High prevalence of severe pain is associated with low opioid availability in patients with advanced cancer: Combined database study and nationwide questionnaire survey in Japan.

OBJECTIVES: Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low-dose opioid prescriptions in patients with advanced cancer in Japan. METHODS: A web-based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end-stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. RESULTS: Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe-to-intolerable cancer-related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe-to-intolerable cancer-related pain was negatively associated with the cumulative opioid consumption expressed as morphine-equivalent doses within 90 days before death. CONCLUSIONS: The very low availability of opioids for patients with end-stage cancer could result in high rate of severe-to-intolerable cancer-related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.

Increased trailing limb angle in hemiplegic patients after training with a knee orthosis: A randomized controlled trial.

BACKGROUND: Stroke often induces gait abnormality, such as buckling knee pattern, compromising walking ability. Previous studies indicated that an adequate trailing limb angle (TLA) is critical for recovering walking ability. OBJECTIVE: We hypothesized that correcting gait abnormality by immobilizing the knee joint using a knee orthosis (KO) would improve walking patterns and increase the TLA, and investigated whether walking training using a KO would increase the TLA in post-stroke patients. METHODS: In a randomized controlled trial, thirty-four participants were assigned to KO (walking training using a KO) and non-KO (without using a KO) groups. Twenty-nine completed the three-week gait training protocol. TLA was measured at baseline and after training. A two-way repeated ANOVA was performed to evaluate TLA increases with training type and time as test factors. A t-test compared TLA changes (ΔTLA) between the two groups. RESULTS: ANOVA showed a main effect for time (F = 64.5, p < 0.01) and interaction (F = 15.4, p < 0.01). ΔTLA was significantly higher in the KO group (14.6±5.8) than in the non-KO group (5.0±7.0, p < 0.001). CONCLUSION: Walking training using a KO may be practical and effective for increasing TLA in post-stroke patients.

Secondary trigeminal neuralgia caused by lung adenocarcinoma metastasis on trigeminal nerve roots successfully relieved by opioids: A case report.

Secondary trigeminal neuralgia (TN) is caused by identifiable diseases or lesions of the trigeminal nerve root, Gasserian ganglion and/or pons. TN is a neuropathic pain disorder characterized by electric shock-like or stabbing pain in the facial region, which can lead to impaired health-related quality of life. The present case report describes a rare case of secondary TN caused by trigeminal nerve metastases from lung adenocarcinoma, in which opioids provided symptomatic relief. The patient was a 46-year-old man with stage IV lung adenocarcinoma. They were admitted to hospital for the introduction of fifth-line chemotherapy because of previous chemotherapy-refractory disease progression. Electric shock-like or stabbing pain in the left facial area and bilateral auditory disturbances coincided with intracranial peri-brainstem metastases. Facial pain was triggered by mastication, making it difficult for the patient to eat. A fentanyl transdermal patch (25 mcg/h) was initiated following a diagnosis of TN secondary to lung adenocarcinoma metastases on the trigeminal nerves by magnetic resonance imaging. Subsequently, the facial pain improved rapidly. In conclusion, unlike classic and idiopathic TN, which is usually treated with carbamazepine as a first-line drug, oncologic secondary TN can be treated with opioids.

Immune checkpoint inhibitor-associated colitis in unresectable hepatocellular carcinoma: two cases of early onset after treatment with durvalumab plus tremelimumab.

The HIMALAYA trial is the first chemotherapeutic trial to demonstrate the efficacy of combined immune checkpoint inhibitors (ICIs) for unresectable hepatocellular carcinoma (u-HCC). The STRIDE regimen used in this trial consists of a cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitor and programmed cell death ligand 1 (PD-L1) inhibitor. Herein, we report two cases of ICI-colitis that occurred immediately after the initiation of the STRIDE regimen for u-HCC. A 73-year-old man and 75-year-old man with u-HCC were treated with the STRIDE regimen. Both patients developed grade 3 diarrhea (Common Terminology Criteria for Adverse Events, ver. 5.0) within 10 days of treatment initiation. Colonoscopy revealed aphthous erosions and erythema extending from the terminal ileum to the rectum in one case, while the other showed aphthous ulcers in the terminal ileum and shallow ulcers in the colorectum. Histopathological examination of a biopsy specimen revealed epithelial cell apoptosis and neutrophil infiltration bodies, consistent with ICI-colitis. Prednisolone (0.5 mg/kg) was effective in both patients. Our experience suggests the need for both careful monitoring and early endoscopic examination of ICI colitis in patients with unresectable HCC treated with the STRIDE regimen.

Predictors indicating the continuous need for a knee-ankle-foot orthosis in stroke patients at 1 month after onset.

OBJECTIVES: To investigate predictors indicating the continuous need for a knee-ankle-foot orthosis (KAFO) at 1 month after stroke onset in patients who cannot walk without a KAFO in the acute period. MATERIALS AND METHODS: We enrolled patients with severe hemiplegia (n = 139) who were unable to walk without a KAFO on day 10 from stroke onset. The patients were divided into two groups depending on the need for a KAFO at 1 month after the onset: the KAFO group and non-KAFO group. Logistic regression analysis was used to identify predictors of the continuous need for a KAFO at 1 month after stroke onset. In addition, significant predictors were analyzed using receiver operating characteristic curves. RESULTS: The number of patients in the KAFO group and non-KAFO group was 72 (51.8 %) and 67 (48.2 %), respectively. Motor deficit, sensation disorder, severity of pusher syndrome, and body mass index were identified as predictors of the continuous need for a KAFO. Moreover, active range of motion of knee extension on the affected side was found to have the highest predictive ability, with an area under the receiver operating characteristic curve of 0.89 (95 % confidence interval, 0.83-0.94). CONCLUSIONS: In this study, multiple factors were associated with the continuous need for a KAFO at 1 month after stroke onset. In particular, active range of motion of knee extension on the affected side is suggested to be a highly accurate predictor for the need for a KAFO in the subacute phase.

Direct Observation of Vacancy-Cluster-Mediated Hydride Nucleation and the Anomalous Precipitation Memory Effect in Zirconium.

Controlling the heterogeneous nucleation of new phases is of importance in tuning the microstructures and properties of materials. However, the role of vacancy-a popular defect in materials that is hard to be resolved under conventional electron microscopy-in the heterogeneous phase nucleation remains intriguing. Here, this work captures direct in situ experimental evidences that vacancy clusters promote the heterogeneous hydride nucleation and cause the anomalous precipitation memory effect in zirconium. Both interstitial and vacancy dislocation loops form after hydride dissolution. Interestingly, hydride reprecipitation only occurs on those vacancy loop decorated sites during cooling. Atomistic simulations reveal that hydrogen atoms are preferentially segregated at individual vacancy and vacancy clusters, which assist hydride nucleation, and stimulate the unusual memory effect during hydride reprecipitation. The finding breaks the traditional view on the sequence of heterogeneous nucleation sites and sheds light on the solid phase transformation related to vacancy-sensitive alloying elements.

Lower limb muscle strength of the affected side in stroke patients is an accurate predictor of the need for a KAFO.

BACKGROUND: Accurate prediction of recovery is essential to determine whether a knee-ankle-foot orthosis (KAFO) is required in the subacute phase of stroke. However, there are currently no reliable methods to predict such recovery. OBJECTIVE: This study aimed to determine whether muscle strength of the affected lower limb (affected side LL strength) in stroke patients in the subacute phase who cannot walk without a KAFO can be used to predict the continuous need for a KAFO, using a hand-held dynamometer. METHODS: We enrolled patients with severe hemiplegia (n = 51) who were unable to walk without a KAFO for 10 days after stroke onset. They were divided into two groups depending on the continuous need for a KAFO at 1 month after onset; the KAFO and non-KAFO groups. Logistic regression analysis was used to investigate whether the affected side LL strength was a predictor of the continuous need for a KAFO at 1 month after onset. In addition, significant predictors were analyzed using receiver operating characteristic (ROC) curves. RESULTS: The KAFO and non-KAFO groups included 23 (45.10%) and 28 (54.90%) patients, respectively. The affected side LL strength and pusher syndrome severity were identified as predictors of the continuous need for a KAFO. The predictor with the highest predictive ability was the affected side LL strength, with an area under the ROC curve of 0.80 (95% CI, 0.68-0.93). CONCLUSIONS: Affected side LL strength may be a highly accurate predictor of the need for a KAFO in the subacute phase of stroke.

Clinical practice recommendations for management of lateropulsion after stroke determined by a Delphi expert panel.

OBJECTIVE: People exhibiting post-stroke lateropulsion actively push their body across the midline to the more affected side and/or resist weight shift toward the less affected side. Despite its prevalence and associated negative rehabilitation outcomes, no clinical practice guidelines exist for the rehabilitation of post-stroke lateropulsion. We aimed to develop consensus-based clinical practice recommendations for managing post-stroke lateropulsion using an international expert panel. DESIGN: This Delphi panel process conformed with Guidance on Conducting and Reporting Delphi Studies recommendations. PARTICIPANTS: Panel members had demonstrated clinical and/or scientific background in the rehabilitation of people with post-stroke lateropulsion. MAIN MEASURES: The process consisted of four electronic survey rounds. Round One consisted of 13 open questions. Subsequent rounds ascertained levels of agreement with statements derived from Round One. Consensus was defined a priori as ≥75% agreement (agree or strongly agree), or ≥70% agreement after excluding 'unsure' responses. RESULTS: Twenty participants completed all four rounds. Consensus was achieved regarding a total of 119 recommendations for rehabilitation approaches and considerations for rehabilitation delivery, positioning, managing fear of falling and fatigue, optimal therapy dose, and discharge planning. Statements for which 'some agreement' (50%-74% agreement) was achieved and those for which recommendations remain to be clarified were recorded. CONCLUSIONS: These recommendations build on existing evidence to guide the selection of interventions for post-stroke lateropulsion. Future research is required to elaborate specific rehabilitation strategies, consider the impact of additional cognitive and perceptual impairments, describe positioning options, and detail optimal therapy dose for people with lateropulsion.

Development of a Japanese Version of the Quality of Life at the End of Life-Cancer Scale.

CONTEXT: The Quality of Life at the End of Life-Cancer Scale (QUAL-EC) is a self-reported instrument to assesses the quality of life of patients with cancer near the end of life. OBJECTIVE: To test the reliability and validity of the QUAL-EC-J, a Japanese translated version of the QUAL-EC. METHODS: A total of 179 Japanese patients with advanced cancer completed the QUAL-EC-J, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Rosenberg Self-Esteem Scale, Multidimensional Scale of Perceived Social Support, Functional Assessment of Cancer Therapy-General Scale, and Functional Assessment of Chronic Illness Therapy-Spiritual questionnaires. We performed confirmatory factor analysis of the four structures of the QUAL-EC and exploratory factor analysis of the QUAL-EC-J. Internal consistency was assessed using Cronbach's α coefficient and validity was examined by calculating correlations with relevant scales. RESULTS: Confirmatory factor analysis showed an inadequate fit to the original QUAL-EC structure. Exploratory factor analysis revealed a three-factor structure of the QUAL-EC-J, with Cronbach's α values of 0.68-0.88. All subscales were negatively correlated with depression and anxiety. Each subscale was correlated with related measures: "symptom control" with "physical well-being"; "acceptance of disease and life" with "social and family well-being" and "meaning/peace"; and "preparation for end of life" with "emotional well-being" and "meaning/peace." CONCLUSIONS: The QUAL-EC-J has a three-factor structure with acceptable reliability and sufficient validity. Differences in the factor structure between the QUAL-EC-J and the QUAL-EC may be due to cultural factors. Study findings suggest that utilization of the QUAL-EC-J could help to improve research and clinical care in advanced cancer in Japan.

Efficacy of treatments for pain and numbness in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Pain and numbness in cancer survivors frequently have negative impacts on quality of life (QoL). This meta-analysis aimed to identify the current treatment options for pain and numbness in cancer survivors and to evaluate their effects. METHODS: Cancer survivors were defined as patients diagnosed with cancer who had completed active cancer treatment, whose conditions were stable, and who had no evidence of recurrent or progressive disease. A systematic search through the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, PsycInfo, and CINAHL databases was conducted, which targeted randomized controlled trials (RCTs) published until April 2022 that evaluated any type of treatment for pain or numbness in cancer survivors. A meta-analysis was conducted using the random-effects model to obtain the effect sizes of 7 types of treatments: opioid therapy, nonopioid pharmacotherapy, interventional therapy, acupuncture, education/cognitive behavioral therapy (CBT), physical exercise, and alternative medicine. RESULTS: A total of 36 studies involving 2,870 cancer survivors were included. Among them, 35 (n=2,813) were included in the meta-analysis for pain. The analysis suggested that physical exercise [n=761; 13 studies; standardized mean difference (SMD) -0.84; 95% confidence interval (CI): -1.14 to -0.55], acupuncture (n=409; 3 studies; SMD -0.80; 95% CI: -1.04 to -0.56), and alternative medicine (n=206; 6 studies; SMD -0.44; 95% CI: -0.71 to -0.16) could significantly reduce pain. Nonopioid pharmacotherapy and education/CBT did not demonstrate significant effects. No studies were identified that investigated the effects of opioid therapy or interventional therapy on pain. Regarding numbness, 5 studies (n=566) were included in the meta-analysis. Acupuncture (n=99; 2 studies) did not demonstrate significant effects on numbness, and the effects of nonopioid pharmacotherapy, education/CBT, and physical exercise could not be determined due to the small number of included studies. No studies were identified that investigated the effects of opioid therapy, interventional therapy, or alternative medicine on numbness. CONCLUSIONS: This meta-analysis suggested that physical exercise, acupuncture, and alternative medicine may reduce pain in cancer survivors, with a very small to moderate amount of evidence. The effect of treatments for numbness could not be determined due to the limited number of included studies. Further studies are needed, particularly on widely used pharmacotherapy.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults: Case-control study.

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)-located on the gene encoding for pleiotrophin on chromosome 7-that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing.

Evaluation of SOX9-Positive Hepatocytes in Human Liver Specimens and Mature Mouse Hepatocytes.

The liver has a remarkable regenerative capacity with different modes of regeneration according to the type and extent of an injury. It has been reported that mature hepatocytes could transdifferentiate into a cholangiocyte phenotype. Sry HMG box protein 9 (SOX9) is one of the earliest biliary markers that regulate bile duct development. We have found that SOX9-positive biphenotypic hepatocytes appear in severe acute liver injury patients' liver specimens accompanied by an elevation in plasma interleukin-8 levels. In vitro assays revealed that interleukin-8 homologs induce the expression of SOX9 in mature mouse hepatocytes. Here, we describe the methods used to detect SOX9-positive hepatocytes in human liver specimens and to induce SOX9-positive hepatocytes in mature mouse hepatocytes.

Relationship Between Sacroiliac Joint-related Pain and Spinopelvic Mobility.

STUDY DESIGN: A case-control study. OBJECTIVE: To evaluate the relationship between sacroiliac joint-related pain (SIJ-RP) and spinopelvic mobility. SUMMARY OF BACKGROUND DATA: No specific radiological findings are available for the diagnosis of SIJ-RP. A previous study reported that a higher pelvic incidence and sacral slope (SS) values were significantly associated with sacroiliac joint pain. The concept of spinopelvic mobility, which is evaluated by the differences between SS in the standing and sitting positions, has been the focus of hip and spine surgeries in recent years. MATERIALS AND METHODS: The SIJ-RP group comprised patients diagnosed with SIJ-RP based on physical findings and their response to analgesic injections. No other lumbar or hip joint diseases were observed. The non-SIJ-RP group comprised patients with lower back pain for reasons other than SIJ-RP. Radiographs of the lateral view of the pelvis in the standing and sitting positions were evaluated for all patients. We compared and analyzed the backgrounds, SS in the two positions, and difference in SS between the two positions in both groups. RESULTS: In total, 245 patients were included in the study, with 49 and 196 patients in the SIJ-RP and non-SIJ-RP groups, respectively. More female patients experienced SIJ-RP than male patients ( P =0.0361). There were significant differences between the groups for SS in standing ( P =0.0076), sitting ( P =0.0005), and those with a difference between sitting and standing of <5° ( P =0.0278) in the univariate analyses. Logistic regression analyses, after adjustment for age and sex, revealed significant differences between the groups with an SS difference <5° ( P =0.0088; 95% confidence interval, 1.280-5.519), with an odds ratio of 2.7. CONCLUSION: On evaluating spinopelvic mobility, we found that SIJ-RP was related to hypomobility of the sacrum, which could indicate the hypermobility of the sacroiliac joint.

Post-stroke lateropulsion terminology: pushing for agreement amongst experts.

Post-stroke lateropulsion is prevalent. The global inconsistency in terminology used to describe the condition presents obstacles in accurately comparing research results, reaching consensus on use of measurement tools, agreeing upon a consistent approach to rehabilitation, and translating research to clinical practice. Commencing in 2021, 20 international experts undertook a Delphi Process that aimed to compile clinical practice recommendations for the rehabilitation of lateropulsion. As a part of the process, the panel agreed to aim to reach consensus regarding terminology used to describe the condition. Improved understanding of the condition could lead to improved management, which will enhance patient outcomes after stroke and increase efficiency of healthcare resource utilisation. While consensus was not reached, the panel achieved some agreement that 'lateropulsion' is the preferred term to describe the phenomenon of 'active pushing of the body across the midline toward the more affected side, and / or actively resisting weight shift toward the less affected side'. This group recommends that 'lateropulsion' is used in future research and in clinical practice.

Excess fructose enhances oleatic cytotoxicity via reactive oxygen species production and causes necroptosis in hepatocytes.

Non-alcoholic fatty liver disease (NAFLD), the hepatic phenotype of metabolic syndrome, has been identified as a major health concern as the number of cirrhosis and deaths associated with NAFLD is expected to increase. Although fructose intake has been considered to be a progressive factor in the pathophysiology of NAFLD, it remains unclear how fructose contributes to hepatocellular damage during lipotoxicity. In the present study, we aimed to analyze the hepatotoxicity of fructose in steatosis. Fructose effects on lipotoxicity were evaluated in HepG2 cells, primary mouse hepatocytes, and in mice fed a high-fat diet with or without sucrose (HFDS/HFD). Oleate induced caspase 3-independent cell death in HepG2 cells and primary mouse hepatocytes cultured in fructose-supplemented medium, and induced cleavage of caspase-1 in primary mouse hepatocytes. In addition, the number of cells stained positive for reactive oxygen species (ROS) was significantly increased, and N-acetyl cysteine was found to inhibit ROS production and cell death. Cell death was confirmed to be through necrotic cell death, and phosphorylation of mixed lineage kinase domain-like (MLKL) protein was observed. Taken together, hepatocyte cytotoxicity was due to excess fructose with oleate-induced ROS-mediated necroptosis. HFDS mice showed progressive hepatic fibrosis and inflammation and a higher NAS score than HFD mice or mice fed a control diet. The expression of hemoxygenase-1, phosphorylation of MLKL, cleavage of caspase1, and apoptosis were significantly increased in the livers of mice fed a HFDS. Overall, excess fructose intake induces necroptosis through the production of ROS and enhances the toxicity of oleatic cytotoxicity.

Gabapentinoid Use Is Associated With Reduced Occurrence of Hyperactive Delirium in Older Cancer Patients Undergoing Chemotherapy: A Nationwide Retrospective Cohort Study in Japan.

BACKGROUND: It is unclear whether gabapentinoids affect the development of delirium. We aimed to determine the association between gabapentinoid use and hyperactive delirium in older cancer patients undergoing chemotherapy. METHODS: We conducted propensity score-matched analyses using data from a nationwide inpatient database in Japan. We included cancer patients with pain ≥70 years of age undergoing chemotherapy between April 2016 and March 2018. Patients receiving gabapentinoids were matched with control patients using propensity scores. The primary outcome was occurrence of hyperactive delirium during hospitalization, and the secondary outcomes were length of hospital stay, in-hospital fractures, and in-hospital mortality. Hyperactive delirium was identified by antipsychotic use or discharge diagnoses from the International Classification of Diseases, 10th Revision. RESULTS: Among 143,132 identified patients (59% men; mean age, 76.3 years), 14,174 (9.9%) received gabapentinoids and 128,958 (90.1%) did not (control group). After one-to-one propensity score matching, 14,173 patients were included in each group. The occurrence of hyperactive delirium was significantly lower (5.2% vs 8.5%; difference in percent, -3.2% [95% confidence interval, -3.8 to -2.6]; odds ratio, 0.60 [0.54-0.66]; P < .001), the median length of hospital stay was significantly shorter (6 days [interquartile range, 3-15] vs 9 days [4-17]; subdistribution hazard ratio, 1.22 [1.19-1.25]; P < .001), and the occurrence of in-hospital mortality was significantly lower in the gabapentinoid group than in the control group (1.3% vs 1.8%; difference in percent, -0.6% [-0.9 to -0.3]; odds ratio, 0.69 [0.57-0.83]; P < .001). Gabapentinoid use was not significantly associated with the occurrence of in-hospital fractures (0.2% vs 0.2%; difference in percent, 0.0% [-0.1 to 0.1]; odds ratio, 1.07 [0.65-1.76]; P = .799). The results of sensitivity analyses using stabilized inverse probability of treatment weighting were consistent with the results of the propensity score-matched analyses. CONCLUSIONS: Our findings suggest that gabapentinoid use is associated with reduced hyperactive delirium in older cancer patients undergoing chemotherapy, with no evidence of an increase in the fracture rate, length of hospital stay, or in-hospital death.

Effect of Antimicrobial Prophylaxis Duration on Health Care-Associated Infections After Clean Orthopedic Surgery: A Cluster Randomized Trial.

Importance: Postoperative health care-associated infections are associated with a greater deterioration in patients' general health status and social and economic burden, with at least 1 occurring in approximately 4% of acute care hospital patients. Antimicrobial prophylaxis prevents surgical site infections in various orthopedic procedures; however, its relationship with health care-associated infections remains unknown. Objective: To examine whether a shorter antimicrobial prophylaxis duration of less than 24 hours after surgery is not inferior to a longer duration in preventing health care-associated infections after clean orthopedic surgery. Design, Setting, and Participants: This open-label, multicenter, cluster randomized, noninferiority clinical trial was conducted in 5 tertiary referral hospitals in greater Tokyo metropolitan area, Japan, from May to December 2018. Adult patients undergoing clean orthopedic surgery were recruited until the planned number of participants was achieved (500 participants per group). Statistical analysis was conducted from July to December 2019. Interventions: Antimicrobial prophylaxis was discontinued within 24 hours after surgery in group 24 and 24 to 48 hours after surgery in group 48. Group allocation was switched every 2 or 4 months according to the facility-based cluster rule. Study-group assignments were masked from participants. Main Outcomes and Measures: The primary outcome was the incidence of health care-associated infections requiring antibiotic therapies within 30 days after surgery. The noninferiority margin was 4%. Results: Of the 1211 participants who underwent cluster allocation, 633 participants were in group 24 (median [IQR] age, 73 [61-80] years; 250 men [39.5%] and 383 women [60.5%]), 578 participants were in group 48 (median [IQR] age, 74 [62-81] years; 204 men [35.3%] and 374 women [64.7%]), and all were eligible for the intention-to-treat analyses. Health care-associated infections occurred in 29 patients (4.6%) in group 24 and 38 patients (6.6%) in group 48. Intention-to-treat analyses showed a risk difference of -1.99 percentage points (95% CI, -5.05 to 1.06 percentage points; P < .001 for noninferiority) between groups, indicating noninferiority. Results of adjusted intention-to-treat, per-protocol, and per designated procedure population analyses supported this result, without a risk of antibiotic resistance and prolonged hospitalization. Conclusions and Relevance: This cluster randomized trial found noninferiority of a shorter antimicrobial prophylaxis duration in preventing health care-associated infections without an increase in antibiotic resistance risk. These findings lend support to the global movement against antimicrobial resistance and provide additional information on adequate antimicrobial prophylaxis for clean orthopedic surgery. Trial Registration: Identifier: UMIN000030929.

Imaging features inferring symptom onset due to spinal metastasis progression: a preliminary study.

BACKGROUND: Spinal metastases can cause intractable pain and neurological deficits, which can markedly worsen both patients' activities of daily living (ADL) and their health-related quality of life (QOL). Early intervention is essential to prevent irreversible neurological deficits and pain associated with spinal metastases. We investigated the imaging features of spinal metastases that led to neurological deficits. METHODS: We analyzed axial cross-sectional computed tomography (CT) images of cervical and thoracic spinal metastases in patients with and without lower limb motor paralysis, neuropathic pain, and local nociceptive pain. We distinguished regions of the spine associated with these respective symptoms, and explored their inferable performance using images obtained before symptom onset. In addition, we analyzed the imaging features and type of bone metastasis (osteolytic and osteoblastic). RESULTS: Spinal lesions occupied the area in and around the spinal canal and around the pedicle in patients with motor paralysis. Lesions around the pedicle and in the most posterior vertebral body part before symptom onset were inferable. In patients with neuropathic pain, spinal metastases spread along the pedicle before symptom onset, and had surrounded the spinal canal circumferentially at symptom onset. Local nociceptive pain was more common near the center of the vertebral body either at or before symptom onset. There was no difference in the imaging features according to the type of bone metastasis. CONCLUSIONS: Lesions in certain regions in the asymptomatic metastatic spine can indicate the onset of spinal metastasis-related symptoms in the next few months. Early therapeutic intervention might be applied to prevent neurological disorder.