Total Response Rate Research Articles

Total neoadjuvant therapy with FOLFOX plus bevacizumab and short-course radiotherapy for Ras mutant, high-risk, locally advanced rectal cancer: The TRAINER trial.

133 Background: Total neoadjuvant therapy (TNT) intensified by the combination of targeted therapy or immunotherapy is warranted to achieve satisfying local and systemic control for high-risk locally advanced rectal cancer (LARC). Our study aimed to explore the efficacy and safety of a FOLFOX-based TNT regimen plus bevacizumab and short-course radiotherapy (SCRT) in Ras-mutant high-risk LARC patients. Methods: In this single-arm, single-center, phase II trial, LARC patients with at least one risk factor (cT3c-4, mesorectal fascia positive, cN2, lateral lymph node involvement, and extramural venous invasion positive) were recruited and only Ras-mutant patients were included. Four cycles of FOLFOX plus bevacizumab were arranged as induction chemotherapy followed by SCRT (25Gy/5Fx) and two cycles of FOLFOX as consolidation chemotherapy. Surgery was performed 8 weeks after completion of radiotherapy. After surgery, high-risk stage III patients (T4 or N2) were recommended to receive an extra 6 cycles of FOLFOX as adjuvant chemotherapy, while low-risk stage III patients were scheduled for regular follow-up. Patients with clinical complete response(cCR) were allowed to choose the “Watch & Wait” (W&W) strategy instead of surgery. The primary endpoint was the complete response (CR) rate, defined as the total rate of cCR plus pathological complete response (pCR). Secondary endpoints included adverse events of TNT, postoperative complications, 2-year disease-free survival, and overall survival. Results: Between April 2, 2021, and March 12, 2024, 47 of 51 enrolled patients were eligible for treatment. All patients completed the prescribed TNT cycles, and six (12.8%) of them had dose reduction. The CR was achieved in 18 (38.3%) patients, including 14 (29.8%) pCR. No grade IV-V toxicity was observed and the incidence of grade III toxicities was 34.0%. Four patients (8.5%) achieved cCR and chose the W&W strategy. The other 43 patients underwent curative surgery and anal preservation was achieved in 39 (90.7%) patients. Seven patients (16.3%) experienced postoperative complications, including four (9.3%) cases of anastomotic leakage. Conclusions: The intensified TNT regimen combined with bevacizumab achieved a satisfying CR rate with acceptable toxicities and complications for Ras-mutant high-risk LARC patients. Long-term survival data of this cohort are needed to validate the efficacy of this regimen further. Clinical trial information: NCT04923620 .

Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study

The potential benefits of pyrotinib for patients with trastuzumab-insensitive, HER2-positive early-stage breast cancer remain unclear. This prospective, multicentre, response-adapted study evaluated the efficacy and safety of adding pyrotinib to the neoadjuvant treatment of HER2-positive breast cancer patients with a poor response to initial docetaxel plus carboplatin and trastuzumab (TCbH). Early response was assessed using magnetic resonance imaging (MRI) after two cycles of treatment. Patients showing poor response, as defined by RECIST 1.1, could opt to receive additional pyrotinib or continue standard therapy. The primary endpoint was the total pathological complete response (tpCR; ypT0/isN0) rate. Of the 129 patients enroled, 62 (48.1%) were identified as MRI-responders (cohort A), 26 non-responders continued with four more cycles of TCbH (cohort B), and 41 non-responders received additional pyrotinib (cohort C). The tpCR rate was 30.6% (95% CI: 20.6–43.0%) in cohort A, 15.4% (95% CI: 6.2–33.5%) in cohort B, and 29.3% (95% CI: 17.6–44.5%) in cohort C. Multivariable logistic regression analyses demonstrated comparable odds of achieving tpCR between cohorts A and C (odds ratio = 1.04, 95% CI: 0.40–2.70). No new adverse events were observed with the addition of pyrotinib. Patients with co-mutations of TP53 and PIK3CA exhibited lower rates of early partial response compared to those without or with a single gene mutation (36.0% vs. 60.0%, P = 0.08). These findings suggest that adding pyrotinib may benefit patients who do not respond to neoadjuvant trastuzumab plus chemotherapy. Further investigation is warranted to identify biomarkers predicting patients’ benefit from the addition of pyrotinib.

Effect of Acupuncture on Anxiety, Depression, and Quality of Life in Patients with Irritable Bowel Syndrome: A Meta-Analysis.

Irritable bowel syndrome (IBS) has been effectively treated with acupuncture, but the significance of quality of life, depression, and anxiety in the assessment of IBS patients has received little consideration. This study examined the impact of acupuncture on depression, anxiety, and quality of life in IBS patients. PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), EMBASE, China Science and Technology Journal Database (VIP), Chinese Biological Medical (CBM, SinoMed) Database, and the Wan Fang Database were among the electronic databases from which relevant randomized controlled trials (RCTs) were systematically retrieved between their inception and July 2023. The outcomes included adverse events, total response rate, anxiety, and symptoms of depression, as well as quality of life. In this study, the heterogeneity, publication bias, standardized mean difference (SMD), and risk ratios (RR) with 95% confidence intervals (CI) were estimated. In this study, 29 RCTs including 3114 participants for analysis (treatment group, 1730; control group, 1384) were included. Compared to other therapies, acupuncture significantly improved the quality of life (SMD = 0.61, 95% CI = [0.26, 0.96], P < 0.001) and alleviated anxiety (SMD = - 0.72, 95% CI = [- 1.76, 0.32], P = 0.18) and depression (SMD = - 0.74, 95% CI = [- 1.18, - 0.3], P < 0.001) in IBS patients. A statistically significant improvement was recorded in their quality of life, and they also displayed fewer symptoms of depression. The total response rate (RR = 1.18, 95% CI = [1.12,1.25], P < 0.001) indicated that acupuncture significantly affected IBS treatment in comparison to other methods. Subgroup analysis of primary outcome indicators revealed that acupuncture demonstrated better results regardless of the duration of intervention and was more effective than Western medicine or sham acupuncture. In addition to the total response rate (I2 = 0%), the other three outcome indicators showed significant heterogeneity (I2 > 50%). No publication bias was noted in RR (P < 0.05); however, a significant publication bias was observed in quality of life (P > 0.05). Acupuncture can enhance the quality of life and relieve anxiety and depression in patients with IBS with apparent safety; however, a large number of high-quality RCTs are still needed.

Clinical efficacy of pyrotinib combined with chemotherapy for neoadjuvant treatment in HER2-positive breast cancer: a single-center study.

This study aimed to evaluate the efficacy of pyrotinib, an orally administered small molecule tyrosine kinase inhibitor, combined with neoadjuvant chemotherapy in treating patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Pyrotinib works by inhibiting the HER2 signaling pathway, thereby preventing tumor cell growth. This single-arm clinical trial aimed to assess the total pathological complete response (tpCR; ypT0/is and ypN0) rate as the primary endpoint. A total of 27 patients were enrolled, each receiving 4-8 cycles of pyrotinib in combination with neoadjuvant chemotherapy. Pyrotinib combined with neoadjuvant chemotherapy demonstrated notable antitumor activity in patients with HER2-positive breast cancer. Among 26 patients, the tpCR rate was 26% (7/26), while the breast pathological complete response rate was 30% (8/26), indicating complete inhibition of the primary tumor in some cases. Notably, patients with HR-negative breast cancer demonstrated a higher tpCR rate compared with those with HR-positive breast cancer. The treatment regimen was well-tolerated. Diarrhea was the most common adverse event, occurring in 92.3% of patients, with 46.2% experiencing grade 3 or higher diarrhea. No severe adverse events or treatment-related fatalities were reported.

A pilot study of tofacitinib citrate with 308-nm excimer laser for the treatment of vitiligo.

Vitiligo is a clinically prevalent acquired skin disorder characterized by depigmentation. Currently, the therapeutic options for vitiligo are restricted, and numerous issues exist, such as a prolonged treatment course, unsatisfactory therapeutic efficacy, adverse reactions, and a high propensity for recurrence after treatment cessation. To assess the safety and efficacy of combined treatment involving oral tofacitinib citrate (TC) and a 308-nm excimer laser (EL), with the aim of discovering a rapid and effective treatment approach to minimize the side effects of various drugs. A total of 63 patients with progressive vitiligo and a Vitiligo Disease Activity Score (VIDA) score of four from January 2022 to January 2024 were enrolled and divided into three groups. The three groups were the TC combined with 308-nm EL and methylprednisolone treatment group, the TC and 308-nm EL treatment group, and the methylprednisolone treatment alone group. The treatment was continued for 24 weeks. Finally, assessment of therapy outcomes was performed. When TC was combined with 308-nm EL and methylprednisolone treatment, the effect was more rapid. When TC was combined with 308-nm EL, it had a more favorable treatment effect than that of methylprednisolone alone, despite having a slower effect onset. After 24 weeks of treatment, there was no significant difference between the two groups in terms of the total response rate or significant efficiency. However, when only methylprednisolone treatment was applied, the effect is relatively slow and inefficient. This study confirmed the rapid and efficient treatment of vitiligo through the combination of TC and 308-nm EL, and no serious adverse reactions were reported, which could offer an optimal treatment plan for patients with vitiligo.

Prognostic factors of immunosuppression therapy combined with eltrombopag in the treatment of childhood severe aplastic anemia

Objective: To analyze the influence factors on the efficacy of immunosuppression therapy (IST) combined with eltrombopag and IST alone in the treatment of childhood severe aplastic anemia (SAA). Methods: A retrospective cohort study. A total of 124 children with SAA who were initially treated with IST at Beijing Children's Hospital from March 2017 to May 2020 were enrolled. Clinical characteristics, laboratory examination and prognosis data were collected at the time of enrollment. According to the treatment plan, the children were divided into the eltrombopag combined with IST group (eltrombopag group) and the IST group. Binary Logistic regression model was used to analyze the factors affecting the efficacy of the two groups at 6 months of treatment, and the factors affecting the efficacy of the eltrombopag group at the end of follow-up. Results: There were 75 cases (45 males and 30 females) in the eltrombopag group. The age of diagnosis was 5.9 (3.5, 8.5) years. There were 49 patients in the IST group, including 23 males and 26 females, whose age at diagnosis was 6.2 (4.4, 8.8) years. The absolute lymphocyte count before treatment in the eltrombopag group was significantly lower than that in the IST group (1.1 (0.4, 1.6)×109 vs. 2.1 (1.4, 2.8)×109/L). Absolute reticulocyte count in the eltrombopag group was significantly higher than that of IST group (26.9 (8.7, 54.2)×109 vs. 9.5 (4.0, 19.0)×109/L) (both P<0.05). Influencing factors of 6-month response: a comparison between response and un-response groups in the eltrombopag treated patients showed that, before treatment, hemoglobin (69 (61, 78) vs. 64 (59, 68) g/L), platelet (10 (6, 16)×109 vs. 6 (3, 8)×109/L), absolute reticulocyte count (ARC) (34.0 (15.8, 57.3)×109 vs. 6.5 (4.6, 16.8)×109/L) and the response rate to granulocyte colony stimulating factor (G-CSF) after treatment (82.4% (47/57) vs. 9/18) were significantly different (all P<0.05). Logistic regression model analysis showed that ARC (OR=1.09, 95%CI 1.02-1.18) and absolute neutrophil count were independent influencing factors of 6-month response rate in the eltrombopag group (OR=0.00, 95%CI 0.00-0.89). ARC was also the independent influencing factors of the end of follow-up response rate in the eltrombopag group (OR=1.04, 95%CI 1.01-1.07). Conclusions: Pre-treatment blood count and response to G-CSF were predictors of overall response to eltrombopag combined with IST. The higher the ARC before treatment, the higher the total response rate and complete response.

Outcomes in randomized controlled trials of traditional Chinese medicine in treatment of diabetic kidney disease

This study systematically analyzed the current status of outcomes in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment of diabetic kidney disease(DKD), aiming to provide a reference for constructing the core outcome set(COS) of TCM treatment of DKD. The clinical RCTs of TCM treatment of DKD that were published from January 2019 to March 2024 were retrieved from seven databases: CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, and Web of Science. The risk of bias was assessed and outcome indicators were qualitatively analyzed. A total of 323 RCTs were included, reporting 199 outcome indicators with the frequency of 3 744 in seven indicator domains: TCM syndromes(196 times, 5.24%), symptoms and signs(275 times, 7.35%), physical and chemical examinations(2 820 times, 75.32%), safety events(422 times, 11.27%), long-term prognosis(21 times, 0.56%), quality of life(9 times, 0.24%), and economic evaluation(1 time, 0.02%). The three most frequently applied outcome indicators were total clinical response rate(268 times, 82.97%), serum creatinine(251 times, 77.71%), and urea nitrogen(206 times, 63.78%). The outcomes in the studies of TCM treatment of DKD had the limitations of high risk of bias, lack of standardization of TCM syndromes and efficacy evaluation, neglect of endpoint indicators, large differences in endpoint indicators and time points of measurement, unclear primary and secondary outcomes, few application of long-term prognosis, quality of life, and economic indicators, and insufficient reporting of safety events. In the future, efforts should be made to actively promote the construction of COS in the studies about the TCM treatment of DKD and enhance the quality of the clinical studies.

Efficacy and safety of magnesium sulfate in the treatment of adult patients with acute severe asthma: a Meta-analysis

To evaluate the efficacy and safety of magnesium sulfate in the treatment of acute severe asthma in adults. Literature searches were conducted on PubMed, Cochrane, CNKI, VIP and Wanfang databases to screen randomized controlled trial (RCT) of magnesium sulfate in the treatment of acute severe asthma in adults, starting from the establishment of the database and ending on May 22, 2024. The control group received conventional treatment. The observation group was given intravenous magnesium sulfate on the basis of routine treatment. The outcome indexes included total effective rate, peak expiratory flow (PEF), forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and other pulmonary function indexes, and incidence of adverse reactions. The selection of relevant literature, the collection of data needed for the study and the risk assessment of bias in the included study were all conducted independently by 2 researchers. Stata 12.0 software was used for Meta-analysis, and funnel plot was used to evaluate publication bias. Sixteen RCT studies with a total of 2 601 patients were included. Meta-analysis results showed that the total effective rate in the observation group was significantly higher than that in the control group [risk ratio (RR) = 1.11, 95% confidence interval (95%CI) was 1.03-1.20, P = 0.008]. In pulmonary function examination, PEF [weighted mean difference (WMD) = 0.70, 95%CI was 0.24-1.15, P = 0.003], FEV1 (WMD = 0.48, 95%CI was 0.29-0.68, P = 0.000) and FVC (WMD = 0.72, 95%CI was 0.47-0.97, P = 0.000) were significantly better than those in the control group. There was no significantly difference in the incidence of adverse reactions between the two groups (RR = 0.51, 95%CI was 0.17-1.55, P = 0.419). The funnel plot was drawn for the total effective rate, which showed that each study presented a symmetrical distribution, and the Begg's test (Z = 1.31, P = 0.189) and Egger's test (t = 1.18, P = 0.261) were combined to consider the small possibility of publication bias. Current evidence shows that the use of magnesium sulfate in the treatment of acute severe asthma in adults increases the total response rate and improves lung function without increasing the incidence of adverse reactions. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies high-quality studies.

Clinical Pharmacology and Side Effects of Venetoclax in Hematologic Malignancies

Venetoclax is a first-in-class B-cell lymphoma/lymphoma-2 (BCL-2) inhibitor that induces apoptosis in malignant cells through the inhibition of BCL-2. The clinical response to venetoclax exhibits heterogeneity, and its sensitivity and resistance may be intricately linked to genetic expression. Pharmacokinetic studies following doses of venetoclax (ranging from 100 to 1200mg) revealed a time to maximum observed plasma concentration of 5-8 hours, with a maximum blood concentration of 1.58-3.89 μg/mL, and a 24-hour area under the concentration-time curve of 12.7-62.8 μg·h/mL. Population-based pharmacokinetic investigations highlighted that factors such as low-fat diet, race, and severe hepatic impairment play pivotal roles in influencing venetoclax dose selection. Being a substrate for CYP3A4, P-glycoprotein, and breast cancer resistance protein, venetoclax undergoes primary metabolism and clearance in the liver, displaying low accumulation in the body.The significance of dose modifications (a 50% decrease with moderate and a 75% reduction with strong CYP3A inhibitors) and a cautious two-hour interval when co-administered with P-glycoprotein inhibitors are highlighted by insights from clinical medication interaction studies. Moreover, an exposure-response relationship analysis indicates that venetoclax exposure significantly correlates not only with overall survival and total response rate but also with the occurrence of ≥ 3-grade neutropenia. In real-world studies, common or severe side effects of venetoclax include tumor lysis syndrome, myelosuppression, nausea, diarrhea, constipation, infection, autoimmune hemolytic anemia, and cardiac toxicity, among others. In this review, we summarize the current clinical pharmacology studies and side effects of venetoclax, which showed that the approved dosage of venetoclax is relatively wide, and the dosage for different hematologic populations can be streamlined in the future.

Knowledge and awareness of emergency department residents and physicians regarding the management of dentofacial traumatic injuries: a cross-sectional study

BackgroundMajority of patients with Dento-Facial Traumatic Injuries (DFTI) seek initial care at an Emergency Department (ED). The timely management of DFTI is of utmost importance in determining long-term prognosis of the tooth and the patient’s overall quality of life. Thus, knowledge and awareness of ED residents & physicians regarding the management of DFTI is crucial for better patient outcomes. Numerous studies have investigated the knowledge of ED specialists regarding initial management of dental trauma, however, scientific evidence in this domain is scarce in our region.ObjectiveThe aim of this study was to evaluate the knowledge and awareness of ED residents and physicians regarding diagnosis and management of DFTI using a web-based survey on REDCap.MethodsAn observational cross-sectional study was conducted among the ED residents and physicians of private and public hospitals in Karachi, Pakistan. Data was collected through a web-based questionnaire, sent via email to the participants. The survey comprised of questions assessing their knowledge regarding the diagnosis and management of various dental and maxillofacial injuries. Responses from the participants were graded as low, moderate or high knowledge levels according to a pre-determined criteria. Pearson’s chi-square test was applied to determine the association between knowledge scores.ResultsThe total response rate was 47.6%. Out of 116 participants, 49 (42%) responses were received from physicians and 67 (58%) from residents. The overall knowledge level of participants was low (46.6%) and there was no significant difference in the knowledge level between residents and physicians (p = 0.157). Participants who had received formal training in dental trauma (p = 0.038) and those with more years of clinical experience (p = 0.004) had higher knowledge scores, that were statistically significant.ConclusionsThe knowledge and awareness of ED residents and physicians in dental trauma management was generally low. Specialized training courses are required to provide timely and adequate management of traumatic dental injuries in order to improve patient-related outcomes.

Global practice variation of suppressive antimicrobial treatment for prosthetic joint infections: A cross-sectional survey study

ObjectivesTo identify global differences in the use of suppressive antimicrobial therapy (SAT) in the management of prosthetic joint infection (PJI). MethodsAn online survey was designed to investigate clinician’s approach to SAT for PJI, including indications, preferred antimicrobial drugs, dosing, treatment duration and follow-up. The survey was distributed to members of four international (bone and joint) infection societies and study groups. ResultsRespondents comprised 330 physicians (204 infectious diseases specialists, 110 orthopedic surgeons, 23 clinical microbiologists) from 43 different countries (Europe, n=134, 41%; Oceania n=112, 34%; North America, n=51, 16%; other, n=33, 10%; total response rate 20%). After debridement, antibiotics and implant retention (DAIR) or one-stage revision, SAT would be initiated often or almost always by 38% of respondents from North America, but only in 6% from Europe and 7% from Oceania. First choices of SAT for staphylococcal PJI were oral cephalosporins (39%) and tetracyclines (31%) in North America; tetracyclines (27%) and anti-staphylococcal penicillins (22%) in Europe; and anti-staphylococcal penicillins (55%) in Oceania. There was no global or regional preferred SAT regimen for Gram-negative PJI. Of all respondents, dosage of SAT was never lowered (n=126, 38%), lowered for specific antibiotics (n=125, 38%) or lowered for all antibiotics (n=79, 24%). SAT was prescribed for a lifelong duration (n=43, 13%), a fixed duration (range 6 months–3 years) (n=104, 32%) or for an undetermined duration (n=154, 47%). ConclusionsApproach to SAT in PJI is highly regional, with no consensus regarding the indication, selection, dose, or duration of SAT between physicians worldwide. This reflects the paucity of data and need for high quality studies to define the optimal use of SAT in the treatment of patients with PJI.

Lentinan combined with docetaxel and nedaplatin in the treatment of pulmonary tuberculosis complicated by nonsmall cell lung cancer

Purpose: To investigate the efficacy and safety of lentinan combined with docetaxel and nedaplatin (DN) in the treatment of pulmonary tuberculosis complicated by non-small cell lung cancer (NSCLC). Methods: A total of 100 patients diagnosed with pulmonary tuberculosis combined with NSCLC in Ankang People's Hospital, Ankang, China were randomized equally into study and control groups. Control group received standard anti-tuberculosis therapy and intravenous chemotherapy regimen based on docetaxel (75 mg/m² on day 1) and nedaplatin (80 – 100 mg/m²), while the study group received, in addition, lentinan (given intravenously every two days). The patients received a total of 2 courses of treatment. Tumor response, survival, adverse reactions, quality of life score, and pulmonary function indices were compared before and after treatment. Results: The study group showed significantly higher total response rate than the control group (p &lt; 0.05). Median overall survival and progression-free survival in the study group was significantly higher than in the control group (p &lt; 0.05). Also, the study group showed significantly lower incidence of adverse reactions compared to control group (p &lt; 0.05). Quality of life score, maximum voluntary ventilation (MVV) and peak expiratory flow (PEF) levels in the study group was significantly higher compared to control group (p &lt; 0.05). Conclusion: Lentinan combination with DN chemotherapy regimen improves response rate, prolongs survival, reduces incidence of adverse reactions, improves quality of life and pulmonary function in patients with pulmonary tuberculosis complicated by NSCLC. These findings provide a new perspective for future studies on the application of lentinan in the treatment of pulmonary tuberculosis complicated by NSCLC.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p= 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

A Healthy Conversation Skills intervention to support changes to physical activity and dietary behaviours in community-dwelling older adults during the COVID-19 pandemic.

Physical activity (PA) and nutrition are important determinants of health in late adulthood. However, low levels of PA and poor nutrition are common in older adults and have become more prevalent during the COVID-19 pandemic. We hypothesised that Healthy Conversation Skills could be used to support health behaviour changes beneficial for health in older adults and thus conducted a study nested within the UK Hertfordshire Cohort Study. Between November 2019 and March 2020, 176 participants were visited at home. A trained researcher administered a questionnaire and undertook anthropometric and physical performance tests. A total of 89 participants were randomised to the control group and received a healthy living leaflet; 87 participants in the intervention group were interviewed using Healthy Conversation Skills at the initial visit with follow-up telephone calls at 1, 3, 6 and 9 months. Follow-up at 1 year by postal questionnaire assessed change in PA and diet. In total, 155 participants (79 control and 76 intervention) completed the baseline and 1-year follow-up. At baseline, median (lower quartile, upper quartile) age (years) was 83.1 (81.5, 85.5) and median PA time (min/day) from walking, cycling and sports was 30.0 (15.0, 60.0). In total, 95% of participants completed the intervention; the total response rate for postal questionnaires was 94%. There were no statistically significant differences in outcomes between the trial arms. In women, there was a tendency for greater increases in diet quality in the intervention group compared to the control group (p = 0.075), while among men, there was a tendency for reduced decline in self-reported physical function in the intervention group compared to the control group (p = 0.081). We have shown that it is viable to utilise Healthy Conversation Skills via telephone to promote healthier lifestyles in older adults. Larger appropriately powered studies to determine the efficacy of such an intervention are now warranted.

Lobaplatin-based concurrent chemoradiotherapy in elderly nasopharyngeal carcinoma

Background The therapeutic benefit of concurrent chemoradiotherapy (CCRT) in elderly nasopharyngeal carcinoma (NPC) patients remains controversial. This study aimed to investigate the efficacy and toxicity of lobaplatin-based CCRT in elderly patients with NPC. Methods We included stage II–IVA NPC patients aged ≥65 years who received lobaplatin concomitant with intensity-modulated radiation therapy (IMRT) between March 2019 and January 2023. Objective response rates and treatment-related toxicity were assessed. Kaplan–Meier’s analysis was performed to calculate survival rates. Results A total of 29 patients were included with a median age of 67 years. There were 19 patients (65.5%) who had comorbidities. All patients had serum EBV-DNA detective before treatment; the median EBV-DNA load was 236 IU/mL. There were 25 (86.2%) patients treated with induction chemotherapy, and the overall response rate was 92.0%. All patients received IMRT and concurrent chemotherapy with lobaplatin. During the CCRT, the most common adverse effect was haematological toxicity. Three patients (10.3%) had grade 3 leucopenia, three patients (10.3%) had grade 3 neutropenia, and eight patients (27.6%) had grade 3–4 thrombocytopenia. The rate of grade 3 mucositis was 34.5%. No patients had liver and kidney dysfunction. The median weight loss was 4 kg during CCRT. After three months of CCRT, the total response rate was 100%. EBV-DNA was not detected in any patients. The median follow-up was 32.1 months. The 3-year locoregional recurrence-free survival, distant metastasis-free survival, progression-free survival and overall survival were 95.8%, 85.7%, 82.5% and 100%, respectively. Conclusions Lobaplatin-based CCRT is safe and feasible for elderly NPC patients, with satisfactory short-term survival outcomes and acceptable toxicities. A phase 2 trial is ongoing to investigate the role of lobaplatin-based CCRT on long-term survival and treatment toxicities for this population.

Midazolam Indications and Dosing in Palliative Medicine: Results from a Multinational Survey.

Despite sparse evidence and limited guidance on indications, use, and dosing, midazolam is widely used in palliative care. We aimed to describe and compare the use of midazolam in three different countries to improve clinical practice in palliative care. We performed an online survey among palliative care physicians in Norway, Denmark, and the United Kingdom (UK). The focus was indications, dosing, administration, and concomitant drugs. A web-based questionnaire was distributed to members of the respective national palliative medicine associations. The total response rate was 9.4%. Practices in the UK, Norway, and Denmark were overall similar regarding the indications of midazolam for anxiety, dyspnoea, and pain treatment in combination with opioids. However, physicians in the UK used a higher starting dose for anxiety, dyspnoea, and pain treatment compared to Norway and Denmark, as well as a higher maximum dose. Danish physicians preferred, to a higher degree, on-demand midazolam administration. Despite practice similarities in the UK, Norway, and Denmark, differences exist for midazolam dosing and administration in palliative medicine. We demonstrated a lack of consensus on how midazolam should be used in palliative care, setting the stage for future studies on the topic.

Effects of Sintilimab Plus Radiotherapy on Levels of Spondin-2 and Glucose Transporter-1 in Patients with Cervical Cancer.

We aimed to evaluate the effects of sintilimab plus radiotherapy on levels of Spondin-2 and glucose transporter-1 (Glut-1) in patients with cervical cancer. A total of 112 patients with cervical cancer treated from January 2019 to January 2021 were selected in this randomized control trial and divided into a control group (n = 56) and a study group (n = 56) using the random number table method. Chemotherapy using docetaxel + cisplatin was performed for both groups, based on which the control group was given radiotherapy (external conformal radiotherapy + intracavitary irradiation), and the study group received sintilimab plus radiotherapy. The treatment lasted for six cycles, with 21 days as one cycle. The total response rate of the study group was higher than that of the control group (55.36% vs 33.93%) (P < 0.05). There were no significant differences in adverse effects between the two groups (P > 0.05). After six cycles of treatment, the levels of carcinoembryonic antigen, squamous cell carcinoma antigen, vascular endothelial growth factor-A, vascular endothelial growth factor receptor 2, Spondin-2 and Glut-1 decreased in both groups compared with those before treatment, and they were lower in the study group (P < 0.05). The survival rate of the study group was higher than that of the control group (87.50% vs 71.43%) (P < 0.05). Sintilimab plus radiotherapy can effectively reduce the levels of serum tumor markers, such as Spondin-2 and Glut-1, and enhance the clinical efficacy on patients with cervical cancer, without increasing adverse effects.

American Shoulder and Elbow Surgeons perspectives on political advocacy

BackgroundPhysician involvement in political advocacy has become increasingly important in recent years. This study aims to explore the types of involvement and barriers to involvement in political advocacy among American Shoulder and Elbow Surgeons (ASES) members, identify issues considered most important by ASES members, and assess demographic factors that might correlate with involvement in political advocacy efforts among ASES members. MethodsThis survey was conducted by the ASES Political Advocacy Committee over a two-week period in June 2021. The survey collected demographic information including sex, ethnicity, years in practice, practice type, political affiliation, and level of current involvement in political advocacy. Additional questions consisted of thoughts regarding current health care policy issues and the role of the American Academy of Orthopaedic Surgeons (AAOS)/ASES regarding such policy issues. ResultsWe received 297 responses for a total response rate of 27%. Of those who responded, 24.6% identified as Democrat, 33% identified as Republican, and 42.4% identified as Independent. There was no difference in political affiliation between membership groups. Physician Reimbursement (82%), Medical Liability Reform (50%), and Physician Ownership (50%) were the most important issues identified among respondents. Physician Ownership, Physician Reimbursement and GME and Student Loan Reform were most important to those in early practice, while Quality and Research was most important to those with greater than 25 years of practice experience. ConclusionThere is strong agreement among surgeons regarding the most important political advocacy issues. The efforts of the AAOS and ASES should focus on these areas. Additionally, the vast majority of respondents felt that advocacy efforts had a positive impact on patients and surgeons.

Relationship between academic stress and sleep issues among students at Pakistani Government Medical Colleges

Objectives: To identify the relationship between academic stress and sleep issues among medical students. Study Design: Cross-sectional study. Place and Duration: From August 6, 2022 to September 28, 2022, at 09 Government Medical Institutes of Pakistan hosted by Rawalpindi Medical University. Methodology: A study on 359 students of the MBBS from 09 Government Colleges all over Pakistan using convenient sampling technique. The study was conducted in several government colleges of Pakistan which involved students from all over Pakistan predominantly from Punjab. The questionnaire was composed of 3 sections: 1. Demographics, 2. Kessler Psychological Distress Scale (K10), 3. Pittsburgh Sleep Quality Index (PSQI). The prevalence of stress was measured along with poor sleep quality and their association with each other. Results: Total response rate was 94%. The total prevalence of stress was (69.5) Mean K10 score of the participants came out as 23.54±7.732 (max=50, min=10). Incidence of poor quality of sleep (PSQI ≥ 5) amongst students came out as 84.7% and mean value of PSQI score came out as 8.54 ± 3.03 (max=21). It was observed that there was a statistically significant association between stress and sleep quality (p&lt;0.01). Conclusion: Our study found that Pakistani medical students frequently experience academic stress and have poor sleep pattern. Stress and sleep disturbances were strongly influenced by academic pressures. Keywords: Psychological Stress, Medical Students, Sleep Quality, Kessler Psychological Distress Scale, Pittsburgh Sleep Quality Index Scale, Academic Stressors.

Predictors of efficacy of ultrasound-guided intra-articular glucocorticoid injection in knee osteoarthritis: A prospective study.

Intra-articular glucocorticoid injection (IAGI) is widely used for treatment of knee osteoarthritis (OA) flares. Response rates are generally around 70%. Several studies have tried to identify predictors of good response, but response to ultrasound (US)-guided injection has not yet been investigated. This study aimed to identify the predictors of response to IAGI performed under US guidance in patients with primary knee OA. A total of 116 patients (116 knees) presenting with unilateral or bilateral primary knee OA were enrolled for this prospective single-center study. All were aged >40 years and met the American College of Rheumatology (ACR) criteria for knee OA. Demographic, clinical, laboratory, and imaging data were collected, injection was performed using US guidance, and tolerance was assessed. The primary efficacy endpoint was ≥40% reduction in total WOMAC score (WOMAC40). Univariate and multivariate logistic regression analyses were conducted to identify the predictors of response. The mean age of the patients was 64.2 ± 9.4 years and mean BMI was 29.9 ± 3.8 kg/m2. Total WOMAC40 response rate was 61.2%. In multivariate analysis, the independent predictors of response were BMI.