Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

Healthcare resource utilisation and economic burden of patients with adequate and inadequate responses to biological and targeted synthetic disease-modifying antirheumatic drugs for rheumatoid arthritis in Japan.

OBJECTIVE: To compare healthcare resource utilisation (HCRU) and direct costs between responders vs non-responders to advanced therapies for rheumatoid arthritis (RA). METHODS: Patients initiating ≥1 advanced therapy (Oct 2018-Sept 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs (direct medical, emergency department [ED], laboratory, and pharmacy) were compared between responders vs non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. RESULTS: Among 2,446 patients (non-responders [n=1,817]; responders [n=629]), non-responders had significantly longer hospitalisation days (IRR: 1.8 [95% CI: 1.2-2.6]), and significantly more ED visits (2.5 [1.5-4.2]) and prescriptions (1.1 [1.1-1.2]). Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders (1.4 [1.3-1.6], ¥530,895 vs ¥357,009 [$;3,992 vs $;2,684] for responders; ¥173,886 [$;1,307] difference); RA-related medical costs showed a similar trend (¥351,306 vs ¥253,030 [$;2,641 vs $1,902]; ¥98,276 [$;739] difference). No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. CONCLUSIONS: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response.

Study of assessment of knowledge and understanding for coping with sick days among patients with diabetes in community pharmacy: a cluster randomized controlled trial (SAKURA trial).

BACKGROUND: Awareness regarding coping with sick days among patients with diabetes is limited. Thus, we evaluated the effectiveness of sick-day education by community pharmacists among patients with type 2 diabetes (T2D) using sick-day educational materials (sick-day cards). METHODS: A cluster randomized controlled trial was conducted. Pharmacists in the intervention group educated patients with T2D on coping with sick days (adjusting medication dosage and seeking medical advice) using sick-day cards compared with the usual counseling. Differences in questionnaire scores ("Anxiety", "Intention", "Attitude", and "Knowledge" about sick days) before and after the intervention were compared between the groups. RESULTS: Overall, 318 patients with T2D (intervention, 119; control, 199) participated in this study, and 270 (intervention, 92; control, 178) patients were examined. There were no significant differences in "Anxiety", "Intention", or "Attitude" scores between the two groups, but "Knowledge" scores improved in the intervention group. For all intervention groups (92/92), a physician reviewed and approved medication and adjustment doses for sick days on the cards. CONCLUSIONS: According to patients' responses, sick-day education using teaching materials improved patient knowledge. This may help patients and their caregivers cope with sick days appropriately through medication dose adjustment and fluid intake. Research registration number: UMIN000043161 (February 1, 2021), https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgifunction=brows&action=brows&recptno=R000048124&type=summary&language=J.

A possible manifestation of pancreas divisum-pancreatic pseudocyst in an infant with no apparent history of pancreatitis: a case report.

BACKGROUND: Pancreas divisum (PD), the most common pancreatic anomaly, is caused by the failure of pancreatic bud fusion in the embryo. Although most cases are asymptomatic, it can cause pancreatitis or epigastric pain. We report an unusual case of PD in an infant. CASE PRESENTATION: The patient was a 9-month-old girl with no pertinent medical history. She had suffered vomiting and diarrhea for 1 week before transfer to our hospital. Her general condition was poor, and abdominal distention was noted. Blood tests revealed microcytic anemia with normal chemical markers. The parents reported no episode of pancreatitis. Ultrasonography revealed massive ascites, which was later found to be bloody. Enhanced computed tomography and magnetic resonance imaging depicted a cystic lesion, approximately 2 cm in size, anterior to the second portion of the duodenum. During exploratory laparotomy, a pinhole was identified on the cyst wall, which was mistakenly identified as a duodenal perforation, and direct closure was performed. Postoperative levels of serum amylase and inflammation markers were elevated, and the amount of ascites increased, impairing oral feeding. The level of pancreatic enzymes in the ascites was high. Imaging studies were repeated, but the cause of pancreatic fistula was not identified. Conservative therapy, including administration of total parenteral nutrition, antibiotics, and octreotide, was initiated, but the situation did not improve. Three months after admission, endoscopic retrograde cholangiopancreatography showed a thick dorsal pancreatic duct communicating with a hypoplastic ventral duct, which was indicative of PD. Contrast medium leaking from the dorsal duct near the minor ampulla revealed the presence of a pseudocyst. Stenting via the minor papilla was impossible because the minor papilla was obstructed. Instead, a stent was inserted into the ventral pancreatic duct. Endoscopic transgastric drainage of the cyst was effective, and the patient was discharged, 7 months after admission. The patient is healthy, but the gastric stent needs to be replaced regularly. CONCLUSION: In children, PD can manifest with pancreatic pseudocyst that causes pancreatic ascites, even in the absence of pancreatitis. This may be a previously unrecognized manifestation of PD in children, and clinicians need to be aware of it.

Associations Among Tooth Loss, Periodontitis, and Carotid Intima-Media Thickness: the Nagahama Study.

AIMS: This study aimed to clarify the relationships among tooth loss, periodontal condition, and subclinical atherosclerosis from the aspect of intensity, extent, and duration of inflammation. METHODS: This cross-sectional study included 9,778 people from the Nagahama Study, a large-scale, general population-based study conducted in Japan. The number of teeth and periodontal status, including the attachment level (AL) and pocket depth (PD) of representative teeth from six regions, were evaluated by dentists. The maximum intima-media thickness (IMT) of the common carotid artery was used as an index of atherosclerosis. RESULTS: In the multivariate analysis adjusted for conventional risk factors, a large number of missing teeth (＜9 remaining teeth), which related to long-lasting inflammation indicative of the highest stage of periodontitis, was identified as an independent determinant of IMT in a general population (coefficient: 0.042; 95% confidence interval [CI]: 0.016 to 0.068). The presence of two or more regions with an AL ≥4 mm, which is indicative of the progressing, long-lasting stages of periodontal inflammation, was also independently associated with IMT (coefficient: 0.016; 95% CI: 0.004 to 0.028). On the contrary, PD, a measure of the early and reversible phases of periodontal inflammation, and loss of AL in the group without tooth loss were not significantly associated with IMT, because of the limited degree of accumulated periodontitis. CONCLUSION: The present results suggest that the association between periodontitis and atherosclerosis depends on the inflammation intensity, extent, and duration.

Neurologists' preferences for device-aided therapy for advanced Parkinson's disease in Japan.

OBJECTIVE: This study measures the relative preference for attributes of device-aided therapies (DATs) for advanced Parkinson's Disease (PD) from the perspective of Japanese neurologists. METHODS: Attributes and levels were elicited based on literature and interviews with certified neurologists experienced with DATs. An online survey including a discrete choice experiment (DCE) was developed, pilot tested, and distributed through an online panel to neurologists treating advanced PD patients. Participants were asked to choose treatments among several choice sets of two hypothetical DATs described only by the attributes, or no DAT (continuing oral treatment). A conditional logit model using the Bayesian framework was developed to estimate the marginal utilities of attributes' levels, and the relative utility of treatments available to Japanese advanced PD patients or being developed in Japan was assessed. RESULTS: The DCE survey completed by 308 neurologists showed that the attributes with the greatest influence on DAT selection were surgery requirement (relative importance of 28%), average increase in the duration of daily "on" time without dyskinesia which affects daily activities (15%), average change in cognitive function related to treatment introduction (15%), device management frequency (14%), average number of pills of oral PD medication after treatment introduction (13%), average influence of treatment on symptoms of depression (12%), and type of device (large/small) (3%). All attributes significantly influenced respondents' choices, except for external device type. Experience with DATs did not influence the directions of preferences. Out of treatment profiles representing DATs, continuous subcutaneous infusion of levodopa-carbidopa had a higher preference score than levodopa-carbidopa intestinal gel infusion and deep brain stimulation. CONCLUSIONS: Our findings suggest that Japanese neurologists would prefer a DAT without surgery requirement. Other factors related to efficacy, safety, and administration mode have a significant, but a smaller influence on prescription choices.

Association Between Tooth Loss and Longitudinal Changes in B-Type Natriuretic Peptide Over 5 Years in Postmenopausal Women: The Nagahama Study.

There is disparity between the sexes in cardiovascular diseases including heart failure (HF). This study aimed to investigate the effect of periodontal disease (PD) on plasma B-type natriuretic peptide (BNP) concentration across sex, age, and menopausal status, as well as the interaction effect of PD and diabetes mellitus (DM) on BNP. This large-scale prospective cohort study enrolled 7539 individuals with no myocardial infarctions or angina pectoris at baseline from the general Japanese population. The association between baseline number of missing teeth (MT) and the longitudinal changes in BNP over 5 years (ΔBNP) was evaluated according to sex and menopausal status. Among 7539 participants, 3190 were postmenopausal women with a mean age ± standard deviation of 61.1 ± 7.6 at baseline. Multivariate analysis revealed a positive association between MT and ΔBNP among postmenopausal women even after adjusting for covariates, including traditional HF risk factors (coefficient, 0.210; 95% confidence interval [CI], 0.107 to 0.312; P < 0.001), but not in men aged > 50. Including an interaction term (MT × DM) in the multivariate model revealed a positive interaction between MT and DM in ΔBNP among postmenopausal women (coefficient for interaction, 1.365; 95% CI, 0.902 to 1.827; P for interaction < 0.001). In conclusion, our study showed a positive association between MT and ΔBNP, as well as a positive effect of the interactive association between MT and DM, among postmenopausal women. Our results suggest a sex difference of an adverse effect of PD on initial myocardial wall stress in the ventricles.

Three Cases of Resection of Late Recurrence of Breast Cancer that Required Differential Diagnosis of Primary Lung Cancer.

We report 3 cases of surgical resection for lung metastasis more than 15 years after initial surgery for breast cancer. Case 1: A 77-year-old woman was referred to our hospital because of a lung nodule in the left lower lobe detected in a computed tomography (CT) scan. She had undergone breast preservation therapy for breast cancer 15 years before the first visit. Left lower lobectomy was performed via video-assisted thoracoscopic surgery (VATS). The pathological diagnosis was lung metastasis of breast cancer, based on positive immunohistochemical staining of estrogen receptor (ER) and gross cystic disease fluid protein 15 (GCDFP-15). Case 2: An 88-year-old woman had undergone a mastectomy for breast cancer 23 years previously. A CT scan revealed a nodule in the upper lobe of the left lung. A wedge resection of the left upper lobe was performed. Because immunostainings for progesterone receptor (PgR) and GCDFP-15 were positive, the pathological diagnosis was metastasis of breast cancer. Case 3: A 78-year-old woman had undergone right mastectomy for the breast cancer 29 years previously. The patient was referred to our hospital because of a nodule in the right lung in a CT scan. Thoracoscopic right upper lobectomy was performed. The pathological diagnosis was lung metastasis of the breast cancer, with immunohistochemical positivity to ER, PgR, and focally to GCDFP-15. A differential diagnosis between primary lung cancer and metastasis of breast cancer on the basis of the findings of a CT scan is often difficult. It is important to obtain the previous clinical information about the breast cancer before VATS, even in patients with a long disease-free interval of more than 15 years.

Dense cancellous bone as evidenced by a high HU value is predictive of late implant failure: a preliminary study.

OBJECTIVES: The mechanism of late implant failure is unclear. This study examined the association between sclerosing cancellous bone images and the risk of late implant failures using multi-detector row computed tomography (CT) imaging data. METHODS: We performed a case-control study. The study group consisted of consecutive patients with implant failures treated at Kyushu Dental University between 2001 and 2016. CT data for late failure of 36 implants in 16 patients were available. The study cohort consisted of 16 patients with 36 late failed implants and 28 patients with 113 successful implants. RESULTS: The mean survival rate was 6.9 months for early implant failure, 76.6 months for late failure with marginal bone resorption, inflammation symptoms, and so-called peri-implantitis, and 95.0 months for late failure caused by implant fracture. The mean HU value for cases in the control group was 507 compared with 1231 for cases with late failure implants. Logistic regression was used for analysis. There were signs of high radiodensity of peri-implant cancellous bone when comparing adjusted radiodensity per 100 HU using CT data (OR 2.35; 95% CI 1.73-3.20; p < 0.001). CONCLUSIONS: Within the limits of our study, the presence of high radiodensity and cancellous bone consolidation on imaging may be related to risk factors for late implant failure. Therefore, CT images of the host cancellous bone status for observation of visible sclerosis could be a useful diagnostic indicator for late implant failure.

Neighborhood social capital and sleep duration: a population based cross-sectional study in a rural Japanese town.

BACKGROUND: Studies on social capital and health outcomes have become common, but the relationship between neighborhood social capital and sleep duration by gender is still unclear. We examined the relationship between neighborhood social capital and sleep duration by gender in adults living in a rural community in Japan. METHOD: We conducted a cross-sectional survey of 12,321 residents aged ≥20 years in a town in Mie Prefecture in January-March 2013. Self-completed questionnaires were collected from the residents (n = 7782; valid participation rate, 63.2%). We used five items to assess the neighborhood social capital (Cronbach's α = 0.86). We summed up the scores of each item, and then divided the participants into four groups by quartile of total scores of neighborhood social capital (lowest, low, high, and highest). Sleep duration of < 7 h/day was defined as insufficient sleep duration according to previous studies. To adjust for potential confounders, we performed a multiple log-binominal regression analysis and estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) for insufficient sleep. RESULTS: Overall 42% of the men and 45% of the women had insufficient sleep. In the men, the lowest group of neighborhood social capital presented a 22% higher prevalence of insufficient sleep (PR 1.22; 95% CIs 1.08-1.38) compared to the highest group of neighborhood social capital. Similarly the low group of neighborhood social capital and the high group of neighborhood social capital had 20 and 19% higher prevalence of insufficient sleep (PR 1.20; 95% CIs 1.06-1.36; PR 1.19; 95% CIs 1.06-1.34, respectively) compared to the highest group of neighborhood social capital. For women there was no significant association between neighborhood social capital and insufficient sleep after controlling for all potential confounders. CONCLUSION: Having lower neighborhood social capital was associated with insufficient sleep among Japanese adults, particularly in the men. This suggests that the context of neighborhood social capital by gender should be considered to promote healthier behaviors with regard to getting enough sleep.

Rural-Urban Disparity in Emergency Care for Acute Myocardial Infarction in Japan.

BACKGROUND: There are few reports examining regional differences between rural prefectures and metropolitan areas in the management of acute myocardial infarction (AMI) in Japan.Methods and Results:In the Rural AMI registry, a prospective, multi-prefectural registry of AMI in 4 rural prefectures (Ishikawa, Aomori, Ehime and Mie), a total of 1,695 consecutive AMI patients were registered in 2013. Among them, 1,313 patients who underwent primary percutaneous coronary intervention (PPCI) within 24 h of onset were enrolled in this study (Rural group), and compared with the cohort data from the Tokyo CCU Network registry for AMI in the same period (Metropolitan group, 2,075 patients). The prevalence of direct ambulance transport to PCI-capable facilities in the Rural group was significantly lower than that in the Metropolitan group (43.8% vs. 60.3%, P<0.01), which resulted in a longer onset-to-balloon time (OTB: 225 vs. 210 min, P=0.02) and lower prevalence of PPCI in a timely fashion (OTB ≤2 h: 11.5% vs. 20.7%, P<0.01) in the Rural group. Multivariate analysis revealed that direct ambulance transport was the strongest predictor for PPCI in a timely fashion (odds ratio=4.13, P<0.001). CONCLUSIONS: AMI patients in rural areas were less likely to be transported directly to PCI-capable facilities, resulting in time delay to PPCI compared with those in metropolitan areas.

Is there an occupational status gradient in the development of periodontal disease in Japanese workers? A 5-year prospective cohort study.

BACKGROUND: Development of periodontal disease (PD) may be affected by socioeconomic status. This study examined the relationship between occupational status and PD in a 5-year prospective cohort of Japanese workers. METHODS: In total, 19,633 participants had initial examinations at the Aichi Health Promotion Foundation, of whom 8210 participants aged 20 years or older did not have PD. Follow-up examinations were conducted for 3757 participants, accounting for 45.8% of baseline participants. Ultimately, 3390 participants were analyzed according to the criterion of job classification at baseline, which was based on the International Standard Classification of Occupations, 1987. Oral examinations were performed using the Community Periodontal Index (CPI). The CPI scores were coded as follows: healthy (score of 0); bleeding after probing (1); dental calculus (2); shallow pockets (3); and deep pockets (4). Participants with one or more sextants with a score >2 were diagnosed with PD. Poisson regression analysis was performed to adjust for age and other potential confounders. RESULTS: Overall, 31.6% of men and 23.8% of women had developed PD (CPI scores of 3 or 4). The adjusted relative risk (RR) for PD (CPI scores of 3 or 4) in men was not significant. On the other hand, the adjusted RRs for PD (CPI score of 4) in men were 2.52-, 2.39-, and 2.74-fold higher for skilled workers, sales persons, and drivers, respectively, than for professionals. In contrast, we found no gradient in women. CONCLUSIONS: We found a gradient related to the risk of developing PD according to occupational status among men in a Japanese worker population.

Worker resignation due to patient nuisance in hospitals: Determinants and prevention.

To investigate determinants and protective strategies for the resignation of health care workers resulting from patient-derived nuisance in medical institutions, we conducted a cross-sectional survey in the 57 hospitals in Mie Prefecture, Japan. A random sampling of 775 employees (physicians, nurses, administrators, and other health care workers) was provided self-administered questionnaires. Among 480 participants who experienced patient-derived nuisance, 132 participants considered resignation as a result, giving an estimated prevalence of 17.1% (95% CI: 14.4%-19.8%) of all respondents. Nonphysical nuisances such as "demand for an unwarranted apology" (OR: 2.57; 95% CI: 1.61-4.12) had higher ORs for considering resignation than other kinds of nuisance. By contrast, OR for the provision of human support by medical institutions was 0.49 (95% CI: 0.28-0.86). Human support was associated with alleviation of the intention to resign.

Does a mandibular overdenture improve nutrient intake and markers of nutritional status better than conventional complete denture? A systematic review and meta-analysis.

OBJECTIVES: The need for denture treatment in public health will increase as the population ages. However, the impact of dentures on nutrition, particularly overdenture treatment, remains unclear although the physical and psychological effects are known. We investigated whether treatment with a mandibular implant supported overdenture improves nutrient intake and markers of nutritional status better than a conventional complete denture in edentulous patients. DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE and the Cochrane Central Register of Controlled Trials were searched for eligible studies published up to April 2016. We included studies which compared the treatment effect of an overdenture to conventional denture on nutrition, in which primary outcomes included changes in intake of macronutrients and/or micronutrients and/or indicators of nutritional status. Two reviewers independently evaluated eligible studies and assessed the risk of bias. We used a fixed effects model to estimate the weighted mean difference (WMD) and 95% CI for change in body mass index (BMI), albumin and serum vitamin B12 between overdenture and conventional denture 6 months after treatment. RESULTS: Of 108 eligible studies, 8 studies involving 901 participants were included in the narrative appraisal. Four studies reported changes in markers of nutritional status and nutrient intake after treatment with a prosthetic, regardless of type. In a meta-analysis of 322 participants aged 65 years or older from three studies, pooled analysis suggested no significant difference in change in BMI between an overdenture and conventional denture 6 months after treatment (WMD=-0.18 kg/m(2) (95% CI -0.52 to 0.16)), and no significant difference in change in albumin or vitamin B12 between the two treatments. CONCLUSIONS: The modifying effect of overdenture treatment on nutritional status might be limited. Further studies are needed to evaluate the effectiveness and efficacy of denture treatments.

The novel association between red complex of oral microbe and body mass index in healthy Japanese: a population based cross-sectional study.

Microbiota has been thought to be one of important environmental factors for obesity or Type 2 diabetes mellitus. Among oral microbe, Porphyromonas gingivalis, Treponema denticola and Tannellera forsythia are known as risk factors, so called red complex, for periodontitis. Red complex could also be a risk factor for obesity. However, recent study indicated that obesity was not improved by periodontal therapy. Thus, we performed a cross sectional study to reveal the association of oral microbe with body mass index in a healthy population. Healthy individuals were randomly recruited. The infections of oral microbe were identified by Taqman polymerase chain reaction. The relationships between number of red complex and body mass index or waist circumference were analyzed. Two hundred and twenty-two apparently healthy Japanese were enrolled. BMI and waist circumference as well as age, periodontitis, number of brushing teeth were significantly associated with the number of red complex after adjusting covariance. The effect size of body mass index or waist circumference was 0.023 (p = 0.028) or 0.024 (p = 0.024), respectively. Body mass index and waist circumference were independently associated with the number of red complex among apparently healthy Japanese. The current observation implies the possibility that oral microbe was associated with obesity in healthy population.

[Analysis of factors related to social functioning in school students with high-functioning pervasive developmental disorder].

OBJECTIVE: To analyze the factors related to social functioning in school students with high-functioning pervasive developmental disorder (HFPDD), we investigated speech delay in infancy, family history of pervasive developmental disorder (PDD), intelligence quotient (IQ), strength of PDD characteristics, age, age at diagnosis of PDD, and social adaptive functioning in students with HFPDD. METHODS: Fifty-eight students with a diagnosis of HFPDD (IQ ≥ 85) were evaluated retrospectively. PDD characteristics were measured by the Pervasive Developmental Disorders Autism Society Japan Rating Scale (PARS), IQ was measured by the Wechsler Intelligence Scale for Children-Third Edition (WISC-III), and social adaptive functioning was measured by the Children's Global Assessment Scale (CGAS). RESULTS: There was a negative correlation between age at diagnosis of PDD and the CGAS score. None of the other factors examined had any significant correlation with social functioning in students with HFPDD. Age at diagnosis of PDD whose social functioning was good was significantly low. CONCLUSIONS: School students with HFPDD who are diagnosed with PDD earlier exhibit better social adaptive functioning.

Periodontitis and Porphyromonas gingivalis in preclinical stage of arthritis patients.

PURPOSE: To determine whether the presence of periodontitis (PD) and Porphyromonas gingivalis (Pg) in the subgingival biofilm associates with the development of rheumatoid arthritis (RA) in treatment naïve preclinical stage of arthritis patients. METHODS: We conducted a prospective cohort study of 72 consecutive patients with arthralgia who had never been treated with any anti-rheumatic drugs or glucocorticoids. Periodontal status at baseline was assessed by dentists. PD was defined stringently by the maximal probing depth≧4 mm, or by the classification by the 5th European Workshop in Periodontology (EWP) in 2005 using attachment loss. Up to eight plaque samples were obtained from each patient and the presence of Pg was determined by Taqman PCR. The patients were followed up for 2 years and introduction rate of methotrexate (MTX) treatment on the diagnosis of RA was compared in patients with or without PD or Pg. RESULTS: Patients with PD (probing depth≧4mm) had higher arthritis activity (p = 0.02) and higher risk for future introduction of MTX treatment on the diagnosis of RA during the follow up than patients without PD (Hazard ratio 2.68, p = 0.03). Arthritis activity and risk for MTX introduction increased with the severity of PD assessed by EWP, although not statistically significant. On the other hand, presence of Pg was not associated with arthritis activity (p = 0.72) or the risk for MTX introduction (p = 0.45). CONCLUSION: In treatment naïve arthralgia patients, PD, but not the presence of Pg, associates with arthritis activity and future requirement of MTX treatment on the diagnosis of RA.

Significant association of periodontal disease with anti-citrullinated peptide antibody in a Japanese healthy population - The Nagahama study.

Anti-citrullinated peptide antibody (ACPA) is a highly specific autoantibody to rheumatoid arthritis (RA). Recent studies have revealed that periodontal disease (PD) is closely associated with RA and production of ACPA in RA. Analyses of associations between PD and ACPA production in a healthy population may deepen our understandings. Here, we analyzed a total of 9554 adult healthy subjects. ACPA and IgM-rheumatoid factor (RF) was quantified and PD status was evaluated using the number of missing teeth (MT), the Community Periodontal Index (CPI) and Loss of Attachment (LA) for these subjects. PD status was analyzed for its association with the positivity and categorical levels of ACPA and RF conditioned for covariates which were shown to be associated with PD, ACPA or RF. As a result, all of MT, CPI and LA showed suggestive or significant associations with positivity (p = 0.024, 0.0042 and 0.037, respectively) and levels of ACPA (p ≤ 0.00031), but none of the PD parameters were associated with those of RF. These association patterns were also observed when we analyzed 6206 non-smokers of the participants. The significant associations between PD parameters and positivity and levels of ACPA in healthy population support the fundamental involvement of PD with ACPA production.

Recent Clinical Evidence in Bisphosphonate-related Osteomyelitis of the Jaw: Focus on Risk, Prevention and Treatment.

Bisphosphonates (BPs) are widely used for the treatment of a range of conditions involving bone, such as osteoporosis and bone metastases of cancer, and their efficacy has been confirmed. Nevertheless, a first case of bisphosphonate- related osteonecrosis of the jaw (BRONJ) as an adverse effect of BP treatment was reported in 2003, and several clinical studies since then have elaborated the risk, prevention and treatment of BRONJ or bisphosphonate-related osteomyelitis of the jaw (BROMJ). However, effective decision making on BP risk is hampered by a lack of accurate information for patients, physicians or dentists. Furthermore, the narrow definition of BRONJ used to date has precluded the wider development of clinical research on risk. In this review, we discuss current issues in BROMJ, with a focus on risk, prevention and treatment. In particular, we reconsider the definition of BRONJ from the standpoint of clinical evidence. Finally, we propose a new strategy for the treatment of BROMJ.

The increase in prescriptions of bisphosphonates and the incidence proportion of osteonecrosis of the jaw after risk communication activities in Japan: a hospital-based cohort study.

PURPOSE: The purpose of this study was to investigate the impact of risk communication about bisphosphonate (BP)-related osteonecrosis of the jaw (ONJ) on the number of reported cases to the Drug Adverse Reactions Reporting System and on the incidence proportion of ONJ in a hospital-based cohort study in Japan. METHOD: We conducted a survey of the safety information on BP-related ONJ available from regulatory authorities, pharmaceutical manufacturers and academic associations. We also performed a trend analysis of a dataset from the Drug Adverse Reactions Reporting System and a sub-analysis, using previously constructed data from a retrospective cohort study. RESULTS: Risk communication from pharmaceutical manufacturers and academic associations began within 1 year after revisions were made to the package inserts, in October 2006. Twenty times more cases of ONJ have been reported to regulatory authority since 2007, compared with the period before 2007. In our cohort, the incidence proportion of ONJ during and after 2009 was four times greater than before 2009. During this period, BPs were frequently prescribed, whereas there was no increase in the use of alternative agents, such as selective estrogen receptor modulators. CONCLUSION: ONJ was increasingly diagnosed after risk communication efforts, but the impact of the communications was not clear. Safety notifications were diligently disseminated after the package insert was revised. However, there was no surveillance for ONJ before the revision.