,0%) and 19 in the second one (90,4%) complained of pain and bleeding gums, which worsened when eating. At the same time, all children noted pain in the muscles that are adjacent to the lower jaw and involved in articulation.&#x0D; On external examination, only 2 children of the first (10,0%) and 1 of the second group (5%) had a red normal-coloured lip border, while the rest had exfoliation, cracks, and angular cheilitis. The oral mucosa mostly looked pale and pasty, except for 7 people of the second group (35,0%), who had manifestations of erythema. Localized erosions covered with fibrinous plaque were detected in 4 of these patients (20,0%) on the background of erythema. In addition, 12 children (60,0%) of the first group and 19 children of the second one (85.7%) showed swelling and redness of the gingival marginal edge, and the probing of the gingival sulcus provoked bleeding in all children of both groups.&#x0D; Green-Vermillion indexes increased by 1,5 and 1,7 times in the first and second groups, PMA increased by 1,4 times in both groups, and RВI was 1,4 and 1,5 times higher in the respective compared groups.&#x0D; The examination of cytograms revealed more pronounced changes in the second group where the epithelium with signs of intermediate stages of the differentiation prevailed. There was increased desquamation of the superficial layer of the gums and the increased number of peripheral blood elements, especially destroyed neutrophils.&#x0D; Thus, the generalization of the results obtained at the end of the second course of chemotherapy showed that the Green-Vermillion index was 1,8 times higher, and PMA and SВI indices were 1,4 times higher in the second observation group which received more cytostatics. That is, the severity of the manifestations of dental status disorders is directly proportional to the severity of the regimen.&#x0D; Conclusion. The prolongation of the second course of chemotherapy in children with abdominal malignant tumors provoked a significant deterioration of dental status. Major changes occurred in the group of children who received more cytostatic drugs simultaneously, which requires a balanced approach to designing differentiated treatment plans and prevention measures depending on the complexity of antitumor therapy regimens.&#x0D; Prospects for further research. The obtained results indicate the need to develop a set of differentiated&#x0D; treatment and prevention measures aimed at eliminating or improving changes in children that occur in the oral cavity under the influence of polychemotherapy.