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Findings | ONCOLOGY, SECONDARY | In this secondary analysis of 3 NRG Oncology randomized clinical trials, prolonged RT duration was associated with inferior disease-free survival. Female patients and those with other (vs White) race and ethnicity were more likely to have prolonged RT duration and to experience RT interruptions. | PMC10122174 | |
Meaning | Findings of this study suggest that RT interruptions should be minimized to optimize outcomes. | PMC10122174 | ||
Importance | epithelial malignant neoplasms | ADVERSE EFFECT | For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. | PMC10122174 |
Objective | esophageal cancer | OESOPHAGEAL CANCER | To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). | PMC10122174 |
Design, Setting, and Participants | nonmetastatic esophageal cancer, Cancer | ONCOLOGY, SECONDARY, BREAST, CANCER | This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute–sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. | PMC10122174 |
Exposures | Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. | PMC10122174 | ||
Main Outcomes and Measures | local-regional failure | The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. | PMC10122174 | |
Results | The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; | PMC10122174 | ||
Conclusions and Relevance | esophageal cancer | OESOPHAGEAL CANCER | Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes. | PMC10122174 |
Introduction | esophageal cancer, head and neck, lung, cervical, and anal cancer, Treatment-related, epithelial malignant neoplasms, inferior tumor | ESOPHAGEAL CANCER, OESOPHAGEAL CANCER | Radiotherapy (RT) and chemoradiotherapy (CRT) are used for the curative treatment of many epithelial malignant neoplasms. Treatment-related toxic effects may lead to treatment interruptions and prolonged treatment duration. In the curative treatment of head and neck, lung, cervical, and anal cancer with RT and/or CRT, treatment interruptions and prolonged treatment duration have been associated with inferior tumor local control and/or survival.In patients with esophageal cancer who were treated with definitive CRT, the effect of RT treatment interruptions and prolonged RT duration on local control and survival has not been well studied. This topic is of elevated relevance and importance in the context of the COVID-19 pandemic, which may force difficult decisions regarding potential disruptions in delivery of RT for patients with esophageal cancer. | PMC10122174 |
Methods | PMC10122174 | |||
Patient Cohorts and Treatment | nonmetastatic esophageal cancer | SECONDARY | This unplanned, post hoc secondary analysis included evaluable patients with nonmetastatic esophageal cancer who underwent definitive CRT in the RTOG 8501, RTOG 9405 ( | PMC10122174 |
Study Flow Diagram | ONCOLOGY | RT indicates radiation therapy; RTOG, Radiation Therapy Oncology Group.RTOG 8501, which was conducted between January 1986 and April 1990 and predated ClinicalTrials.gov, was a prospective, multi-institutional randomized phase 3 trial that compared high-dose RT alone with CRT.RTOG 9405, which was conducted between June 1995 and July 1999, was a prospective, multi-institutional randomized phase 3 trial that compared standard-dose CRT with high-dose CRT.RTOG 0436, which was conducted between June 2008 and February 2013, was a prospective, multi-institutional randomized phase 3 trial that compared standard-dose CRT without cetuximab and with cetuximab. | PMC10122174 | |
RT Duration and RT Interruptions | Radiotherapy duration was defined as the interval from the date of the first fraction of RT to the date of the last fraction of RT. Radiotherapy duration was analyzed as a dichotomized variable using its median value as a cut point, using X-Tile software (Yale School of Medicine) to choose a cut-point value, and as a continuous variable. | PMC10122174 | ||
Outcomes Assessed | local-regional failure, death, Regional failure | CELIAC, DISEASE PROGRESSION, RECURRENCE, DISEASE, PRIMARY TUMOR | Outcomes assessed included local-regional failure (LRF), distant failure (DF), DFS, and overall survival (OS). Local failure was defined as disease recurrence or progression in the primary tumor. Patients who never had a local clearance were considered to have failure at day 1. Regional failure was defined as a recurrence or progression in regional lymph nodes. In the RTOG 8501 trial, nodal failure was considered to be disease present in the cervical, supraclavicular, scalene, celiac, abdominal (gastric), and other (esophageal, mediastinal, and intrathoracic) lymph nodes. In the RTOG 9405 trial, nodal failure was considered to be disease present in the cervical, supraclavicular, scalene, hilar, mediastinal, and abdominal (epigastric) lymph nodes. In the RTOG 0436 trial, nodal failure was considered to be nodal disease progression within the radiated field or recurrence after complete response in the radiated field. Local-regional failure was defined as local failure and/or regional failure. Distant failure was defined as disease progression in the liver, peritoneum, lung, distant lymph nodes, or other sites. Disease-free survival was defined as freedom from death, LRF, and DF. Overall survival was defined as freedom from death due to any cause. For LRF and DF, death without failure was a competing risk. All outcomes were measured from the date of randomization to the date of death or failure. | PMC10122174 |
Statistical Analysis | squamous cell vs, weight loss | ONCOLOGY, ADENOCARCINOMA, PRIMARY TUMOR | All data analyses were performed between March 2022 and February 2023 using SAS, version 9.4 (SAS Institute Inc). A 2-sided Local-regional failure and DF were estimated in the univariable analysis using the cumulative incidence method, and dichotomized RT duration and RT interruptions were compared using the Gray test.For the multivariable analyses, after RT duration or RT interruptions and the NRG Oncology trial were forced into the models, a stepwise selection procedure was used to choose other variables using an α ≥ .05 level as the entry and exit criteria for the model building. The following additional variables were assessed in the models: age (continuous); sex (male vs female); race and ethnicity, which were derived from electronic health records and categorized as White vs other (including Black, Asian, and other in the RTOG 8501 trial; Black or African American, Hispanic, Native American [Aleutian, American Indian, and Eskimo], Native Hawaiian or other Pacific Islander, and Asian [Chinese, Japanese, Korean, and Southeast Asian] in the RTOG 9405 trial; and American Indian or Alaska Native, Asian, Black or African American, more than 1 race, and unknown in the RTOG 0436 trial); Zubrod performance status score (0 vs 1 or 2); histological subtype (squamous cell vs adenocarcinoma); primary tumor size (<5cm vs ≥5 cm); weight loss (<10% vs ≥10%); N category (NX or N1 vs N0); and 80% or greater of protocol-specified concurrent chemotherapy (yes vs no). | PMC10122174 |
Results | The cohort included 509 patients, of whom 117 evaluable patients were from the RTOG 8501 trial, 105 evaluable patients were from the RTOG 9405 trial, and 287 evaluable patients were from the RTOG 0436 trial ( | PMC10122174 | ||
Patient, Tumor, and Treatment Characteristics | ONCOLOGY | Abbreviations: Gy, gray; RT, radiation therapy; RTOG, Radiation Therapy Oncology Group.Race and ethnicity were derived from electronic health records.Other category included Black, Asian, and other in the RTOG 8501 trial; Black or African American, Hispanic, Native American (Aleutian, American Indian, and Eskimo), Native Hawaiian or other Pacific Islander, and Asian (Chinese, Japanese, Korean, and Southeast Asian) in the RTOG 9405 trial; and American Indian or Alaska Native, Asian, Black or African American, more than 1 race, and unknown in the RTOG 0436 trial.With the median value as a cut point, RT duration was 39 days or less in 271 patients (53%) and more than 39 days in 238 patients (47%) (eTable 2 in | PMC10122174 | |
Outcomes for RT Duration Dichotomized by X-Tile Software Cut Point | In univariable analysis, RT duration longer than 45 days (vs ≤45 days) was associated with inferior LRF and DFS and a pattern of inferior OS (eFigure 1 in | PMC10122174 | ||
Outcomes for RT Duration as a Continuous Variable | ONCOLOGY | After controlling for an NRG Oncology trial, a 1-week increase in RT duration was associated with a 17% increased risk of having a DFS failure (HR, 1.17; 95% CI, 1.04-1.32; | PMC10122174 | |
Outcomes for RT Duration Dichotomized by Median | In univariable analysis, RT duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF but not DF, DFS, or OS (eFigure 2 in | PMC10122174 | ||
Outcomes for RT Interruptions | In univariable analysis, patients with RT interruptions (vs no interruptions) had patterns of inferior DFS and LRF (eFigure 3 in | PMC10122174 | ||
Discussion | esophageal cancer, cancer | ESOPHAGEAL CANCER, OESOPHAGEAL CANCER, CANCER, SECONDARY, ONCOLOGY | In this secondary analysis of patients with esophageal cancer treated with definitive CRT in NRG Oncology trials, the frequency of RT interruptions and the length of RT duration were characterized. The association between RT interruptions and RT duration and outcomes, including LRF, DFS, and OS, was examined. Key findings were (1) RT interruptions were common, occurring in 41% of patients; (2) RT interruptions and prolonged RT duration were more common in female than male patients and in those with other vs White race and ethnicity; and (3) RT interruptions and prolonged RT duration were associated with worse LRF and DFS in several models, supporting the hypothesis of correlation with inferior outcomes.There are few published reports evaluating the effect of RT interruptions and duration on outcomes for patients receiving definitive RT or CRT for esophageal cancer. In patients with localized esophageal cancer treated with RT alone (without chemotherapy), a meta-analysis of 11 randomized clinical trials conducted in mainland China found improved local control and survival following late-course accelerated, hyperfractionated RT regimens that delivered 60 to 70 Gy in 5 to 6 weeks compared with standard regimens delivering 60 to 70 Gy in 6 to 7 weeks.In the context of the COVID-19 pandemic, patients and oncologists have faced substantial uncertainty and challenging decisions, including consideration of cancer treatment breaks. Recommendations have been proposed regarding management of esophageal cancer in the context of COVID-19, but none specifically address the issue of RT interruptions.Patients with other race and ethnicity and/or female sex were more likely to experience RT interruptions and prolonged RT duration. Race and ethnicity were not independently associated with inferior outcomes in the multivariable models, although US population–based studies have observed a higher rate of mortality in Black than in White patients with esophageal cancer, which may be explained in part by higher T category at diagnosis and decreased use of surgery. | PMC10122174 |
Strengths and Limitations | cancer | ONCOLOGY, CANCER | Strengths of this study included the prospective data collection using NRG Oncology trials. Length of follow-up was relatively long, with a median follow-up of 4 years for surviving patients. Additionally, the cohort was relatively large with a relatively uncommon cancer.Study limitations included the cohort not being sufficiently large to exclude the possibility of modest, although clinically relevant, differences in survival associated with RT interruptions and duration. There was an association between RT duration and inferior LRF, DFS, and OS in some, but not all, models. Because this study was an unplanned post hoc analysis, we could not account for potential sources of bias. Enrollment in these NRG Oncology trials spanned approximately 3 decades, during which there were improvements in staging, RT planning and delivery, and supportive care. Such changes contributed to the heterogeneity of these trials, although the trial was included as a variable in the models to account for this heterogeneity. Furthermore, the trials were not associated with OS, DFS, LRF, or DF in the multivariable models. | PMC10122174 |
Conclusions | ONCOLOGY, SECONDARY | In this secondary analysis of 3 NRG Oncology randomized clinical trials, prolonged RT duration was associated with inferior outcomes. Female patients and those with other race and ethnicity were more likely to have prolonged RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes. As a practical recommendation, for a patient starting a course of 28 fractions of RT on a Monday, the goal should be to complete the treatment course by Friday of the sixth week (ie, <40 days). Treatment interruptions should be minimized by using aggressive supportive care and interventions to reduce patient nonadherence. If interruptions occur, incorporating weekend and/or twice-daily treatments, if appropriate, could be considered to keep the treatment duration less than 40 days. Findings from the present study suggest that investigating further reduction in RT duration (<5 weeks) might be warranted, such as through use of moderate hypofractionation RT regimens. | PMC10122174 | |
Background | GDM, pain | GDM, GESTATIONAL DIABETES MELLITUS | Edited by: Chunjiang Wang, Central South University, ChinaReviewed by: Yunping Li, Beth Israel Deaconess Medical Center and Harvard Medical School, United States; Shanglong Yao, Huazhong University of Science and Technology, ChinaPregnant women with gestational diabetes mellitus (GDM) require more analgesics after cesarean delivery than those who do not have GDM. Uncontrolled pain following cesarean delivery is a major problem in women with GDM. We investigate the efficacy of low-dose esketamine combined with sufentanil intravenous patient-controlled analgesia (PCA)for postcesarean analgesia in women with GDM. | PMC10454896 |
Methods | GDM, pain | GDM, SECONDARY | One hundred forty pregnant women with GDM were enrolled participate in this randomized controlled trial and were randomized into two groups (70 in each group). The esketamine (S) group was given esketamine +sufentanil + ondansetron, and the control (C) group was given sufentanil +ondansetron. The primary outcome is sufentanil consumption at 24 hours postoperatively, the secondary outcomes are sufentanil consumption at 6 hours postoperatively, pain scores at 6, 24 and 48 hours postoperatively. | PMC10454896 |
Results | pain | Compared with group C, group S had significantly lower sufentanil consumption at 6 and 24 hours postoperatively (P= 0.049 and P<0.001), significantly lower activities VAS(pain during activities)scores at 6 hours postoperatively, rest and activities VAS (pain at rest and pain during activities)scores at 24 hours postoperatively, and activities VAS scores at 48 hours postoperatively(P=0.022, P =0.002, P=0.001 and P=0.007). Compared to group C, the time to bowel function return was significantly shorter in group S. There was no significant difference in rest VAS (pain at rest) scores at 6 and 48 hours postoperatively (P>0.05). The time to first lactation was not significantly different between the two groups (P>0.05). There was no significant difference in neonatal neurobehavioral scores between the two groups (P>0.05). | PMC10454896 | |
Conclusion | GESTATIONAL DIABETES | Compared to sufentanil PCA, adding low dose of esketamine significantly reduced the consumption of sufentanil while providing equally effective post cesarean analgesia in the patients with gestational diabetes. | PMC10454896 | |
Background | GDM | GDM, COMPLICATION OF PREGNANCY | GDM is a common complication of pregnancy, and the incidence of GDM rapidly increased in recent years (Esketamine is a noncompetitive antagonist of the N-methyl-D-aspartate receptor (NMDA receptor), which binds to the NMDA receptor and blocks the NMDA receptor from binding to glutamate to exert analgesic and antinociceptive effects (We hypothesized that esketamine might produce better analgesia and higher patient satisfaction than conventional anesthetics after cesarean section in women with GDM. To test our hypothesis, we designed this prospective randomized controlled study to evaluate the effect of low-dose esketamine with sufentanil for intravenous patient-controlled analgesia as an analgesic regimen in GDM women. | PMC10454896 |
Materials and methods | PMC10454896 | |||
Study design | This prospective study was approved by the Ethics Committee of Hunan Provincial Maternal and Child Health Hospital [No. 2020-S068], and the study participants signed the informed consent form and was conducted between March 1, 2021 and December, 2022. | PMC10454896 | ||
Population selection criteria | GDM, diabetes mellitus, opioid dependence, pain | GDM, DIABETES MELLITUS, ADVERSE EVENT | Full-term singleton pregnancies with GDM (those with ASA scores of I-II) were included. Exclusion criteria: (1) patients with ASA scores of III and above; (2) patients with contraindications to neuraxial anesthesia; (3) patients with a history of opioid dependence; (4) patients who were diagnosed as having diabetes mellitus before pregnancy. Withdrawal criteria: (1) any clinical adverse event; (2) severe pain; (3) pregnant woman or family member who were unwilling to complete the study. | PMC10454896 |
Interventions | Pain, sinus bradycardia, blood loss, hallucinatory, pain, dizziness, GDM, nausea, vomiting | SINUS BRADYCARDIA, BLOOD LOSS, GDM, ADVERSE EFFECTS, DECUBITUS | We screened 150 patients with GDM undergoing elective cesarean section, and then 140 patients were enrolled based on inclusion, exclusion and withdrawal criteria. They were randomly divided into the esketamine (S) group, esketamine 0.5 mg/kg + sufentanil 150ug + ondansetron 4mg and the control (C) group,sufentanil 150ug + ondansetron 4mg, with 70 in each group.Maternal blood glucose was checked on the morning of the cesarean section. Maternal age, height, weight, gestational week and cesarean section data were recorded. The patients fasted from solid foods for >6 hours and from alcohol for 2 hours before the operation, and no premedication was administrated before the surgery. Patients were educated how to use the PCA pump (FORNIA pump model CPE-101, Zhuhai California Medical Equipment Co., Ltd.) and how to assess pain using a Visual Analog Scale (VAS) before surgery.After entering the operation room, noninvasive blood pressure (NBP), electrocardiogram (ECG), HR, and SPO2 were standard monitored. Oxygen was administered via nasal catheter at 2L/min, compound sodium chloride was injected. The anesthesiologist adjusted the infusion rate according to the patient’s circulatory status. All patients were placed in the left decubitus position, received CSEA at L3-4 space using the needle-through-needle technique. After the epidural space was identified, a spinal needle was used to puncture the dura mater and enter the subarachnoid space, with 15mg ropivacaine was diluted with cerebrospinal fluid to 2 ml for intrathecal injection, and the epidural catheter was immediately inserted cephalad 3–4 cm. The patients were positioned supine and tilted 15° to the left until fetal extraction. The operation was started when T6 was blocked, and additional ropivacaine can be added to the epidural if necessary. The mean intraoperative blood pressure was maintained at ≥65 mmHg, and if the mean blood pressure fell below 65 mmHg, methoxamine was administered and repeated as needed; in addition, in the case of sinus bradycardia (heart rate <50 bpm), 0.3 mg of intravenous atropine was administered and repeated as needed. After delivery, flurbiprofen ester 50 mg and ondansetron 4 mg are administered intravenously. The epidural catheter was removed at the end of the procedure. The duration of the procedure and the blood loss were recorded. After surgery, use PCA pump. Group S received esketamine 0.5mg/kg + sufentanil 150µg + ondansetron 4mg, and group C received sufentanil 150µg + ondansetron 4 mg, both were diluted to 100ml with saline, the sufentanil concentration was1.5ug/mL, the maintenance dose was 2ml/h, PCA bolus 2 ml at lock out interval of 15 minutes. If the VAS score was ≥7, flurbiprofen was readministered and the patient was excluded from the group. Research assistant who was blinded to the randomization recorded the patients’ PCA pump use (sufentanil consumption), and any adverse effects, such as nausea, vomiting, dizziness, and hallucinatory symptoms. Pain was assessed using the score VAS at 6, 24, and 48 hours postoperatively, with “0 “ indicating no pain and “10 “ indicating the most severe pain imaginable. The time to bowel function return, time to first lactation, and neonatal neurobehavioral scores were recorded. | PMC10454896 |
Outcomes | postoperative nausea, vomiting, dizziness, hallucinations | ADVERSE EFFECTS, SECONDARY | The primary outcome was sufentanil consumption at 24 hours postoperatively, and secondary outcomes were sufentanil consumption at 6 hours postoperatively, VAS scores at rest and during activities at 6, 24, and 48 hours postoperatively, time to bowel function return(the time to pass flatus as the sign of bowel function return), time to first lactation, adverse effects such as postoperative nausea, vomiting, dizziness, and hallucinations, and neonatal neurobehavioral scores. | PMC10454896 |
Sample size | The primary endpoint of this study was the consumption of sufentanil at 24 hours after surgery. We used a two-tailed test with α = 0.05 and β = 0.1 based on the pre-experimental 24-hour postoperative sufentanil consumption in groups S (95.1 ± 5.5) and C (99.3 ± 7.0), with a minimum of 60 patients required in each group. Ultimately, each group included 75 patients, taking into account a 20% attrition rate. | PMC10454896 | ||
Randomization and blinding | The investigators used the SAS statistical software package on a computer to generate random numbers in a 1:1 ratio to determine groups S and C. Neither the blinded investigators (the surgeon and the anesthesia resident physician) nor the patients were aware of the study groupings. Before the patients entered the operating room, the attending anesthetist opened the envelope, and the patients were assigned to group S or C according to the randomization entry number. Another anesthetist resident physician did not know the group assignment, and performed the subsequent anesthesia and the postoperative follow-up. A CONSORT diagram shows the participant flow (Flow chart of participants. | PMC10454896 | ||
Statistical analysis | SPSS 25.0 was used for the statistical analysis, and a P value < 0.05 was considered statistically significant. Continuous variables were analyzed with the Mann-Whitney U test or independent samples t test, and the Kolmogorov-Smirnov test was performed first to confirm whether the data were normally distributed. Normally distributed measurements are expressed as the mean ± standard deviation, and non-normally distributed variables are expressed as the median (interquartile range). Categorical variables were compared using the chi-square test or Fisher’s exact test and expressed as percentages. Statistical analyses were performed using SPSS software version 25.0. Two-sided p values less than 0.05 were considered statistically significant. | PMC10454896 | ||
Results | GDM | GDM, DIABETES MELLITUS, GESTATIONAL HYPERTENSION | A total of 150 women with GDM were screened in this study from March 2021 to December 2022. Based on exclusion criteria, 10 women with GDM were excluded prior to randomization (6 with GDM combined with gestational hypertension, 2 with contraindications to neuraxial anesthesia, and 2 with a prepregnancy diagnosis of diabetes mellitus). A total of 140 women with GDM were included in the study, 70 in each group ( | PMC10454896 |
Demographic data | There were no significant differences in the basic information of the two groups, including age, height, weight, gestational week, number of cesarean deliveries, preoperative glucose, and duration of surgery (Demographic data.
| PMC10454896 | ||
Comparison of the postoperative analgesic effects between groups | Compared with group C, sufentanil consumption was significantly reduced in group S at 6 and 24 hours postoperatively (P=0.049 and P<0.001),The activities VAS scores at 6 hours, the rest and activities VAS scores at 24 hours, the activities VAS scores at 48 hours were significantly lower in group S (P=0.022, P=0.002, P=0.001 and P=0.007), with no significant difference in rest VAS scores at 6 hours and at 48 hours postoperatively (Comparison the postoperative analgesic effects between Groups.
| PMC10454896 | ||
Comparison of the postoperative adverse effects between groups | dizziness, nausea, vomiting | ADVERSE EFFECTS | Compared with group C, the time to bowel function return (P=0.031) was significantly shorter in group S, and there was no significant difference in the time to first lactation (Comparison the postoperative adverse effects between Groups.
There was no significant difference in the postoperative adverse effects (nausea, vomiting, and dizziness) between the two groups ( | PMC10454896 |
Discussion | gestational diabetes, gastrointestinal adverse, breast milk, pain, hyperglycemia, dizziness, GDM, hallucinations, hypertension, nausea, vomiting | GESTATIONAL DIABETES, ADVERSE EFFECT, GDM, HYPERGLYCEMIA, ABNORMAL THYROID, COMPLICATED PREGNANCIES, HYPERTENSION | This randomized controlled trial evaluated the postoperative analgesic regimen for GDM women undergoing cesarean delivery. Our results showed that low-dose esketamine combined with sufentanil PCA in group S not only reduced the amount of sufentanil used at 6 and 24 hours postoperatively in GDM women undergoing cesarean delivery, but also significantly lowered the rest VAS scores at 24 hours postoperatively and significantly lowered the activities VAS scores at 6, 24, and 48 hours postoperatively compared with group C.Many previous studies (Esketamine, the dextroisomer of ketamine, has a higher affinity for NMDA receptors and U-opioid receptors and is used at only 1/2 the dose of ketamine. Previous studies (The presence of hyperglycemia in gestational diabetes patients undergoing surgery had an adverse effect on gastrointestinal function, and this study showed that the proportion of mothers in group S with bowel function return times <24h and 24-48h was significantly higher than that in group C. This result may be related to the fact that esketamine effectively relieved the adverse stress caused by pain, and that esketamine reduced the amount of sufentanil, thus controlling the resulting gastrointestinal adverse effects and facilitating the recovery of bowel function after surgery. However, we need to monitor more indicators related to gastrointestinal function to corroborate this result, and the specific mechanism needs to be further investigated.Postpartum lactation was mainly the result of the combined action of prolactin and lactogen, and the results of our study showed no significant difference in the time to the first lactation between the two groups. Consistent with the findings of a previous study (The incidence of nausea, vomiting, dizziness, and hallucinations in this study was not significantly different between the two groups. Consistent with the findings of a previous study (This study has some limitations. First, esketamine is contraindicated in patients with severe hypertension and abnormal thyroid function; therefore, the population selected for this study did not include mothers with complicated pregnancies. Second, we did not measure esketamine levels in breast milk, and although studies have reported that low-dose esketamine has no effect on breastmilk or newborns, it is possible to monitor esketamine levels in breast milk in subsequent studies. None of the newborns in this study had any adverse outcomes. | PMC10454896 |
Conclusion | GDM | GDM | In conclusion, based on the results from our study, it can be concluded that low-dose esketamine combined with sufentanil for intravenous patient-controlled analgesia can reduce the amount of sufentanil and enhance the analgesic effect after cesarean section in women with GDM, providing new data for the analgesic protocol after cesarean section in women with GDM.The combination of low-dose esketamine with sufentanil for PCA can enhance the analgesic effect. | PMC10454896 |
Data availability statement | The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation. | PMC10454896 | ||
Ethics statement | The studies involving human participants were reviewed and approved by Hunan Provincial Maternal and Child Health Hospital. The patients/participants provided their written informed consent to participate in this study. | PMC10454896 | ||
Author contributions | LC and TH designed the study. TH and QC organized the data. JZ and JH analyzed the data and wrote the first draft of the manuscript. AL, WX, ZL, and ZP revised the manuscript. All the authors contributed to the article and approved the submitted version. | PMC10454896 | ||
Acknowledgments | We are deeply grateful to all the participants of this study. We would like to thank all the people who contributed to this study. | PMC10454896 | ||
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10454896 | ||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10454896 | ||
References | PMC10454896 | |||
1. Introduction | gastrointestinal distress, weight loss, chronic disease | ADVERSE EVENTS, SECONDARY, CHRONIC DISEASE | Exogenous ketone ester and ketone ester mixed with ketone free acid formulations are rapidly entering the commercial marketspace. Short-term animal and human studies using these products suggest significant potential for primary or secondary prevention of a number of chronic disease conditions. However, a number of questions need to be addressed by the field for optimal use in humans, including variable responses among available exogenous ketones at different dosages; frequency of dosing; and their tolerability, acceptability, and efficacy in long-term clinical trials. The purpose of the current investigation was to examine the tolerability, acceptability, and circulating R-beta-hydroxybutyrate (R-βHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-βHB compared with placebo control (PC). Fourteen healthy young adults (age: 21 ± 2 years, weight: 69.7 ± 14.2 kg, percent fat: 28.1 ± 9.3%) completed each of the five study conditions: placebo control (PC), 5 g KME (KME5), 10 g KME (KME10), 5 g (KMES5), and 10 g KMES (KMES10) in a randomized crossover fashion. Circulating concentrations of R-βHB were measured at baseline (time 0) following an 8–12 h overnight fast and again at 15, 30, 60, and 120 min following drink ingestion. Participants also reported acceptability and tolerability during each condition. Concentrations of R-βHB rose to 2.4 ± 0.1 mM for KME10 after 15 min, whereas KMES10 similarly peaked (2.1 ± 0.1 mM) but at 30 min. KME5 and KMES5 achieved similar peak R-βHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-βHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-βHB and glucose at the 30 min time point for each condition except KME10 and PC. Tolerability was similar among KME and KMES, although decreases in appetite were more frequently reported for KMES. Acceptability was slightly higher for KMES due to the more frequently reported aftertaste for KME. The results of this pilot investigation illustrate that the KME and KMES products used increase circulating R-βHB concentrations to a similar extent and time course in a dose-dependent fashion with slight differences in tolerability and acceptability. Future studies are needed to examine variable doses, frequency, and timing of exogenous ketone administration for individuals seeking to consume ketone products for health- or sport performance-related purposes.During periods of low glucose availability, long-chain fatty acids are partially oxidized to water-soluble four-carbon molecules referred to as ketones, which include acetoacetate (AcAc) and beta-hydroxybutyrate (βHB) [Several studies show that a standard low-carbohydrate (<5% by kcals), high-fat (≥80% fat ketogenic diet (KD) increases circulating ketone concentrations and consistently produces weight loss [A number of studies from our laboratory and others have shown that exogenous ketones produce consistent and robust effects on energy homeostasis, energy metabolism, and body composition in rodents [While the number of published studies in humans is limited, most studies show that exogenous ketones can safely and effectively increase circulating ketone concentrations without introducing extensive dietary changes such as energy or carbohydrate restriction. Exogenous ketones are commercially available as ketone salts, ketone esters, or the combination of the two. Veech and colleagues showed that the ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KME), increased R-βHB and acetoacetate concentrations in a dose-dependent fashion at 140 mg/kg, 357 mg/kg, and 714 mg/kg body weight [Most studies conducted in humans today have examined high concentrations of exogenous ketones in the range of 10–50 g when consumed as a single dose or short term (less than one month) [The purpose of the current investigation was to examine the responses to a single dose of the KME at lower doses (5 and 10 g) and to compare those responses with a ketone ester + R-βHB salt (single enantiomer) mixture (KMES) at 5 and 10 g doses. The primary outcome variables for this study were whole-blood concentrations of R-βHB and glucose produced by condition and over time. Because the KME drink contained a higher concentration of KME, compared with KMES and PC, we hypothesized that the KME would raise circulating ketone concentrations to a greater magnitude and duration than KMES and PC. We also hypothesized that both exogenous ketones would lower circulating ketone concentrations. Secondary outcomes included tolerability, acceptability, and assessment of adverse events. A limited number of past studies in exogenous ketones have reported adverse side effects and severity of such effects. While high doses of KME have been associated with mild gastrointestinal distress [ | PMC10708260 |
2. Materials and Methods | ADVERSE EVENTS | Fourteen participants between the ages of 18 and 25 years with a body mass index (BMI) between 18.5 and 29.9 kg/mThe exogenous ketones used in this study were purchased from KetoneAid (Falls Church, VA, USA) and included a KME and a KMES drink. The drinks provided at each condition were diluted with water to a total volume of 110 mL for blinding and consistency. Participants included in this study had never consumed either ketone drink prior to the study.During the first study visit, baseline measurements of body weight, height, body fat percentage, lean body mass percentage, waist–hip ratio, and personal demographic information (name, sex, age, race, and ethnicity) were recorded from each participant. Body weight was measured using a balance scale, while height was measured using a stadiometer. Body composition was measured using bioelectrical impedance analysis (BIA, Omron, HBF-514C, Kyoto, Japan), while waist and hip measurements were conducted using a cloth tension tape measure. Waist circumference was measured once at the start of this study at the narrowest part of the torso between the umbilicus and xiphoid process. Hip circumference was measured once at the start of this study at the maximal circumference of the gluteus maximus.On the day prior to each study condition, participants were asked to record all food and drink consumed and were encouraged to consume a similar diet before every visit. However, participants were not required to change their typical diet during this study. Participants were asked to fast for 8–12 h prior to each visit with all sessions occurring in the morning before 1100 h and after 0630 h. Participants were also told to avoid vigorous or planned physical activity on the morning of the study procedure to avoid any potential confounding effects of exercise metabolism on the variables of interest.Participants were administered with KME, KMES, or PC after obtaining baseline measurements of R-βHB and glucose (0-min). The PC consisted of stevia, potassium sorbate, natural flavors, and denatonium benzoate mixed in distilled water. While the PC did not perfectly match the taste of KME and KMES, participants were naïve to the taste of either experimental drink and thus blinded to what they were receiving. The research team member administering the drinks did not undergo blinding but did not share responses with participants until the completion of the study. Following ingestion, R-βHB and glucose were measured at 15, 30, 60, and 120 min. Capillary blood was measured using a commercially available ketone meter (Keto-Mojo, Napa, CA, USA), which measures circulating R-βHB and glucose concentrations. At the end of each condition, participants completed a symptom questionnaire to report any adverse events, acceptability, and tolerability.The primary outcomes were circulating R-βHB and glucose concentrations. Temporal responses over time were compared using a five condition (PC, KME5, KME10, KMES5, KMES10, and PC) × time (0, 15, 30, 60, and 120 min) ANOVA with repeated measures on time and condition. Total and incremental area under the curve (AUC) were calculated as previously reported [ | PMC10708260 | |
3. Results | PMC10708260 | |||
3.1. Participant Recruitment and Characteristics | Fifteen individuals volunteered for this study and were screened for eligibility with one excluded for not meeting the BMI requirements (Participant retention was 100% with all 14 participants who joined this study completing each of the five conditions. Participant characteristics are shown in | PMC10708260 | ||
3.2. Effects of KME and KMES Drinks on Circulating R-βHB and Glucose Concentrations | There were no significant differences in R-βHB and glucose responses or other variables observed between male and female participants. Thus, results are presented with data from male and female participants combined. R-βHB concentrations were significantly higher than baseline for each condition (Glucose concentrations were not significantly different among conditions at any time point ( | PMC10708260 | ||
3.3. Acceptability and Tolerability of KME and KMES Drinks | nausea | Although taste was not quantitatively assessed, participants were encouraged to explain the flavor of each study drink either by writing in the “Additional Comments” section of the questionnaire or by verbally reporting to the research team; these data are shown in All reported side-effects were reported as “mild” except for one instance of nausea, which was reported as “moderate” for KME5 ( | PMC10708260 | |
4. Discussion | gastrointestinal distress | ADVERSE EFFECTS, SECONDARY | The purpose of the current investigation was to examine the tolerability and acceptability of a KME and KMES drink and their effects on circulating R-βHB and glucose concentrations in healthy young adults. Our hypothesis was that KME would raise circulating ketone concentrations to a greater magnitude and duration than KMES and PC. Both KME and KMES increased circulating R-βHB concentrations in a dose-dependent fashion with KME producing a more rapid rise than KMES at 15 min with similar responses by 30 min. Both total and incremental AUC for R-βHB concentrations were significantly higher for KME10 compared with KMES10 and PC. This supports part of our hypothesis, as KME raised circulating ketone concentrations to a greater magnitude than KMES and PC. However, duration was similar between KME and KMES, as concentrations decreased in a similar fashion and reached baseline by 120 min. Our secondary hypothesis was that KMES would have higher acceptability but lower tolerability compared with KME due to its unpleasant flavor and higher salt load. Supporting part of this hypothesis, acceptability was slightly lower for KME due to its more frequently reported aftertaste. However, reported adverse effects did not noticeably differ between exogenous ketone drinks.The dosage amounts in the present study were approximately 74.5 ± 14.8 mg/kg body weight (BW) for the 5 g doses and 149.1 ± 29.6 mg/kg BW for the 10 g doses when accounting for the weight of all participants. At a similar dosage to the highest concentration used in the present study, Stubbs and colleagues administered KME at 141 mg/kg body weight while fasting in healthy participants [A study by Veech and colleagues examined the effects of KME in healthy participants at a similar dose (140 mg/kg BW) [While we did not observe a statistically significant reduction in circulating glucose concentrations with the ketone drinks at either concentration, we found a negative correlation between R-βHB and glucose at 30 min for each condition except KME10. A similar effect was found in the study by Stubbs and colleagues, where both exogenous ketone drinks significantly decreased circulating glucose from 5.7 to 4.8 mM at one hour following administration [Although both exogenous ketone drinks had “unpleasant” flavor reported, the KME drink in the current study was slightly less acceptable than the KMES drink due to its more frequently reported aftertaste. To the best of our knowledge, previous studies have not characterized the flavor of exogenous ketone products. However, a limited number of studies have examined tolerability and noted mild adverse effects such as gastrointestinal distress [In the present study, participants were not required to alter their regular diet or exercise routine. As a result, the participants had diverse diet and exercise regimens. Future studies should aim to characterize the effects of meals, meal composition, and various forms of exercise on circulating concentrations of R-βHB. Understanding these effects will help define how exogenous ketones may affect consumers who are consuming ketone products on a regular basis. This study also applied what we determined was a more practical approach to dosing exogenous ketones, as drinks were provided in absolute amounts of total ketones as opposed to being dosed according to individual body mass. While there are disadvantages to this approach, namely that differences in body mass are likely to affect circulating concentrations, this strategy more realistically models how a consumer may purchase and utilize ketone products. Despite differences in body weight and sex within the study cohort, there were no significant differences in the magnitude of R-βHB observed. In fact, correlational analysis showed no significant associations between body weight or body weight normalized R-βHB concentrations at either dose for both exogenous ketones. Future studies are needed to determine if a relationship exists with higher doses of exogenous ketones.Additional studies are needed to investigate the acute, short-, and long-term effects of exogenous ketones, particularly as it relates to dosing, frequency of dosing, and duration of responses. It is possible that smaller, but more frequent, dosing not only can sustain higher concentrations but also can produce a scaffolding effect depending on when additional dosing occurs. Overall, single doses of the exogenous ketones used in this study increased circulating ketone concentrations rapidly and transiently. However, future studies that examine the effects of multiple doses of exogenous ketones are critical to establish the short- and long-term effects on circulating ketones to establish correlations between the magnitude and duration of circulating ketones on the outcomes desired. Circulating ketone concentrations reflect only a snapshot in time and do not fully appreciate absorption, uptake by central and peripheral tissues, and excretion, which are likely to play a significant role in the efficacy of certain outcomes desired.In the present study, KME increased R-βHB concentrations more rapidly than KMES, although peaks in R-βHB concentrations were similar for both. When consumed as repeated doses throughout the day, KME and KMES may achieve similarly sustained levels of R-βHB. Additionally, participants in the current study reported KMES as slightly more acceptable than KME. | PMC10708260 |
Author Contributions | Conceptualization, M.L.B., R.D.S., G.F. and E.P.P.; methodology, M.L.B., K.R.F., R.D.S., G.F. and E.P.P., formal analysis, E.P.P.; investigation, M.L.B., C.M.G. and E.P.P.; resources, E.P.P.; data curation, M.L.B. and E.P.P.; writing—original draft preparation, M.L.B. and E.P.P.; writing—review and editing, M.L.B., K.R.F., R.D.S., G.F. and E.P.P.; visualization, M.L.B. and E.P.P.; supervision, E.P.P.; project administration, M.L.B. and E.P.P.; funding acquisition, E.P.P. All authors have read and agreed to the published version of the manuscript. | PMC10708260 | ||
Institutional Review Board Statement | This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of the University of Alabama at Birmingham (protocol code IRB-300009075, date of approval 09/22/2022). | PMC10708260 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in this study. | PMC10708260 | ||
Data Availability Statement | The data in this study are available on request. | PMC10708260 | ||
Conflicts of Interest | The authors declare no conflict of interest. The funders had no role in the design of this study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. | PMC10708260 | ||
Purpose | prostate cancer | PROSTATE CANCER, URINARY INCONTINENCE | The study compared the efficacy of commencing supervised exercise in men with prostate cancer before and after prostatectomy on objective and patient-reported outcomes, hospital length of stay, and urinary incontinence. | PMC10645629 |
Methods | urinary incontinence, fatigue | PAD, URINARY INCONTINENCE | Forty-one men were randomised to a 6-week prehabilitation or rehabilitation exercise programme. Prehabilitation involved resistance and aerobic exercise thrice weekly pre-surgery, while rehabilitation comprised the same commencing 6-weeks post-surgery. Assessments included strength, function (chair rise, stair climb, 400-m, 6-m usual, fast, and backwards walk), body composition, fatigue and quality of life, undertaken at pre-surgery, early post-surgery and late post-surgery phase, with urinary incontinence (24-h pad test) assessed at 2, 6, and 12-weeks post-surgery. Intention-to-treat and sensitivity analyses were undertaken. | PMC10645629 |
Results | URINARY INCONTINENCE | Of thirty-eight men (48–73 years), 29 completed all assessments with most undergoing robotic-assisted laparoscopic prostatectomy (92.1%). In the pre-surgery phase, prehabilitation improved muscle strength (leg press: 17.2 kg; chest press: 2.9 kg; p ≤ 0.001), 400-m, chair rise, 6-m fast and backward walk tests (p ≤ 0.001–0.028). Strength and function declines in the early post-surgery phase were maintained late post-surgery. Rehabilitation showed declines of these outcomes after surgery with improvement late post-surgery (leg press: 14.6 kg, p < 0.001; chest press: 6.8 kg, p < 0.001; 400-m walk: -12.0 s, p = 0.005), resulting in no difference between groups at 12 weeks. There were no significant differences between groups for patient-reported outcomes, hospital length of stay or urinary incontinence. | PMC10645629 | |
Conclusion | Pre-surgical exercise enhanced strength and function, protecting against post-surgery declines. Although exercise post-surgery is beneficial for recouping strength and function, where possible men undergoing prostatectomy are encouraged to exercise pre-surgery. | PMC10645629 | ||
Trial registration | ACTRN12617001115325 registered 31 July 2017. | PMC10645629 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s00432-023-05409-3. | PMC10645629 | ||
Keywords | Open Access funding enabled and organized by CAUL and its Member Institutions | PMC10645629 | ||
Introduction | cancer, Prostate cancer | CANCER, PROSTATE CANCER | Prostate cancer is the most diagnosed cancer in men in Western countries such as the United States, United Kingdom and Australia (AIHW Although we (Singh et al. | PMC10645629 |
Materials and methods | Forty-six patients were referred for participation between June 2016 and September 2018 in Perth, Western Australia, and their progress through the study is shown in Fig. Study flow chart | PMC10645629 | ||
Study design | urinary incontinence, fatigue | URINARY INCONTINENCE | This randomised controlled trial compared the effectiveness of a 6-week supervised multimodal exercise programme before surgery (Prehabilitation) versus the identical exercise programme delivered post-surgery (Rehabilitation) in patients undergoing prostatectomy. Patients were randomly assigned using a computer random assignment programme to either group stratified for physical activity level (i.e., cut-off value of 150 min/week). Allocation was concealed using sealed opaque envelopes. Following familiarisation and baseline assessment, prehabilitation comprised combined resistance and aerobic exercise for 6 weeks pre-surgery with no formal intervention post-surgery, whilst rehabilitation exercise commenced 6 weeks post-surgery. All patients were instructed to rest and not exercise for at least 6 weeks after surgery to allow for recovery. Measurements were undertaken at baseline, pre-surgery, 6 and 12 weeks post-surgery. Quality of life and fatigue were additionally assessed at 2 weeks post-surgery, while urinary incontinence was assessed at 2, 6, and 12 weeks post-surgery. In this report, the time between baseline to pre-surgery is defined as the pre-surgery phase, the period from discharge to 6 weeks post-surgery as the early post-surgery phase, and between 6 and 12 weeks post-surgery as the late post-surgery phase (Figure S1). | PMC10645629 |
Exercise programme | Exercise was undertaken thrice weekly in small groups of 5–8 participants, supervised by accredited exercise physiologists in an exercise clinic. Each session was ~ 90 min and included resistance and aerobic exercises. Resistance training consists of exercises targeting major muscle groups, such as leg press, leg extension, leg curl, chest press, seated row, lat pulldown, triceps extension, biceps curl and calf raises (Singh et al. The aerobic-based component involved various modes of exercise such as treadmill walking/jogging and cycling or rowing on a stationary ergometer with intensity set at 60–80% of the individual participant’s estimated maximum heart rate (220—age in years) for 20–30 min. All sessions commenced with a warm-up comprising low-level aerobic exercise (~ 60% maximum heart rate) and stretching exercises for the major muscle groups and concluded with a cooldown of stretching exercises. Rehabilitation participants were instructed to maintain their customary physical activity and dietary patterns before surgery. | PMC10645629 | ||
Primary and secondary endpoints | The primary study endpoint was dynamic muscle strength for the chest press and leg press using one-repetition maximum (1-RM) (Taaffe et al. | PMC10645629 | ||
Other measures | DISEASE | Demographic and clinical data including disease stage, comorbidities, surgical approach and medications were recorded and collected by self-report records. Height and body weight were assessed, with body mass index (BMI, kg.m | PMC10645629 | |
Statistical analysis | The sample size estimate was based on projected changes in muscle strength (Galvão et al. Data were analysed using IBM SPSS version 27 (SPSS Inc., IBM Corp., Armonk, NY, USA). Normality of the distribution for outcome measures was evaluated using the Kolmogorov–Smirnov test. Differences in baseline characteristics between groups were assessed using independent t-tests or the Mann–Whitney U-test, as appropriate, for continuous data and chi-square for categorical data. Data were analysed on an intention-to-treat basis, with sensitivity analyses undertaken to ensure data robustness using complete cases approach (Thabane et al. | PMC10645629 | ||
Muscle strength | There were no differences between groups at baseline (Fig. Muscle strength absolute values and change over the assessment time points. Results are presented as mean and standard error. | PMC10645629 | ||
Physical function | There was no difference between groups at baseline for physical function (p = 0.060–0.685). Over the study period, there were no significant interactions except for 6-m usual walk (p = 0.033) and a significant time effect for 400-m walk, chair rise, stair climb, 6-m fast and backward walk tests (p = < 0.001–0.001) (Fig. Physical function absolute values and change over the different assessment time points. Results are presented as mean and standard error. When comparing 12 weeks post-surgery to baseline, prehabilitation had significant improvement of – 16.3 s (95% CI: – 26.2 to – 6.3 s, p < 0.001) in 400-m walk, – 1.7 s (95% CI: – 3.0 to – 0.4 s, p = 0.004) in chair rise, – 0.3 s (95% CI: – 0.5 to – 0.0 s, p = 0.050) in stair climb, − 0.2 s (95% CI: – 0.4 to – 0.0 s, p = 0.047) in 6-m fast walk and – 3.9 s (95% CI: – 6.6 to – 1.3 s, p = 0.001) in backwards walk. In the rehabilitation group, there was a significant improvement of – 16.1 s (95% CI: – 24.8 to – 7.4 s, p < 0.001) in 400-m walk, – 1.2 s (95% CI: – 2.3 to – 0.2 s, p = 0.010) in chair rise, – 0.4 s (95% CI: – 0.7 to – 0.0 s, p = 0.034) in stair climb, – 0.5 s (95% CI: – 0.9 to – 0.2 s, p < 0.001) in 6-m usual walk and – 3.3 s (95% CI: – 5.6 to – 1.0 s, p = 0.001) in backwards walk following exercise post-surgery compared to baseline. As a result, there was no significant difference in physical function between groups at 12 weeks post-surgery. Similar results were observed when analysing complete cases except for a significant reduction (improvement) in chair rise (p = 0.036) for rehabilitation comparing 6 to 12 weeks post-surgery (Table S2). | PMC10645629 | ||
Body composition | At baseline, prehabilitation had lower whole-body LM (p = 0.007) and trunk FM (p = 0.038) compared to rehabilitation (Table Body composition outcomes at baseline, pre-surgery, and 6 and 12 weeks post-surgery*Within-group multiple comparisons for baseline, pre-surgery, 6 and 12-weeks post-surgery, with a Bonferroni-corrected p < 0.05; (a) Baseline, (b) Pre-surgery, (c) 6-weeks post-surgery, (d) 12-weeks post-surgery | PMC10645629 | ||
Urinary incontinence and length of hospital stay | urinary incontinence | URINARY INCONTINENCE | At 2 weeks post-surgery, there was no difference between groups for urinary incontinence (p = 0.790) (Table | PMC10645629 |
Discussion | cancer, prostate cancer, urinary incontinence, fatigue | CANCER, PROSTATE CANCER, URINARY INCONTINENCE, POSTOPERATIVE COMPLICATIONS | In this study, we compared prehabilitation and rehabilitation supervised exercise in the setting of prostatectomy. There were three main findings. First, 6 weeks of supervised exercise before prostatectomy enhanced muscle strength, physical function at pre-surgery and at 6 weeks post-surgery despite reductions in lean mass so that even though these patients were in the postsurgical recovery period, their physical performance was comparable to or better than prior to surgery when compared to rehabilitation. In addition, improvements in strength and function were accompanied by reduced fatigue prior to surgery. Second, for those initiating exercise post-surgery, supervised exercise helped recoup losses and enhance muscle strength and physical function. Third, both groups experienced comparable resolution in urinary incontinence with similar hospital LOS.We demonstrated that commencing exercise 6 weeks before surgery substantially improved muscle strength and physical function, which may act to buffer the effects of surgery. As a result of the patient’s improved reserve capacity, declines that do occur in strength and function do not typically result in the patient falling below their pre-exercise levels. In addition, we observed a reduction in fatigue levels in those who exercised before surgery. These findings support previous research in the prehabilitation setting (Singh et al. The rehabilitation programme also showed important benefits for patients who are unable to engage in exercise before surgery due to numerous medical appointments and commitments or the short time between diagnosis and prostatectomy (e.g., the urgency of the prostate cancer condition and surgeon availability). Exercise that commenced after this initial period, with rehabilitative intent, is also beneficial to recoup losses and enhance muscle strength and physical function while maintaining or improving QoL. These findings are clinically important as increasing physical reserve capacity is associated with reduced risk of postoperative complications and all-cause mortality in cancer patients (Ezzatvar et al. Although improvements in both muscle strength and physical function resulted from the training program in both groups, there was an absence of improvement in whole body LM. Consequently, improvements in strength and function are likely attributable to neural adaptations to exercise (Carli and Zavorsky The evidence regarding prehabilitative exercise for reducing post-operative urinary incontinence is conflicting in patients with prostate cancer (Xiangyun et al. The strengths of this study include a comprehensive clinic-based exercise programme with supervision, a high attendance rate, a battery of physical function and muscle strength assessments, and use of DXA for body composition. Nevertheless, there are limitations worthy of comment. Most participants underwent a less invasive surgical technique, which may have limited our ability to observe the effects of exercise on urinary incontinence and hospital LOS. Additionally, the study participants may not represent all prostate cancer patients undergoing surgery, as they agreed to participate in an exercise intervention during a challenging period. Lastly, the study did not have a long-term follow-up to assess the persistence of exercise over time, such as 6 months or longer. Nevertheless, we found that a relatively brief programme of supervised resistance and aerobic exercise undertaken either before or after prostatectomy can be safely undertaken and results in improvements in muscle strength and physical function. The time period between diagnosis and surgery, despite being a relatively short time frame, provides a window of opportunity to introduce targeted exercise programmes.In conclusion, exercise before prostatectomy enhances muscle strength and physical function, and reduces fatigue in patients with prostate cancer. If exercise before surgery is not possible, starting supervised exercise after prostatectomy may recoup losses and enhance muscle strength, physical function and potentially body composition while maintaining QoL. It may well be that exercising both before and after surgery may provide the most significant physical enhancement. Clinicians should encourage patients to engage in exercise either before or as soon as possible after the acute post-operative phase to assist with their recovery. | PMC10645629 |
Acknowledgements | Daniel A. Galvão, Prostate Cancer | PROSTATE CANCER | We acknowledge all the participants who despite their difficult schedules provided the time to participate and contribute to this study. Special acknowledgement also goes to the support staff, both administration and the research assistants, in assisting in their various capacities. Pedro Lopez is supported by the National Health and Medical Research Council (NHMRC) Centre of Research Excellence (CRE) in Prostate Cancer Survivorship Scholarship. Daniel A. Galvão and Robert U. Newton are funded by an NHMRC CRE in Prostate Cancer Survivorship | PMC10645629 |
Author contributions | RECRUITMENT | FS: had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. FS, RUN, DAG, and DRT: contributed to the study conception and design. Patient recruitment was contributed by FS, JT, MB, EO, and DH. Material preparation, data collection and analysis were performed by FS, RUN, DAG, DRT and PL. The first draft of the manuscript was written by FS: and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. | PMC10645629 | |
Funding | Open Access funding enabled and organized by CAUL and its Member Institutions. This work was supported by funding through the Edith Cowan University Early Career grant fund (Grant Number: G1002267). | PMC10645629 | ||
Availability of data and material | The datasets generated during and/or analysed during the current study are available from the corresponding author upon reasonable request. | PMC10645629 | ||
Declarations | PMC10645629 | |||
Conflict of interest | The authors declare that they have no conflicts of interest and have no relevant financial or non-financial interests to disclose. | PMC10645629 | ||
Ethical approval | This study was performed in line with the principle of the Declaration of Helsinki. Ethics approval has been obtained from the Human Research Ethics Committee of Edith Cowan University (14320_Singh) and the South Metropolitan Health Service (2016–171). | PMC10645629 | ||
Consent to participate | Informed consent was obtained from all individual participants included in the study. | PMC10645629 | ||
References | PMC10645629 | |||
Methods | Process evaluation data were collected alongside intervention data and included both quantitative and qualitative data sources. Midwives at the health facilities which were randomized as intervention sites completed tracking logs to measure feasibility of the intervention. Research team members traveled to intervention sites where they conducted structured observations and completed fidelity and learning methods checklists to determine adherence to the model of group antenatal care delivery. In addition, midwives facilitating group antenatal care meetings were interviewed and focus groups were conducted with women participating in group antenatal care. | PMC10629640 | ||
Results | In the majority of cases, midwives facilitating group antenatal care completed all components of the meetings with fidelity, following best practices such as sitting with the group rather than standing. Across 7 intervention sites, 7 groups (622 pregnant women) were documented in the tracking logs and of these participants, the majority (74%) attended more than half of the meetings, with 32% attending all 8 group meetings. Three themes were identified in both the midwife interviews and focus groups with pregnant women: 1) information sharing, 2) sense of community, and 3) time management challenges. An additional theme emerged from the focus groups with the women: women who had already given birth noticed a disconnect between what they learned and treatment received during labor and birth. | PMC10629640 | ||
Conclusion | This process evaluation determined that group antenatal care can be implemented with fidelity in low and middle-income countries. Time management was the biggest challenge, however both midwives and pregnant women found the model of care not only acceptable, but preferable to traditional care. The knowledge shared and sense of community built during the meetings was a valuable addition to the individual model of antenatal care. | PMC10629640 | ||
Data Availability | The data is available on Deep Blue: | PMC10629640 | ||
Introduction | deaths | COMPLICATION | Maternal and infant health have long been at the forefront of global health initiatives. Through concerted efforts to improve maternal and newborn health, some progress has been made. In 1990, newborn deaths worldwide were 5 million and by 2019 that had decreased to 2.4 million [Antenatal care (ANC) defined by the World Health Organization as “care provided by skilled health-care professionals to pregnant women and adolescent girls to ensure the best health conditions for both mother and baby during pregnancy” [A National Institute of Health funded study (Clinical Trial # NCT04033003) entitled “Group antenatal care to promote a healthy pregnancy and optimize maternal and newborn outcomes: A cluster randomized controlled trial” (GRAND) has been implemented in Ghana to determine the effectiveness of the group ANC model of care. This report focuses on the process evaluation of the implementation of the intervention (group ANC). The overarching goal of the GRAND study is to determine whether group ANC facilitated by trained midwives, utilizing a fixed group model of 10–14 pregnant women by gestational age for the duration of the pregnancy, improves outcomes when compared with participants in routine, individual antenatal care. The randomization occurred at the facility level whereby 7 facilities were randomized to routine ANC and 7 were randomized to offer group ANC to pregnant women seeking ANC at the facility. Primary outcomes include birth preparedness, complication readiness, increased care-seeking behavior, and improved maternal and newborn outcomes. Enrollment in the study and participating in group ANC was voluntary. The project used a Health Literacy Skills Framework and details of the framework and project protocol have been described elsewhere [While program outcomes measure the success of an intervention, a process evaluation is important to understand why an intervention is, or is not, successful and to ensure that the outcomes seen are a result of the intervention, particularly when implementation occurs in different cultures and contexts [ | PMC10629640 |
Components of the GRAND—Group antenatal care model. | The purpose of this process evaluation was to identify and document barriers and facilitators to implementation of the group ANC intervention. Using both quantitative and qualitative methods, we aimed to identify potential and actual influences on the quality and conduct of the intervention’s operations, implementation, and antenatal care delivery. The data collected were used for formative and summative purposes as a continuous monitoring and problem-solving approach to oversee group ANC model fidelity. | PMC10629640 | ||
Methods | PMC10629640 | |||
Overview of the intervention | During the summer of 2019, research team members with expertise in group ANC from the United States met with research partners in Ghana to conduct a train-the-trainer course for a selected group of midwives that would then serve as champions to train the midwives working at the intervention sites. The training was undertaken in the same manner in which the group ANC would be conducted; in small groups, in a circle, where discussion and participation were encouraged. The ten champion trainers then traveled to the districts where they were supported by members of the research team as they trained an additional 52 midwives as facilitators for group ANC. Each training session lasted 3 full days and included opportunities for each midwife to practice being the facilitator. Each participant was given a Facilitator Guide and a set of facilitation tools to use to prepare for and use during each group ANC meeting. | PMC10629640 | ||
Process evaluation design | Following the midwife facilitator training, the champion trainers as well as other members of the Ghana research team received additional training in the data collection methods for the process evaluation of group ANC including facilitation of focus groups among pregnant women participating in group ANC at the intervention sites and conducting interviews with the midwife facilitators of group ANC at those sites. The process evaluation included both qualitative and quantitative data sources ( | PMC10629640 |
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