Association between respiratory and heart rate fluctuations and death occurrence in dying cancer patients: continuous measurement with a non-wearable monitor.

BACKGROUND: The present study aimed to explore the association between impending death and continual changes in respiratory and heart rates measured using a non-wearable monitor every minute for the final 2 weeks of life in dying cancer patients. METHODS: In this longitudinal study, we enrolled patients in a palliative care unit and continuously measured their respiratory and heart rates via a monitor and additionally captured their other vital signs and clinical status from medical records. RESULT: A dataset was created comprising every 24-h data collected from every-minute raw data, including information from 240 days prior to death from 24 patients (345,600 data); each patient's data were measured for 3-14 days until death. After confirming the associations between the respiratory and heat rate values on the day of death (n = 24) or other days (2-14 days before death, n = 216) and the mean, maximum, minimum, and variance of respiratory and heart rates every 24 h by univariate analyses, we conducted a repeated-measures logistic regression analysis using a generalized estimating equation. Finally, the maximum respiratory rate and mean heart rate were significantly associated with death occurring within the following 3 days (0-24 h, 0-48 h, and 0-72 h), except for the maximum respiratory rate that occurs within 0-24 h. CONCLUSION: The maximum respiratory rate and mean heart rate measured every minute using a monitor can warn family caregivers and care staff, with the support of palliative care professionals, of imminent death among dying patients at home or other facilities.

Segmental resection with partial mesopancreatic and mesojejunal excision (pMME) for duodenal carcinoma of the third or fourth portion.

INTRODUCTION: Pancreatoduodenectomy is the standard procedure for duodenal carcinoma of the third or fourth portion. As an alternative option, we developed a novel segmental resection (SR) with partial mesopancreatic and mesojejunal excision (pMME) that enhances radicality. In this report, the surgical technique with video and outcomes are described. METHOD: We performed SR with pMME on seven consecutive patients with third or fourth duodenal carcinoma between 2009 and 2021. We divided the procedure into four sections, including (1) wide Kocher's maneuver, (2) supracolic anterior artery-first approach, (3) dissection of the mesopancreas and mesojejunum, and (4) devascularization of the uncinate process and dissection of duodenum. RESULT: Median operative time was 348 min (range, 222-391 min), and median blood loss was 100 mL (range, 30-580 mL). Major complications of Clavien-Dindo classification grade 3a or more occurred in one patient. All patients achieved R0 resections with 10 mm or more proximal margin. Six cases (85%) were alive without recurrence. CONCLUSION: We developed a radical and safe procedure of SR with pMME as an alternative and less invasive approach for duodenal carcinoma of the third or fourth portion.

Nonwearable actigraphy to assess changes in motor activity before and after rescue analgesia in terminally ill patients with cancer: A pilot study.

AIMS: This study aimed to investigate the usefulness of nonwearable actigraphy to assess changes in motor activity before and after rescue analgesic administration in terminally ill cancer patients. BACKGROUND: Evaluating pain in terminally ill cancer patients is difficult; pain assessment tools are needed. METHODS: This was an exploratory descriptive study conducted within a palliative care unit. A nonwearable actigraph was used to measure the activity score and movement index of terminally ill patients with weeks-long prognosis and pain. The actigraph and medical data were integrated, and data were compared 6 h before and after rescue analgesic administration. RESULTS: Among 10 patients (age: 75.8 ± 12.3 years; six men), we evaluated 28 pain episodes (mean activity score: 130.9 ± 180.5 counts per minute; movement index: 68.8%). When pain was relieved at night following rescue analgesic administration, activity score and movement index decreased significantly (6 h before vs. 6 h after analgesics, respectively: 113.1 to 69.7 counts per minute; 64.3% to 41.8%; both p < 0.0001). With no relief after rescue analgesic administration, activity score did not differ significantly 6 h before and after analgesics: 147.3 to 137.7 counts per minute. CONCLUSION: Pain in terminally ill cancer patients could be assessed using a nonwearable actigraph to capture motor activity and improve pain assessment.

Assessing timewise changes over 15 months in life-space mobility among community-dwelling elderly persons.

BACKGROUND: The purpose of this study was to examine the differences of timewise changes in life-space mobility between elderly people living alone and those living with others among community-dwelling elderly people from a day care facility with a rehabilitation service for seniors. METHODS: The present study used a longitudinal design with repeated measures every 3 months. In conformity with our inclusion criteria, this study included 233 community-dwelling elderly users of a day care facility with rehabilitation services for seniors in Japan. We analyzed the life-space assessment (LSA) scores collected at five time points (baseline, 3 months, 6 months, 9 months, and 12 months) using mixed-effects models with random intercepts and slopes over time. In the present study, the explanatory variables of interest were time, and living situation (living alone or with others). As possible confounders, we considered the following: (a) age, (b) sex, (c) social frailty, (d) physical frailty, (e) mild cognitive impairment (MCI), (f) depression, and (g) economic satisfaction. RESULTS: The mean age of participants was 78.9 years (SD = 7.7), their mean LSA score was 60.1 points (SD = 25.7), and 42.9% of the participants were men. After adjusting for age, gender, frailty, depression, MCI, and economic satisfaction, the mean LSA score of older adults who lived with others was significantly lower (7.42 points, 95%CI = - 18.30 to - 0.15, p = 0.048) than that older adults who lived alone. DISCUSSION: Community-dwelling older adults who used a day care center with rehabilitation services and lived with others had a smaller life-space at baseline than those who lived alone. This suggests that there is a need to pay more attention to social frailty among both older adults who live alone and those who live with others. CONCLUSIONS: According to a multilevel analysis growth model, elderly persons who lived with others had significantly lower life-space mobility than those who lived alone.

Association between salivary flow rate and depressive symptoms with adjustment for genetic and family environmental factors in Japanese twin study.

OBJECTIVES: The association between salivary flow rate (SFR) and depressive symptoms have been inconclusive. The present study aimed to investigate the association between SFR and depressive symptoms with and without adjustment for genetic and family environmental factors. MATERIALS AND METHODS: We conducted a cross-sectional study using twins and measured SFR and depressive symptoms as the outcome and explanatory variables, respectively. We also performed three-step regression analyses by first analysing the association between SFR and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed between-within analyses using monozygotic (MZ) and same-sex dizygotic (DZ) twin pairs, and finally using only MZ twin pairs. These between-within analyses estimated the coefficients adjusted for genetic and family environmental factors. Furthermore, differences in the associations between individual-level and between-within suggest confounding by genetic and family environmental factors. RESULTS: We conducted 448 twins aged ≥20 years. In individual-level analyses in males and between-within analyses using MZ and same-sex DZ male twin pairs, SFR associated with depressive symptoms. In between-within analyses using only MZ male twin pairs, SFR did not associate with depressive symptoms. In females, SFR did not associate with depressive symptoms in both individual-level and between-within analyses. CONCLUSIONS: The present study revealed that the association between SFR and depressive symptoms was affected by common genetic factors in males. CLINICAL RELEVANCE: Understanding this association between SFR and depressive symptoms with adjustment for genetic and family environmental factors could lead to an important consideration for the prevention and treatment of hyposalivation.

Prenatal vitamin A supplementation associated with adverse child behavior at 3 years in a prospective birth cohort in Japan.

BACKGROUND: Many pregnant women take vitamin supplements during pregnancy. The aim of this paper was to clarify the effects of dietary supplementation prior to and/or during pregnancy on child behavior. METHODS: A prospective birth cohort study from pregnancy to 3 years of age involving 1271 pairs of Japanese pregnant women and their newborns, was carried out. The women completed a self-administered questionnaire during the third trimester of pregnancy. To evaluate deviations in child behavior as an endpoint, each mother completed the Japanese Child Behavior Checklist for ages 2-3 years after 3 years of birth. Participant characteristics were compared between supplement takers and non-takers. RESULTS: Among many kinds of supplements, intake of supplemental vitamin A/ß-carotene prior to and/or during pregnancy was associated with hazardous effects on child behavior at 3 years of age (total t-score, P = 0.003; internal t-score, P = 0.027; external t-score, P = 0.013). This association held true even after adjusting for age, number of deliveries, infertility treatment, consumption of fast food, smoking status, maternal and paternal education, maternal and paternal income, gestational age at birth, anthropometry at birth (weight, height, head circumference and body circumference), and the State-Trait Anxiety Inventory at 3 years of age by means of multiple imputation. CONCLUSIONS: Intake of supplemental vitamin A prior to and/or during pregnancy may worsen child behavior at 3 years of age.

Association between subjective memory complaints and depressive symptoms after adjustment for genetic and family environmental factors in a Japanese twin study.

OBJECTIVES: The aim of this study was to investigate the association between subjective memory complaints (SMCs) and depressive symptoms, with and without adjustment for genetic and family environmental factors. METHODS: We conducted a cross-sectional study using twins and measured SMCs and depressive symptoms as outcomes and explanatory variables, respectively. First, we performed regression analyses using generalized estimating equations to investigate the associations between SMCs and depressive symptoms without adjustment for genetic and family environmental factors (individual-level analyses). We then performed regression analyses for within-pair differences using monozygotic (MZ) and dizygotic (DZ) twin pairs and MZ twin pairs to investigate these associations with adjustment for genetic and family environmental factors by subtracting the values of one twin from those of co-twin variables (within-pair level analyses). Therefore, differences between the associations at individual- and within-pair level analyses suggested confounding by genetic factors. RESULTS: We included 556 twins aged ≥ 20 years. In the individual-level analyses, SMCs were significantly associated with depressive symptoms in both males and females [standardized coefficients: males, 0.23 (95% CI 0.08-0.38); females, 0.35 (95% CI 0.23-0.46)]. In the within-pair level analyses using MZ and same-sex DZ twin pairs, SMCs were significantly associated with depressive symptoms. In the within-pair level analyses using the MZ twin pairs, SMCs were significantly associated with depressive symptoms [standardized coefficients: males, 0.32 (95% CI 0.08-0.56); females, 0.24 (95% CI 0.13-0.42)]. CONCLUSIONS: This study suggested that SMCs were significantly associated with depressive symptoms after adjustment for genetic and family environmental factors.

The relationship between body mass index and uric acid: a study on Japanese adult twins.

OBJECTIVES: The present study aimed to investigate the association between body mass index (BMI) and uric acid (UA) using the twin study methodology to adjust for genetic factors. METHODS: The association between BMI and UA was investigated in a cross-sectional study using data from both monozygotic and dizygotic twins registered at the Osaka University Center for Twin Research and the Osaka University Graduate School of Medicine. From January 2011 to March 2014, 422 individuals participated in the health examination. We measured height, weight, age, BMI, lifestyle habits (Breslow's Health Practice Index), serum UA, and serum creatinine. To investigate the association between UA and BMI with adjustment for the clustering of a twin within a pair, individual-level analyses were performed using generalized linear mixed models (GLMMs). To investigate an association with adjustment for genetic and family environmental factors, twin-pair difference values analyses were performed. RESULTS: In all analysis, BMI was associated with UA in men and women. Using the GLMMs, standardized regression coefficients were 0.194 (95 % confidence interval: 0.016-0.373) in men and 0.186 (95 % confidence interval: 0.071-0.302) in women. Considering twin-pair difference value analyses, standardized regression coefficients were 0.333 (95 % confidence interval: 0.072-0.594) in men and 0.314 (95 % confidence interval: 0.151-0.477) in women. CONCLUSIONS: The present study shows that BMI was significantly associated with UA, after adjusting for both genetic and familial environment factors in both men and women.

Inferior Pole Sleeve Fracture of the Patella in an Adolescent: A Case Report.

An 11-year-old boy was admitted to our hospital due to severe pain in his right knee when he landed after jumping over a vaulting box. A plain X-ray image and computed tomography scan showed an avulsion fracture of the lower pole of the patella and patella alta. Furthermore, magnetic resonance imaging (MRI) revealed an articular cartilage lesion and rupture between the inferior pole of the patella and the patella tendon. We diagnosed a sleeve fracture of the patella and performed surgical treatment. Open reduction and internal fixation were performed by the pull-out technique using transosseous no. 2 MaxBraid™â€‹â€‹â€‹â€‹â€‹â€‹ ​(Zimmer Biomet, Tokyo, Japan) sutures. While postoperative weight-bearing was permitted, the knee joint was immobilized in a brace for four weeks. Three months of postoperative assessment revealed excellent functional outcomes.

Indocyanine green-fluorescent imaging for a detection of accessory pancreatic duct in pancreas-preserving duodenectomy.

Pancreas-preserving duodenectomy is indicated for select patients with a duodenal tumor in the second portion. In this procedure, identification and closure of the accessory pancreatic duct is important to prevent postoperative pancreatic fistula. A 63-y-old man was diagnosed with duodenal mucosal carcinoma in the second portion, with invasion of the major ampullary. We performed pancreas-preserving duodenectomy. Intraoperatively, indocyanine green-fluorescent imaging identified the accessory pancreatic duct clearly and it was successfully closed. Postoperative pancreatic fistula did not occur. Indocyanine green-fluorescent imaging is effective in identifying the accessory pancreatic duct in pancreas-preserving duodenectomy.

Mixed neuroendocrine carcinoma and hepatocellular carcinoma in the liver.

BACKGROUND: Mixed neuroendocrine carcinoma (NEC) and hepatocellular carcinoma (HCC) is extremely rare, thus radiological features have not been fully clarified. CASE: A male patient (age: 70 years) visited our hospital due to a tumor in the liver. Examination using contrast-enhanced computed tomography (CT) revealed a tumor (diameter: 5.0 cm) in hepatic segment 5, with early enhancement of the peripheral area and slight internal heterogeneous enhancement in the arterial and delayed phases, respectively. F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET)/CT revealed intratumoral heterogeneity, characterized by increased uptake (standardized uptake value, 12.10) in the corresponding low-density area detected using enhanced CT relative to the surrounding areas of the tumor. On magnetic resonance imaging, diffusion-weighted imaging also showed high intensity in the corresponding low-density area detected using CT. Preoperatively, the patient was diagnosed with HCC and underwent anterior sectionectomy. Pathological findings revealed both HCC and NEC components, and the patient was diagnosed with mixed NEC and HCC. Comparison of component distribution with FDG-PET/CT revealed an increased uptake area was congruent with the NEC component in the tumor. CONCLUSION: In this case, the difference in tumor components affected the uptake in FDG-PET/CT. Such heterogeneous uptake with an enhanced spot may be useful for suspecting the presence of mixed NEC and HCC in patients with atypical HCC.

Sequential therapy of portal vein embolization and systemic chemotherapy for locally advanced perihilar biliary tract cancer.

BACKGROUND: Curative resection is the only potential treatment for cure in patients with perihilar biliary tract cancer (PBTC). However, post hepatectomy liver failure (PHLF) due to insufficient future liver remnant volume (FRLV) remains a lingering risk even after portal vein embolization (PVE). This study aimed to investigate the feasibility and efficacy of a sequential treatment strategy consisting of PVE followed by preoperative chemotherapy before surgery. METHODS: Between April 2019 and December 2021, 15 patients with locally advanced PBTC (LA-PBTC) underwent sequential treatment consisting of PVE followed by preoperative chemotherapy. The feasibility and efficacy, including resection rate, changes of FRLV, and chemotherapeutic effect, were investigated retrospectively. RESULTS: Thirteen of 15 patients (86.6%) underwent curative resection. The median duration time between PVE and surgery was 144 days. FRLV/TLV ratio was 31.3% at prePVE, 38.4%, at two weeks after PVE, and 45.7% before surgery, respectively. There was significant increase in FRLV/TLV ratio two weeks after PVE. Additional increase in FRLV/TLV ratio was significantly achieved before surgery. PHLF occurred in 5 patients (38.4%). Pathological complete response was found in 2 of 13 patients (15.3%). CONCLUSIONS: Sequential PVE and systemic chemotherapy contribute to the sufficient hypertrophy of FRLV without compromising resectability in patients with LA-PBTC.

Effects of a Nanophase-Separated Structure on Mechanical Properties and Proton Conductivity of Acid-Infiltrated Block Polymer Electrolyte Membranes under Non-Humidification.

Acid-infiltrated block polymer electrolyte membranes adopting a spherical or lamellar nanophase-separated structure were prepared by infiltrating sulfuric acid (H2SO4) into polystyrene-b-poly(4-vinylpyridine)-b-polystyrene (S-P-S) triblock copolymers to investigate the effects of its nanophase-separated structure on mechanical properties and proton conductivities under non-humidification. Lamellae-forming S-P-S/H2SO4 membranes with a continuous hard phase generally exhibited higher tensile strength than sphere-forming S-P-S/H2SO4 membranes with a discontinuous hard phase even if the same amount of Sa was infiltrated into each neat S-P-S film. Meanwhile, the conductivities of lamellae-forming S-P-S/H2SO4 membranes under non-humidification were comparable or superior to those of sphere-forming S-P-S/H2SO4 membranes, even though they were infiltrated by the same weight fraction of H2SO4. This result is attributed to the conductivities of S-P-S/H2SO4 membranes being greatly influenced by the acid/base stoichiometry associated with acid-base complex formation rather than the nanophase-separated structure adopted in the membranes. Namely, there are more free H2SO4 moieties that can release free protons contributing to the conductivity in lamellae-forming S-P-S/H2SO4 membranes than sphere-forming S-P-S/H2SO4, even when the same amount of H2SO4 was infiltrated into the S-P-S.

Acute intestinal necrosis due to multiple thrombosis in COVID-19 patient. Report of a case.

BACKGROUND: While thrombosis is a well-known complication of coronavirus disease 2019 (COVID-19) infection, reports on intestinal necrosis due to intestinal ischemia caused by thrombosis are extremely rare. We herein report a case of intestinal necrosis due to multiple thrombosis in a COVID-19 patient. CASE PRESENTATION: The patient was a 64-year-old man. He was admitted to hospital after being diagnosed with COVID-19, the severity was classified as moderate II. Nasal High Flow™ management was conducted along with treatment with tocilizumab, remdesivir, and dexamethasone. Heparin was also administered due to high D-dimer values. As abdominal pain appeared from the 6th day of hospitalization, contrast-enhanced CT was performed, which confirmed multiple thrombosis in the aorta. However, no obvious intestinal ischemia was found. On the 10th day of hospitalization, the patient's abdominal pain was exacerbated. Upon re-evaluation by CT, he was diagnosed with perforative peritonitis due to ileal ischemic necrosis and emergency surgery was performed. Intraoperative examination revealed perforation due to necrosis at multiple sites in the ileum; thus, partial ileectomy was carried out. Pathological findings also revealed discontinuous multiple intestinal necrosis due to the frequent occurrence of thrombosis. Following surgery, the patient recuperated and was discharged after ventilator management and multimodal therapy at the ICU. CONCLUSIONS: Thrombosis due to COVID-19 complications is rare in the intestinal tract, but also occur. Its initial symptoms might not be captured by CT images, therefore caution is required.

The Differential Heritability of Social Adjustment by Sex.

Sex differences in social adjustment are frequently observed; however, there has been very little research on adaptability in the individual and social domains. The aim of this study was to investigate the sex difference in social abilities, such as high self-appeal, sociability, school adaptation, and home adaptation between school-age males and females. The sample for this study included both same-sex and opposite-sex twin pairs: a total of 467 twin pairs. We classified them into three groups: a group of those in lower classes of elementary school, a group of those in higher classes of elementary school, and a group of those in junior high school. The heritability of school adaptation was estimated to be 95% in males and 54% in females in the junior high school group. The full sex-limitation model showed a better fit in this group, and this means that a qualitative genetic difference exists. For school adaptation, there was no sex difference in lower elementary school classes; however, a quantitative difference appeared in higher classes of elementary school. Moreover, a qualitative difference appeared in junior high school. From this research, it became clear that sex differences in heritability exist for school adaptation, and there was a marked increase from the elementary school children to the junior high school children.

The change over time of vital signs with consideration for opioid use in the last 2 weeks of life among cancer patients in a palliative care unit: Continuous measurement of vital signs using a non-wearable monitor.

OBJECTIVES: The aim of this study was to examine the following by using a non-wearable monitor: (ⅰ) the trajectory of vital signs (VS) in the last 2 weeks of life among cancer patients, and (ⅱ) the difference in change over time of VS between cancer patients with and without opioid use. METHODS: We conducted a longitudinal study involving cancer patients in a palliative care unit (PCU) from April 2018 to October 2019. VS were collected continuously using a non-wearable monitor, and we calculated the means of respiratory rate (RR) and heart rate (HR) per hour, and counts of apnea per hour as outcome variables. Explanatory variables were time (subtracting time of death from measurement time of VS, divided by 36) and opioid use. Mean difference (MD) of time represented the slope per hour of VS values. First, we analyzed the associations between VS per hour and time using a linear mixed model (LMM) with random intercepts and slope over time. Second, we analyzed the associations between VS and interaction term between time and opioid use. RESULTS: We analyzed 26 cancer patients. RR (MD: 0.27 beats/min [95% CI: 0.27-0.28]), HR (MD: 1.51 beats/min [95% CI: 1.50-1.52]), and apnea (MD: 0.71 count/hour [95% CI: 0.70-0.72]) significantly increased hourly. In addition, RR was significantly associated with interaction term (MD: -1.59 beats/min [95% CI: -3.11 to -0.07]), which indicates that there is a difference in the slope of RR between opioid users and non-users. CONCLUSIONS: We have successfully described the trajectory of VS in high-resolution under conditions of a natural end of life in PCU.

Clinical evaluation of TRCRapid M.TB for detection of Mycobacterium tuberculosis complex in respiratory and nonrespiratory specimens.

The rapid and accurate diagnosis of tuberculosis is crucial to providing optimal treatment and reducing the spread of infection. We evaluated respiratory and nonrespiratory clinical specimens using a new automated Mycobacterium tuberculosis complex (MTBC) rRNA detection kit (TRCRapid M.TB; Tosoh Bioscience, Tokyo, Japan), which is based on the transcription-reverse transcription concerted reaction (TRC). TRC enables the rapid and completely homogeneous real-time monitoring of isothermal RNA sequence amplification without any postamplification procedures. The results were compared with those obtained by M. tuberculosis culture. A total of 1,155 respiratory specimens and 420 nonrespiratory specimens collected from 1,282 patients were investigated. Of the 45 specimens culture positive for MTBC, 42 were TRC positive, and of the 1,530 specimens culture negative for MTBC, 1,523 were TRC negative. Compared to the results of culture, the overall sensitivity and specificity of TRC were 96.6% and 99.9%, respectively, for respiratory specimens and 87.5% and 98.5%, respectively, for nonrespiratory specimens. The sensitivities of TRC were 100% for smear-positive respiratory and nonrespiratory specimens, 88.9% for smear-negative respiratory specimens, and 80% for smear-negative nonrespiratory specimens. No significant differences in test performance between respiratory and nonrespiratory specimens were observed. The TRC method proved to be clinically useful for the rapid identification of MTBC in respiratory and nonrespiratory specimens and in both smear-positive and smear-negative samples.

Methotrexate-related lymphoproliferative disorder of the lumbar spine origin presenting with severe low-back pain: case report.

The use of methotrexate (MTX) to treat rheumatoid arthritis (RA) is increasing. Recently, MTX-associated lymphoproliferative disorder (MTX-LPD) has been frequently reported as lymphoma occurring during MTX therapy. The authors report their experience with a relatively rare case of MTX-LPD presenting in the lumbar spine. The patient, a 73-year-old woman who experienced low-back pain while receiving MTX therapy for RA, was suspected of having developed MTX-LPD based on her medical history, images of the L1 vertebra, and transpedicular biopsy results. One week after discontinuing MTX, the patient's low-back pain reportedly improved. The woman was diagnosed with MTX-LPD based on histopathological findings. MTX discontinuation alone coincided with spontaneous tumor regression. Because MTX-LPD can occur in tissues other than lymph nodes, such as in bones and joints, it is a disease that should be considered when diagnosing spinal tumors in patients receiving MTX therapy.

Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition: Analysis of a family-based cohort and twin study.

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]). CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms.