Baseline characteristics of people experiencing homelessness with a recent drug overdose in the PHOENIx pilot randomised controlled trial.

BACKGROUND: Drug-related deaths in Scotland are the highest in Europe. Half of all deaths in people experiencing homelessness are drug related, yet we know little about the unmet health needs of people experiencing homelessness with recent non-fatal overdose, limiting a tailored practice and policy response to a public health crisis. METHODS: People experiencing homelessness with at least one non-fatal street drug overdose in the previous 6 months were recruited from 20 venues in Glasgow, Scotland, and randomised into PHOENIx plus usual care, or usual care. PHOENIx is a collaborative assertive outreach intervention by independent prescriber NHS Pharmacists and third sector homelessness workers, offering repeated integrated, holistic physical, mental and addictions health and social care support including prescribing. We describe comprehensive baseline characteristics of randomised participants. RESULTS: One hundred and twenty-eight participants had a mean age of 42 years (SD 8.4); 71% male, homelessness for a median of 24 years (IQR 12-30). One hundred and eighteen (92%) lived in large, congregate city centre temporary accommodation. A quarter (25%) were not registered with a General Practitioner. Participants had overdosed a mean of 3.2 (SD 3.2) times in the preceding 6 months, using a median of 3 (IQR 2-4) non-prescription drugs concurrently: 112 (87.5%) street valium (benzodiazepine-type new psychoactive substances); 77 (60%) heroin; and 76 (59%) cocaine. Half (50%) were injecting, 50% into their groins. 90% were receiving care from Alcohol and Drug Recovery Services (ADRS), and in addition to using street drugs, 90% received opioid substitution therapy (OST), 10% diazepam for street valium use and one participant received heroin-assisted treatment. Participants had a mean of 2.2 (SD 1.3) mental health problems and 5.4 (SD 2.5) physical health problems; 50% received treatment for physical or mental health problems. Ninety-one per cent had at least one mental health problem; 66% had no specialist mental health support. Participants were frail (70%) or pre-frail (28%), with maximal levels of psychological distress, 44% received one or no daily meal, and 58% had previously attempted suicide. CONCLUSIONS: People at high risk of drug-related death continue to overdose repeatedly despite receiving OST. High levels of frailty, multimorbidity, unsuitable accommodation and unmet mental and physical health care needs require a reorientation of services informed by evidence of effectiveness and cost-effectiveness. Trial registration UK Clinical Trials Registry identifier: ISRCTN 10585019.

Pharmacist and Homeless Outreach Engagement and Non-medical Independent prescribing Rx (PHOENIx): a study protocol for a pilot randomised controlled trial.

INTRODUCTION: The number of people experiencing homelessness (PEH) is increasing worldwide. Systematic reviews show high levels of multimorbidity and mortality. Integrated health and social care outreach interventions may improve outcomes. No previous studies have targeted PEH with recent drug overdose despite high levels of drug-related deaths and few data describe their health/social care problems. Feasibility work suggests a collaborative health and social care intervention (Pharmacist and Homeless Outreach Engagement and Non-medical Independent prescribing Rx, PHOENIx) is potentially beneficial. We describe the methods of a pilot randomised controlled trial (RCT) with parallel process and economic evaluation of PEH with recent overdose. METHODS AND ANALYSIS: Detailed health and social care information will be collected before randomisation to care-as-usual plus visits from a pharmacist and a homeless outreach worker (PHOENIx) for 6-9 months or to care-as-usual. The outcomes are the rates of presentations to emergency department for overdose or other causes and whether to progress to a definitive RCT: recruitment of ≥100 participants within 4 months, ≥60% of patients remaining in the study at 6 and 9 months, ≥60% of patients receiving the intervention, and ≥80% of patients with data collected. The secondary outcomes include health-related quality of life, hospitalisations, treatment uptake and patient-reported measures. Semistructured interviews will explore the future implementation of PHOENIx, the reasons for overdose and protective factors. We will assess the feasibility of conducting a cost-effectiveness analysis. ETHICS AND DISSEMINATION: The study was approved by South East Scotland National Health Service Research Ethics Committee 01. Results will be made available to PEH, the study funders and other researchers. TRIAL REGISTRATION NUMBER: ISRCTN10585019.

Digital smartphone intervention to recognise and manage early warning signs in schizophrenia to prevent relapse: the EMPOWER feasibility cluster RCT.

BACKGROUND: Relapse is a major determinant of outcome for people with a diagnosis of schizophrenia. Early warning signs frequently precede relapse. A recent Cochrane Review found low-quality evidence to suggest a positive effect of early warning signs interventions on hospitalisation and relapse. OBJECTIVE: How feasible is a study to investigate the clinical effectiveness and cost-effectiveness of a digital intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? DESIGN: A multicentre, two-arm, parallel-group cluster randomised controlled trial involving eight community mental health services, with 12-month follow-up. SETTINGS: Glasgow, UK, and Melbourne, Australia. PARTICIPANTS: Service users were aged > 16 years and had a schizophrenia spectrum disorder with evidence of a relapse within the previous 2 years. Carers were eligible for inclusion if they were nominated by an eligible service user. INTERVENTIONS: The Early signs Monitoring to Prevent relapse in psychosis and prOmote Wellbeing, Engagement, and Recovery (EMPOWER) intervention was designed to enable participants to monitor changes in their well-being daily using a mobile phone, blended with peer support. Clinical triage of changes in well-being that were suggestive of early signs of relapse was enabled through an algorithm that triggered a check-in prompt that informed a relapse prevention pathway, if warranted. MAIN OUTCOME MEASURES: The main outcomes were feasibility of the trial and feasibility, acceptability and usability of the intervention, as well as safety and performance. Candidate co-primary outcomes were relapse and fear of relapse. RESULTS: We recruited 86 service users, of whom 73 were randomised (42 to EMPOWER and 31 to treatment as usual). Primary outcome data were collected for 84% of participants at 12 months. Feasibility data for people using the smartphone application (app) suggested that the app was easy to use and had a positive impact on motivations and intentions in relation to mental health. Actual app usage was high, with 91% of users who completed the baseline period meeting our a priori criterion of acceptable engagement (> 33%). The median time to discontinuation of > 33% app usage was 32 weeks (95% confidence interval 14 weeks to ∞). There were 8 out of 33 (24%) relapses in the EMPOWER arm and 13 out of 28 (46%) in the treatment-as-usual arm. Fewer participants in the EMPOWER arm had a relapse (relative risk 0.50, 95% confidence interval 0.26 to 0.98), and time to first relapse (hazard ratio 0.32, 95% confidence interval 0.14 to 0.74) was longer in the EMPOWER arm than in the treatment-as-usual group. At 12 months, EMPOWER participants were less fearful of having a relapse than those in the treatment-as-usual arm (mean difference -4.29, 95% confidence interval -7.29 to -1.28). EMPOWER was more costly and more effective, resulting in an incremental cost-effectiveness ratio of £3041. This incremental cost-effectiveness ratio would be considered cost-effective when using the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year gained. LIMITATIONS: This was a feasibility study and the outcomes detected cannot be taken as evidence of efficacy or effectiveness. CONCLUSIONS: A trial of digital technology to monitor early warning signs that blended with peer support and clinical triage to detect and prevent relapse is feasible. FUTURE WORK: A main trial with a sample size of 500 (assuming 90% power and 20% dropout) would detect a clinically meaningful reduction in relapse (relative risk 0.7) and improvement in other variables (effect sizes 0.3-0.4). TRIAL REGISTRATION: This trial is registered as ISRCTN99559262. FUNDING: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 27. See the NIHR Journals Library website for further project information. Funding in Australia was provided by the National Health and Medical Research Council (APP1095879).

WHAT WAS THE PROBLEM?: Relapse is a considerable problem for people with a diagnosis of schizophrenia. Relapse can be predicted by early warning signs that are unique to the person. They include withdrawal, fear and paranoia. WHAT WAS THE QUESTION?: Is it possible to investigate the effectiveness of an intervention to recognise and promptly manage early warning signs of relapse in schizophrenia with the aim of preventing relapse? WHAT DID WE DO?: We spoke with 88 mental health staff, 40 carers and 21 service users before we designed a system that used a mobile phone to help people monitor early warning signs. We included peer support to help people using the system reflect on their experiences. We hoped the overall system, called EMPOWER, would help people to be more in charge of their mental health. After consenting 86 people to the study, we were able to randomly assign 73 people either to use the EMPOWER system (42 people) or to receive their normal treatment alone (31 people). We used research measures over 1 year to help us better understand people's experiences. We also involved carers (for example family or friends) and mental health service providers in the research. WHAT DID WE FIND?: We found that it was possible to recruit people to the study and to gather research data. We also found that people used the EMPOWER system and found it acceptable. We found that those who used EMPOWER had a lower rate of relapse over 12 months than people who did not. They were also less likely to be fearful of relapse. We found that EMPOWER was likely to be cost-effective. WHAT DOES THIS MEAN?: This means that a study to investigate the effectiveness of a system to recognise and respond to early warning signs of relapse in schizophrenia is possible.

The failure of a sentinel node biopsy due to an absence of nodal uptake of nuclear isotope in consecutive melanomas in a single patient - a physiological aberration.

Nodal metastasis is an independent prognostic factor in patients with melanoma. Sentinel lymph node biopsy (SNB) is a recommended component of the management of patients with AJCC stage T1b or above. The dermal scar is injected with a Technetium-99 m (99MTc) Nanocolloid, a radiotracer that drains into sentinel nodes to be identified on a preoperative SPECT/CT scan. Intraoperatively the sentinel nodes are located using a gamma probe and patent blue dye. A 79-year-old male was referred to the Plastics Outpatient Department for management of a biopsy proven pT4b melanoma on the right flank and a suspicious lesion on the right shoulder. He was scheduled for a SNB and wide local excision of the flank melanoma and excisional biopsy of the shoulder lesion. He received injections of 99MTc Nanocolloid around the flank biopsy scar, however, preoperative, and intraoperative attempts to locate a node using radiological and surgical techniques were unsuccessful. The biopsy of the shoulder lesion sent for histopathology revealed a pT1b melanoma. A subsequent second SNB on the shoulder melanoma was unsuccessful, as 99MTc Nanocolloid failed to drain into a sentinel node for a second time. The drainage function of lymphatic vessels declines with age however the complete failure of nodal uptake is exceptionally rare. Novel radiotracers such as 99MTc Tilmanocept have shown superior lymph node tracking in recent tracers.

Examining the Relationship Between Wound Complications and the Use of Resorbable Plates in Cranial Vault Reconstruction.

BACKGROUND: Resorbable plates are commonly used in cranial vault reconstruction surgery. There are few published papers examining their safety profile. The authors examined the prevalence of wound complications associated with the use of resorbable plates (Inion CPS Fixation System) in pediatric patients undergoing cranial vault reconstruction. METHODS: A retrospective review of patients (n = 182) who underwent cranial vault reconstruction using resorbable plate fixation was undertaken. All procedures were performed by a single Craniofacial Surgeon at the National Pediatric Craniofacial Center from 2008 to 2016. Wound complications were identified from a prospectively maintained database and medical note review. Several key patient characteristics and surgical variables were also recorded and tested for associations with wound complications. RESULTS: A total of 58.8% (107 of 182) of patients were male with a median age at surgery of 16.2 months. Overall, 12.1% (22 of 182) experienced a postoperative wound complication requiring hospital admission. A total of 2.73% (5 of 182) of the patients that returned to theatre had remnants of plates removed. The authors had a mean time from primary operation to secondary reoperation of 103 days. In univariate statistical analysis, females were more likely to develop a wound complication. However, in stratified analyses excluding patients with an underlying genetic syndrome, increasing age, and lower weight but not gender were associated with wound complications. CONCLUSIONS: A 12.1% (22 of 182) wound complication rate with the use of the Inion CPS Fixation System was observed. Inion plates appear to have an equivalent safety profile to other fixation devices. Increasing age and lower weight were associated with an increased risk of wound complications in nonsyndromic patients.

A case-control study examining the association of smad7 and TLR single nucleotide polymorphisms on the risk of colorectal cancer in ulcerative colitis.

AIM: Ulcerative colitis (UC) is characterized by chronic mucosal inflammation and an increased risk of colorectal cancer. smad7, TLR2 and TLR4 modulate intestinal inflammation and their polymorphisms affect the risk of development of sporadic colorectal cancer. The aim of the current study was to examine the association between single nucleotide polymorphisms (SNPs) in smad7, TLR2 and TLR4 and the development of colorectal cancer in patients with UC. METHOD: DNA was extracted from formalin-fixed, paraffin-embedded tissue from 90 patients with UC who had undergone panproctocolectomy between 1985 and 2013 (30 with UC-associated colorectal cancer and 60 control UC patients). Control cases were matched 2:1 for age at diagnosis of colitis, duration of disease and gender. Genotyping was performed for the smad7 rs4464148, rs11874392, rs12953717 and rs4939827 SNPs, the TLR2 rs5743704 and rs5743708 SNPs and the TLR4 rs4986790 and rs4986791 SNPs. RESULTS: Sixty three of the 90 patients (70%) were men and the mean age at diagnosis of UC was 38.6 ± 1.6 years. The mean time to the diagnosis of UC-associated colorectal cancer was 13.5 ± 1.9 years. The 5-year recurrence-free and cancer-specific survival rates were 76% and 88%, respectively. All eight SNPs were in Hardy-Weinberg equilibrium. None of the eight SNPs assessed in smad7, TLR2 or TLR4 were associated with the development of UC-associated colorectal cancer at an allelic or genotypic level. CONCLUSIONS: These data do not support an association between polymorphisms in smad7, TLR2 or TLR4 and the development of UC-associated colorectal cancer.

Single access laparoscopic total colectomy for severe refractory ulcerative colitis.

BACKGROUND: Single port laparoscopic surgery allows total colectomy and end ileostomy for medically uncontrolled ulcerative colitis solely via the stoma site incision. While intuitively appealing, there is sparse evidence for its use beyond feasibility. AIM: To examine the usefulness of single access laparoscopy (SAL) in a general series experience of patients sick with ulcerative colitis. METHODS: All patients presenting electively, urgently or emergently over a three-year period under a colorectal specialist team were studied. SAL was performed via the stoma site on a near-consecutive basis by one surgical team using a "surgical glove port" allowing group-comparative and case-control analysis with a contemporary cohort undergoing conventional multiport surgery. Standard, straight rigid laparoscopic instrumentation were used without additional resource. RESULTS: Of 46 consecutive patients requiring surgery, 39 (85%) had their procedure begun laparoscopically. 27 (69%) of these were commenced by single port access with an 89% completion rate thereafter (three were concluded by multi-trocar laparoscopy). SAL proved effective in comparison to multiport access regardless of disease severity providing significantly reduced operative access costs (> 100€case) and postoperative hospital stay (median 5 d vs 7.5 d, P = 0.045) without increasing operative time. It proved especially efficient in those with preoperative albumin > 30 g/dL (n = 20). Its comparative advantages were further confirmed in ten pairs case-matched for gender, body mass index and preoperative albumin. SAL outcomes proved durable in the intermediate term (median follow-up = 20 mo). CONCLUSION: Single port total colectomy proved useful in planned and acute settings for patients with medically refractory colitis. Assumptions regarding duration and cost should not be barriers to its implementation.

Is There Variability in Scoring of Student Surgical OSCE Performance Based on Examiner Experience and Expertise?

OBJECTIVE: To investigate the influence of clinical experience and content expertise on global assessment scores in a Surgical Objective Structured Clinical Exam (OSCE) for senior medical undergraduate students. DESIGN: Scripted videos of simulated student performance in an OSCE at two standards (clear pass and borderline) were awarded a global score on each of two rating scales by a range of clinical assessors. Results were analysed by examiner experience and content expertise. SETTING: The study was designed in a large Medical School in Ireland. Examiners were consultant and training grade doctors from three university teaching hospitals. PARTICIPANTS: 147 assessors participated. Of these, 75 (51%) were surgeons and 25 (17%) had sub-speciality surgical expertise directly relevant to the OSCE station. 41 were consultants. RESULTS: Responsible academic scoring set the benchmark. By multivariable linear regression analysis, neither clinical experience (consultant status) nor relevant content expertise in surgery was independently predictive of assessor grading for either clear pass or borderline student performance. No educational factor (previous examining experience/training, self-rated confidence in assessment or frame of reference) was significant. Assessor gender (male) was associated with award of a fail grade for borderline performance. Trainees were reliable graders of borderline performance but more lenient than the gold standard for clear pass. We report greater agreement with the gold standard score using the global descriptive scale, with strong agreement for all assessors in the borderline case. CONCLUSIONS: Neither assessor clinical experience nor content expertise is independently predictive of grade awarded in an OSCE. Where non-experts or trainees assess, we find evidence for use of a descriptive global score to maximise agreement with expert gold standard, particularly for borderline performance. These results inform the fair and reliable participation of a range of examiners across subspecialty stations in the surgical OSCE format.

Early Signs Monitoring to Prevent Relapse in Psychosis and Promote Well-Being, Engagement, and Recovery: Protocol for a Feasibility Cluster Randomized Controlled Trial Harnessing Mobile Phone Technology Blended With Peer Support.

BACKGROUND: Relapse in schizophrenia is a major cause of distress and disability and is predicted by changes in symptoms such as anxiety, depression, and suspiciousness (early warning signs [EWSs]). These can be used as the basis for timely interventions to prevent relapse. However, there is considerable uncertainty regarding the implementation of EWS interventions. OBJECTIVE: This study was designed to establish the feasibility of conducting a definitive cluster randomized controlled trial comparing Early signs Monitoring to Prevent relapse in psychosis and prOmote Well-being, Engagement, and Recovery (EMPOWER) against treatment as usual (TAU). Our primary outcomes are establishing parameters of feasibility, acceptability, usability, safety, and outcome signals of a digital health intervention as an adjunct to usual care that is deliverable in the UK National Health Service and Australian community mental health service (CMHS) settings. We will assess the feasibility of candidate primary outcomes, candidate secondary outcomes, and candidate mechanisms for a definitive trial. METHODS: We will randomize CMHSs to EMPOWER or TAU. We aim to recruit up to 120 service user participants from 8 CMHSs and follow them for 12 months. Eligible service users will (1) be aged 16 years and above, (2) be in contact with local CMHSs, (3) have either been admitted to a psychiatric inpatient service or received crisis intervention at least once in the previous 2 years for a relapse, and (4) have an International Classification of Diseases-10 diagnosis of a schizophrenia-related disorder. Service users will also be invited to nominate a carer to participate. We will identify the feasibility of the main trial in terms of recruitment and retention to the study and the acceptability, usability, safety, and outcome signals of the EMPOWER intervention. EMPOWER is a mobile phone app that enables the monitoring of well-being and possible EWSs of relapse on a daily basis. An algorithm calculates changes in well-being based on participants' own baseline to enable tailoring of well-being messaging and clinical triage of possible EWSs. Use of the app is blended with ongoing peer support. RESULTS: Recruitment to the trial began September 2018, and follow-up of participants was completed in July 2019. Data collection is continuing. The database was locked in July 2019, followed by analysis and disclosing of group allocation. CONCLUSIONS: The knowledge gained from the study will inform the design of a definitive trial including finalizing the delivery of our digital health intervention, sample size estimation, methods to ensure successful identification, consent, randomization, and follow-up of participants, and the primary and secondary outcomes. The trial will also inform the final health economic model to be applied in the main trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 99559262; http://isrctn.com/ISRCTN99559262. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/15058.

Negative Predictors of Outcomes of Flexor Tendon Repairs.

The current trend in hand surgery has streamlined the treatment of acute hand trauma to the modern-day surgery unit. As the volume of hand trauma caseloads continues to increase, it is becoming increasingly difficult to schedule patients for theater on the day of injury. It, therefore, becomes paramount to adequately triage patients in accordance with best clinical evidence and predictors of poor clinical outcomes. Animal models suggest that the earlier flexor tendons are repaired, the better the patient functional outcome. The largest study to date examining the timing of injury to functional post-operative outcome also recognizes that the faster these injuries are repaired, the better the patient outcome. Age-related changes to tendon biomechanics and structure are well-documented. However, no conclusive evidence exists specific to the degenerative changes and mechanical properties of flexor tendons in humans. The animal model strongly suggests that increasing age is associated with local architectural and biological changes that directly affect the tendon repair functional outcome. Although retrospective analyses to date suggest that smoking is a negative outcome predictor for functional tendon outcome, no prospective large-scale studies exist. A large, single-center prospective study specifically examining the positive and negative outcome predictors of flexor tendon repairs and functional post-operative outcome is warranted. The negative predictive model of patient care may enable us to further council patients preoperatively and stratify patients according to clinical need.

Incidence, risks and outcome of radiological leak following early contrast enema after anterior resection.

INTRODUCTION: Anastomotic leak (AL) is a major complication following anterior resection for colorectal cancer. Early contrast enema may diagnose subclinical anastomotic leakage. Knowledge of factors concerning AL is vital to its detection. The aim of this study was to define the incidence, risks and outcome of radiological leak following routine early contrast enema after anterior resection. METHODS: A cohort of 129 patients who underwent anterior resection for colorectal cancer and had an early Gastrografin enema between July 2008 and December 2012 in a tertiary referral centre was identified from a prospective database. The severity of AL was defined using the International Study Group of Rectal Cancer (ISREC) grading system. RESULTS: Of the 129 patients, 65.1 % were male, and the mean age at surgery was 64.6 ± 1.1 years. Gastrografin enema was performed on average on post-operative day 4.8 ± 0.2. Eighteen patients (14.0 %) had a radiological leak on Gastrografin enema, and nine patients (7.0 %) had a clinical AL. On multivariate analysis, only being of male sex and having a loop ileostomy increased the risk of radiological AL. Gastrografin enema had a sensitivity of 100 % (95 % CI 66-100 %) and specificity of 93 % (95 % CI 86-97 %) for predicting clinical AL. Of the 18 patients with radiological leaks, 11 were ISREC grade A, 3 were grade B and 4 were grade C. CONCLUSIONS: In the current series, early Gastrografin enema following anterior resection identifies a 14 % radiological leak rate and has a high sensitivity and specificity for predicting clinical AL. The majority of radiological leaks may be managed conservatively.

Outcomes from building system courseware for teaching and testing in a discipline-based human structure curriculum.

This study investigated the educational benefits of system-based lecture notes and interactive learning objects in a peripheral nervous system component of a traditional first-year medical school human anatomy course. The impetus for the investigation was anecdotal evidence suggesting enhanced learner satisfaction with the learning resources. Retrospective review of existing data from 2006 to 2009 was undertaken to quantify (1) the effects of Web-based system courseware on examination item performance, and (2) differences among learner opinions regarding the benefit level of the five different types of interactive learning objects as evaluated by instructional design questionnaires. Interactive patient-based case studies (IPCS) and review games (Games), simulated interactive patients (SIP), flashcards, and unit quizzes (Quizzes) developed in-house have been peer-reviewed and published in MedEdPORTAL. Statistics included one-way analysis of variance, Tukey's post hoc test, and power meta-analysis (d). Examination item analysis scores remained significantly higher (P ≤ 0.05; d = 0.3938) for learners receiving the instructional treatment incorporating system-based lecture notes and interactive learning objects than for those not receiving this treatment. Using questionnaires with a five-point Likert scale, students reported favorably on the benefit level of all learning objects. They rated the SIP and IPCS significantly higher (P ≤0.05) and games significantly lower (P ≤ 0.05) than in previous years, indicating a change in learner preferences. This study reaffirms that online system-based instructional techniques improve student examination performance and overall student satisfaction. Learners indicated stronger preferences for SIP and IPCS over exercises encouraging passive memorization of anatomical content.

Does endurance fatigue increase the risk of injury when performing drop jumps?

Although from an athletic performance perspective it may be beneficial to undertake drop jump training when fatigued (principle of "specificity" of training), such endurance fatigue may expose the body to a greater risk of injury if it causes an increase in peak impact accelerations. This study aimed to determine if endurance fatigue resulted in an increase in tibial peak impact acceleration and an associated change in knee kinematics when completing plyometric drop jumps. Fifteen females performed drop jumps from 3 heights (15, 30, and 45 cm) when fatigued and nonfatigued. Treadmill running was used to induce endurance fatigue. The following variables were assessed: tibial peak impact acceleration, knee angle at initial ground contact, maximum angle of flexion, range of flexion, and peak knee angular velocity. Fatigue resulted in significantly greater (p < 0.05) tibial peak impact acceleration and knee flexion peak angular velocity in drop jumps from 15 and 30 cm, but not from 45 cm. Fatigue had no effect on any of the knee angles assessed. The neuromuscular system was affected negatively by endurance fatigue at 15 and 30 cm, indicating that coaches should be aware of a potential increased risk of injury in performing drop jumps when fatigued. Because from the greater drop height of 45 cm the neuromuscular system had a reduced capacity to attenuate the impact accelerations per se, whether nonfatigued or fatigued, this would suggest that this height may have been too great for the athletes examined.

Insulin enhances proliferation and viability of human umbilical vein endothelial cells.

This investigation is a follow-up to our previous in vivo studies revealing that rapid stretch increases tissue insulin in murine skin flaps, coincident with the up-regulation of key angiogenic effectors and enhanced vascularization. In the present study, we used human umbilical vein endothelial cells (HUVECs) as an in vitro model system to determine the role of insulin in the chemical signals regulating the processes of proliferation and viability (survival). MTT-based colorimetric methods demonstrated that insulin enhances proliferation and survival of HUVECs. Western blot analysis revealed that protein kinase B (pAkt [Thr(308)]) and vascular endothelial growth factor (VEGF) were the insulin-responsive intermediates in proliferating endothelial cells (ECs). In insulin-enhanced survival, both pAkt (Thr(308)) and pAkt (Ser(473)) were activated in HUVECs. However, no change in VEGF expression accompanied pAkt activation. The beneficial effects of insulin were abrogated by insulin receptor (IR)/insulin-like growth factor receptor (IGFR) or phosphoinositide-3 kinase (PI3-K) blockade, suggesting that insulin-induced EC proliferation and viability are mediated through pIR/pIGFR and PI3-K effectors. These data provide new insights into the beneficial effects of insulin on vascularization and tissue viability, providing a mechanistic link to the enhancement of healing in acutely stretched skin.

Acute stretch promotes endothelial cell proliferation in wounded healing mouse skin.

We have developed a novel in vivo model utilizing acute stretch to investigate endothelial cell proliferation as a marker of vascular growth in healing mouse skin. This study is a follow-up to ones revealing immediate stretch improves blood flow, decreases total tissue necrosis, and induces tissue insulin transcription. Dorsal distally based flaps of skin were stretched for 3 min using linear (skin hook) plus hemispherical load cycling (inflated subcutaneous silicone catheter). Unstretched, wounded skin along the back and sternum served as postoperative controls. Laser Doppler flowmetry demonstrated a threefold increase in flap perfusion at postoperative day 7. A stretch-induced sixfold increase in endothelial cell mitogenesis accompanied enhancements in blood flow and extracorporal wound healing over the sternum. Western blots revealed up-regulation/activation of insulin and mitogenic signaling intermediates in stretched skin. Activated insulin and insulin growth factor receptors (pIR/pIGFR), protein kinase B (Akt, pAkt), vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (flk-1) were among the identified stretch-responsive intermediates. These results indicate the benefits of acute stretch are mediated through enhanced vascularity as evidenced by endothelial cell mitogenesis and up-regulation/activation of insulin and key angiogenic effectors in dorsal distally based skin flaps.

Effects of interactive instructional techniques in a web-based peripheral nervous system component for human anatomy.

BACKGROUND: This study investigated the effects of interactive instructional techniques in a web-based peripheral nervous system (PNS) component of a first year medical school human anatomy course. METHOD: Existing data from 9 years of instruction involving 856 students were used to determine (1) the effect of web-based interactive instructional techniques on written exam item performance and (2) differences between student opinions of the benefit level of five different types of interactive learning objects used. The interactive learning objects included Patient Case studies, review Games, Simulated Interactive Patients (SIP), Flashcards, and unit Quizzes. RESULTS: Exam item analysis scores were found to be significantly higher (p < 0.05) for students receiving the instructional treatment incorporating the web-based interactive learning objects than for students not receiving this treatment. Questionnaires using a five-point Likert scale were analysed to determine student opinion ratings of the interactive learning objects. Students reported favorably on the benefit level of all learning objects. Students rated the benefit level of the Simulated Interactive Patients (SIP) highest, and this rating was significantly higher (p < 0.05) than all other learning objects. CONCLUSION: This study suggests that web-based interactive instructional techniques improve student exam performance. Students indicated a strong acceptance of Simulated Interactive Patient learning objects.