Real-world safety and effectiveness of recombinant porcine sequence factor VIII in acquired haemophilia A: A non-interventional,post-authorization safety study

Introduction

Recombinant porcine factor VIII (rpFVIII, susoctocog alfa) is indicated for the treatment of bleeding episodes in adults with acquired haemophilia A (AHA).

Aim

To provide long-term real-world safety and effectiveness data for rpFVIII in the management of AHA bleeding episodes.

Methods

US PASS (NCT02610127) was a multicentre, uncontrolled, open-label, post-marketing safety surveillance study conducted in adults with AHA. Data were collected retrospectively or prospectively for 180 days after rpFVIII treatment. The primary outcome was the incidence of treatment-related serious adverse events (SAEs). Secondary outcomes included haemostatic effectiveness of rpFVIII and rpFVIII utilization.

Results

Fifty-three patients were enrolled from December 2015 to June 2019 (prospective, n = 30; retrospective, n = 23). Six patients experienced seven treatment-related SAEs (incidence 12.0%). The most common treatment-related SAE was FVIII inhibition (inhibiting antibodies to rpFVIII; incidence 8.0%, 95% CI: 2.2–19.2). Five patients reported seven thromboembolic events; one was an SAE and possibly related to rpFVIII. Of bleeding events treated with rpFVIII, 80.3% (57/71) of bleeds resolved with rpFVIII. The median (range) dose of rpFVIII per infusion was 50 (10–300) units/kg, with a median (range) of 6.0 (1–140) infusions and a median (range) time from bleed onset to bleed resolution of 14.0 (2.0–132.7) days.

Conclusion

In this real-world study of rpFVIII for AHA, no new safety signals were identified compared with previous clinical trial findings. Eighty percent of bleeds resolved with rpFVIII treatment.     

Social participation and incident disability and mortality among frail older adults: A JAGES longitudinal study

Background

Frailty is the highest risk factor for incident disability and mortality. Social participation is a modifiable factor for reducing adverse outcomes among independent older adults. However, the association between social participation and incident disability and mortality among frail older adults remains unclear. Therefore, we examined the association between various social activities and incident disability and mortality.

Methods

This nationwide prospective cohort study (The Japan Gerontological Evaluation Study) recruited older adults with frailty, aged 65 years and older (N = 9090) who were followed up for 6 years (2010–2016). We examined incident disability and all-cause mortality at the end of the follow-up period. Frailty was assessed using the Kihon Checklist. The independent variable was social participation in 2010, grouped into the following seven categories: hobby groups, sports groups or clubs, volunteer groups, senior citizens' clubs, industries, neighborhood communities, and paid work.

Results

The incidence of disability among participants was 19.5% (1770) and that of mortality was 19.2% (1753). Belonging to sports groups or clubs (Hazard Ratios [HR] = 0.74; 95% Confidence Interval [CI] = 0.57, 0.98) or hobby groups (HR = 0.77; 95% CI = 0.60, 0.98) was significantly associated with a lower risk of incident disability. Meanwhile, hobby groups (HR = 0.68; 95% CI = 0.56, 0.83), sports groups or clubs (HR = 0.71; 95% CI = 0.57, 0.88), volunteer groups (HR = 0.69; 95% CI = 0.54, 0.88), and senior citizens' club (HR = 0.75; 95% CI = 0.61, 0.90) were associated with lower risk of incident mortality.

Conclusions

Social participation was associated with a lower risk of incident disability and mortality, not only in healthy older adults but also in frail older adults who are at higher risk of incident disability and mortality. This suggests that frail older adults should be encouraged to participate in all the seven types of social participation examined in this study, as this may lower the risk of subsequent disability and mortality.     

Long-term outcome of liver transplantation for autoimmune hepatitis: A French nationwide study over 30 years

Background & Aims

Autoimmune hepatitis (AIH) is a rare indication for liver transplantation (LT). The aims of this study were to evaluate long-term survival after LT for AIH and prognostic factors, especially the impact of recurrent AIH (rAIH).

Methods

A multicentre retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Early deaths and retransplantations (≤6 months) were excluded.

Results

The study population consisted of 301 patients transplanted from 1987 to 2018. Median age at LT was 43 years (IQR, 29.4–53.8). Median follow-up was 87.0 months (IQR, 43.5–168.0). Seventy-four patients (24.6%) developed rAIH. Graft survival was 91%, 79%, 65% at 1, 10 and 20 years respectively. Patient survival was 94%, 84% and 74% at 1, 10 and 20 years respectively. From multivariate Cox regression, factors significantly associated with poorer patient survival were patient age ≥58 years (HR = 2.9; 95% CI, 1.4–6.2; p = 0.005) and occurrence of an infectious episode within the first year after LT (HR = 2.5; 95% CI, 1.2–5.1; p = 0.018). Risk factors for impaired graft survival were: occurrence of rAIH (HR = 2.7; 95% CI, 1.5–5.0; p = 0.001), chronic rejection (HR = 2.9; 95% CI, 1.4–6.1; p = 0.005), biliary (HR = 2.0; 95% CI, 1.2–3.4; p = 0.009), vascular (HR = 1.8; 95% CI, 1.0–3.1; p = 0.044) and early septic (HR = 2.1; 95% CI, 1.2–3.5; p = 0.006) complications.

Conclusion

Our results confirm that survival after LT for AIH is excellent. Disease recurrence and chronic rejection reduce graft survival. The occurrence of an infectious complication during the first year post-LT identifies at-risk patients for graft loss and death.     

Liver transplantation for autoimmune hepatitis: Pre-transplant does not predict the early post-transplant outcome

Background and Aims

Autoimmune hepatitis (AIH) is a rare indication (<5%) for liver transplantation (LT). The aim of this study was to describe the early outcome after LT for AIH.

Methods

A multicenter retrospective nationwide study including all patients aged ≥16 transplanted for AIH in France was conducted. Occurrences of biliary and vascular complications, rejection, sepsis, retransplantation and death were collected during the first year after LT.

Results

A total of 344 patients (78.8% of women, 17.0% of (sub)fulminant hepatitis and 19.2% of chronic liver diseases transplanted in the context of acute-on-chronic liver failure [ACLF]) were included, with a median age at LT of 43.6 years. Acute rejection, sepsis, biliary and vascular complications occurred in respectively 23.5%, 44.2%, 25.3% and 17.4% of patients during the first year after LT. One-year graft and patient survivals were 84.3% and 88.0% respectively. The main cause of early death was sepsis. Pre-LT immunosuppression was not associated with an increased risk for early infections or surgical complications. Significant risk factors for septic events were LT in the context of (sub)fulminant hepatitis or ACLF, acute kidney injury at the time of LT (AKI) and occurrence of biliary complications after LT. AKI was the only independent factor associated with graft (HR = 2.5; 95% CI: 1.1–5.4; p = .02) and patient survivals (HR = 2.6; 95% CI: 1.0–6.5; p = .04).

Conclusion

Early prognosis is good after LT for AIH and is not impacted by pre-LT immunosuppression but by the presence of AKI at the time of LT.     

Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort

Objectives

The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.

Design and setting

An observational study was conducted including 255 patients (mean age 60 years, range 15–93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head‐up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C‐terminal pro‐arginine vasopressin (CT‐proAVP), C‐terminal endothelin‐1 precursor fragment (CT‐proET‐1), midregional fragments of pro‐atrial natriuretic peptide (MR‐proANP) and pro‐adrenomedullin (MR‐proADM).

Results

A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty‐five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR‐proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86–16.74; P < 0.001] and CT‐proET‐1 (OR 7.17, 95% CI 2.43–21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT‐proET‐1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49–30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR‐proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62–26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT‐proET‐1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97–696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT‐proET‐1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15–5.02; P = 0.02), whereas low CT‐proET‐1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25–0.70; P = 0.001).

Conclusions

The levels of MR‐proANP and CT‐proET‐1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.     

Major life events and risk of alcohol use disorders: a prospective cohort study

Aims

To estimate associations of individual major life events as well as accumulated major life events in childhood, adult private life and adult work life with risk of alcohol use disorders (AUD).

Design

Prospective cohort study with baseline examination in 1991–93 and linkage to national registers to identify AUD at follow‐up.

Setting

Copenhagen, Denmark.

Participants

Individuals (aged 21–93 years) who participated in the Copenhagen City Heart Study in 1991–93 (n = 8758).

Measurements

The primary outcome was first registration with AUD during follow‐up (n = 249). AUD was identified in the Danish National Patient Register, in the Danish Psychiatric Central Register and in an outpatient treatment register. Major life events were assessed by a questionnaire in the Copenhagen City Heart study. Data were analysed by Cox proportional hazards models adjusted for age, sex, educational level, household income, cohabitation status and psychiatric comorbidity.

Findings

Serious family conflicts in childhood [hazard ratio (HR) = 1.35; 95% confidence interval (CI) = 1.00, 1.83] and serious economic problems in adult life (HR = 2.22; 95% CI = 1.64, 3.01) were associated significantly with increased risk of AUD. Prospective analyses did not show consistent effects of accumulation of major life events in childhood or adult life, but an additional analysis based on all AUD registrations suggested an association between accumulated childhood events and risk of AUD.

Conclusions

Serious economic problems in adult life are associated strongly with risk of alcohol use disorders, and there may be an influence of accumulated childhood events on risk of alcohol use disorders.     

Effectiveness of blood pressure–lowering treatment by the levels of baseline Framingham risk score: A post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)

This was a post hoc analysis of Systolic Blood Pressure Intervention Trial (SPRINT), aimed to investigate whether intensive blood pressure treatment has differential therapeutic outcomes on patients with different baseline Framingham risk score (FRS). The 9298 SPRINT participants were categorized into low‐risk (baseline FRS < 10%), intermediate‐risk (FRS = 10%‐20%), or high‐risk (FRS > 20%) arms. The primary outcome was a composite of myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, stroke, acute decompensated heart failure, or death from cardiovascular causes. Serious adverse events were defined as hypotension, syncope, and bradycardia. Multiple Cox regression was used to calculate hazard ratios for study outcomes with intensive compared with standard SBP treatment between these three groups. After a median follow‐up time of 3.26 years, the primary outcome hazard ratio (HR) for intensive versus standard treatment was 0.73 (95% CI: 0.61‐0.88, P = .0044) in the high‐risk arm. And, for all‐cause mortality, the hazard ratio with intensive SBP treatment was 1.58 (95% CI: 0.55‐1.06), 0.9 (95% CI: 0.26‐9.50), and 0.53 (95% CI: 0.34‐0.82) in three arms (all P values for interaction > 0.05). Effects of intensive versus standard SBP control on serious adverse events were similar among patients with different FRS. Our results suggested that regardless of the FRS level, the intensive blood pressure control was beneficial.     

Graft-versus-host disease and graft-versus-leukaemia effects in secondary acute myeloid leukaemia: a retrospective,multicentre registry analysis from the Acute Leukaemia Working Party of the EBMT

We assessed the susceptibility of secondary acute myeloid leukaemia (sAML) to graft-versus-leukaemia effects. Data from 2414 sAML patients in first (n = 2194) or second (n = 220) complete remission were included. They were given grafts from human leucocyte antigen (HLA)-matched sibling (MSD, n = 1085), 10/10 unrelated donor (MUD, n = 1066) or 9/10 mismatched unrelated donor (MMUD, n = 263). The 100-day incidence of grade II-IV acute graft-versus-host disease (GVHD) was 25% while 2-year incidence of chronic GVHD was 38%. Relapse rates declined steadily by duration of follow-up and were significantly lower in patients with chronic GVHD (P < 0·001). Limited (hazard ratio [HR] = 0·66, P < 0·001) and extensive (HR = 0·52, P < 0·001) chronic GVHD were associated with a lower incidence of relapse. Each grade III-IV acute (HR = 7·04, P < 0·001) as well as limited (HR = 1·42, P = 0·03) and extensive (HR = 3·97, P < 0·001) chronic GVHD were associated with higher non-relapse mortality (NRM). This translated to better overall survival (OS; HR = 0·61, P < 0·001) in patients with limited chronic GVHD. In contrast, grade III-IV acute and extensive chronic GVHD were associated with worse OS (HR = 3·16, P < 0·001 and HR = 1·21, P = 0·03, respectively). Further, in comparison to HLA-identical sibling recipients, MUD recipients had a lower risk of relapse (HR = 0·82, P = 0·03) but higher NRM (HR = 1·38, P = 0·004). In conclusion, these data demonstrate that sAML is susceptible to graft-versus-leukaemia effects.     

Low exercise blood pressure and risk of cardiovascular events and all-cause mortality: Systematic review and meta-analysis

Objective

The independent prognostic significance of abnormally low systolic blood pressure (SBP) during exercise stress testing (LowExBP) across different clinical and exercise conditions is unknown. We sought by systematic review and meta-analysis to determine the association between cardiovascular/all-cause outcomes and LowExBP across different patient clinical presentations, exercise modes, exercise intensities and categories of LowExBP.

Methods

Seven online databases were searched for longitudinal studies reporting the association of LowExBP with risk of fatal and non-fatal cardiovascular events and/or all-cause mortality. LowExBP was defined as either: SBP drop below baseline; failure to increase >10 mmHg from baseline or; lowest SBP quantile among reporting studies.

Results

After review of 13,257 studies, 19 that adjusted for resting SBP were included in the meta-analysis, with a total of 45,895 participants (average follow-up, 4.4 ± 3.0 years). For the whole population, LowExBP was associated with increased risk for fatal and non-fatal cardiovascular events and all-cause mortality (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.59–2.53, p < 0.001). In continuous analyses, a 10 mmHg decrease in exercise SBP was associated with higher risk (n = 9 HR: 1.13, 95% CI: 1.06–1.20, p < 0.001). LowExBP was associated with increased risk regardless of clinical presentation (coronary artery disease, heart failure, hypertrophic cardiomyopathy or peripheral artery disease), exercise mode (treadmill or bike), exercise intensity (moderate or maximal), or LowExBP category (all p < 0.05). However, bias toward positive results was apparent (Eggers test p < 0.001 and p = 0.009).

Conclusion

Our data show that irrespective of clinical or exercise conditions, LowExBP independently predicts fatal and non-fatal cardiovascular events and all-cause mortality.     

Prevalence and One-year Outcome of Carotid Sinus Hypersensitivity in Unexplained Syncope: A Prospective Cohort Study from South India

Background

Carotid sinus syndrome accounts for one third of patients who presents with unexplained syncope. Prevalence of carotid sinus hypersensitivity (CSH) in Indians has not been studied till now.

Prevalence and predictive factors of left atrial tachycardia occurring after second‐generation cryoballoon ablation of atrial fibrillation

1 Introduction

Assess the prevalence and predictors of left atrial tachycardia (LAT) after cryoballoon ablation of pulmonary veins.

2 Methods and results

Patients who underwent catheter ablation of pulmonary veins with a second‐generation cryoballoon for symptomatic paroxysmal (151 of 270, 56%) or persistent (119 of 270, 44%) atrial fibrillation were entered in a single‐center prospective registry. Patients who experienced postcryoballoon LAT (pcryo‐LAT) were selected on the basis of 12‐lead ECG characteristics. Left atrial origin was confirmed during conventional EP study and electroanatomical activation mapping, and patients were treated by RF catheter ablation. Pcryo‐LAT was observed in 15 (5.6%) of 270 patients and was attributed to a reentrant mechanism in 11 patients (73%). The other four cases of pcryo‐LAT were due to focal atrial tachycardia associated with reconnection of one pulmonary vein. In comparison with patients who remained in sinus rhythm, LA area (HR = 1.09; CI 1.01, 1.2; P = 0.02), LVEF (HR = 0.94; CI 0.90, 0.97; P < 0.001), and LVEF <50% (HR = 8.5; CI 3.1, 23.6; P < 0.001) were predictors of pcryo‐LAT. After multivariate Cox analysis, only left ventricular ejection fraction < 50% remained predictive of pcryo‐LAT, (HR = 7.8, CI 2.3 26.7, P = 0.002). With a mean survival of 23 months, 73% of patients who experienced pcryo‐LAT were in sinus rhythm versus 78% of patients without pcryo‐LAT (log rank P = 0.85).

3 Conclusion

The prevalence of pcryo‐LAT in patients with atrial fibrillation is low. Left ventricular ejection fraction < 50% is associated with an increased risk of pcryo‐LAT. When treated by RF catheter ablation, the presence of pcryo‐LAT is not a predictive factor of subsequent recurrence of atrial fibrillation during follow‐up.     

Orthostatic Syndromes Differ in Syncope Frequency

Background

There are conflicting opinions on whether postural tachycardia syndrome predisposes to syncope. We investigated this relationship by comparing the frequency of syncope in postural tachycardia syndrome and orthostatic hypotension.

Methods

We queried our autonomic laboratory database of 3700 patients. Orthostatic hypotension and postural tachycardia syndrome were defined in standard fashion, except that postural tachycardia syndrome required the presence of orthostatic symptoms and a further increase in heart rate beyond 10 minutes. Syncope was defined as an abrupt decrease in blood pressure and often, heart rate, requiring termination of the tilt study. Statistical analysis utilized Fisher's exact test and Student's t test, as appropriate.

Results

Of 810 patients referred for postural tachycardia syndrome, 185 met criteria while another 328 patients had orthostatic hypotension. Of the postural tachycardia syndrome patients, 38% had syncope on head-up tilt, compared with only 22% of those with orthostatic hypotension (P <.0001). In the postural tachycardia group, syncope on head-up tilt was associated with a clinical history of syncope in 90%, whereas absence of syncope on head-up tilt was associated with a clinical history of syncope in 30% (P <.0001). In contrast, syncope on head-up tilt did not bear any relationship to clinical history of syncope in the orthostatic hypotension group (41% vs 36%; P = .49).

Conclusion

Our results demonstrate that syncope (both tilt table and clinical) occurs far more commonly in patients who have postural tachycardia syndrome than in patients with orthostatic hypotension. These findings suggest that one should be clinically aware of the high risk of syncope in patients with postural tachycardia syndrome, and the low-pressure baroreceptor system that is implicated in postural tachycardia syndrome might confer more sensitivity to syncope than the high pressure system implicated in orthostatic hypotension.     

Hospital Fall Prevention: A Systematic Review of Implementation,Components, Adherence,and Effectiveness

Objectives

To systematically document the implementation, components, comparators, adherence, and effectiveness of published fall prevention approaches in U.S. acute care hospitals.

Design

Systematic review. Studies were identified through existing reviews, searching five electronic databases, screening reference lists, and contacting topic experts for studies published through August 2011.

Setting

U.S. acute care hospitals.

Participants

Studies reporting in‐hospital falls for intervention groups and concurrent (e.g., controlled trials) or historic comparators (e.g., before–after studies).

Intervention

Fall prevention interventions.

Measurements

Incidence rate ratios (IRR, ratio of fall rate postintervention or treatment group to the fall rate preintervention or control group) and ratings of study details.

Results

Fifty‐nine studies met inclusion criteria. Implementation strategies were sparsely documented (17% not at all) and included staff education, establishing committees, seeking leadership support, and occasionally continuous quality improvement techniques. Most interventions (81%) included multiple components (e.g., risk assessments (often not validated), visual risk alerts, patient education, care rounds, bed‐exit alarms, and postfall evaluations). Fifty‐four percent did not report on fall prevention measures applied in the comparison group, and 39% neither reported fidelity data nor described adherence strategies such as regular audits and feedback to ensure completion of care processes. Only 45% of concurrent and 15% of historic control studies reported sufficient data to compare fall rates. The pooled postintervention incidence rate ratio (IRR) was 0.77 (95% confidence interval = 0.52–1.12, P = .17; eight studies; I²: 94%). Meta‐regressions showed no systematic association between implementation intensity, intervention complexity, comparator information, or adherence levels and IRR.

Conclusion

Promising approaches exist, but better reporting of outcomes, implementation, adherence, intervention components, and comparison group information is necessary to establish evidence on how hospitals can successfully prevent falls.     

Psychosocial factors are independent risk factors for the development of Type 2 diabetes in Japanese workers with impaired fasting glucose and/or impaired glucose tolerance1

Aims We prospectively studied Japanese workers with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and analysed possible risk factors for diabetes, including psychosocial factors such as stress. Methods The participants were 128 male Japanese company employees (mean age, 49.3 ± 5.9 years) with IFG and/or IGT diagnosed by oral glucose tolerance test (OGTT). Participants were prospectively studied for 5 years with annual OGTTs. The Kaplan–Meier method and Cox's proportional hazard model were used to analyse the incidence of diabetes and the factors affecting glucose tolerance, including anthropometric, biochemical and social–psychological factors. Results Of 128 participants, 36 (28.1%) developed diabetes and 39 (30.5%) returned to normal glucose tolerance (NGT) during a mean follow‐up of 3.2 years. Independent risk factors for diabetes were night duty [hazard ratio (HR) = 5.48, P = 0.002], higher fasting plasma glucose (FPG) levels within 6.1–6.9 mmol/l (HR = 1.05, P = 0.031), stress (HR = 3.81, P = 0.037) and administrative position (HR = 12.70, P = 0.045), while independent factors associated with recovery were lower FPG levels (HR = 0.94, P = 0.017), being a white‐collar worker (HR = 0.34, P = 0.033), non‐smoking (HR = 0.31, P = 0.040) and lower serum alanine aminotransferase (ALT) levels (HR = 0.97, P = 0.042). Conclusions In addition to FPG levels at baseline, psychosocial factors (night duty, stress and administrative position) are risk factors for Type 2 diabetes, while being a white‐collar worker, a non‐smoker and lower serum ALT levels are factors associated with return to NGT in Japanese workers with IFG and/or IGT.     

Bradycardia is associated with future cardiovascular diseases and death in men from the general population

Background

Although a higher heart rate is known to be a risk factor for cardiovascular disease (CVD) events, there have been no reports concerning bradycardia. Whether lower and higher resting pulse rates (RPRs) are associated with cardiovascular risk was investigated in subjects from a community-based, prospective cohort study.

Methods

After subjects with atrial fibrillation, subjects with a history of CVD, and subjects receiving antihypertensive treatment were excluded, 17,766 subjects (5958 men), aged 40–79 (mean 61.5) years, were analyzed. The RPR at baseline was categorized into four groups (RPR<60, 60–69.5, 70–79.5, ≥80 beats per minute (bpm)) using the average value of two consecutive measurements. The endpoint was set as the composite outcome of myocardial infarction, stroke, or sudden death.

Results

During a mean follow-up of 5.6 years, there were 213 events in men and 186 events in women. In Cox regression models, increased risks of CVD were found in the men group with RPR<60 bpm, as well as the group with RPR≥80 bpm, compared with the reference group with RPR 60–69.5 bpm (hazard ratio [HR] = 1.73, p = 0.005 and HR = 2.01, p < 0.001). These increased risks were found even when adjusted for age and other CVD risk factors (HR = 1.55, p = 0.026 with RPR<60 bpm and HR = 1.72, p = 0.009 with RPR≥80 bpm). In women, there were no significant associations between RPR and CVD risk.

Conclusion

Bradycardia, as well as a higher pulse rate, may be an independent risk factor for future cardiovascular events in apparently healthy men.     

Effects of benzodiazepines on orthostatic blood pressure in older people

BackgroundOlder people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to cognitive and psychomotor effects. BDZs may also have hypotensive effects. We investigated the association between BDZs and orthostatic blood pressure behaviour in older people.MethodsWe retrospectively analysed data from an outpatient clinic where people aged 60 or older underwent a geriatric assessment. Non-invasive beat-to-beat orthostatic systolic blood pressure (SBP) was assessed at regular time intervals before and after an active stand test. We compared clinical characteristics between BDZs users and non-users and also investigated if BDZs use was an independent predictor of baseline SBP. Factors associated with SBP change were investigated using a repeated measures general linear model.ResultsOf 538 participants (67.7% female, mean age 72.7), 33 (6.1%) reported regular BDZs use. BDZ users had lower baseline SBP (149 versus 161 mmHg, P < 0.05). Multiple linear regression confirmed BDZs use as independent predictor of baseline SBP in N = =538. At 10 s post-stand, the SBP difference between BDZs use groups became maximum (21 mmHg); at this point, SBP still seemed to be decreasing in BDZ-users, whereas in controls it seemed to be recovering. After adjustment (age, sex, hypertension, frailty, comorbidity, antihypertensives), BDZs were associated with greater SBP reduction between baseline and 10 s post-stand (P < 0.05).ConclusionOlder people taking BDZs may have a higher risk of orthostatic hypotension, perhaps due to an exaggerated immediate BP drop. This adds to other BDZ-related falls risks. BDZs should be avoided in older people at risk of falling.     

Exploring assessment of balance using virtual reality in patients at risk of chemotherapy-induced peripheral neuropathy

Background

Chemotherapy-induced peripheral neuropathy (CIPN) is a common dose-limiting toxicity for people treated for cancer. Impaired balance and falls are functional consequences of CIPN. Virtual reality (VR) technology may be able to assess balance and identify patients at risk of falls.

Aims

To assess the impact of potentially neurotoxic chemotherapy on balance using VR, and explore associations between VR balance assessment, falls and CIPN.

Methods

This prospective, repeated measures longitudinal study was conducted at two Australian cancer centres. Eligible participants were commencing adjuvant chemotherapy containing a taxane for breast cancer, or oxaliplatin for colorectal cancer (CRC), per institutional guidelines. Balance assessments using VR were conducted at baseline, end of chemotherapy and 3 and 6 months after completion of chemotherapy. Participants also completed a comprehensive CIPN assessment comprising clinical and patient-reported outcomes, and recorded falls or near falls.

Results

Out of 34 participants consented, 24 (71%) had breast cancer and 10 (29%) had CRC. Compared to baseline, balance threshold was reduced in 10/28 (36%) evaluable participants assessed at the end of chemotherapy, and persistent in 7/22 (32%) at 6 months. CIPN was identified in 86% at end of chemotherapy and persisted to 6 months after chemotherapy completion in 73%. Falls or near falls were reported by 12/34 (35%) participants, and were associated with impaired VR balance threshold (P = 0.002).

Conclusions

While VR balance assessment was no better at identifying CIPN than existing measures, it is a potential surrogate method to assess patients at risk of falls from CIPN.     

Winter morning surge in blood pressure after the Great East Japan Earthquake

This study investigated the association between winter morning surge in systolic blood pressure (SBP) as measured by ambulatory BP monitoring and the housing conditions of subjects in an area damaged by the Great East Japan Earthquake. In 2013, 2 years after disaster, hypertensives who lived in homes that they had purchased before the disaster (n = 299, 74.6 ± 8.1 years) showed significant winter morning surge in SBP (+5.0 ± 20.8 mmHg, P < 0.001), while those who lived in temporary housing (n = 113, 76.2 ± 7.6 years) did not. When we divided the winter morning surge in SBP into quintiles, the factors of age ≥75 years and occupant‐owned housing were significant determinants for the highest quintile (≥20 mmHg) after adjustment for covariates. The hypertensives aged ≥75 years who lived in their own homes showed a significant risk for the highest quintile (odds ratio 5.21, 95% confidence interval 1.49‐18.22, P = 0.010). It is thus crucial to prepare suitable housing conditions for elderly hypertensives following a disaster.     

Non-high-density lipoprotein cholesterol and the development of coronary heart disease and stroke subtypes in a general Japanese population: The Hisayama Study

Background and purpose

It has not been fully determined whether non-high-density lipoprotein cholesterol (non-HDLC) levels are involved in vascular events, especially stroke, in general Asian populations. We evaluated the association between non-HDLC levels and the risk of type-specific cardiovascular disease in a prospective cohort study in Japan.

Methods

A total of 2452 community-dwelling Japanese subjects aged ≥40 years were followed prospectively for 24 years.

Results

The age- and sex-adjusted incidence of coronary heart diseases (CHD) significantly increased with elevating non-HDLC levels (P for trend < 0.001), but no such association was observed for ischemic and hemorrhagic strokes. With regard to ischemic stroke subtypes, the age- and sex-adjusted incidence of lacunar infarction significantly increased with elevating non-HDLC levels (P for trend < 0.01), and such tendency was seen for atherothrombotic infarction (P for trend = 0.098), while a significant inverse association was observed for cardioembolic infarction (P for trend = 0.007). After adjustment for confounders, namely, age, sex, diabetes, body mass index, systolic blood pressure, electrocardiogram abnormalities, current drinking, current smoking, and regular exercise, the associations remained significant for CHD [adjusted hazard ratio (HR) for a 1 standard deviation of non-HDLC concentrations = 1.17, 95% confidence interval (CI) = 1.02 to 1.35], atherothrombotic infarction (adjusted HR = 1.39, 95% CI = 1.09 to 1.79), and cardioembolic infarction (adjusted HR = 0.64, 95% CI = 0.47 to 0.85).

Conclusions

Our findings suggest that elevated non-HDLC levels are a significant risk factor for the development of atherothrombotic infarction as well as CHD but reduce the risk of cardioembolic infarction in the general Japanese population.     

The effect of viscous soluble fiber on blood pressure: A systematic review and meta-analysis of randomized controlled trials

Aims

Dietary fiber intake, especially viscous soluble fiber, has been established as a means to reduce cardiometabolic risk factors. Whether this is true for blood pressure remains controversial. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to investigate the effects of viscous soluble fiber supplementation on blood pressure and quantify the effect of individual fibers.