In sickness and health? Examining the co-occurrence and concordance of healthy lifestyle behaviours among spouses in Namibia.

OBJECTIVES: This study examines the extent to which healthy lifestyle behaviours co-occur in individuals. We also explore within-couples concordance in healthy lifestyle behaviours in Namibia. STUDY DESIGN: Cross-sectional study. METHODS: We used data from 910 couples (1820 individuals) who were interviewed in the Namibia Demographic and Health Survey conducted in 2013. We assessed five different healthy lifestyle behaviours (alcohol non-consumption, non-cigarette smoking, healthy diet, physical exercise, and normal body mass index). An individual healthy lifestyle index (HLI) was derived by summing values across the five behaviours, with a binary indicator categorising each individual's lifestyle behaviour as 'healthy' (HLI ≥ 3) or 'unhealthy' (HLI < 3). Multivariate logistic regression models were fitted to explore the association between binary indicators of men's and their female partner's healthy lifestyles. RESULTS: About 48% of men and 57% of women had at least three co-occurring healthy lifestyle behaviours. A third of couples were concordant in reporting a healthy lifestyle (HLI ≥ 3), while 27% were concordant in reporting an unhealthy lifestyle (HLI < 3). In multivariate analysis, Namibian men were almost twice (aOR, 1.90; 95%CI, 1.43-2.52) as likely to have a healthy lifestyle if their female partner also had a healthy lifestyle, compared with those who had a female partner who had an unhealthy lifestyle, after adjusting for relevant individual, partner and household characteristics. CONCLUSION: The observed co-occurrence of healthy lifestyle behaviours and spousal concordance suggests it may be beneficial to consider couples a target for intervention when aiming to promote healthy behaviours and reduce cardiovascular diseases in Namibia.

The Novel Small Molecule Inhibitor, OSU-T315, Suppresses Vestibular Schwannoma and Meningioma Growth by Inhibiting PDK2 Function in the AKT Pathway Activation.

Activation of PKB/AKT signaling, which requires PDK1 and PDK2 function, drives Vestibular Schwannoma (VS) and meningioma growth. PDK2 function is defined as a molecule that phosphorylates AKT-Ser473. Integrin-Linked Kinase (ILK) functions as PDK2 in PKB/AKT activation in many cancers; therefore, we hypothesized that OSU-T315, a small molecule ILK inhibitor, will inhibit the ILK-PDK2 function in PKB/AKT signaling activation in VS and meningioma cell growth. OSU-T315 decreased cell viability at IC50 < 2µM in VS (HEI193) and meningioma (Ben-Men-1) cell lines, in primary cells at < 3.5µM, while in normal primary Schwann cells at 7.1µM. OSU-T315 inhibits AKT signaling by decreasing phosphorylation at AKT-Ser473, AKT-Thr308, ILK-Ser246 and ILK-Thr173. In addition, OSU-T315 affected the phosphorylation or expression levels of AKT downstream proliferation effectors as well as autophagy markers. Flow cytometry shows that OSU-T315 increased the percentage of cells arrested at G2/M for both, HEI193 (39.99%) and Ben-Men-1 (26.96%) cells, compared to controls (21.54%, 8.47%). Two hours of OSU-T315 treatment increased cell death in both cell lines (34.3%, 9.1%) versus untreated (12.1%, 8.1%). Though longer exposure increased cell death in Ben-Men-1, TUNEL assays showed that OSU-T315 does not induce apoptosis. OSU-T315 was primarily cytotoxic for HEI193 and Ben-Men-1 inducing a dysregulated autophagy. Our studies suggest that OSU-T315 has translational potential as a chemotherapeutic agent against VS and meningioma.

Ozonated water is inferior to propanol-based hand rubs for disinfecting hands.

Ozone is a strong oxidizing biocide that has broad-spectrum antimicrobial properties. The aim of the study was to compare the efficacy of ozone to a propanol-based hand rub for hand disinfection. Twenty subjects were enrolled in an in-vivo cross-over trial (prEN 12791). Subjects treated their hands with the reference procedure (propan-1-ol 60%) or with ozone (4 ppm). Post-wash bacterial counts were determined from one hand (immediate effect), and from the other hand that had been gloved for 3h (delayed effect). The investigation indicated that ozone is inferior to propan-1-ol 60% hand rub for hand asepsis.

Metaphyseal osteopathy in three Australian Kelpie siblings.

CASE REPORT: Metaphyseal osteopathy (MO) was diagnosed in three Australian Kelpie puppies that were presented for veterinary assessment of lameness. The three puppies were siblings. Each was from a different litter by the same breeding pair. The puppy in case one was seen by the authors, and the puppies in cases two and three were patients at other veterinary hospitals. However, the medical records and radiographs were examined and reviewed for this report. Radiographic investigation of the lameness revealed pathognomonic appearance of MO affecting the metaphyseal region of the long bones in all three puppies. The diagnosis was confirmed on histopathology in one patient. CONCLUSION: MO is considered a disease of large and giant-breed dogs, being rarely reported in non-large-breed dogs, and has not been reported in the Australian Kelpie, which is considered a medium-breed dog. This case series suggests a previously unreported breed predisposition to MO in the Australian Kelpie.

Medical radiation exposure in children with bleeding disorders: an institutional experience.

Patients with bleeding disorders may be exposed to ionizing radiation during medical care. We hypothesized that children with severe haemophilia may have higher radiation exposure than those with mild bleeding disorders (MBDs). To compare medical radiation exposure rates between children with severe haemophilia and MBDs. Charts of 35 pediatric patients with severe haemophilia were randomly selected from a database of active male patients followed in our bleeding disorders clinic from 2000 to 2010. Case patients were age and sex matched with two control patients with MBDs [Type 1 von Willebrand disease (VWD) or mild platelet function defect (PFD)]. By retrospective review, data on radiation exposure in millisieverts (mSv) was collected from radiological studies performed within Emory/CHOA. The rates of exposure between cohorts were compared using the Mann-Whitney Test. Case patients had a mean of 11.3 (median 8, IQR = 29) radiographic studies compared with 1.8 (median 1, IQR = 11) for controls (P < 0.001). The mean effective dose of radiation per patient per year of study was two mSv for case patients (median 0.4, IQR = 3) and 0.4 mSv for control patients (median 0.01, IQR = 0.3) (P < 0.001). Overall, 1.4% of controls and 31.4% of cases accumulated high to very high levels of exposure ( > 20 mSv). Case patients with severe hemophilia accumulated significantly more medical radiation exposure than controls. While the use of ionizing radiation is often necessary for management of these patients, avoidance of unnecessary exposure along with exploration of alternative imaging techniques and low dose protocols should be considered whenever possible.

Osteosarcoma at the site of titanium orthopaedic implants in a dog.

An Alaskan Malamute underwent unilateral tibial tuberosity advancement (TTA) surgery to stabilise a stifle joint with a deficient cranial cruciate ligament. The dog made an excellent recovery with no postoperative complications, until 20 months post-surgery when he presented with acute onset ipsilateral pelvic limb lameness. Osteosarcoma (OSA) was diagnosed adjacent to the titanium implants. Currently, there is a paucity of information on the epidemiology of OSA adjacent to orthopaedic implants in canine patients. The clinical, radiological and pathological findings of this case of periprosthetic OSA, and a potential causal relationship between titanium implants and bone neoplasia, are discussed.

Prevalence of malignancies among U.S. male patients with haemophilia: a review of the Haemophilia Surveillance System.

The prevalence of malignancies in US male patients with haemophilia, with or without concomitant viral infections, remains unknown. To estimate the prevalence of malignancy in US male patients with haemophilia. We investigated the prevalence of malignancies among male patients with haemophilia using data from a six-state haemophilia surveillance project. Case patients with malignancies were identified using International Classification of Diseases, 9th Revision, Clinical Modification codes abstracted from hospital records and death certificates during the surveillance period. Cancer prevalence rates were calculated for each year during the surveillance and compared with age- and race-specific prevalence rates among the U.S. male population obtained from the Surveillance, Epidemiology and End Results (SEER) Program. A total of 7 cases of leukaemia, 23 cases of lymphoma and 56 classifiable solid malignancies were identified among 3510 case patients during a total of 15,330 annual data abstraction collections. The rates of leukaemia, lymphoma and liver cancer among case patients were significantly higher than the rates among U.S. males as judged by prevalence ratios of 3.1 [95% confidence interval (CI) = 1.4-7.0] and 2.9 (95% CI =1.8-4.6), respectively. In contrast, the prevalence ratio of prostate cancer was lower than expected at 0.49 (95% CI = 0.31-0.77). Overall the prevalence of most cancers among case patients was similar to that of the U.S. male population. However, patients with haemophilia who have unexplained symptoms should be evaluated for malignancy.

Cell friction.

Cells sense and respond to their environment. Mechanotransduction is the process by which mechanical forces, stress, and strains are converted into biochemical signals that control cell behavior. In recent decades it has been shown that appropriate mechanical signals are essential to tissue health, but the role of friction and direct contact shearing across cell surfaces has been essentially unexplored. This, despite the obvious existence of numerous biological tissues whose express function depends on sliding contacts. In our studies on frictional interactions of corneal cells we find that the friction coefficients are on the order of mu = 0.03-0.06 for in vitro and in vivo experiments. Additionally, we observe cell death after single cycles of sliding at contact pressures estimated to be approximately 12 kPa. These experimental results suggest that frictional contact forces produce mechanical stresses and strains that are in the cellular mechanosensing ranges.

Challenges in measuring the impact of interruption on patient safety and workflow outcomes.

OBJECTIVE: To examine the problem of studying interruption in healthcare. METHODS: Review of the interruption literature from psychology, human-computer interaction; experimental studies of electronic prescribing and error behaviour; observational studies in emergency and intensive care. RESULTS: Primary task and interruption variables which contribute to the outcomes of an interruption include the type of task (primary and interrupting task); point of interruption; duration of interruption; similarity of interruptive task to primary task; modality of interruption; environmental cues; and interruption handling strategy. Effects of interruption on task performance can be examined by measuring errors, the time on task, interruption lag and resumption lag. CONCLUSIONS: Interruptions are a complex phenomenon where multiple variables including the characteristics of primary tasks, the interruptions themselves, and the environment may influence patient safety and workflow outcomes. Observational studies present significant challenges for recording many of the process variables that influence the effects of interruptions. Controlled experiments provide an opportunity to examine the specific effects of variables on errors and efficiency. Computational models can be used to identify the situations in which interruptions to clinical tasks could be disruptive and to investigate the aggregate effects of interruptions.

Alternative splicing and polyadenylation contribute to the generation of hERG1 C-terminal isoforms.

The human ether-a-go-go-related gene 1 (hERG1) encodes the pore-forming subunit of the rapidly activating delayed rectifier potassium channel. Several hERG1 isoforms with different N- and C-terminal ends have been identified. The hERG1a, hERG1b, and hERG1-3.1 isoforms contain the full-length C terminus, whereas the hERG1(USO) isoforms, hERG1a(USO) and hERG1b(USO), lack most of the C-terminal domain and contain a unique C-terminal end. The mechanisms underlying the generation of hERG1(USO) isoforms are not understood. We show that hERG1 isoforms with different C-terminal ends are generated by alternative splicing and polyadenylation of hERG1 pre-mRNA. We identified an intrinsically weak, noncanonical poly(A) signal, AGUAAA, within intron 9 of hERG1 that modulates the expression of hERG1a and hERG1a(USO). Replacing AGUAAA with the strong, canonical poly(A) signal AAUAAA resulted in the predominant production of hERG1a(USO) and a marked decrease in hERG1 current. In contrast, eliminating the intron 9 poly(A) signal or increasing the strength of 5' splice site led to the predominant production of hERG1a and a significant increase in hERG1 current. We found significant variation in the relative abundance of hERG1 C-terminal isoforms in different human tissues. Taken together, these findings suggest that post-transcriptional regulation of hERG1 pre-mRNA may represent a novel mechanism to modulate the expression and function of hERG1 channels.

Adenotonsillectomy in patients with desmopressin responsive mild bleeding disorders: a review of the literature.

SUMMARY: Many patients with mild inherited bleeding disorders such as von Willebrand disease (VWD), mild haemophilia A (HA) and platelet function defects (PFD) undergo adenoidectomy and/or tonsillectomy (AT) procedures each year. Management of bleeding in these patients can be challenging, as little published data exist to guide haemostatic management during these relatively common procedures. Therefore, the literature was reviewed to identify AT procedures in patients with 1-deamino-8-D-argine vasopressin responsive mild bleeding disorders. The review revealed no randomized prospective trials of haemostatic management in this patient population. Case reports and small case series identified 144 patients who had AT procedures. Frequency of desmopressin and antifibrinolytic dosing varied widely. Fifteen percentage of patients experienced postoperative bleeding with nearly half being early (<24 h) bleeding and half being late (>24 h) bleeding. Hyponatraemia complicated the procedures in 47% of cases and six hyponatremic seizures were reported. Issues identified by this review that need to be addressed in future clinical trials include type and amount of fluid restriction when utilizing desmopressin, duration of antifibrinolytic therapy and duration and frequency of desmopressin dosing.

Malignancy in patients with haemophilia: a review of the literature.

Haemophilia A and B are rare X-linked conditions. Elevated rates of HIV and hepatitis C related malignancies in these patients are well reported, however rates of other types of cancers are not. Therefore, a retrospective literature review of cancer in patients with haemophilia was conducted. A Medline search of articles from January 1966 to July 2009 utilizing the keywords haemophilia, leukaemia, malignancy, mortality, neoplasm and cancer was performed. The articles were reviewed and additional relevant publications were located from the references. Data on age, type and severity of haemophilia, HIV status, type of malignancy and outcomes were recorded as available. Thirty-two cases of leukaemia were identified as well as 159 malignant solid tumours. Specific incidence and prevalence rates could not be calculated due to the limited nature of the information available in the reports. Many types of malignancy have been reported in persons with haemophilia irrespective of infection with HIV and hepatitis C yet prevalence and incidence rates compared to the general population remain unknown. Patients with haemophilia can manifest non infectious related malignancies and symptomatic patients should be evaluated accordingly.

Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience.

Auto-SCT has been shown to be a potentially curative treatment for a variety of hematological malignancies. Auto-SCT is dependent on the successful mobilization and collection of hematopoietic stem cells to ensure engraftment. The inability to mobilize sufficient number of hematopoietic stem cells using standard cytokine-assisted mobilization strategies excludes eligible patients from potentially curative auto-SCT. Plerixafor (AMD3100; Mozobil), a novel bicyclam antagonist of the SDF-1alpha/CXCR4 complex, has been reported previously to augment PBSC mobilization in patients undergoing their first planned stem cell mobilization and collection attempt. In our experience, 17 of 20 patients otherwise eligible for auto-SCT who failed previous mobilization attempts had successful mobilization of CD34(+) hematopoietic stem cells with one apheresis procedure, and an additional patient required two aphereses procedures, when treated with the combination of plerixafor and G-CSF on a compassionate use protocol available at our institution.

The use of the cemented Exeter Universal femoral stem in a District General Hospital: a minimum ten-year follow-up.

We describe the survivorship of the Exeter femoral component in a District General Hospital. Between 1994 and 1996, 230 Exeter Universal cemented femoral components were implanted in 215 patients who were reviewed at a mean of 11.2 years (10 to 13). We used one acetabular implant, the Elite Ogee component, in 218 of the 230 hips. During the period of this study 76 patients (79 hips) died. Of the remaining 139 patients (151 hips), 121 were able to attend for radiological analysis at a minimum of ten years. One patient was lost to follow-up. No femoral component was revised for aseptic loosening. Three hips were revised for deep infection and six acetabular components required revision, four for loosening and two for recurrent dislocation. Taking the 'worst-case scenario' including the one patient lost to follow-up, the overall survival rate was 94.4% at 13 years. Our results confirm excellent medium-term results for the Exeter Universal femoral component, implanted in a general setting. The excellent survival of this femoral component, when used in combination with the Ogee acetabular component, suggests that this is a successful pairing.

Bridging therapy in patients on long-term oral anticoagulants who require surgery: the Prospective Peri-operative Enoxaparin Cohort Trial (PROSPECT).

BACKGROUND: The peri-operative management of patients on oral anticoagulants (OACs) is a common clinical problem. Our aim was to determine the incidence of major bleeding during peri-operative administration of treatment-dose enoxaparin and the impact of the extensiveness of the procedure on the risk of bleeding. METHODS: We performed a prospective cohort study of 260 patients at 24 North American sites on OACs for atrial fibrillation or a history of deep vein thrombosis (DVT) requiring invasive or surgical procedures whose treating physician felt that bridging therapy was required. Warfarin was withheld, and once-daily s.c. enoxaparin (1.5 mg kg(-1)) was given peri-operatively. Patients were followed for 28 days after OAC was therapeutic. RESULTS: Major bleeding was observed in nine of 260 patients (3.5%, 95% CI: 1.6-6.5). The bleeding risk varied markedly by extensiveness of procedure: the incidence of major bleeding for invasive procedures, minor surgery and major surgery was 0.7% (95% CI: 0.02-3.7), 0% (95% CI: 0-5.0), and 20.0% (95% CI: 9.1-35.7), respectively. There were five thromboembolic events in total (1.9%, 95% CI: 0.6-4.4). There were four arterial events (2.3%, 95% CI: 0.6-5.7) in 176 patients with atrial fibrillation, and one venous event (1.0%, 95% ci: 0.03-5.7) in 96 patients with prior DVT/ CONCLUSIONS: Bridging therapy with once-daily therapeutic-dose enoxaparin administered primarily in an outpatient setting has a low incidence of major bleeding for patients undergoing invasive procedures and minor surgery. Further studies are needed to optimize the bridging strategy for patients undergoing major surgery.

The roles of corticotropin-releasing factor-related peptides and their receptors in the cardiovascular system.

Corticotropin-releasing factor (CRF), CRF-related peptides and their receptors are present in the central nervous system and in peripheral tissues including the immune, reproductive and cardiovascular systems. CRF and urocortin (urocortin 1) bind to the CRF receptor type 1 (CRF(1) receptor) and the CRF receptor type 2 (CRF(2) receptor), whereas urocortin 2 (formerly known as stresscopin related peptide) and urocortin 3 (formerly known as stresscopin) bind with high affinity to the CRF(2) receptor. Recent studies show that urocortin 1, urocortin 2 and urocortin 3 are potent regulators of cardiovascular function. This review highlights the role of cardiovascular CRF and related peptides and its relevance in mediating the adaptive response of the cardiovascular system to stressful conditions.

Clinical outcomes with unfractionated heparin or low-molecular-weight heparin as bridging therapy in patients on long-term oral anticoagulants: the REGIMEN registry.

BACKGROUND: Patients who receive long-term oral anticoagulant (OAC) therapy often require interruption of OAC for an elective surgical or an invasive procedure. Heparin bridging therapy has been used in these situations, although the optimal method has not been established. No large prospective studies have compared unfractionated heparin (UFH) with low-molecular-weight heparin (LMWH) for the perioperative management of patients at risk of thromboembolism requiring temporary interruption of long-term OAC therapy. PATIENTS/METHODS: This multicenter, observational, prospective registry conducted in North America enrolled 901 eligible patients on long-term OAC who required heparin bridging therapy for an elective surgical or invasive procedure. Practice patterns and clinical outcomes were compared between patients who received either UFH alone (n = 180) or LMWH alone (n = 721). RESULTS: Overall, the majority of patients (74.5%) requiring heparin bridging therapy had arterial indications for OAC. LMWH, in mostly twice-daily treatment doses, represented approximately 80% of the study population. LMWH-bridged patients had significantly fewer arterial indications for OAC, a lower mean Charlson comorbidity score, and were less likely to undergo major or cardiothoracic surgery, receive intraprocedural anticoagulants or thrombolytics, or receive general anesthesia than UFH-bridged patients (all P < 0.05). The LMWH group had significantly more bridging therapy completed in an outpatient setting or with a < 24-h hospital stay vs. the UFH group (63.6% vs. 6.1%, P < 0.001). In the LMWH and UFH groups, similar rates of overall adverse events (16.2% vs. 17.1%, respectively, P = 0.81), major composite adverse events (arterial/venous thromboembolism, major bleed, and death; 4.2% vs. 7.9%, respectively, P = 0.07) and major bleeds (3.3% vs. 5.5%, respectively, P = 0.25) were observed. The thromboembolic event rates were 2.4% for UFH and 0.9% for LMWH. Logistic regression analysis revealed that for postoperative heparin use a Charlson comorbidity score > 1 was an independent predictor of a major bleed and that vascular, general, and major surgery were associated with non-significant trends towards an increased risk of major bleed. CONCLUSIONS: Treatment-dose LMWH, mostly in the outpatient setting, is used substantially more often than UFH as bridging therapy in patients with predominately arterial indications for OAC. Overall adverse events, including thromboembolism and bleeding, are similar for patients treated with LMWH or UFH. Postoperative heparin bridging should be used with caution in patients with multiple comorbidities and those undergoing vascular, general, and major surgery. These findings need to be confirmed using large randomized trials for specific patient groups undergoing specific procedures.