Enoxaparin for VTE thromboprophylaxis during inpatient rehabilitation care: assessment of the standard fixed dosing regimen.

BACKGROUND: We aimed to examine the efficiency of fixed daily dose enoxaparin (40 mg) thromboprophylaxis strategy for patients undergoing inpatient rehabilitation. METHODS: This was an observational, prospective, cohort study that included 63 hospitalized patients undergoing rehabilitative treatment following sub-acute ischemic stroke (SAIS) or spinal cord injury (SCI), with an indication for thromboprophylaxis. Anti-Xa level measured three hours post-drug administration (following three consecutive days of enoxaparin treatment or more) was utilised to assess in vivo enoxaparin activity. An anti-Xa level between 0.2-0.5 U/ml was considered evidence of effective antithrombotic activity. RESULTS: We found sub-prophylactic levels of anti-Xa (<0.2 U/ml) in 19% (12/63). Results were within the recommended prophylactic range (0.2-0.5 U/ml) in 73% (46/63) and were supra-prophylactic (>0.5 U/ml) in 7.9% (5/63) of patients. Anti-Xa levels were found to inversely correlate with patients' weight and renal function as defined by creatinine clearance (CrCl) (p<0.05). CONCLUSIONS: Our study confirmed that a one-size-fits-all approach for venous thromboembolism (VTE) prophylaxis may be inadequate for rehabilitation patient populations. The efficacy of fixed-dose enoxaparin prophylaxis is limited and may be influenced by renal function and weight. This study suggests that anti-Xa studies and prophylactic enoxaparin dose adjustments should be considered in certain patients, such as those who are underweight, overweight and or have suboptimal renal function. TRIAL REGISTRATION: No. NCT103593291, registered August 2018.

Differences in Attitudes Toward Immunosuppressant Therapy in a Multi-ethnic Sample of Kidney Transplant Recipients.

Barriers for renal transplant patients to immunosuppressant medication adherence are poorly understood, despite the high rate and toll of non-adherence. We sought to assess factors that contribute to barriers to immunosuppressive medication adherence in an ethnically diverse sample of 312 renal transplant patients recruited from three transplant centers across New York City. Transplant patients who were at least 6 months post-transplant completed questionnaires while waiting for their medical appointment. Ethnic differences were observed on barriers to immunosuppressant adherence. Black and Hispanic participants reported significantly more barriers to adherence compared to Caucasian participants. Differences in perception about the potential harm and necessity of immunosuppressant medications also were present. Using hierarchical multiple regression, age and income were significant predictors of reported barriers to adherence, even while controlling for ethnicity. The most robust predictor of reported barriers was the perception of the medication cost-benefit differential, i.e., the balance between concerns about immunosuppressant medications and their perceived helpfulness (B = - 0.5, p < .001), indicating that varying beliefs about the medication's necessity and utility rather than ethnicity explain the differences in barriers to medication adherence. Future interventions targeting non-adherence should aim to reduce the barriers to adherence by addressing perceived risks and benefits of taking immunosuppressant medication.

Cognitive Dysfunction: Part and Parcel of the Diabetic Foot.

OBJECTIVE: The presence of a foot ulcer increases the self-treatment burden imposed on the individual with diabetes. Additionally, this condition increases the cognitive demands needed for adherence to medical recommendations. A potential gap could exist between medical recommendations and the individual's ability to implement them. Hence, the goal of this study was to examine whether the cognitive profile of people with diabetic foot ulcers differs from that of people with diabetes without this complication. RESEARCH DESIGN AND METHODS: This was a case-control study. Ninety-nine individuals with diabetic foot ulcers (case patients) and 95 individuals with type 2 diabetes (control subjects) (age range 45-75 years), who were matched for diabetes duration and sex, underwent extensive neuropsychological evaluation using a NeuroTrax computerized battery, digit symbol, and verbal fluency tests. A global cognitive score after standardization for age and education was computed as well as scores in the following six cognitive domains: memory, executive function, reaction time, attention, psychomotor abilities, and estimated premorbid cognition. RESULTS: Individuals with diabetic foot ulcers had significantly (P < 0.001) lower cognitive scores than individuals with diabetes without this complication, in all tested cognitive domains, excluding estimated premorbid cognition. Individuals with diabetic foot ulcers demonstrated a significant difference between precognitive and current cognitive abilities, as opposed to the nonsignificant difference among control subjects. The differences persisted in multivariable analysis after adjusting for depression and smoking. CONCLUSIONS: Individuals with diabetic foot ulcers were found to possess fewer cognitive resources than individuals with diabetes without this complication. Thus, they appear to face more self-treatment challenges, while possessing significantly fewer cognitive resources.

Psychosocial intervention improves depression, quality of life, and fluid adherence in hemodialysis.

Patients with ESRD have high rates of depression, which is associated with diminished quality of life and survival. We determined whether individual cognitive behavioral therapy (CBT) reduces depression in hemodialysis patients with elevated depressive affect in a randomized crossover trial. Of 65 participants enrolled from two dialysis centers in New York, 59 completed the study and were assigned to the treatment-first group (n=33) or the wait-list control group (n=26). In the intervention phase, CBT was administered chairside during dialysis treatments for 3 months; participants were assessed 3 and 6 months after randomization. Compared with the wait-list group, the treatment-first group achieved significantly larger reductions in Beck Depression Inventory II (self-reported, P=0.03) and Hamilton Depression Rating Scale (clinician-reported, P<0.001) scores after intervention. Mean scores for the treatment-first group did not change significantly at the 3-month follow-up. Among participants with depression diagnosed at baseline, 89% in the treatment-first group were not depressed at the end of treatment compared with 38% in the wait-list group (Fisher's exact test, P=0.01). Furthermore, the treatment-first group experienced greater improvements in quality of life, assessed with the Kidney Disease Quality of Life Short Form (P=0.04), and interdialytic weight gain (P=0.002) than the wait-list group, although no effect on compliance was evident at follow-up. In summary, CBT led to significant improvements in depression, quality of life, and prescription compliance in this trial, and studies should be undertaken to assess the long-term effects of CBT on morbidity and mortality in patients with ESRD.

A pilot investigation of cognitive improvement across a single hemodialysis treatment.

BACKGROUND: Uremia has long been associated with cognitive deficits. This study explored the importance of the time of measurement of neurocognitive functioning, by directly comparing changes in neurocognitive functioning from immediately after hemodialysis treatment to immediately before treatment. METHODS: Twenty-five hemodynamically stable hemodialysis patients and 6 peritoneal dialysis controls completed 2 computer-based assessment batteries (ANAM), one immediately before dialysis and the second upon completion of that dialysis session. Paired sample t-tests were used to compare postdialysis with predialysis neurocognitive functioning scores for both a composite measure of global functioning and the neurocognitive subtests. RESULTS: There was significant improvement in global neuropsychological functioning from predialysis to postdialysis (t (24) = -7.5, p<0.001), showing an average of 18% improvement in the hemodialysis group, with no significant change in the peritoneal dialysis group. CONCLUSION: This study suggests that computer-based testing can offer information on the cognitive fluctuations of medically complex populations and suggests that the end of the session may be a better time to discuss important and complex health messages with hemodialysis patients. It further implies that some of the neurocognitive impairment that is associated with end-stage renal disease is a consequence of uremia and is improved by hemodialysis.

Depression and nonadherence predict mortality in hemodialysis treated end-stage renal disease patients.

The scientific evaluation of depression's impact on mortality in hemodialysis (HD) patients has yielded mixed results, with the more recent, more rigorous studies detecting a significant relationship. In this study, 130 HD patients from an urban North American hospital were evaluated for depressive affect and then observed for up to 5 years. In a corrected Cox regression model, which held constant age, gender, dialysis vintage, illness severity and diabetic status, depressive affect emerged as a modest but significant predictor of mortality (relative risk = 1.05, 95% confidence interval = 1.01-1.08). When the subjects were divided according to depressive affect severity, those with severe depressive affect had significantly shorter time to death (ß = 0.452, P = 0.044). In a subgroup of 85 subjects, self-reported medication adherence was also predictive of mortality, with higher rates of nonadherence being associated with increased mortality risk. This paper lends support to the burgeoning literature on depression and reduced survival in HD populations, as well as begins the investigation of understanding the underlying mechanisms.

The nature and course of sensory changes following spinal cord injury: predictive properties and implications on the mechanism of central pain.

Central pain below the injury level after spinal cord injury is excruciating, chronic and resistive to treatment. Animal studies suggest that pretreatment may prevent central pain, but to date there are no measures to predict its development. Our aim was to monitor changes in the sensory profile below the lesion prior to the development of below-level central pain in order to search for a parameter that could predict its risk and to further explore its pathophysiology. Thirty patients with spinal cord injury and 27 healthy controls underwent measurement of warm, cold, heat-pain and touch thresholds as well as graphaesthesia, allodynia, hyperpathia and wind-up pain in intact region and in the shin and feet (below level). Patients were tested at 2-4 weeks, 1-2.5 months and 2.5-6 months after the injury or until central pain had developed. At the end of the follow-up, 46% of patients developed below-level central pain. During the testing periods, individuals who eventually developed central pain had higher thermal thresholds than those who did not and displayed high rates of abnormal sensations (allodynia and hyperpathia), which gradually increased with time until central pain developed. Logistic regressions revealed that the best predictor for the risk of below-level central pain was allodynia in the foot in the second testing session with a 77% probability (90.9% confidence). The results suggest that neuronal hyperexcitability, which may develop consequent to damage to spinothalamic tracts, precedes central pain. Furthermore, it appears that below-level central pain develops after a substantial build-up of hyperexcitability. To the best of our knowledge, this is the first systematic report establishing that neuronal hyperexcitability precedes central pain. Predicting the risk for central pain can be utilized to initiate early treatment in order to prevent its development.

Risk factors for failure of heparin thromboprophylaxis in patients with acute traumatic spinal cord injury.

UNLABELLED: Venous thromboembolism (VTE) is a well-recognized complication of Acute Traumatic Spinal Cord Injury (ATSCI). Despite prophylaxis by heparins, VTE occurs in a substantial number of ATSCI patients without an obvious explanation. In this matched case-control study we examined whether thrombophilia and other risk factors are associated with failure of thromboprophylaxis. Cases and controls receiving heparin thromboprophylaxis were selected from consecutively admitted ATSCI patients. Patients who developed a new, objectively confirmed, symptomatic VTE despite prophylaxis at hospital were matched by gender, age, level and mechanism of ATSCI with 2-3 controls without VTE. Patients were interviewed about VTE risk factors and tested for factor V Leiden (FVL), prothrombin G20210A (PT), methylenetetrahydrofolate reductase C677T homozygosity (MTHFR), lupus anticoagulant, homocysteine (Hcy) and plasma factor VIII (FVIII) levels. Twenty-two patients with new VTE episodes and 64 controls were ascertained. The total number of gene alterations for MTHFR, FVL and PT or elevated levels of Hcy or FVIII was significantly more common in patients compared to controls (82% vs. 48%, p=0.006). Multiple logistic regression proved the PT mutation, a positive family history of thrombosis and elevated levels of either FVIII or Hcy to be predictors of thrombosis. CONCLUSION: A positive family history of VTE, carriership of the prothrombin mutation and elevated FVIII or Hcy levels were significantly associated with failure to prevent VTE by heparin therapy following ATSCI. Testing for thrombophilia in patients with ATSCI and possibly a more intense thromboprophylactic regimen seem desirable but need to be verified by a prospective study.

Serious hazards of transfusion: a decade of hemovigilance in the UK.

The Serious Hazards of Transfusion (SHOT) scheme is a UK-wide, independent, professionally led hemovigilance system focused on learning from adverse events. SHOT was established in 1996 as a confidential reporting system for significant transfusion-related events, building an evidence base to support blood safety policy decisions, clinical guidelines, clinician education, and improvements in transfusion practice. Recommendations are formulated by an independent steering group drawn from medical royal colleges and professional bodies. Ten years after its inception, SHOT has analyzed 2630 transfusion safety events, published 8 annual reports with recommendations, and presented data nationally and internationally. These recommendations have underpinned key initiatives, in particular the UK Department of Health "Better Blood Transfusion" strategy. SHOT has encouraged open reporting of adverse events and "near-misses" in a supportive, learning culture, vigilance in hospital transfusion practice, and evaluation of information technology to support this process. The importance of education and training has been emphasized. Detailed analysis of events has identified weaknesses in the transfusion chain. A collaborative initiative between SHOT, the Chief Medical Officer for England's National Blood Transfusion Committee, and the National Patient Safety Agency aims to reduce ABO-incompatible transfusions by improving bedside practice. Cumulative SHOT data have documented the decline in transfusion-related graft vs host disease after implementation of leucodepletion and have highlighted transfusion-related acute lung injury and bacterial contamination of platelets as important causes of death and morbidity. The UK blood services have developed strategies to reduce these risks. Future SHOT data will evaluate the success of these and other blood safety improvements.