Differences In Background Factors Research Articles

Comparison between rheumatoid arthritis with malignant lymphoma and other malignancies: Analysis of a National Database of Rheumatic Disease in Japan

BackgroundThe background status and the current treatment options of patients with rheumatoid arthritis (RA) who develop malignant lymphoma (ML) and other malignancies are unclear. This study investigated the differences in background factors between ML and other malignancies that occur in RA patients and post-malignancy treatment. MethodsWe identified 935 RA patients with new-onset malignancies among 110,571 person-years registered in the National Database of Rheumatic Disease in Japan from 2012 to 2018. Analysis cohorts 1 and 2 included 597 and 490 patients with available data for 1 year before and after the development of malignancies, respectively. Factors associated with the development of ML were longitudinally evaluated by multiple logistic regression analyses. ResultsOf the 935 patients (mean age 70.5, standard deviation 9.9), 15.5% had ML; this was comparable to the rate of lung cancer (14.3%). In cohort 1, methotrexate (MTX), biological disease-modifying anti-rheumatic drugs (bDMARDs), and non-steroidal anti-inflammatory drugs (NSAIDs) were used in 74.4%, 23.4%, and 56.7% of ML and in 56.8%, 25.4%, and 35.3% of other malignancies 1 year before the occurrence of malignancies. Clinical disease activity index (CDAI) and C-reactive protein were similar between the two groups. Multivariable analysis showed that MTX use (odds ratio [OR]: 2.22, 95% CI [confidence interval]: 1.32–3.73, p=0.003) and NSAID use (OR: 2.51, 95% CI: 1.58–3.98, p <0.001) were significantly associated with the development of ML versus other malignancies. However, this association was not observed with bDMARDs. In cohort 2, one year after the development of malignancies, MTX was used in none of ML and 41.8% of patients who developed other malignancies. In both malignancy groups, approximately 15% of patients received bDMARDs and 50% received glucocorticoids. IL-6 inhibitors were preferentially prescribed in patients with ML versus those with other malignancies. At year 1, CDAI remission was achieved in 37.3% and 31.1% of patients in the ML and other malignancy groups, respectively. ConclusionPatients receiving long-term treatment with MTX and NSAIDs may be at a relatively high risk of developing ML. The treatment landscape after developing malignancies differed considerably between patients with ML and other malignancies, and different treatment strategies should be established.

Impact of TP53-induced glycolysis and apoptosis regulator on malignant activity and resistance to ferroptosis in intrahepatic cholangiocarcinoma.

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04-3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03-4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

Sodium-glucose cotransporter 2 inhibitors in Asian patients with heart failure.

To the Editor: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors are recognized as one of the essential drugs for the treatment of heart failure (HF). Recent randomized controlled trials (RCTs) have shown that the SGLT-2 inhibitors significantly reduced the occurrence of HF hospitalizations or cardiovascular mortality in HF patients.[1–3] In addition, a comprehensive meta-analysis confirmed that SGLT-2 inhibitors improve the prognosis of patients with HF regardless of left ventricular ejection fraction.[4] However, the analysis by race is not highlighted in this meta-analysis. Since some studies have suggested a poorer prognosis for HF patients in Asia compared to those in Western countries,[5–7] we hypothesized that SGLT-2 inhibitors would have different efficacy in Asians compared to Western HF patients. Therefore, we performed a meta-analysis to elucidate the effectiveness of SGLT-2 inhibitors for Asian HF patients. We analyzed three large-scale RCTs (>1000 patients), having data of sub-analysis stratified by race (Asian, white and black).[1–3] A total of 13,857 patients with HF, including 2612 (19%) Asian, 10,504 (76%) white, and 741 (5%) black patients, were analyzed. Two studies used empagliflozin,[1,3] and one used dapagliflozin.[2] The hazard ratio (HR) for the primary endpoint (composite of cardiovascular death and hospitalization for HF) was pooled using the random-model generic inverse variance method after logarithm conversion (RevMan ver 5.4. Cochrane Collaboration, London, UK). Figure 1 demonstrates the comparison of HR for the primary endpoint. Treatment with SGLT-2 inhibitors resulted in a significant reduction in the primary endpoint in Asian (HR: 0.62, 95% confidence interval [CI]: 0.51–0.74, P <0.001, I2 = 0, P for heterogeneity = 0.83), White (HR: 0.82, 95% CI: 0.75–0.90, P <0.001, I2 = 0, P for heterogeneity = 0.56), and Black (HR: 0.58, 95% CI: 0.43–0.78, P <0.001, I2 = 0, P for heterogeneity = 0.44). The effect of the SGLT-2 inhibitor was higher in Asian HF patients than in white HF patients (P = 0.006) and similar to black HF patients (P = 0.74) [Figure 1].Figure 1: The HR of composite cardiac events across the races (Asian, white and black). CI: Confidence interval; HF: Heart failure; HR: Hazard ratio; SGLT-2: Sodium-glucose cotransporter 2. SE: Standard error.Approximately 60% of the world's population lives in Asian countries, but the information is limited regarding the characteristics and outcomes of Asian HF patients. Several studies indicated the difference in prognosis between Asian and Western countries. Dewan et al[5] examined the prognosis of 13,174 patients with HF with reduced ejection fraction and have shown the differences in the characteristics of HF patients in Asia and Western countries. For example, Asian HF patients are younger, have lower BMI, and have a lower prevalence of hypertension and diabetes. The low prevalence of chronic obstructive pulmonary disease, kidney disease, and atrial fibrillation is also intriguing. In addition, there was a generally low trend for complications of ischemic heart disease, although there was regional variation. In Asia, the use of diuretics and devices decreased while the use of digoxin increased. Most notably, there are differences in prognosis, with Asia having a higher incidence of cardiovascular death/HF hospitalization than Western countries (China 14.9; Western Europe 10.4; North America 12.8 per 100 patient-years).[5] The ATTEND Registry[8] (registry from Japan) revealed that the in-hospital mortality rate of HF patients was 6.4%, which was slightly higher than that reported in the ADHERE (4.0%)[9] and OPTIMIZE-HF (3.8%)[10] (both registries from the USA). The causal relationship between these differences in background factors and prognosis is unclear. In light of this, we hypothesized that the prognostic efficacy of SGLT-2 inhibitors may differ in Asian populations versus Western populations. In our analysis, we have shown that the favorable effects of SGLT-2 inhibitors are significantly higher in Asian HF patients than in white HF patients. This finding may provide hope for improving the prognosis of Asian HF patients, who have a higher risk of death than HF patients in Western countries. Future RCTs focusing on the Asian population were required to confirm the efficacy of SGLT-2 inhibitors. Funding The study was supported by a grant from the Research Grant, Japan Society for the Promotion of Science: Grant-in-Aid for Early-Career Scientists(C).

Postoperative Physical Therapy Program Focused on Low Back Pain Can Improve Treatment Satisfaction after Minimally Invasive Lumbar Decompression.

Patient satisfaction is crucial in pay-for-performance initiatives. To achieve further improvement in satisfaction, modifiable factors should be identified according to the surgery type. Using a prospective cohort, we compared the overall treatment satisfaction after microendoscopic lumbar decompression between patients treated postoperatively with a conventional physical therapy (PT) program (control; n = 100) and those treated with a PT program focused on low back pain (LBP) improvement (test; n = 100). Both programs included 40 min outpatient sessions, once per week for 3 months postoperatively. Adequate compliance was achieved in 92 and 84 patients in the control and test cohorts, respectively. There were no significant differences in background factors; however, the patient-reported pain score at 3 months postoperatively was significantly better, and treatment satisfaction was significantly higher in the test than in the control cohort (−0.02 ± 0.02 vs. −0.03 ± 0.03, p = 0.029; 70.2% vs. 55.4%, p = 0.045, respectively). In the multivariate logistic regression analysis, patients treated with the LBP program tended to be more satisfied than those treated with the conventional program, independent of age, sex, and diagnosis (adjusted odds ratio = 2.34, p = 0.012). Postoperative management with the LBP program could reduce pain more effectively and aid spine surgeons in achieving higher overall satisfaction after minimally invasive lumbar decompression, without additional pharmacological therapy.

Background factors in people living with HIV in Japan who switch to cabotegravir plus rilpivirine: A pilot study

Long-acting therapy of cabotegravir and rilpivirine is expected to free people from the negative emotions of living with HIV associated with taking drugs, but problems such as increased number of hospital visits, lack of anti-HBV activity, and limited convenience in people with concomitant drugs have been noted. In this single-center, prospective, cross-sectional study, we investigated background factors of people living with HIV in Japan who chose cabotegravir plus rilpivirine. Forty-seven percent (36 of 76) of individuals chose this regimen, but many people living with HIV who visited the hospital once every 3 months or needed concomitant medications due to complications chose this regimen and there were no significant differences in background factors that could affect convenience between the groups of those who switched and those who did not.

Difference in background factors between responders to gabapentin enacarbil treatment and responders to placebo: pooled analyses of two randomized, double-blind, placebo-controlled studies in Japanese patients with restless legs syndrome

ObjectiveRestless legs syndrome (RLS) is a sensorimotor disorder that is characterized by uncomfortable and unpleasant sensations mainly in the legs. Two placebo-controlled studies (Phase II/III and post-marketing) in Japanese patients with RLS failed to demonstrate the efficacy of gabapentin enacarbil (GE) 600 mg in the change from baseline in International Restless Legs Syndrome Rating Scale (IRLS) score at the end of the treatment period. The high response to placebo is thought to be a possible reason why the post-marketing study failed. The objectives of these post hoc analyses were to determine potential predictive factors associated with improvement in IRLS score with GE treatment and to identify subgroups with higher placebo responses. MethodsWe combined data from the two Japanese studies and analyzed change from baseline in IRLS score in the pooled population and subgroups defined by several patient characteristics. Moreover, we calculated the variable importance of each factor and performed predictive enrichment analysis to identify an enrichable subpopulation with greater improvement by GE treatment. ResultsThe post hoc analyses suggested that higher baseline IRLS score (≥21) and higher body mass index (≥25 kg/m2) were associated with higher placebo responses. On the other hand, positive family history of RLS, prior use of dopaminergic receptor agonists, and higher baseline ferritin level (≥50 ng/mL) were associated with higher responses to GE. ConclusionsOur results suggest that patients with typical idiopathic RLS characteristics, including positive family history and no low ferritin level, would be expected to derive the greatest benefits from GE treatment.

A multicenter, propensity score-matched cohort study about short-term and long-term outcomes after laparoscopic versus open surgery for locally advanced rectal cancer.

This study evaluated the results of laparoscopic surgery (LAP) compared to open surgery (OP) for locally advanced mid-to-lower rectal cancer. From February 2008 to December 2014, we collected patient data with clinical stage II/III mid-to-lower rectal cancer who underwent resection with LAP or OP at 13 institutions associated with the Yokohama Clinical Oncology Group (YCOG). The short-term outcomes and long-term prognoses associated with LAP and OP were analyzed after adjusting for the patients' backgrounds using propensity score matching. Among 1091 eligible cases, a propensity score matching with six covariates-age, sex, body mass index, American Society of Anesthesiologists physical status category, tumor location, and clinical stage-extracted 237 cases each for the LAP and OP groups, respectively. After matching, there were no differences in background factors between the two groups except for the presence or absence of preoperative treatment. Operative time was significantly longer in the LAP group than that in the OP group (p < 0.001), while the amount of bleeding and the length of postoperative hospital stay were significantly lower in the LAP group than that in the OP group (p < 0.001 and p = 0.001, respectively). There were no significant differences between groups in the incidence of postoperative complications. The 3-year overall survival and relapse-free survival rates were 90.5% and 88.6% and 78.3% and 71.6% in the LAP and OP groups, respectively, which did not differ significantly. The short-term outcomes and long-term prognoses of LAP in this cohort study indicated that LAP could be a therapeutic option for locally advanced rectal cancer. UMIN000040406.

Working conditions and compensated sickness absence among nurses and care assistants in Sweden during two decades: a cross-sectional biennial survey study

ObjectivesThe aims of the study were to trace the patterns of work environment factors and compensated sickness absence (SA) among nurses and care assistants compared with other occupations and to...

Effectiveness of Endoscopic Sclerotherapy with Aluminum Potassium Sulfate and Tannic Acid as a Non-Surgical Treatment for Internal Hemorrhoids.

Background/AimsSclerotherapy with aluminum potassium sulfate and tannic acid (ALTA) has a potent effect on internal hemorrhoids. In this retrospective study, we compared the effects of endoscopic ALTA therapy and standard ALTA therapy. MethodsWe investigated patients who underwent treatment for internal hemorrhoids at our institution between 2014 and 2016. They were divided into a standard ALTA group (n=33, treated using proctoscopy) and an endoscopic ALTA group (n=48). We compared the clinical findings between the 2 groups. ResultsThere were no intergroup differences in background factors. The mean ALTA dose was 21.9±7.2 mL and 17.8±3.4 mL in the standard and endoscopic ALTA groups, respectively (p<0.01). Adverse events occurred in 4 patients (12.1%) from the standard ALTA group and 6 patients (12.5%) from the endoscopic ALTA group. In both groups, the patients reported good satisfaction with the therapeutic effect at 1 month after the procedure. Hemorrhoids recurred in 2 patients (6.3%) from the standard ALTA group and 4 patients (8.3%) from the endoscopic ALTA group. ConclusionsEndoscopic ALTA sclerotherapy is equivalent to standard ALTA therapy in terms of efficacy, adverse events, and recurrence. Therefore, it is a useful non-surgical option for patients with internal hemorrhoids who prefer a less invasive treatment.

The Cognitive Profile of Children with Nonsyndromic Craniosynostosis.

Long-term neuropsychological and cognitive outcomes in patients with nonsyndromic craniosynostosis have proven difficult to evaluate objectively because of methodologic problems with published studies based on their small and biased samples of patients, wide age ranges, and testing with unacceptable psychometric properties. This study evaluated the Full-Scale Intelligence Quotient and its subscales in a cohort with a small selection bias. Patients aged 7 to 16 years, born with nonsyndromic craniosynostosis and surgically treated, were tested using the Wechsler Intelligence Scale for Children, Fourth Edition. Ninety-one patients were invited, and 73 patients were tested. There was no difference in Full-Scale Intelligence Quotient score between patients who had undergone operations for sagittal synostosis or metopic synostosis and norms provided by the test. Patients operated on for sagittal synostosis showed a significantly higher perceptual reasoning intelligence quotient, but also significantly lower working-memory intelligence quotient and processing-speed intelligence quotient compared with the norms. Patients operated on for metopic synostosis showed no differences in any intelligence quotient index compared with the norm. In addition, attrition analysis showed no differences in background factors between responders and nonresponders. These results derived from a group of patients with uniform age range, and tested using an established tool, revealed that nonsyndromic children having undergone surgery for craniosynostosis exhibited average intellectual ability. However, the analysis indicated possible issues with working memory and processing speed in patients operated on for sagittal synostosis, highlighting impairments potentially associated with neuropsychological problems and that might contribute to learning disabilities.

Liquid chromatography-mass spectrometry identification of serum biomarkers for nocturia in aged men.

We aimed to investigate the association between nocturia and serum metabolites identified using metabolomics analysis. This study enrolled 66 men aged 65-80years, recruited from the outpatient department of a university hospital. The participants were stratified as follows: Nocturia group [45 men with any total international prostate symptom score (IPSS) and an average of 3 nights ≥ 1.5 micturitions/night] and Control group (21 men with total IPSS < 8 and an average of 3 nights < 1.5 micturitions/night). The 24-h frequency-volume chart, IPSS, and Quality-of-Life questionnaire were used to evaluate micturition behavior. Serum metabolite profiles were obtained using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics analysis and compared between the two groups using the unpaired t test. The relationship between serum metabolites and nocturia was determined using multivariable logistic regression analysis. There were no differences in background factors between the Nocturia and Control groups. In the IPSS, mean total scores in the Nocturia and Control groups were 12.4 and 4.0, respectively. On frequency-volume chart analysis, nocturnal urine volume and micturition frequency during daytime and nighttime were significantly higher in the Nocturia group. LC-MS highlighted 13 serum metabolites as potential biomarkers of nocturia. On multivariate analysis, increased levels of palmitoylethanolamide, 4-hydroxydocosahexaenoic acid, 9-hydroxyoctadecadienoic acid, 20-hydroxydocosahexaenoic acid, 13-hydroxyoctadecadienoic acid, arachidonoylethanolamide, eicosapentaenoic acid, 12-hydroxy-eicosatetraenoic acid, and arachidonic acid were associated with nocturia. In aged men, the pathogenesis of nocturia involves abnormal metabolism in several signaling pathways involving omega-3 and omega-6 polyunsaturated fatty acids, as well as endocannabinoids.

Metabolomics analysis of blood identifies potential biomarkers and possible treatment targets for nocturia.

Background:Our aim was to investigate the association between serum metabolites and nocturia.Methods:A total of 66 males aged 65–80 years were enrolled in this study and stratified according to micturition behavior, which was characterized in terms of the 24 h frequency volume chart (FVC) for 3 consecutive days, the International Prostate Symptom Score (IPSS), and quality-of-life score. The nocturia group included participants with any total IPSS and ⩾1.5 micturitions/night as the mean of 3 nights, while the control group included participants with total IPSS < 8 and <1.5 micturitions/night. We conducted a comprehensive capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) study of plasma metabolites. Between-group comparisons of metabolite levels employed the Welch t test. The relationship between nocturia and metabolite profiles was determined using multivariable logistic regression analysis.Results:Of 66 participants, 45 were included in the nocturia group and 21 in the control group. There were no differences in background factors between the two groups. FVC analysis revealed that urine production during night-time, as well as micturition frequency during daytime and night-time were significantly higher in the nocturia group. CE-TOFMS identified eight metabolites whose plasma levels differed between the two groups. Multivariate analysis indicated that increased levels of lauric acid and imidazolelactic acid, as well as decreased levels of thiaproline and glycerol, contribute to the etiology of nocturia in aged men.Conclusions:Our findings suggest that abnormal serum levels of metabolites in several pathways play a role in the pathogenesis of nocturia in aged men.

Lack of Change in the Adaptation Ability of the Bladder for the Urine Production Rate in Aged Men with Nocturia

Introduction: To investigate the association between bladder capacity and the urine production rate in aged men with or without nocturia using a frequency volume chart (FVC). Materials and Methods: One-hundred and thirty-eight men aged 65–80 years were enrolled. After the International Prostate Symptom Score (IPSS) and 3 consecutive days FVC were evaluated, men were divided into 2 groups: Nocturia group, with any total IPSS, and ≥1.5 micturition on average at night; and Control group, with total IPSS < 8 and < 1.5 micturition on average at night. Each parameter was compared between the 2 groups using unpaired t tests. Linear and multiple regression analyses were performed between the urine production rate and volume/voids. Results: Men numbering 45 and 21 were assigned to the Nocturia and Control groups respectively. There were no differences in background factors between the 2 groups. Volume/voids positively correlated with the urine production rate in both groups for day and night. A multivariate regression model also showed the same results. In the Control group, the degree of slope at night was higher than that during the day. However, in the Nocturia group, there were no differences in the degree of slope between day and night. Conclusions: This novel finding has led to a possibility for resolving nocturia.

Use of Beta-Blockers on Maintenance Dialysis Patients and Ischemic Cerebral and Cardiovascular Deaths: An Examination Using Propensity Score.

Beta-blockers are frequently used in dialysis patients because of their cardioprotective properties. However, the effect of beta-blockers on reducing dialysis mortality has not been sufficiently examined to date. Thus, we sought to examine the effects on cardiovascular prognosis of beta-blockers using our outpatient dialysis database. From 389 dialysis patients registered in our database, subjects taking beta-blockers were extracted and matched with patients not taking beta-blockers using propensity scores based on 39 variables. Cardiovascular mortality, mortality of heart failure/sudden cardiac death, and mortality of ischemic cerebral and cardiovascular death were estimated using Kaplan-Meier method, and a log-rank test was used to analyze the difference between these survival curves for significance. A total of 216 patients, 108 matched pairs, were extracted from the whole cohort. There was no difference in background factors between the two groups. During mean observation periods of 4.4 years, 76 patients died, including 51 cases of cardiovascular death. Cardiovascular deaths included 30 heart failure/sudden deaths and 13 ischemic cerebral and cardiovascular deaths. For both cardiovascular and heart failure/sudden death, the survival curves did not indicate a significant difference between the 2 groups. On the contrary, in case of ischemic cerebral and cardiovascular deaths, 11 patients died in the beta-blocker group, with a significantly poor prognosis observed in the survival curve (p = 0.0132). Through the use of beta-blockers, a significant increase in ischemic cerebral and cardiovascular deaths was observed. The administration of beta-blockers to dialysis patients was found to worsen the cardiovascular prognosis, so sufficient examination will be needed in the future.

Risk factors for injuries associated with damage claims following groin hernia repair

PurposeSurgical repair of groin hernia should be carried out with minimal complication rates, and it is important to have regular quality control and accurate means of assessment. The Swedish healthcare system has a mutual insurance company (LÖF) that receives claims from patients who have suffered healthcare-related damage or malpractice. The Swedish Hernia Register (SHR) currently covers around 98% of all Swedish groin hernia operations. The aim of this study was to analyse damage claims following groin hernia repair surgery and link these with entries in the SHR, in order to identify risk factors and causes of injuries and malpractice associated with hernia repair.MethodsData on all 48,574 groin hernia operations registered in the SHR between 2008 and 2010 were compared and linked with data on claims made to the Swedish National Patient Injury Insurance (LÖF).ResultsOf the 130 damage claims received by LÖF, 26 dealt with bleeding, 20 with testicular injury and 7 with intestinal lesions. Eighty (62%) of the complications were considered malpractice according to the Swedish Patient Injury Act. Acute and recurrent surgery, sutured repair and general anaesthesia were associated with a significantly increased risk for a damage claim independently the patients were compensated or not. Females filed claims in greater proportion than males. There was no significant difference in background factors between claims accepted by LÖF and compensated and those who were rejected compensation.ConclusionRisk factors for filing a damage claim included acute surgery, operation for recurrence, sutured repair and general anaesthesia, whereas local anaesthesia reduced the risk.

The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community: A Natural Experiment

BackgroundWe examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s. MethodsThe child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV were offered from 3months of age at these sessions. Due to the 3-monthly intervals between sessions, the children were allocated by birthday in a ‘natural experiment’ to receive vaccinations early or late between 3 and 5months of age. We included children who were <6months of age when vaccinations started and children born until the end of December 1983. We compared mortality between 3 and 5months of age of DTP-vaccinated and not-yet-DTP-vaccinated children in Cox proportional hazard models. ResultsAmong 3–5-month-old children, having received DTP (±OPV) was associated with a mortality hazard ratio (HR) of 5.00 (95% CI 1.53–16.3) compared with not-yet-DTP-vaccinated children. Differences in background factors did not explain the effect. The negative effect was particularly strong for children who had received DTP-only and no OPV (HR=10.0 (2.61–38.6)). All-cause infant mortality after 3months of age increased after the introduction of these vaccines (HR=2.12 (1.07–4.19)). ConclusionDTP was associated with increased mortality; OPV may modify the effect of DTP.

Oral-health-related background factors and dental service utilisation among Sudanese children with and without a congenital heart defects.

BackgroundSudanese children with congenital heart defects (CHDs) were found to have poorer oral health than those without CHDs. The aims of this study were to: describe the patterns of oral-health-related background factors in children with and without CHD and explore any differences, and to evaluate the effects of background factors on caries and gingivitis prevalence and dental services utilisation.MethodsIn this analytical cross-sectional study, caregivers of children aged 3–12 years with (CHD cases n = 111) and without CHDs (Controls n = 182), underwent face-to-face interviews using a structured questionnaire. The questionnaire items covered several oral health background factors (independent variables) including: child’s health status, oral hygiene practices, dental services utilization, mother’s level of education, and caregiver’s perception and awareness of their child’s oral health. The relationship between these factors and occurrence of ‘caries’ and ‘gingivitis’ as well as ‘child’s dental services utilisation’ (dependent variables) were explored using multiple adjusted and hierarchal logistic regression analyses.ResultsCompared with controls, CHD cases had lower frequencies of brushing and use of fluoridated toothpaste, and their caregivers were less knowledgeable about caries. Among CHD cases, the variables (brushing and fluoridated toothpaste use) had significant impacts on caries prevalence (odd ratio (OR) =5.6, 95% confidence interval (CI): 1.4–22.8 and OR = 0.3, 95% CI: 0.1–0.8 for infrequent compared to frequent ones, respectively) as well as the mother’s level of education (OR = 2.6, 95% CI: 1.0–6.4). When differences in background factors were controlled for, the adjusted ORs for caries and gingivitis prevalence in CHD cases compared with controls were 1.8, (95% CI: 1.1–3.2) and 5.3 (95% CI: 2.9–9.4), respectively. Among CHD cases, the child’s age (8–12 years: OR = 11.9, 95% CI: 1.9–71.6), and the mother’s level of education (lower education: OR = 0.2, 95% CI: 0.03–0.9) were significantly associated with the child’s dental services utilisation.ConclusionsLower frequencies of brushing and use of fluoride tooth paste were reported among CHD cases, and brushing had the predominant significant impact on caries prevalence. The child’s age and the mother’s level of education were the main factors affecting the child’s (CHD cases) dental services utilisation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12903-016-0318-5) contains supplementary material, which is available to authorized users.

Abstract P5-12-07: Hormone dynamics, pharmacokinetics, safety and efficacy of leuprorelin acetate 6-month depot formulation and tamoxifen adjuvant endocrine therapy combination in premenopausal patients with hormone receptor-positive breast cancer

Abstract Background: Luteinizing hormone-releasing hormone agonist + tamoxifen is standard postoperative adjuvant endocrine therapy for premenopausal patients with hormone receptor-positive breast cancer. Postoperative adjuvant endocrine therapy is now used for a longer period, and the longer-lasting leuprorelin acetate 6-month depot formulation (TAP-144-SR[6M]) is expected to increase patients' quality of life and decrease medical practitioners' burden. Methods: The hormone dynamics, pharmacokinetics (PK), safety, and efficacy of TAP-144-SR(6M) were compared with those of the 3-month depot formulation (TAP-144-SR[3M]) in a 96-week, phase 3 open-label parallel-group comparison study in premenopausal breast cancer patients after surgery (ClinicalTrial.gov ID: NCT01546649). Inclusion criteria were estrogen receptor (ER) and/or progesterone receptor (PgR) positive; TNM classification of T1-T3, any N, M0; and premenopausal (menstruation confirmed within the previous 12 weeks or both follicle-stimulating hormone [FSH] &amp;lt;40 mIU/mL and estradiol [E2] ≥10 pg/mL at enrollment). Patients were randomized to TAP-144-SR(6M) (6M group [6MG]) or TAP-144-SR(3M) (3M group [3MG]) based on number of axillary lymph node metastases, tumor size, age, ER/PgR status, chemotherapy or not, and study site. The primary endpoint was serum E2 suppression rate based on the menopausal level (≤30 pg/mL) from 4 to 48 weeks after the first administration. Secondary endpoints were serum hormone dynamics, efficacy (disease-free survival [DFS] and distance DFS [DDFS]), PK and safety. The planned number of patients was 164 (82 in each group). Results: A total of 180 patients were enrolled from Apr 2012 to Feb 2013 and 167 patients were randomized. We compared 83 patients in 6MG (age: mean 44.2; SD 4.90) and 84 patients in 3MG (44.0; 5.18). There were no significant differences in background factors between the groups. 6MG showed non-inferior suppression of serum E2 levels to 3MG (See Table). Serum LH and FSH levels were also decreased. DFSs and DDFSs at 96 weeks after randomization were similar in both groups. A double-peak PK profile and sustainable release of the study drug for 24 weeks were found with 6MG. All-grade adverse events (AEs) occurred in 98.8% and 97.6% and grade 3 or higher AEs in 18.1% and 21.4% with 6MG and 3MG, respectively. There were no significant differences in lumbar spine bone mineral density change rates in both groups. Table Serum E2 suppression rate based on the menopausal level (≤30 pg/mL) from 4 to 48 weeks after the first administration 6MG (n = 83)3MG (n = 84)Serum E2 suppression rate (%) (95% CI)97.6 (91.565, 99.707)96.4 (89.916, 99.257)6MG − 3MG (95% CI)1.2 (−5.241, 7.806)Note: Noninferiority margin of 10%. Conclusion: This first clinical study of TAP-144-SR(6M) in premenopausal breast cancer patients showed clinically noninferior serum E2 suppression levels to TAP-144-SR(3M), and no significant safety differences between the groups. TAP-144-SR(6M) was confirmed to have excellent usability in premenopausal breast cancer patients after surgery, and is considered valuable for the appropriate treatment of these patients. Citation Format: Kurebayashi J, Toyama T, Sumino S, Fujimoto T. Hormone dynamics, pharmacokinetics, safety and efficacy of leuprorelin acetate 6-month depot formulation and tamoxifen adjuvant endocrine therapy combination in premenopausal patients with hormone receptor-positive breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-07.

人工膝関節全置換術適用患者のバリアンス発生に対する背景因子と術後早期の機能回復の違い

人工膝関節全置換術適用患者のバリアンス発生に対する背景因子と術後早期の機能回復の違い

Prevention of joint destruction by tacrolimus in patients with early rheumatoid arthritis: a post hoc analysis of a double-blind, randomized, placebo-controlled study

Objectives A multicenter, randomized, double-blind, placebo-controlled study of the oral calcineurin inhibitor tacrolimus was performed in patients with early rheumatoid arthritis who had responded poorly to disease-modifying antirheumatic drugs (DMARDs), and factors related to suppression of joint destruction were investigated.Methods The change in the total Sharp score (∆TSS) was assessed by univariate analysis in patients with X-ray films to identify the main determinant of a ∆TSS of <0.5 in week 52. Patients with this factor were then investigated further.Results Univariate analysis showed that a baseline C-reactive protein (CRP) level of <1.5 mg/dL was the major determinant of ∆TSS <0.5 at week 52 in the tacrolimus group. Detailed analysis of patients with a baseline CRP of <1.5 mg/dL revealed no significant differences in background factors between the two groups. In week 52, ∆TSS was significantly smaller in the tacrolimus group than in the placebo group (2.67 ± 5.40 vs. 8.05 ± 10.32, respectively, p = 0.017). Both groups had a similar incidence of adverse reactions.Conclusions Adding tacrolimus to DMARDs significantly suppressed disease activity and joint destruction in patients with early rheumatoid arthritis, a disease duration ≤3 years, a CRP <1.5 mg/dL, and a poor response to oral DMARDs.