Lifestyle and fertility-specific quality of life affect reproductive outcomes in couples undergoing in vitro fertilization.

Objective: A Mediterranean dietary pattern, sleeping habits, physical activity, and lifestyle appear to affect reproductive health. There are few reports about whether fertility-specific quality of life (QOL) is linked to infertility treatment outcomes. The aim of this study is to investigate when lifestyle factors and fertility-specific QOL are comprehensively considered, which factors influence assisted reproductive technology (ART) outcomes. Methods: This prospective cohort includes 291 women undergoing a first ART treatment at multiple centers in Japan and was designed to evaluate the influence of diet, physical activity, sleeping pattern, computer use duration, and fertility-specific quality of life tool (FertiQoL) score on ART treatment outcomes using a questionnaire. The primary endpoint was the good-quality blastocyst rate per oocyte retrieval and the secondary endpoints were a positive pregnancy test and gestational sac (GS) detection. Results: The good-quality blastocyst rate per oocyte retrieval tended to be negatively associated with frequent fish consumption. After all embryo transfer (ET) cycles, a positive pregnancy test tended to be positively associated with longer sleep and longer computer use (OR = 1.6, 95% CI = 0.9-2.7 and OR = 1.7, CI = 1.0-2.8, respectively) and negatively associated with a smoking partner (OR = 0.6, CI = 0.3-1.0). GS detection was positively and significantly associated with frequent olive oil intake and longer computer use (OR = 1.7, CI = 1.0-3.0 and OR = 1.7, CI = 1.0-3.0, respectively). After ET cycles with a single blastocyst, a positive pregnancy test was positively and significantly associated with longer computer use (OR = 2.0, CI = 1.1-3.7), while GS detection was significantly more likely in women with longer computer use (OR = 2.1, CI = 1.1-3.8) and tended to be more likely in women with a higher FertiQoL Total scaled treatment score (OR = 1.8, CI = 1.0-3.3). p < 0.05 was considered statistically significant and 0.05 ≤ p <0.01 as tendency. Conclusions: Olive oil may be an important factor in dietary habits. Fertility-specific QOL and smoking cessation guidance for partners are important for infertile couples.

Motion capture device reveals a quick learning curve in vascular anastomosis training.

PURPOSE: Surgical procedures are often evaluated subjectively, and an objective evaluation has been considered difficult to make and rarely reported, especially in open surgery, where the range of motion is wide. This study evaluated the effectiveness of surgical suturing training as an educational tool using the Leap Motion Controller (LMC), which can capture hand movements and reproduce them as data comprising parametric elements. METHODS: We developed an off-the-job training system (Off-JT) in our department, mainly using prosthetic grafts and various anastomotic methodologies with graded difficulty levels. We recruited 50 medical students (novice group) and 6 vascular surgeons (expert group) for the study. We evaluated four parameters for intraoperative skills: suturing time, slope of the roll, smoothness, and rate of excess motion. RESULTS: All 4 parameters distinguished the skill of the novice group at 1 and 10 h off-JT. After 10 h of off-JT, all 4 parameters of the novices were comparable to those of the expert group. CONCLUSION: Our education system using the LMC is relatively inexpensive and easy to set up, with a free application for analyses, serving as an effective and ubiquitous educational tool for young surgeons.

Alterations in Intratumoral Immune Response before and during Early-On Nivolumab Treatment for Unresectable Advanced or Recurrent Gastric Cancer.

We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR; objective response rate, OS; overall survival, PFS; progression-free survival) to previous trials. The immunograms of individual subjects displayed no significant changes before or early in the treatment, except for the regulatory T cell (Treg) score. Moreover, there were no consistent alterations observed among cases experiencing DCB. The intratumoral immune response was suppressed by previous treatments in most third- or later-line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in early-on-treatment tumors, but clonal replacement did not impact efficacy. High T cell/Treg ratios and a low UV-radiation-response gene signature were linked to DCB and treatment response. This study emphasizes the tumor immune response's importance in nivolumab efficacy for gastric cancer. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. The tumor-infiltrating immune response was compromised by prior treatments in third-line therapy, implying that, to enhance immunotherapeutic outcomes, commencing treatment at an earlier stage might be preferable. Larger cohort validation is crucial to optimize immune-checkpoint inhibitors in gastric cancer treatment.

A case of carotid-axillary bypass for subclavian steal syndrome in an 83-year-old female undergoing hemodialysis.

INTRODUCTION: Patients undergoing hemodialysis exhibit a high incidence of subclavian steal syndrome. Many cases of endovascular treatment for subclavian artery stenosis were only reported recently; however, the long-term results of surgical treatment are also important. Herein, we report a case of subclavian steal syndrome treated with common carotid-axillary bypass surgery in a patient undergoing hemodialysis. PRESENTATION OF CASE: An 83-year-old woman experienced dizziness and pain in her left hand during hemodialysis. Computed tomography and angiography revealed severe stenosis and calcified lesions in the left subclavian artery. Ultrasonography revealed a retrograde blood flow waveform in the left vertebral artery. The patient was diagnosed with subclavian steal syndrome. We performed common carotid-axillary bypass for lesions that were difficult to revascularize via endovascular therapy. The post-operative course was uneventful, and the dizziness and numbness in the patient's left hand during dialysis disappeared. Post-operative ultrasonography revealed an antegrade blood flow waveform in the left vertebral artery. DISCUSSION: Subclavian steal syndrome is an indication for revascularization in symptomatic patients. Endovascular treatment should be considered the first choice; however, surgery should be considered for patients in whom endovascular treatment is difficult, such as those with severe calcification. We chose common carotid-axillary artery bypass because the subclavian approach is a more familiar technique. Until 1 year post-operatively, the patient had not experienced any symptom recurrence, and the shunt flow was well maintained. CONCLUSION: Common carotid-axillary bypass can be useful for revascularization of lesions for which endovascular therapy is considered difficult in patients with subclavian steal syndrome.

Impact of correlations between prioritized outcomes on the net benefit and its estimate by generalized pairwise comparisons.

Benefit-risk balance is gaining interest in clinical trials. For the comprehensive assessment of benefits and risks, generalized pairwise comparisons are increasingly used to estimate the net benefit based on multiple prioritized outcomes. Although previous research has demonstrated that the correlations between the outcomes impact the net benefit and its estimate, the direction and magnitude of this impact remain unclear. In this study, we investigated the impact of correlations between two binary or Gaussian variables on the true net benefit values via theoretical and numerical analyses. We also explored the impact of correlations between survival and categorical variables on the net benefit estimates based on four existing methods (Gehan, Péron, Gehan with correction, and Péron with correction) in the presence of right censoring via simulation and application to actual oncology clinical trial data. Our theoretical and numerical analyses revealed that the true net benefit values were impacted by the correlations in various directions depending on the outcome distributions. With binary endpoints, this direction was governed by a simple rule with a threshold of 50% for a favorable outcome. Our simulation showed that the net benefit estimates based on Gehan's or Péron's scoring rule could be substantially biased in the presence of right censoring, and that the direction and magnitude of this bias were associated with the outcome correlations. The recently proposed correction method greatly reduced this bias, even in the presence of strong outcome correlations. The impact of correlations should be carefully considered when interpreting the net benefit and its estimate.

Impacts of the preceding cancer-specific health-related quality of life instruments on the responses to the subsequent EQ-5D-5L.

BACKGROUND: In clinical studies, the EQ-5D-5L is often employed with disease-specific health-related quality of life instruments. The questions in the former are more general than the latter; however, it is known that responses to general questions can be influenced by preceding specific questions. Thus, the responses to the EQ-5D-5L have the possibility of being influenced by the preceding disease-specific health-related quality of life instruments. This may lead to bias in the cost-effectiveness analysis results. Therefore, this study aimed to evaluate the impact of the preceding cancer-specific health-related quality of life instruments on the EQ-5D-5L responses. METHODS: We prepared questionnaire booklets containing the EQ-5D-5L, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, and the Functional Assessment of Cancer Therapy General with different orders. Using a quasi-randomized design, they were distributed to the patients undergoing drug therapy for advanced cancer, who were classified into three groups: Groups 1, 2, and 3 (the EQ-5D-5L placed first, second, and last, respectively). We compared the EQ-5D-5L index and the missingness of EQ-5D-5L among the groups. RESULTS: The mean EQ-5D-5L index was 0.796, 0.760, and 0.789 for groups 1 (n = 300), 2 (n = 306), and 3 (n = 331), respectively. The difference between Groups 2 and 1 was - 0.036 (95% CI - 0.065 to - 0.007; p = 0.015). The proportion of patients with an incomplete EQ-5D-5L was 0.11, 0.11, and 0.05 for Groups 1, 2, and 3, respectively. The difference of the proportions between group 3 and 1 and between 3 and 2 was - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003) and - 0.06 (95% CI - 0.10 to - 0.02; p = 0.003), respectively. CONCLUSIONS: Although the EQ-5D-5L index differed according to the instrument orders, the difference size would not be considerably larger than the minimally important difference. The patients tended to complete the EQ-5D-5L when they were placed at the end of the questionnaire.

Gradient Boosted Tree Approaches for Mapping European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Onto 5-Level Version of EQ-5D Index for Patients With Cancer.

OBJECTIVES: This study aimed to develop direct and response mapping algorithms from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 onto the 5-level version of EQ-5D index based on the gradient boosted tree (GBT), a promising modern machine learning method. METHODS: We used the Quality of Life Mapping Algorithm for Cancer study data (903 observations from 903 patients) for training GBTs and testing their predictive performance. In the Quality of Life Mapping Algorithm for Cancer study, patients with advanced solid tumor were enrolled, and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and 5-level version of EQ-5D were simultaneously evaluated. The Japanese value set was used for direct mapping, whereas the Japanese and US value sets were used for response mapping. We trained the GBTs in the training data set (80%) with cross-validation and tested the predictive performance measured by the root mean squared error (RMSE), mean absolute error (MAE), and mean error in the test data set (20%). RESULTS: The RMSE and MAE in the test data set were larger in the GBT approaches than in the previously developed regression-based approaches. The mean error in the test data set tended to be smaller in the GBT approaches than in the previously developed regression-based approaches. CONCLUSIONS: The predictive performances in the RMSE and MAE did not improve by the GBT approaches compared with regression approaches. The flexibility of the GBT approaches had the potential to reduce overprediction and underprediction in poor and good health, respectively. Further research is needed to establish the role of machine learning methods in mapping a nonpreference-based measure onto health utility.

The relationship between satisfaction with care and quality of life among family caregivers of of patients living with terminal cancer in general wards: a cross-sectional study.

BACKGROUND: Family caregivers of terminal cancer patients have reported experiencing low quality of life (QOL). Satisfaction with care has gained attention as a factor that correlates with QOL. AIM: To examine the relationship between 'satisfaction with care' and QOL of family caregivers of patients with terminal cancer. METHODS: The study used a cross-sectional design and included family caregivers of patients with terminal cancer in general wards. The authors assessed family caregivers' QOL using the caregiver quality of life index-cancer; a multivariable regression analysis was conducted to identify the factors associated with QOL. FINDINGS: A total of 51 family caregivers enrolled in the study. Their satisfaction with care and the months since their initial diagnosis were positively associated with a more positive QOL. CONCLUSION: Satisfaction with care is correlated with QOL among family caregivers of patients with terminal cancer in general wards. Enhancing family caregivers' satisfaction with care may contribute to improving their QOL.

Practical guidance to handle missing values in the 25-question Geriatric Locomotive Function Scale (GLFS-25): a simulation study.

OBJECTIVES: Despite the possible large number of missing values on the 25-question Geriatric Locomotive Function Scale (GLFS-25), how we should treat them is unknown. In a simulation study, we investigated how to handle missing values in the GLFS-25. DESIGN, SETTING AND PARTICIPANTS: We used three datasets with different participant characteristics: community dwellers who could walk by themselves, outpatients of orthopaedics owing to pain, and patients who required surgery for total knee replacement or lumbar spinal canal stenosis. OUTCOME MEASURES: The missing items of the datasets were artificially created, and four statistical methods, complete case analysis, multiple imputation, single imputation using individual mean, and single imputation using individual domain average, were compared in terms of bias and mean squared error. Simulation studies were conducted to compare them under varying numbers of participants with missing values (5%-40%) and under varying numbers of missing items of GLFS-25 (4-16). RESULTS: Multiple imputation had the lowest root mean squared error. Complete case analysis showed the largest bias, and the performances of the single imputation were between those methods. The relative performances were similar across the three datasets. The absolute bias of the single imputation was<0.1. The bias and mean squared error of multiple imputation and single imputation were comparable when the number of missing items was less than or equal to eight. CONCLUSIONS: Multiple imputation is preferable, although single imputation using subject average/subject domain average can be used with practically negligible bias as long as the number of missing items is up to 8 out of 25 items in each individual of the population.

Adjuvant trastuzumab without chemotherapy for treating early HER2-positive breast cancer in older patients: A propensity score-adjusted analysis of a prospective cohort study.

PURPOSE: To gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT). METHODS: Patients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed. RESULTS: We enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15-9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32-26.2, P < 0.0001). There were no significant intergroup differences in the proportions of patients showing HRQoL deterioration at 36 months (P = 0.717). CONCLUSION: Trastuzumab-treated patients had better prognoses than patients not treated with trastuzumab without deterioration of HRQoL. Trastuzumab monotherapy could be considered for older patients who reject chemotherapy.

Wearable, wireless, multi-sensor device for monitoring tissue circulation after free-tissue transplantation: a multicentre clinical trial.

Wearable sensors have seen remarkable recent technological developments, and their role in healthcare is expected to expand. Specifically, monitoring tissue circulation in patients who have undergone reconstructive surgery is critical because blood flow deficiencies must be rescued within hours or the transplant will fail due to thrombosis/haematoma within the artery or vein. We design a wearable, wireless, continuous, multipoint sensor to monitor tissue circulation. The system measures pulse waves, skin colour, and tissue temperature to reproduce physician assessment. Data are analysed in real time for patient risk using an algorithm. This multicentre clinical trial involved 73 patients who underwent transplant surgery and had their tissue circulation monitored until postoperative day 7. Herein, we show that the overall agreement rate between physician and sensor findings is 99.2%. In addition, the patient questionnaire results indicate that the device is easy to wear. The sensor demonstrates non-invasive, real-time, continuous, multi-point, wireless, and reliable monitoring for postoperative care. This wearable system can improve the success rate of reconstructive surgeries.

Statistical methods and graphical displays of quality of life with survival outcomes in oncology clinical trials for supporting the estimand framework.

BACKGROUND: Although there are discussions regarding standards of the analysis of patient-reported outcomes and quality of life (QOL) in oncology clinical trials, that of QOL with death events is not within their scope. For example, ignoring death can lead to bias in the QOL analysis for patients with moderate or high mortality rates in the palliative care setting. This is discussed in the estimand framework but is controversial. Information loss by summary measures under the estimand framework may make it challenging for clinicians to interpret the QOL analysis results. This study illustrated the use of graphical displays in the framework. They can be helpful for discussions between clinicians and statisticians and decision-making by stakeholders. METHODS: We reviewed the time-to-deterioration analysis, prioritized composite outcome approach, semi-competing risk analysis, survivor analysis, linear mixed model for repeated measures, and principal stratification approach. We summarized attributes of estimands and graphs in the statistical analysis and evaluated them in various hypothetical randomized controlled trials. RESULTS: Graphs for each analysis method provide different information and impressions. In the time-to-deterioration analysis, it was not easy to interpret the difference in the curves as an effect on QOL. The prioritized composite outcome approach provided new insights for QOL considering death by defining better conditions based on the distinction of OS and QOL. The semi-competing risk analysis provided different insights compared with the time-to-deterioration analysis and prioritized composite outcome approach. Due to the missing assumption, graphs by the linear mixed model for repeated measures should be carefully interpreted, even for descriptive purposes. The principal stratification approach provided pure comparison, but the interpretation was difficult because the target population was unknown. CONCLUSIONS: Graphical displays can capture different aspects of treatment effects that should be described in the estimand framework.

Effectiveness and safety of chemotherapy for patients with malignant gastrointestinal obstruction: A Japanese population-based cohort study.

BACKGROUND: The impacts of chemotherapy on patients with malignant gastrointestinal obstructions remain unclear, and multicenter evidence is lacking. AIM: To evaluate the effectiveness and safety of chemotherapy in patients with unresectable malignant gastrointestinal obstructions. METHODS: We conducted a multicenter retrospective cohort study that compared the chemotherapy group who received any chemotherapeutics after interventions, including palliative surgery or self-expandable metal stent placement, for unresectable malignant gastrointestinal obstruction vs the best supportive care (BSC) group between 2014 and 2019 in nine hospitals. The primary outcome was overall survival, and the secondary outcomes were patency duration and adverse events, including gastrointestinal perforation and gastrointestinal bleeding. RESULTS: In total, 470 patients in the chemotherapy group and 652 patients in the BSC group were analyzed. During the follow-up period of 54.1 mo, the median overall survival durations were 19.3 mo in the chemotherapy group and 5.4 mo in the BSC group (log-rank test, P < 0.01). The median patency durations were 9.7 mo [95% confidence interval (CI): 7.7-11.5 mo] in the chemotherapy group and 2.5 mo (95%CI: 2.0-2.9 mo) in the BSC group (log-rank test, P < 0.01). The perforation rate was 1.3% (6/470) in the chemotherapy group and 0.9% (6/652) in the BSC group (P = 0.567). The gastrointestinal bleeding rate was 1.5% (7/470) in the chemotherapy group and 0.5% (3/652) in the BSC group (P = 0.105). CONCLUSION: Chemotherapy after interventions for unresectable malignant gastrointestinal obstruction was associated with increased overall survival and patency duration.

Association of change in health-related quality of life and treatment discontinuation in metastatic breast cancer: a post hoc, exploratory analysis of two randomized clinical trials.

PURPOSE: Identifying factors associated with treatment alteration (treatment discontinuation and dose reduction) may help to attain the treatment goals for metastatic breast cancer. The value of changes in the quality of life (QOL) in predicting treatment alteration remained unclear. This study aimed to examine the relationship between changes in the QOL and treatment alteration of first-line chemotherapy for metastatic breast cancer. METHODS: We merged data from two randomized clinical trials in Japan, conducted from 2006 to 2017, that included patients who were diagnosed with human epidermal growth factor receptor 2-negative and endocrine treatment-resistant breast cancer, with metastatic disease at presentation or recurrence after surgery. The European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 was used to assess QOL. The association between change in time-dependent QOL (worsening by 10-point or not) and time to treatment alteration was assessed using the Cox regression models controlling for patient characteristics (age, liver metastasis, hormone status, and treatment regimen) and baseline QOL. RESULTS: Worsening physical functioning, global health status, and dyspnea were significantly associated with treatment discontinuation. Worsening role functioning, global health status, and fatigue were significantly associated with dose reduction. The threshold for defining worsening did not have a significant impact on the relationship. CONCLUSION: Changes in QOL are associated with the probability of treatment alteration among metastatic breast cancer patients. Physical functioning, role functioning, global health status, dyspnea, and fatigue should be prioritized for symptom management in patients with metastatic breast cancer.

The impact of the covalently closed circular DNA level on recurrence of hepatocellular carcinoma after initial hepatectomy: an analysis of patients with resolved hepatitis B virus infection.

BACKGROUND: We assessed whether or not covalently closed circular DNA (cccDNA) levels in the background liver influence the recurrence of hepatocellular carcinoma (HCC) in patients with resolved hepatitis B virus (HBV) infection. METHODS: Among 425 patients who underwent initial hepatectomy for HCC between 2010 and 2018, a retrospective review was performed in 44 with resolved HBV infection. The clinicopathologic characteristics were analyzed for correlation with tumor recurrence. The HBV cccDNA levels were tested via a droplet digital polymerase chain reaction assay. RESULTS: HBV cccDNA was detected in 27 of 44 patients (61%), and the median level was 1.0 copies/1000 ng (range, 0-931.3 copies/1000 ng). Anti-HBc ≥8.9 S/CO was associated with cccDNA detection (odds ratio, 11.08; 95% confidence interval [95% CI], 2.48-49.46; P = 0.002). Twenty-eight patients (64%) developed HCC recurrence after hepatectomy. The overall 3- and 5-year recurrence-free survival rates were 45.7% and 34.3%, respectively.19 HBV cccDNA levels was not significantly associated with HCC recurrence, while the presence of multiple tumors was an independent risk fact or (hazard ratio, 6.53; 95% CI, 2.48-17.19; P < 0.001. CONCLUSION: HBV cccDNA levels did not influence HCC recurrence after hepatectomy. Anti-HBc levels may be used as a surrogate marker for cccDNA.

Diagnostic value of a new cryoprobe for peripheral pulmonary lesions: a prospective study.

BACKGROUND: Cryobiopsy is an established technique that yields larger and higher-quality samples than does a forceps biopsy. However, it remains underutilised in the diagnosis of peripheral pulmonary lesions (PPLs), mainly because of difficulties in handling conventional cryoprobes. A recently introduced single-use cryoprobe with a smaller diameter and more flexibility than conventional ones may improve its diagnostic ability for PPLs. We conducted this prospective study to evaluate the feasibility of transbronchial cryobiopsy in the diagnoses of PPLs, using a new 1.7-mm cryoprobe. METHODS: The study included patients with PPLs less than 30 mm in diameter scheduled to undergo bronchoscopy. All the procedures were performed using a combination of virtual bronchoscopic navigation, radial endobronchial ultrasound (R-EBUS) and X-ray fluoroscopy, and all the samples were collected using the cryoprobe alone. Thereafter, we assessed the diagnostic outcomes and safety profiles. RESULTS: A total of 50 patients were enrolled and underwent cryobiopsy. The median lesion size was 20.8 mm (range, 8.2-29.6 mm), and the negative bronchus sign was seen in 34% of lesions. The diagnostic yield was 94% (95% confidence interval, 83.5-98.8%). A positive bronchus sign had a significantly higher diagnostic yield than did a negative bronchus sign (100% vs. 82.4%; P = 0.035). The yield was achieved regardless of other variables, including lesion size, location, and R-EBUS findings. The major complications were mild and moderate bleeding in 28% and 62% of patients, respectively. Pneumothorax was identified in one patient. CONCLUSION: Transbronchial cryobiopsy using the new 1.7-mm cryoprobe is a feasible procedure that has the potential to increase the diagnostic accuracy for PPLs. TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCT1032200065. Registered July 8 2020, https://jrct.niph.go.jp/en-latest-detail/jRCT1032200065.

Intercountry and intracountry variations in opinions of palliative care specialist physicians in Germany, Italy, Japan and UK about continuous use of sedatives: an international cross-sectional survey.

OBJECTIVES: To explore intercountry and intracountry differences in physician opinions about continuous use of sedatives (CUS), and factors associated with their approval of CUS. SETTINGS: Secondary analysis of a questionnaire study. PARTICIPANTS: Palliative care physicians in Germany (N=273), Italy (N=198), Japan (N=334) and the UK (N=111). PRIMARY AND SECONDARY OUTCOME MEASURES: Physician approval for CUS in four situations, intention and treatment goal, how to use sedatives and beliefs about CUS. RESULTS: There were no significant intercountry or intracountry differences in the degree of agreement with statements that (1) CUS is not necessary as suffering can always be relieved with other measures (mostly disagree); (2) intention of CUS is to alleviate suffering and (3) shortening the dying process is not intended. However, there were significant intercountry differences in agreement with statements that (1) CUS is acceptable for patients with longer survival or psychoexistential suffering; (2) decrease in consciousness is intended and (3) choice of neuroleptics or opioids. Acceptability of CUS for patients with longer survival or psychoexistential suffering and whether decrease in consciousness is intended also showed wide intracountry differences. Also, the proportion of physicians who agreed versus disagreed with the statement that CUS may not alleviate suffering adequately even in unresponsive patients, was approximately equal. Regression analyses revealed that both physician-related and country-related factors were independently associated with physicians' approval of CUS. CONCLUSION: Variations in use of sedatives is due to both physician- and country-related factors, but palliative care physicians consistently agree on the value of sedatives to aid symptom control. Future research should focus on (1) whether sedatives should be used in patients with longer survival or with primarily psychoexistential suffering, (2) understanding physicians' intentions and treatment goals, (3) efficacy of different drugs and (4) understanding the actual experiences of patients receiving CUS.

Thoracic mediastinal-occupying ratio predicts recovery and prognosis after lung transplantation.

OBJECTIVES: Even after transplantation of favourable donor lungs, some recipients require prolonged weaning from mechanical ventilation, indicating a poor prognosis. We investigated the effects of prolonged mechanical ventilation (PMV) for >14 days on the recovery and survival of patients who underwent cadaveric lung transplantation in relation to their physical traits. METHODS: We retrospectively reviewed patients who underwent cadaveric lung transplantation (age ≥15 years) at a single centre between April 2015 and December 2020 and classified them into PMV and non-PMV groups (>14 and ≤14 days of mechanical ventilation postoperatively, respectively). The factors predicting PMV comprised clinical factors (e.g. marginal donor) and physical features, namely flat chest, narrow fourth intercostal space (length, <5 mm), mediastinal shift, thoracic mediastinal-occupying ratio (TMOR) >40% and sarcopenia, according to the logistic regression analysis. The log-rank test was used to examine the association between TMOR >40% and 3-year prognosis. RESULTS: The PMV group comprised 17 (33%) of 51 recipients. Multivariable logistic analysis showed that the TMOR >40% (odds ratio, 7.3; 95% confidence interval, 1.3-40.1; P = 0.023) was an independent preoperative predictive factor for PMV postoperatively. Stepwise analysis revealed intraoperative extracorporeal membrane oxygenation and reoperation as postoperative predictive factors in addition to TMOR >40%. Recipients with TMOR >40% had significantly worse 3-year survival than other recipients (71.2% vs 100.0%, respectively; P = 0.008). CONCLUSIONS: Recipients with a TMOR >40% may be long-term ventilator dependent and have a poor prognosis.

Cost-Effectiveness of Trastuzumab With or Without Chemotherapy as Adjuvant Therapy in HER2-Positive Elderly Breast Cancer Patients: A Randomized, Open-Label Clinical Trial, the RESPECT Trial.

BACKGROUND AND OBJECTIVE: Trastuzumab is a standard care as adjuvant chemotherapy (AdjCT) for patients with human epidermal growth factor receptor 2 (HER2)-positive primary breast cancer (BC) in Japan. However, no reports have evaluated its economics for patients with HER2-positive BC over 70 years of age. The objective of this study was to evaluate the cost-effectiveness of HER2-targeted trastuzumab + chemotherapy in Japan, comparing it with trastuzumab monotherapy. METHODS: A three-state-partitioned survival model was developed to evaluate the cost-effectiveness of trastuzumab + chemotherapy versus trastuzumab monotherapy for AdjCT in elderly patients with HER2-positive BC. We derived the efficacy data, utilities, and costs of both arms from individual patient data in the RESPECT trial (NCT01104935) and published studies. The costs and quality-adjusted life years (QALYs) were discounted at 2% per annum using a payer perspective. The respective cost estimates were reported in 2019 Japanese Yen (JPY) or US dollars (US$). The primary outcome was the incremental cost-effectiveness ratio (ICER). We assured robustness with deterministic and probabilistic sensitivity analyses. RESULTS: The cost per patient for trastuzumab + chemotherapy was JPY 14.6 million (US$137,000), and their QALYs were 9.308, compared with JPY 14.2 million (US$131,000) and 9.101, respectively, for trastuzumab monotherapy. The ICER of trastuzumab + chemotherapy versus trastuzumab monotherapy was JPY 2.7 milllion/QALY (US$17,200/QALY). The ICER for trastuzumab with chemotherapy varied from "Dominant" to "Dominated" in one-way sensitivity analysis. CONCLUSIONS: The base-case analysis suggests that AdjCT with trastuzumab + chemotherapy is likely to be a cost-effective choice for patients with HER2-positive BC aged 70 years or older. However, the sensitivity analysis suggested uncertainty regarding the cost-effectiveness of trastuzumab + chemotherapy.

Chemoprevention for Colorectal Cancers: Are Chemopreventive Effects Different Between Left and Right Sided Colorectal Cancers?

BACKGROUND AND AIMS: Recent studies have suggested that right- and left-sided colorectal cancers (CRCs) are molecularly distinct. In this study, we examined the association between the risk of right- and left-sided CRC and drug use to estimate their chemopreventive effects METHODS: This multicenter retrospective cohort study was conducted using the data of hospitalized patients between 2014 and 2019 from nine hospital databases. The primary outcomes were right- and left-sided CRC. We evaluated the association of CRCs with drug use and clinical factors. Odds ratios adjusted for age, sex, Charlson Comorbidity Index scores, and smoking status were calculated. We also compared the transcriptional profiling in precancerous lesions, including sessile serrated lesions (SSLs) RESULTS: A total of 307,938 patients, including 2745 with right-sided CRC and 4819 with left-sided CRC, were analyzed. The use of nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, cyclooxygenase-2 inhibitors, and steroids was associated with a lower risk of both right- and left-sided CRCs. In contrast, statins, other lipid-lowering agents, and metformin were associated with a lower risk of left-sided CRC. Transcriptomic analysis showed that SSL, which predominantly develops in the right colon, was associated with a lower expression of lipid metabolism-related genes. CONCLUSIONS: Targeting lipid metabolism may be useful for chemoprevention of left-sided CRCs, while development of right-sided CRCs may be independent of this pathway.