Significance of definitive concurrent chemoradiotherapy for vulvar cancer: a Japanese Gynecologic Oncology Group nationwide survey study.

OBJECTIVE: This study aimed to show the results of radical radiation therapy (RT) and concurrent chemoradiotherapy (CCRT) for vulvar cancer (VC) based on data from a Japanese nationwide survey. MATERIALS AND METHODS: We collected data from 108 institutions on cases of VC diagnosed between January 2001 and December 2010. Patients with histologically proven squamous cell carcinoma and adenocarcinoma with curative intent were selected, and 172 patients with VC were included in this study. The collected data were analyzed for overall survival (OS) using the Kaplan-Meier method. Univariate and multivariate analyses were performed to examine the prognostic factors for patients with VC. RESULTS: The median follow-up period was 16.8 (range; 3.2-154.8) months. Fifty-five patients received CCRT, and 117 patients received RT alone. The 2-year OS rates (95% confidence interval [CI]) for stages I, II, III, and IV were 77.9% (55.8-100.0), 71.9% (53.8-89.9), 55.4% (42.5-68.3), and 41.5% (27.3-55.7) respectively. Univariate analyses showed that the FIGO stage (p = 0.001), tumor diameter (p = 0.005), and lymph node (LN) status (p = 0.001) were associated with OS. The concurrent use of chemotherapy resulted in a significantly longer OS in Stage III (p = 0.013). Multivariate analysis showed that the hazard ratios (95% CI) for tumor diameter, positivity for LN metastasis, and RT alone (no concurrent chemotherapy) were 1.502 (1.116-2.021), 1.801 (1.287-2.521), and 1.936 (1.187-3.159), respectively. CONCLUSIONS: Our analysis revealed that CCRT should be recommended, especially for Stage III VC patients. Further studies are warranted to determine who benefits from CCRT, considering primary tumor size and LN status. The study was registered at the University Hospital Medical Information Network (protocol number: UMIN000017080) on April 8th, 2015.

Clinical and Diagnostic Utility of Genomic Profiling for Digestive Cancers: Real-World Evidence from Japan.

The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne® CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively. APC, KRAS, and CDKN2A alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.

Impact of lymph node dissection on the efficacy of immune checkpoint inhibitors in patients with postoperative recurrence of non-small cell lung cancer.

Background: The effect of lymph node dissection (LND) on the efficacy of immune checkpoint inhibitor (ICI) remains unclear. The purpose of this study was to examine the difference in the effect of ICI between patients with non-small cell lung cancer (NSCLC) according to the extent of LND performed in surgery prior to postoperative recurrence. Methods: A total of 134 patients with postoperative recurrence (surgery group, n=26) or unresectable advanced lung cancer (non-surgery group, n=108) who were treated with ICIs between January 2016 and December 2022 were included for analysis. In the surgery group, 16 patients underwent systematic LND, whereas the remaining 10 patients underwent selective LND. Progression-free survival with ICI treatment (ICI-PFS) and overall survival (OS) were compared between the surgery and non-surgery groups and between the systematic and selective LND groups using the inverse probability of treatment weighting (IPTW) method to adjust for patient background characteristics. Results: In the IPTW-adjusted analysis, the 2-year PFS rate with ICI treatment was 31.2% in the surgery group and 27.3% in the non-surgery group (P=0.19); the corresponding 2-year OS rates were 69.6% and 62.2%, respectively (P=0.10). In the surgery group, the 2-year PFS rates under ICI were 20.0% in the systematic LND group and 45.7% in the selective LND group (P=0.03). Conclusions: IPTW-adjusted analysis indicated no difference in prognosis between patients with postoperative recurrence and those with advanced unresectable lung cancer. However, in patients with postoperative recurrence, the extent of LND was a significant predictor of ICI-PFS. These findings suggest that systematic LND may reduce the efficacy of ICI, indicating that preoperative ICI administration may be warranted.

Development and validation of a recurrent prediction model for patients with unilateral chronic subdural hematoma without hematoma volumetric analysis.

OBJECTIVE: Approximately 10 % of patients with chronic subdural hematoma (CSDH) undergo reoperation after initial surgery. This study aimed to develop a predictive model for the recurrence of unilateral CSDH at initial surgery without hematoma volumetric analysis. METHODS: This single-center retrospective cohort study evaluated pre- and postoperative computed tomography (CT) images of patients with unilateral CSDH. The pre- and postoperative midline shift (MLS), residual hematoma thickness, and subdural cavity thickness (SCT) were measured. CT images were classified based on the internal architecture of the hematoma (homogenous, laminar, trabecular, separated, and gradation subtypes). RESULTS: Total 231 patients with unilateral CSDH underwent burr hole craniostomy. After receiver operating characteristic analysis, preoperative MLS and postoperative SCT showed better areas under the curve (AUCs) (0.684 and 0.756, respectively). According to the CT classification of preoperative hematomas, the recurrence rate was significantly higher in the separated/gradation group (18/97, 18.6 %) than in the homogenous/laminar/trabecular group (10/134, 7.5 %). Four-point score was derived from the multivariate model using the preoperative MLS, postoperative SCT, and CT classification. The AUC of this model was 0.796, and the recurrence rates at 0-4 points were 1.7 %, 3.2 %, 13.3 %, 25.0 %, and 35.7 %, respectively. CONCLUSION: Pre- and postoperative CT findings without hematoma volumetric analysis may predict CSDH recurrence.

Multimorbidity patterns and the relation to self-rated health among older Japanese people: a nationwide cross-sectional study.

OBJECTIVES: Classifying individuals into multimorbidity patterns can be useful to identify the target population with poorer clinical outcomes. Self-rated health (SRH) is one of the core outcomes in multimorbidity patients. Although studies have reported that multimorbidity is associated with poor SRH, whether certain patterns have stronger associations remains unknown. Therefore, this study aimed to identify the prevalence and patterns of multimorbidity and investigate the association between multimorbidity patterns and SRH in an older Japanese population. DESIGN: Cross-sectional study. SETTING: Data were obtained from the 2013 Comprehensive Survey of Living Conditions, a nationally representative survey of the general Japanese population. PARTICIPANTS: This study mainly examined 23 730 participants aged ≥65 years who were not hospitalised or institutionalised. PRIMARY OUTCOME MEASURE: Poor SRH was defined as choosing 'not very good' or 'bad' from five options: 'excellent', 'fairly good', 'average', 'not very good' and 'bad'. RESULTS: The prevalence of multimorbidity was 40.9% and that of poor SRH was 23.8%. Three multimorbidity patterns were identified by exploratory factor analysis: (1) degenerative/mental health, (3) malignant/digestive/urological/haematological and (3) cardiovascular/metabolic. Multivariable modified Poisson regression analysis revealed that high malignant/digestive/urological/haematological, degenerative/mental health and cardiovascular/metabolic pattern scores, corresponding to the number of affected body systems in each pattern, were significantly associated with poor SRH (adjusted risk ratio (aRR)=1.68, 95% CI: 1.60 to 1.76; aRR=1.63, 95% CI: 1.58 to 1.69; and aRR=1.31, 95% CI: 1.26 to 1.36, respectively). When including the Kessler 6 score, a screening scale for psychological distress, in the analysis, the association between each multimorbidity pattern score and poor SRH decreased. CONCLUSIONS: Malignant/digestive/urological/haematological and degenerative/mental health patterns may be associated with a high risk for poor SRH. Further research should focus on interventions to improve SRH in multimorbidity patients.

Associations of primary care structures with polypharmacy and patient-reported indicators in patients with complex multimorbidity: a multicentre cross-sectional study in Japan.

OBJECTIVES: Evidence supporting the effects of primary care structures on the quality of care for patients with complex multimorbidity, which is one of the most important challenges facing primary care, is scarce internationally. This study aimed to examine the associations of the types of primary care facilities with polypharmacy and patient-reported indicators in patients with complex multimorbidity, with a focus on differences between community clinics and hospitals. DESIGN: Multicentre cross-sectional study. SETTING: A total of 25 primary care facilities (19 community clinics and 6 small- and medium-sized hospitals). PARTICIPANTS: Adult outpatients with complex multimorbidity, which was defined as the co-occurrence of three or more chronic conditions affecting three or more different body systems within one person. PRIMARY OUTCOME MEASURE: Polypharmacy, the Patient-Reported Experience Measure using the Japanese version of Primary Care Assessment Tool Short Form (JPCAT-SF) and the Patient-Reported Outcome Measure using self-rated health status (SRH). RESULTS: Data were analysed for 492 patients with complex multimorbidity. After adjustment for possible confounders and clustering within facilities, clinic-based primary care practices were significantly associated with a lower prevalence of polypharmacy, higher JPCAT-SF scores in coordination and community orientation, and a lower prevalence of poor or fair SRH compared with hospital-based primary care practices. In contrast, the JPCAT-SF score in first contact was significantly lower in clinic-based practices. The associations between the types of primary care facilities and JPCAT-SF scores in longitudinality and comprehensiveness were not statistically significant. CONCLUSIONS: Clinic-based primary care practices were associated with a lower prevalence of polypharmacy, better patient experience of coordination and community orientation, and better SRH in patients with complex multimorbidity compared with hospital-based primary care practices. In the primary care setting, small and tight teams may improve the quality of care for patients with complex multimorbidity.

Effect of multimorbidity patterns on the decline in health-related quality of life: a nationwide prospective cohort study in Japan.

OBJECTIVES: Longitudinal studies, which consider multimorbidity patterns, are useful for better clarifying the effect of multimorbidity on health-related quality of life (HRQoL) and for identifying the target population with poorer clinical outcomes among patients with multimorbidity. This study aimed to examine the effects of different multimorbidity patterns on the decline in HRQoL. DESIGN: Nationwide prospective cohort study. SETTING: Japanese adult residents. PARTICIPANTS: Residents aged ≥50 years selected by the quota sampling method. PRIMARY OUTCOME MEASURE: Clinically relevant decline in HRQoL was defined as a 0.50 SD (5-point) decrease in the 36-Item Short Form Health Survey (SF-36) component summary scores for 1 year. RESULTS: In total, 1211 participants completed the follow-up survey. Among the multimorbidity patterns identified using confirmatory factor analysis, multivariable logistic regression analyses revealed that high cardiovascular/renal/metabolic and malignant/digestive/urologic pattern scores were significantly associated with the clinically relevant decline in SF-36 physical component summary score (adjusted OR (aOR)=1.25, 95% CI: 1.08 to 1.44 and aOR=1.28, 95% CI: 1.04 to 1.58, respectively). High cardiovascular/renal/metabolic pattern score was also significantly associated with the clinically relevant decline in SF-36 role/social component summary score (aOR=1.23, 95% CI: 1.06 to 1.42). CONCLUSIONS: Our study revealed that multimorbidity patterns have different effects on the clinically relevant decline in HRQoL for 1 year. These findings can be useful in identifying populations at high risk and with poor clinical outcomes among patients with chronic diseases and multimorbidity for efficient resource allocation.

Effect of Second-generation vs Third-generation Chemotherapy Regimens With Thoracic Radiotherapy on Unresectable Stage III Non-Small-Cell Lung Cancer: 10-Year Follow-up of a WJTOG0105 Phase 3 Randomized Clinical Trial.

IMPORTANCE: Insufficient data are available regarding the long-term outcomes and cumulative incidences of toxic effects that are associated with chemoradiotherapy (CRT) for patients with stage III non-small-cell lung cancer. OBJECTIVE: To evaluate survival and late toxic effects 10 years after patients were treated with curative CRT. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, phase 3 West Japan Thoracic Oncology Group (WJTOG) 0105 randomized clinical trial was conducted between September 2001 and September 2005 in Japan. Patients with histologically or cytologically confirmed non-small-cell lung cancer with unresectable stage III disease were assessed for eligibility. Additional data were analyzed from January 2018 to December 2019. INTERVENTIONS: A total of 440 eligible patients were randomly assigned to groups as follows: A (control), 4 cycles of mitomycin/vindesine/cisplatin plus thoracic radiotherapy (TRT) of 60 Gy; B, weekly irinotecan/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of irinotecan/carboplatin consolidation; or C, weekly paclitaxel/carboplatin for 6 weeks plus TRT of 60 Gy followed by 2 courses of paclitaxel/carboplatin consolidation. MAIN OUTCOMES AND MEASURES: The primary outcome was 10-year survival probability after CRT. The secondary outcome was late toxic effects that occurred more than 90 days after initiating CRT. RESULTS: From September 2001 to September 2005, 440 patients (group A, n = 146 [33.2%; median (range) age, 63 (31-74) years; 18 women (12.3%)]; group B, n = 147 [33.4%; median (range) age, 63 (30-75) years; 22 women (15.0%)]; group C, n = 147 [33.4%; median (range) age, 63 (38-74) years; 19 women (12.9%)]) were enrolled. The median (range) follow-up was 11.9 (7.6-13.3) years. In groups A, B, and C, median (range) overall survival times were 20.5 (17.5-26.0), 19.8 (16.7-23.5), and 22.0 (18.7-26.2) months, respectively, and 10-year survival probabilities were 13.6%, 7.5%, and 15.2%, respectively. There were no significant differences in overall survival among treatment groups. The 10-year progression-free survival probabilities were 8.5%, 6.5%, and 11.1% in groups A, B, and C, respectively. Grade 3 or 4 late toxic effect rates were 3.4% (heart, 0.7%; lung, 2.7%) in group A, and those only affecting the lung represented 3.4% and 4.1% in groups B and C, respectively. No other cases of late toxic effects (grades 3/4) were observed since the initial report. CONCLUSION AND RELEVANCE: In this 10-year follow-up of a phase 3 randomized clinical trial, group C achieved similar efficacy and toxic effect profiles as group A 10 years after initiating treatment. These results serve as a historical control for the long-term comparisons of outcomes of future clinical trials of CRT. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000030811.

Sequential therapy of crizotinib followed by alectinib for non-small cell lung cancer harbouring anaplastic lymphoma kinase rearrangement (WJOG9516L): A multicenter retrospective cohort study.

BACKGROUND: The data of sequential therapy of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) in clinical practice have been limited. METHODS: We reviewed the clinical data of patients with ALK-rearranged non-small cell lung cancer who received crizotinib (CRZ) or alectinib (ALEC) between May 2012 and December 2016. Patients were divided into two groups based on the first-administered ALK-TKI, the CRZ or ALEC group. The combined time-to-treatment failure (TTF) was defined as the sum of the 'TTF of CRZ' plus the 'TTF of ALEC' if patients were treated with CRZ followed by ALEC in the CRZ group. The primary end-point is the comparison between the combined TTF and the TTF of ALEC in the ALEC group. RESULTS: Of 864 patients enrolled from 61 institutions, 840 patients were analysed. There were 535 of 305 patients in the CRZ/ALEC groups. The combined TTF in the CRZ group was significantly longer than TTF in the ALEC group (median, 34.4 versus 27.2 months; hazard ratio [HR], 0.709; P = 0.0044). However, there was no significant difference in overall survival (OS) between the patients who received ALEC after CRZ in the CRZ group and the patients in the ALEC group (median, 88.4 months versus. not reached; HR, 1.048; P = 0.7770). In the whole population, the CRZ group had a significantly shorter OS than the ALEC group (median, 53.6 months versus not reached; HR, 1.821, P < 0.0001). CONCLUSION: The combined TTF in the CRZ group was significantly longer than the TTF in the ALEC group; however, OS benefit of sequential therapy against ALEC as the first ALK-TKI was not shown.

Transudative Pleural Effusion Associated with Extramedullary Hematopoiesis.

The authors report a case of transudative pleural effusion associated with extramedullary hematopoiesis due to the presence of a myeloproliferative neoplasm, which was unclassified. A 71-year-old man presented with right pleural effusion during an exacerbation of thrombocytosis. The pleural effusion was transudative, although there was no history of cardiac failure or hypoalbuminemia, and treatment with diuretics failed. Extramedullary hematopoiesis was diagnosed in bilateral paravertebral soft tissue and the liver on 111In bone marrow scintigraphy. The administration of hydroxyurea simultaneously reduced peripheral blood platelet count and pleural effusion within 2 weeks. The possible cause of transudative pleural effusion in association with extramedullary hematopoiesis is discussed.

Translation, Inter-rater Reliability, Agreement, and Internal Consistency of the Japanese Version of the Cumulated Ambulation Score in Patients after Hip Fracture Surgery.

OBJECTIVES: The aim of this study was to translate the Cumulated Ambulation Score (CAS) from English into Japanese in cooperation with different types of healthcare providers and to investigate its inter-rater reliability and internal consistency. METHODS: Two physical therapists at each of three general hospitals in Japan measured the mobility of 50 consecutive post-operative hip fracture patients on two occasions between 2 and 6 days after surgery using the Japanese version of the CAS (CAS-JP). We analyzed the inter-rater reliability and agreement using both the linear weighted kappa and the interclass correlation coefficient; we also analyzed the internal consistency using Cronbach's alpha coefficient. RESULTS: The mean age of patients was 81 (SD: 11.6) years and 82% were women. Approximately half of the patients had severe cognitive impairment. Kappa was ≥ 0.93 for the three mobility activities and for the total CAS-JP score, the percentage agreement was ≥ 0.98, the ICC was ≥ 0.95, and Cronbach's alpha coefficient was 0.85. CONCLUSIONS: We found that the CAS-JP possessed good inter-rater reliability, agreement, and internal consistency. The CAS-JP is a reliable and easy-to-use evaluation tool suitable for daily clinical practice across different healthcare providers to monitor mobility in older hip fracture patients in Japan. We suggest that CAS-JP be evaluated in future studies for use in younger patients and in other patient groups with mobility problems.

Successful Treatment of a Patient with Lung Adenocarcinoma Harboring Compound EGFR Gene Mutations, G719X and S768I, with Afatinib.

Mutations in the gene encoding epidermal growth factor receptor (EGFR) are the most frequent driver mutations in lung adenocarcinoma in Japan. Exon 19 deletion and L858R mutation in exon 21 are the most common EGFR mutations. Uncommon mutations, such as G719X, S768I, and L861Q, and compound mutations, combinations of 2 common or uncommon mutations, have also been reported. EGFR tyrosine kinase inhibitors (TKIs) are effective against cancers harboring common mutations; however, their efficacy against cancers with uncommon or compound mutations remains unclear. We report the case of a 67-year-old man with lung adenocarcinoma (clinical stage IIIA [cT1N2M0]), harboring an uncommon compound mutation, G719X and S768I. The cancer progressed within 2 months of initial chemoradiotherapy. Treatment with afatinib (40 mg/day) produced a partial response, which was maintained for 17 months with continued treatment. A literature review revealed that lung cancer with G719X/S768I compound mutation exhibited good response to EGFR-TKIs, even better than that of lung cancers with single uncommon mutations.

Multimorbidity and patient-reported diagnostic errors in the primary care setting: multicentre cross-sectional study in Japan.

OBJECTIVES: There is lack of evidence for the association between multimorbidity and diagnostic errors. Information on diagnostic errors from patients' perspectives is crucial to improve the diagnostic process. In this study, we aimed to investigate patient-reported diagnostic errors and to examine the relationship between multimorbidity and patient-reported diagnostic errors in the primary care setting. DESIGN: Multicentre cross-sectional study. SETTING: A primary care practice-based research network in Japan (25 primary care facilities). PARTICIPANTS: Adult outpatients filled out a standardised questionnaire. PRIMARY OUTCOME MEASURE: Patient-reported diagnostic errors. RESULTS: Data collected from 1474 primary care outpatients were analysed. The number of participants who reported diagnostic errors was 57 (3.9%). Most of the missed diagnoses were common conditions in primary care, such as cancer, dermatitis and hypertension. After adjustment for possible confounders and clustering within facilities, multimorbidity was positively associated with patient-reported diagnostic errors (adjusted OR=1.83, 95% CI 1.01 to 3.31). The results of the sensitivity analysis were consistent with those of the primary analysis. CONCLUSIONS: The present study showed a lower proportion of patients reporting experiences of diagnostic errors in primary care than those reported in previous studies in other countries. However, patients with multimorbidity are more likely to report diagnostic errors in primary care; thus, further research is necessary to improve the diagnostic process for patients with multimorbidity.

Associations of types of primary care facilities with adult vaccination and cancer screening in Japan.

OBJECTIVE: To examine the association between primary care facility types and the quality of preventive care, especially adult vaccination and cancer screening, with a focus on the differences between community clinics and hospitals. DESIGN: Multicenter cross-sectional study. SETTING: A primary care practice-based research network in Japan (25 primary care facilities). PARTICIPANTS: Adult outpatients for whom the participating facility serves as their usual source of care. INTERVENTION: None. MAIN OUTCOME MEASURES: Influenza and pneumococcal vaccination delivery and performance of colorectal, breast and cervical cancer screening. RESULTS: Data collected from 1725 primary care outpatients were analyzed. After adjustment of possible confounders and clustering within facilities, hospital-based practices were significantly associated with poorer uptake of influenza [adjusted odds ratio (aOR) = 0.64, 95% confidence interval (CI) 0.42-0.96] and pneumococcal vaccines (aOR = 0.55, 95% CI 0.40-0.75) and colorectal cancer screening (aOR = 0.59, 95% CI 0.39-0.88) compared with clinic-based practices. In contrast, the associations of types of primary care facilities with uptake of breast and cervical cancer screening were not statistically significant. CONCLUSIONS: Differences in the performance of adult vaccination and cancer screening raised concerns about the provision of preventive care at hospital-based compared with clinic-based primary care practices. Efforts to improve preventive care at hospital-based primary care practices should help to promote equalization of the quality of primary care. Further study is needed on the comparisons of other quality indicators among different structures of primary care facilities.

Physical multimorbidity patterns and depressive symptoms: a nationwide cross-sectional study in Japan.

Objective: The associations of physical multimorbidity with depressive symptoms have been investigated in a number of studies. However, whether patterns of chronic physical conditions have comparatively different associations with depressive symptoms remains unclear. This study aimed to investigate the associations of physical multimorbidity patterns with depressive symptoms. Design: This study was designed as a nationwide cross-sectional survey in Japan. Setting: General sample of the Japanese population. Participants: Adult Japanese residents were selected by a quota sampling method. Data were analysed from 1788 residents who reported one or more chronic health conditions. Results: Among four physical multimorbidity patterns: cardiovascular-renal-metabolic (CRM), skeletal-articular-digestive (SAD), respiratory-dermal (RDE) and malignant-digestive-urologic (MDU), multivariable logistic regression analyses revealed that the RDE pattern showed the strongest association with depressive symptoms (aOR=1.68, 95% CI: 1.21 to 2.31 for the pattern score highest quartile, compared with the lowest quartile), followed by SAD and MDU patterns (aOR=1.41, 95% CI: 1.01 to 1.98 for the SAD pattern score highest quartile; 1.41, 95% CI: 1.01 to 1.96 for the MDU pattern score highest quartile, compared with the lowest quartile). In contrast, the CRM pattern score was not significantly associated with depressive symptoms (aOR=1.31, 95% CI: 0.90 to 1.89 for the pattern score highest quartile, compared with the lowest quartile). Conclusions: Physical multimorbidity patterns have different associations with depressive symptoms. Among these patterns, patients with the RDE pattern may be at a higher risk for developing depressive symptoms. This study reinforces the evidence that cluster pattern of chronic health conditions is a useful measure for clinical management of multimorbidity as it is differently associated with mental health status, which is one of the crucial outcomes for multimorbid patients.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Factors associated with patient preferences towards deprescribing: a survey of adult patients on prescribed medications.

Background Deprescribing is a patient-centered intervention with inherent uncertainties and requires shared decision making and patient involvement. Objective In the present study, we aimed to investigate factors associated with patient preferences toward deprescribing in a representative sample in Japan. Methods We conducted a nationwide cross-sectional survey and used a quota sampling method to select representative samples of the Japanese general population. We collected data on participant demographic and clinical factors including the number of chronic health conditions and the number of regular prescription medications. Patients' willingness to deprescribe was assessed using the patients' attitudes towards deprescribing questionnaire. Multivariable logistic regression analyses were conducted to determine factors associated with the outcome measure. Results Data were analyzed for 1483 adult outpatients. The proportion of patients having willingness to deprescribe was 67.8%. After adjustment for age and gender, multimorbidity was significantly positively associated with patients' willingness to deprescribe [adjusted odds ratio (aOR) 1.35; 95% confidence interval (CI) 1.06-1.72]. A similar association was found with polypharmacy (aOR 1.43; 95% CI 1.08-1.88). The number of visits to medical institutions and increasing age were also found to be associated with patients' willingness to deprescribe. Conclusion Our study indicated that patient preferences towards deprescribing are consistent with the established clinical evidence regarding the efficacy of deprescribing for patients with multimorbidity and polypharmacy. These findings may be beneficial for health care providers to implement shared decision making regarding deprescribing effectively.

Effect of hip fracture surgery within 24 hours on short-term mobility.

BACKGROUND: Hip fracture constitutes a high-mortality injury in elderly patients. In addition, caregiver burden is also a relevant issue, as patients after hip fracture surgery lose ambulation and require support in the perioperative period and after discharge. Early surgery is recommended to improve mortality. However the positive effect of early surgery on the short-term postoperative ambulatory function is unknown. The objective of this study was to determine whether a shorter waiting time for hip fracture surgery improves short-term postoperative mobility in elderly patients. We used the cumulated ambulation score (CAS), a feasible function scoring system using low-demand activities, to measure short-term postoperative mobility. METHODS: In this retrospective, observational study of 175 hip fracture patients at a single hospital, the patients were divided based on the waiting period for surgery (within 24 hours of arrival, early group; after 24 hours of arrival, delayed group). The primary outcome was postoperative mobility, assessed using the CAS. Multivariable linear regression analysis with adjustment for covariates, age, sex, mobility before injury, comorbidity, presence of dementia and type of fracture. As a subgroup analysis, cognitive function and the interaction between the surgical waiting time and the presence of dementia were considered. RESULTS: The early group had a significantly better CAS (adjusted beta = 1.36; 95% confidence interval [95% CI]: 0.24-2.48, p = 0.02) than the delayed group. Significant CAS improvement was observed among cognitively intact patients (adjusted beta = 2.66; 95% CI: 0.62-4.69, p = 0.01), but not among those with dementia (adjusted beta = 0.43; 95% CI: -0.93 to 1.79, p = 0.53). However, the interaction between the surgical waiting time and the presence of dementia in the entire population did not reach statistical significance (p for interaction = 0.15). CONCLUSIONS: Hip fracture surgery within 24 hours could improve the recovery of postoperative ambulatory function faster. The postoperative caregiver burden would be reduced by early surgery.

Proportion and clinical characteristics of non-asthmatic non-smokers among adults with airflow obstruction.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) mainly develops after long-term exposure to cigarette or biomass fuel smoke, but also occurs in non-smokers with or without a history of asthma. We investigated the proportion and clinical characteristics of non-smokers among middle-aged to elderly subjects with airflow obstruction. METHODS: We retrospectively analyzed 1,892 subjects aged 40-89 years who underwent routine preoperative spirometry at a tertiary university hospital in Japan. Airflow obstruction was defined as a forced expiratory volume in 1 second (FEV1)/forced vital capacity < 0.7 or as the lower limit of the normal. RESULTS: Among 323 patients presenting with FEV1/forced vital capacity < 0.7, 43 had asthma and 280 did not. Among the non-asthmatic patients with airflow obstruction, 94 (34%) were non-smokers. A larger number of women than men with airflow obstruction had asthma (26% vs. 7.6%, p < 0.001), or were non-smokers among non-asthmatics (72% vs. 20%, p < 0.001). Non-asthmatic non-smokers, rather than non-asthmatic smokers, asthmatic non-smokers, and asthmatic smokers, exhibited better pulmonary function (median FEV1: 79% of predicted FEV1 vs. 73%, 69%, and 66%, respectively, p = 0.005) and less dyspnea on exertion (1% vs. 12%, 12%, and 28%, respectively, p = 0.001). Pulmonary emphysema on thoracic computed tomography was less common in non-smokers (p < 0.001). Using the lower limit of the normal to define airflow obstruction yielded similar results. CONCLUSIONS: There are a substantial number of non-smokers with airflow obstruction compatible with COPD in Japan. In this study, airflow obstruction in non-smokers was more common in women and likelier to result in mild functional and pathological abnormalities than in smokers. Further studies are warranted to investigate the long-term prognosis and appropriate management of this population in developed countries, especially in women.

Multimorbidity patterns in relation to polypharmacy and dosage frequency: a nationwide, cross-sectional study in a Japanese population.

In the present study, we aimed to identify multimorbidity patterns in a Japanese population and investigate whether these patterns have differing effects on polypharmacy and dosage frequency. Data was collected on 17 chronic health conditions via nationwide cross-sectional survey of 3,256 adult Japanese residents. Factor analysis was performed to identify multimorbidity patterns, and associations were determined with excessive polypharmacy [concurrent use of ≥ 10 prescription or over-the-counter (OTC) medications] and higher dosage frequency ( ≥ 3 doses per day). Secondary outcomes were the number of concurrent prescription medications and the number of concurrent OTC medications. We used a generalized linear model to adjust for individual sociodemographic characteristics. Five multimorbidity patterns were identified: cardiovascular/renal/metabolic, neuropsychiatric, skeletal/articular/digestive, respiratory/dermal, and malignant/digestive/urologic. Among these patterns, malignant/digestive/urologic and cardiovascular/renal/metabolic patterns showed the strongest associations with excessive polypharmacy and the number of concurrent OTC medications. Malignant/digestive/urologic, respiratory/dermal, and skeletal/articular/digestive patterns were also associated with higher dosage frequency. Multimorbidity patterns have differing effects on excessive polypharmacy and dosage frequency. Malignant/digestive/urologic pattern may be at higher risk of impaired medication safety and increased treatment burden, than other patterns. Continued study is warranted to determine how to incorporate multimorbidity patterns into risk assessments of polypharmacy and overall treatment burden.