Clinical outcomes of intravenous immunoglobulin therapy in COVID-19 related acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Intravenous immunoglobulin (IVIG) has been used as an immunomodulatory therapy to counteract severe systemic inflammation in coronavirus disease 2019 (COVID-19). But its use in COVID-19 related acute respiratory distress syndrome (ARDS) is not well established. METHODS: We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to intensive care units (ICUs) at Hazm Mebaireek General Hospital, Qatar, between March 7, 2020 and September 9, 2020. Patients receiving invasive mechanical ventilation for moderate-to-severe ARDS were divided into two groups based on whether they received IVIG therapy or not. The primary outcome was all-cause ICU mortality. Secondary outcomes studied were ventilator-free days and ICU-free days at day-28, and incidence of acute kidney injury (AKI). Propensity score matching was used to adjust for confounders, and the primary outcome was compared using competing-risks survival analysis. RESULTS: Among 590 patients included in the study, 400 received routine care, and 190 received IVIG therapy in addition to routine care. One hundred eighteen pairs were created after propensity score matching with no statistically significant differences between the groups. Overall ICU mortality in the study population was 27.1%, and in the matched cohort, it was 25.8%. Mortality was higher among IVIG-treated patients (36.4% vs. 15.3%; sHR 3.5; 95% CI 1.98-6.19; P < 0.001). Ventilator-free days and ICU-free days at day-28 were lower (P < 0.001 for both), and incidence of AKI was significantly higher (85.6% vs. 67.8%; P = 0.001) in the IVIG group. CONCLUSION: IVIG therapy in mechanically ventilated patients with COVID-19 related moderate-to-severe ARDS was associated with higher ICU mortality. A randomized clinical trial is needed to confirm this observation further.

The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial.

OBJECTIVE: Epidemiological data suggest low serum 25-hydroxyvitamin D3 (25-OH-D3) levels are associated with radiological progression of knee osteoarthritis (OA). This study aimed to assess whether vitamin D supplementation can slow the rate of progression. METHOD: A 3-year, double-blind, randomised, placebo-controlled trial of 474 patients aged over 50 with radiographically evident knee OA comparing 800 IU cholecalciferol daily with placebo. Primary outcome was difference in rate of medial joint space narrowing (JSN). Secondary outcomes included lateral JSN, Kellgren & Lawrence grade, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function, stiffness and the Get up and Go test. RESULTS: Vitamin D supplementation increased 25-OH-D3 from an average of 20.7 (standard deviation (SD) 8.9) µg/L to 30.4 (SD 7.7) µg/L, compared to 20.7 (SD 8.1) µg/L and 20.3 (SD 8.1) µg/L in the placebo group. There was no significant difference in the rate of JSN over 3 years in the medial compartment of the index knee between the treatment group (average -0.01 mm/year) and placebo group (-0.08 mm/year), average difference 0.08 mm/year (95% confidence interval (CI) [-0.14-0.29], P = 0.49). No significant interaction was found between baseline vitamin D levels and treatment effect. There were no significant differences for any of the secondary outcome measures. CONCLUSION: Vitamin D supplementation did not slow the rate of JSN or lead to reduced pain, stiffness or functional loss over a 3-year period. On the basis of these findings we consider that vitamin D supplementation has no role in the management of knee OA.

Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE.

INTRODUCTION: The current mainstay of the treatment of thrombotic antiphospholipid syndrome (APS) is long-term anticoagulation with vitamin K antagonists (VKAs) such as warfarin. Non-VKA oral anticoagulants (NOACs), which include rivaroxaban, have been shown to be effective and safe compared with warfarin for the treatment of venous thromboembolism (VTE) in major phase III prospective, randomized controlled trials (RCTs), but the results may not be directly generalizable to patients with APS. AIMS: The primary aim is to demonstrate, in patients with APS and previous VTE, with or without systemic lupus erythematosus (SLE), that the intensity of anticoagulation achieved with rivaroxaban is not inferior to that of warfarin. Secondary aims are to compare rates of recurrent thrombosis, bleeding and the quality of life in patients on rivaroxaban with those on warfarin. METHODS: Rivaroxaban in antiphospholipid syndrome (RAPS) is a phase II/III prospective non-inferiority RCT in which eligible patients with APS, with or without SLE, who are on warfarin, target international normalized ratio (INR) 2.5 for previous VTE, will be randomized either to continue warfarin (standard of care) or to switch to rivaroxaban. Intensity of anticoagulation will be assessed using thrombin generation (TG) testing, with the primary outcome the percentage change in endogenous thrombin potential (ETP) from randomization to day 42. Other TG parameters, markers of in vivo coagulation activation, prothrombin fragment 1.2, thrombin antithrombin complex and D-dimer, will also be assessed. DISCUSSION: If RAPS demonstrates i) that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin and ii) the absence of any adverse effects that cause concern with regard to the use of rivaroxaban, this would provide sufficient supporting evidence to make rivaroxaban a standard of care for the treatment of APS patients with previous VTE, requiring a target INR of 2.5.

ARSACS, a spastic ataxia common in northeastern Québec, is caused by mutations in a new gene encoding an 11.5-kb ORF.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS or SACS) is an early onset neurodegenerative disease with high prevalence (carrier frequency 1/22) in the Charlevoix-Saguenay-Lac-Saint-Jean (CSLSJ) region of Quebec. We previously mapped the gene responsible for ARSACS to chromosome 13q11 and identified two ancestral haplotypes. Here we report the cloning of this gene, SACS, which encodes the protein sacsin. The ORF of SACS is 11,487 bp and is encoded by a single gigantic exon spanning 12,794 bp. This exon is the largest to be identified in any vertebrate organism. The ORF is conserved in human and mouse. The putative protein contains three large segments with sequence similarity to each other and to the predicted protein of an Arabidopsis thaliana ORF. The presence of heat-shock domains suggests a function for sacsin in chaperone-mediated protein folding. SACS is expressed in a variety of tissues, including the central nervous system. We identified two SACSmutations in ARSACS families that lead to protein truncation, consistent with haplotype analysis.

Quantitative trait loci for cellular defects in glucose and fatty acid metabolism in hypertensive rats.

Coronary heart disease, hypertension, non-insulin-dependent diabetes and obesity are major causes of ill health in industrial societies. Disturbances of carbohydrate and lipid metabolism are a common feature of these disorders. The bases for these disturbances and their roles in disease pathogenesis are poorly understood. The spontaneously hypertensive rat (SHR), a widely used animal model of essential hypertension, has a global defect in insulin action on glucose metabolism and shows reduced catecholamine action on lipolysis in fat cells. In our study we used cellular defects in carbohydrate and lipid metabolism to dissect the genetics of defective insulin and catecholamine action in the SHR strain. In a genome screen for loci linked to insulin and catecholamine action, we identified two quantitative trait loci (QTLs) for defective insulin action, on chromosome 4 and 12. We found that the major (and perhaps only) genetic determinant of defective control of lipolysis in SHR maps to the same region of chromosome 4. These linkage results were ascertained in at least two independent crosses. As the SHR strain manifests many of the defining features of human metabolic Syndrome X, in which hypertension associates with insulin resistance, dyslipidaemia and abdominal obesity, the identification of genes for defective insulin and catecholamine action in SHR may facilitate gene identification in this syndrome and in related human conditions, such as type-2 diabetes and familial combined hyperlipidaemia.

Rhabdomyolysis in Critically Ill Patients With COVID-19: A Retrospective Study.

INTRODUCTION: The total number of ICU admissions for COVID-19 patients has increased steadily. Based on the research team's clinical observations, many patients developed rhabdomyolysis, but few cases were reported in the literature. This study explores the incidence of rhabdomyolysis and its outcomes, like mortality, the need for intubation, acute kidney injury, and the need for renal replacement therapy (RRT). METHODS: We retrospectively reviewed the characteristics and outcomes of patients admitted to the ICU at a COVID-19-designated hospital in Qatar between March and July 2020. Logistic regression analysis was used to determine factors associated with mortality. RESULTS: 1079 patients with COVID-19 were admitted to the ICU, and 146 developed rhabdomyolysis. Overall, 30.1% died (n = 44), and 40.4% developed Acute Kidney Injury (AKI) (n = 59), with only 19 cases (13%) recovering from the AKI. AKI was significantly associated with increased mortality rates among rhabdomyolysis patients. Moreover, significant differences were found between groups regarding the subject's age, calcium level, phosphorus level, and urine output. However, the AKI was the best predictor of mortality for those who got the COVID-19 infection and rhabdomyolysis. CONCLUSION: Rhabdomyolysis increases the risk of death in COVID-19 patients admitted to the ICU. The strongest predictor of a fatal outcome was acute kidney injury. The findings of this study emphasize the importance of early identification and prompt treatment of rhabdomyolysis in patients with severe COVID-19.

National audit of the use of surgery and radiological embolization after failed endoscopic haemostasis for non-variceal upper gastrointestinal bleeding.

BACKGROUND: Following non-variceal upper gastrointestinal bleeding (NVUGIB), 10-15 per cent of patients experience further bleeding. Although surgery has been the traditional salvage therapy, there is renewed interest in transcatheter arterial embolization (TAE). This study examined the use, clinical characteristics and outcomes of patients receiving salvage surgery or TAE after failed endoscopic haemostasis for NVUGIB. METHODS: A UK national audit of upper gastrointestinal bleeding was undertaken in May and June 2007. A logistic regression model was used to identify clinical predictors of endoscopic failure. RESULTS: Data were analysed from 4478 patients involving 212 UK centres. Some 533 (11·9 per cent) experienced further bleeding, of whom 163 (30·6 per cent) proceeded to salvage therapy with surgery (97), TAE (60) or both (6). Among surgical patients (mean age 71 years), 66·0 per cent (68 of 103) had a Rockall score of at least 3 and emergency surgery was carried out between midnight and 08.00 hours in 21 per cent, with a consultant surgeon present in 89 per cent of operations. Some 9 per cent of patients had further bleeding after TAE, resulting in later surgery. The mortality rate was 29 per cent after surgery, 10 per cent after TAE and 23·2 per cent among those with further bleeding after the index endoscopy that was managed by endoscopy alone. The strongest predictors of endoscopic failure were coagulopathy (odds ratio 3·27, 95 per cent confidence interval 2·37 to 4·53) and a haemoglobin level of 10 g/dl or less (odds ratio 2·22, 1·71 to 2·87, for haemoglobin 8-10 g/dl). CONCLUSION: Salvage surgery and embolization are required in fewer than 4 per cent of patients with NVUGIB. The high postoperative mortality rate, reflecting age, co-morbidity and severity of bleeding, warrants a prospective study to establish the effectiveness and safety of TAE as an alternative to surgery in the management of bleeding after failure of endoscopic therapy.

Outcomes following acute nonvariceal upper gastrointestinal bleeding in relation to time to endoscopy: results from a nationwide study.

BACKGROUND AND STUDY AIMS: Despite the established efficacy of therapeutic endoscopy, the optimum timeframe for performing endoscopy in patients with nonvariceal upper gastrointestinal bleeding (NVUGIB) remains unclear. The aim of the current audit study was to examine the relationship between time to endoscopy and clinical outcomes in patients presenting with NVUGIB. PATIENTS AND METHODS: This study was a prospective national audit performed in 212 UK hospitals. Regression models examined the relationship between time to endoscopy and mortality, rebleeding, need for surgery, and length of hospital stay. RESULTS: In 4478 patients, earlier endoscopy ( < 12 hours) was not associated with a lower mortality or need for surgery compared with later ( > 24 hours) endoscopy (odds ratio [OR] for mortality 0.98, 95 % confidence interval [CI] 0.88 - 1.09 for endoscopy > 24 hours vs. < 12 hours; P = 0.70). In patients receiving therapeutic endoscopy, there was a nonsignificant trend towards an increase in rebleeding associated with later endoscopy (OR 1.13, 95 %CI 0.97 - 1.32 for endoscopy > 24 hours vs. < 12 hours), with the converse seen in patients not requiring therapeutic endoscopy (OR 0.83, 95 %CI 0.73 - 0.95 for endoscopy > 24 hours vs. < 12 hours; interaction P = 0.003). Later endoscopy ( > 24 hours) was associated with an increase in risk-adjusted length of hospital stay (1.7 days longer, 95 %CI 1.39 - 1.99 vs. < 12 hours; P < 0.001). CONCLUSIONS: Earlier endoscopy was not associated with a reduction in mortality or need for surgery. However, it was associated with an increased efficiency of care and potentially improved control of hemorrhage in higher risk patients, supporting the routine use of early endoscopy unless specific contraindications exist. These results may help inform the debate about emergency endoscopy service provision.

Patients' views on an education booklet following spinal surgery.

PURPOSE: This study evaluated an evidence-based education booklet developed for patients undergoing spinal surgery which was used as a treatment intervention in a multi-centre, factorial, randomised controlled trial (FASTER: Function after spinal treatment, exercise and rehabilitation) investigating the post-operative management of spinal surgery patients. This study sought to determine the acceptability and content of the booklet to patients. METHODS: Patients receiving the educational booklet before discharge from hospital as part of the FASTER study were asked to complete an evaluation, which rated the booklet "Your Back Operation" with regard to content, information, usability, etc. using forced and open questions. This assessment was conducted at the same time as the initial 6-week post-operative review performed as part of the larger study. RESULTS: Therefore, 97% of the 117 trial participants who returned their 6-week evaluation and randomised to receive a booklet returned their questionnaire. The booklet was highly rated receiving an overall rating of 7 or more out of 10 from 101/111 (91%), and high ratings for content, readability and information. The booklet's key messages were clear to the majority of patients; however, many patients highlighted deficiencies with respect to content particularly in relation to wound care and exercise. CONCLUSIONS: Patients valued the booklet and rated its content highly. Many suggested that the booklet be developed further and there was a clear desire for specific exercises to be included even though there is no evidence to support specific exercise prescription.

Neutrophil-to-lymphocyte ratio as a predictor of clinical outcomes in critically ill COVID-19 patients: A retrospective observational study.

Background: Timely identification of patients at risk of worse clinical outcomes is vital in managing coronavirus disease 2019 (COVID-19). The neutrophil-to-lymphocyte ratio (NLR) calculated from complete blood count can predict the degree of systemic inflammation and guide therapy accordingly. Hence, we did a study to investigate the role of NLR value on intensive care unit (ICU) admission in predicting clinical outcomes of critically ill COVID-19 patients. Methods: We conducted a retrospective analysis of electronic health records of COVID-19 patients admitted to ICUs at Hazm Mebaireek General Hospital, Qatar, from March 7, 2020 to July 18, 2020. Patients with an NLR equal to or higher than the cut-off value derived from the receiver operating characteristic curve were compared to those with an NLR value below the cut-off. The primary outcome studied was all-cause ICU mortality. The secondary outcomes evaluated were the requirement of mechanical ventilation and ICU length of stay (LOS). Results: Five hundred and nineteen patients were admitted to ICUs with severe COVID-19 infection during the study period. Overall, ICU mortality in the study population was 14.6% (76/519). NLR on ICU admission of ≥6.55 was obtained using Youden's index to predict ICU mortality, with a sensitivity of 81% and specificity of 41%. Mortality was significantly higher in patients with age ≥60 years (p < 0.001), chronic kidney disease (p = 0.03), malignancy (p < 0.002), and NLR ≥ 6.55 (p < 0.003). There was also a significant association between the requirement of mechanical ventilation (34.7% vs. 51.8%, p < 0.001) and increased ICU LOS (8 vs. 10 days, p < 0.01) in patients with ICU admission NLR ≥ 6.55. Conclusion: Higher NLR values on ICU admission are associated with worse clinical outcomes in critically ill COVID-19 patients.

Characteristics and clinical outcomes of COVID-19 patients with pulmonary disorders: A single-center, retrospective observational study.

INTRODUCTION: Mortality rates and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU) vary significantly. OBJECTIVES: To describe the data of patients with pulmonary comorbidities who were admitted to the ICU with COVID-19 in Qatar in terms of demographic characteristics, coexisting conditions, imaging findings, and outcomes. METHODS: We conducted a retrospective study of the outcomes with regard to mortality and requirement of invasive ventilation, demographic characteristics, coexisting conditions, secondary infections, and imaging findings for critical care patients with COVID-19 in Qatar who had pulmonary comorbidities between March and June 2020. RESULTS: A total of 923 patients were included, 29 (3.14%) were found to have pulmonary disease. All these 29 patients' respiratory disease was noted to be asthma. Among these, three patients (10.3%) died in the ICU within 28 days of ICU admission. They were all above 50 years old. Nineteen (66%) patients required intubation and mechanical ventilation. Twenty-one (72.4%) patients were males. The most common comorbidities included diabetes mellitus (55.1%) and hypertension (62%). Eighteen (62%) patients developed secondary infections in the ICU. Five (17.24%) patients developed renal impairment. Twenty (69%) patients received tocilizumab as part of their COVID-19 management, and out of these 16 (80%) patients developed a coinfection. CONCLUSION: Patients with pulmonary disorders had higher mortality rates than other patients admitted to ICU during the same time frame with similar comorbidities; these patients require extra consideration and care to avoid disease progression and death.

Predictors of mortality and morbidity in critically ill COVID-19 patients: An experience from a low mortality country.

Background and Aims: Clinical characteristics and factors associated with mortality in patients admitted to the intensive care unit (ICU) in countries with low case fatality rates (CFR) are unknown. We sought to determine these in a large cohort of critically ill COVID-19 patients in Qatar and explore the early mortality predictors. Methods: We retrospectively studied the clinical characteristics and outcomes in patients admitted to the ICU at the national referral hospital for COVID-19 patients in Qatar. Logistic regression analysis was used to determine factors associated with mortality. Results: Between March 7 and July 16, 2020, a total of 1079 patients with COVID-19 were admitted to the ICU. The median (IQR) age of patients was 50 (41-59) years. Diabetes (47.3%) and hypertension (42.6%) were the most common comorbidities. In-hospital mortality was 12.6% overall and 25.9% among those requiring mechanical ventilation. Factors independently associated with mortality included older age ([OR]; 2.3 [95% CI; 1.92-2.75] for each 10-year increase in age, p < 0.001), chronic kidney disease (OR; 1.9 [95% CI; 1.02-3.54], p = 0.04), active malignancy (OR; 6.15 [95% CI; 1.79-21.12], p = 0.004), lower platelet count at ICU admission (OR; 1.41 [95% CI; 1.13-1.75] for each 100 × 103/µl decrease, p = 0.002), higher neutrophil-to-lymphocyte ratio at admission (OR; 1.01 [95% CI; 1-1.02] for each 1- point increase, p = 0.016), higher serum ferritin level at admission (OR; 1.05 [(95% CI; 1.02-1.08] for each 500 µg/L increase, p = 0.002), and higher serum bilirubin level at admission (OR; 1.19 [95% CI; 1.04-1.36] for each 10 µmol/L increase, p = 0.01). Conclusions: The mortality rate among critically ill COVID-19 patients is low in Qatar compared to other countries. Older age, chronic kidney disease, active malignancy, higher neutrophil-to-lymphocyte ratios, lower platelet counts, higher serum ferritin levels, and higher serum bilirubin levels are independent predictors of in-hospital mortality.

Cytomegalovirus meningoencephalitis in a case of severe COVID-19 Pneumonia. A case report.

The use of steroids and other immune modulatory therapies in the treatment of severe COVID-19 pneumonia predisposes patients to the reemergence of opportunistic infections. Cytomegalovirus (CMV) reactivation can be one of them. A 55-year-old gentleman with severe COVID-19 pneumonia and hypoxic respiratory failure who was ventilated and received steroids but no other immunomodulatory drugs; had altered sensorium and multiple episodes of seizures in the later course of his illness. Brain MRI showed leptomeningeal enhancement and encephalopathy changes, electroencephalography (EEG) was suggestive of diffuse encephalopathy and his cerebrospinal fluid (CSF) analysis revealed high Cytomegalovirus PCR DNA titers (103,614). The patient made a complete recovery after treatment with Ganciclovir. Altered sensorium in cases of COVID-19 can be multifactorial. High index of suspicion for reactivation of dormant infections is warranted. CMV meningoencephalitis is one of the differential diagnoses. We believe this is the first case reported of CMV meningoencephalitis in the setting of severe COVID-19 infection.

Clinical outcomes of post-renal transplant patients with COVID-19 infection in the ICU: A single-center case series.

Most of the post-renal transplant patients are taking immunosuppressive medications, including calcineurin inhibitors, anti-proliferative agents, and steroids. This case series highlights the clinical characteristics and outcomes of eight post-renal transplant patients with severe COVID-19 infection admitted to the intensive care unit.

Comparison of the clinical outcomes of non-invasive ventilation by helmet vs facemask in patients with acute respiratory distress syndrome.

ABSTRACT: The main aim of this study is to compare the use of non-invasive ventilation (NIV) via helmet versus face mask where different interfaces and masks can apply NIV. However, some of the limitations of the NIV face mask were air leak, face mask intolerance, and requirement of high positive end expiratory pressure, which could be resolved with the use of the helmet NIV. NIV facemask will be applied as per the facial contour of the patient. NIV helmet is a transparent hood and size will be measured as per the head size. Both groups will have a standard protocol for titration of NIV.Patients aged more than 18 years old and diagnosed with acute respiratory distress syndrome as per Berlin definition will be enrolled in the study after signing the informed consent. Subjects who met the inclusion criteria will receive 1 of the 2 interventions; blood gases, oxygenation status [Po2/Fio2] will be monitored in both groups. The time of intubation will be the main comparison factor among the 2 groups. The primary and secondary outcomes will be measured by the number of patients requiring endotracheal intubation after application of helmet device, Improvement of oxygenation defined as PaO2/FiO2 ≥ 200 or increase from baseline by 100, duration of mechanical ventilation via an endotracheal tube, intensive care unit length of stay, death from any cause during hospitalization at the time of enrolment, need for proning during the hospital stay, intensive care unit mortality, and the degree to which overt adverse effects of a drug can be tolerated by a patient including feeding tolerance. TRIAL REGISTRATION NUMBER: NCT04507802. PROTOCOL VERSION: May 2020.

A randomised controlled trial of subcutaneous sodium salicylate therapy for osteoarthritis of the thumb.

BACKGROUND: Current treatment for osteoarthritis (OA) is limited. Many patients with OA of the hand have areas of tender subcutaneous thickening in the forearm and upper scapular region. A pilot study showed an improvement in pain from OA at the first carpometacarpal joint after injection of such areas with 0.5% sodium salicylate or saline, an inexpensive treatment that can be administered by general practitioners and nurses. The study indicated that a randomised, sham-controlled trial was justified. METHODS: 40 patients with OA of the first carpometacarpal joint were randomised to receive either injections of sodium salicylate into tender, thickened areas of subcutaneous tissue on the forearm (baseline) and upper scapular region (week 1) or sham injections consisting of pressure without skin penetration. Blinded assessments were made at weeks 3, 7 and 13 after baseline. RESULTS: Pain and tenderness during follow-up were both significantly lower in the active treatment group compared with the sham group: 19% and 14% greater reduction in mean visual analogue scale (VAS) score, respectively (p=0.007 and 0.02, baseline mean 5.65 and 5.35 cm, average difference in change from baseline VAS 1.9 and 1.4 cm, 95% CI 0.6 to 3.2 and 0.2 to 2.5). Active and sham injections were painful, the former significantly more so; however, there was no significant correlation between the pain of active injections and response. CONCLUSION: The data show that subcutaneous sodium salicylate injections are an effective symptomatic treatment for OA of the thumb. The results provide a basis for further physiological and therapeutic research in this area.

Function after spinal treatment, exercise and rehabilitation (FASTER): improving the functional outcome of spinal surgery.

BACKGROUND: The life-time incidence of low back pain is high and diagnoses of spinal stenosis and disc prolapse are increasing. Consequently, there is a steady rise in surgical interventions for these conditions. Current evidence suggests that while the success of surgery is incomplete, it is superior to conservative interventions. A recent survey indicates that there are large differences in the type and intensity of rehabilitation, if any, provided after spinal surgery as well as in the restrictions and advice given to patients in the post-operative period. This trial will test the hypothesis that functional outcome following two common spinal operations can be improved by a programme of post-operative rehabilitation that combines professional support and advice with graded active exercise and/or an educational booklet based on evidence-based messages and advice. METHODS/DESIGN: The study design is a multi-centre, factorial, randomised controlled trial with patients stratified by surgeon and operative procedure. The trial will compare the effectiveness and cost-effectiveness of a rehabilitation programme and an education booklet for the postoperative management of patients undergoing discectomy or lateral nerve root decompression, each compared with "usual care"using a 2 x 2 factorial design. The trial will create 4 sub-groups; rehabilitation-only, booklet-only, rehabilitation-plus-booklet, and usual care only. The trial aims to recruit 344 patients, which equates to 86 patients in each of the four sub-groups. All patients will be assessed for functional ability (through the Oswestry Disability Index - a disease specific functional questionnaire), pain (using visual analogue scales), and satisfaction pre-operatively and then at 6 weeks, 3, 6 and 9 months and 1 year post-operatively. This will be complemented by a formal analysis of cost-effectiveness. DISCUSSION: This trial will determine whether the outcome of spinal surgery can be enhanced by either a post-operative rehabilitation programme or an evidence-based advice booklet or a combination of the two and as such will contribute to our knowledge on how to manage spinal surgery patients in the post-operative period.

Risk factors and recommendations for rate stratification for surveillance of neonatal healthcare-associated bloodstream infection.

Neonates are among the most vulnerable patient groups for healthcare-associated infection with multiple endogenous and exogenous risks. Interpretation of neonatal bloodstream infection (BSI) rates requires stratification for case-mix. We assessed 1367 consecutive admissions to a single neonatal unit over a 34-month period. Four intrinsic and seven extrinsic risks were evaluated using Poisson regression analyses both individually and in combination. Nine of the 11 evaluated risk factors were significantly associated with BSI on univariate analyses. The only significant independent risks were parenteral nutrition, whether administered centrally or peripherally [incidence rate ratio (IRR): 14.2; 95% confidence interval (CI): 8.8-22.9; P<0.001], and gestational age <26 weeks (IRR: 2.5; 95% CI: 1.7-3.8; P<0.001). The rate of BSI per 1000 patient-days was 40 times higher in infants with both of these than in infants with neither. If validated in other settings, stratification of neonatal BSI rate by two unambiguous risk factors, parenteral nutrition and birth gestational age <26 weeks, offers a simple method to make meaningful intra- and inter-hospital comparisons.

Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects.

Previous studies investigating homocysteine and vascular disease have relied on total plasma homocysteine as the sole index of homocysteine status. We examined the dynamic relationship between vascular endothelial function and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine to identify the homocysteine form associated with endothelial dysfunction in humans. We investigated 14 healthy volunteers (10 men, 4 women). Brachial artery flow-mediated dilatation was measured at baseline and at 30, 60, 120, 240, and 360 minutes after oral (1) L-methionine (50 mg/kg), (2) L-homocysteine (5 mg/kg), and (3) placebo. Plasma concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine were measured at each time point, and nitroglycerin-induced dilatation at was assessed at 0, 120, and 360 minutes. Flow-mediated dilatation fell, and concentrations of total, protein-bound oxidized, free oxidized, and reduced homocysteine increased after oral homocysteine and oral methionine (all P<0.05 for difference in time course compared with placebo). Flow-mediated dilatation showed a reciprocal relationship with reduced homocysteine during both homocysteine and methionine loading. In both loading studies, peak reduction in flow-mediated dilatation coincided with maximal reduced homocysteine concentrations. In contrast, there was no consistent relationship between flow-mediated dilatation and free oxidized homocysteine, protein-bound oxidized homocysteine, or related species. Nitroglycerin-induced dilatation was unchanged by oral homocysteine and oral methionine (P>0.10 compared with placebo). Reduced homocysteine is closely associated with endothelial dysfunction during oral methionine and oral homocysteine loading. Our observations support the hypothesis that reduced homocysteine is the deleterious form of homocysteine for vascular function in vivo and suggest a less important role for other homocysteine species.

Accelerated postnatal head growth follows preterm birth.

BACKGROUND: Poor growth after preterm birth, particularly poor head growth, is associated with impaired neurodevelopmental outcome. OBJECTIVE: To evaluate weight gain and head growth between birth and term in a contemporary cohort of preterm infants, taking into account breast milk intake and illness severity. METHODS: Subjects were inborn infants or=37 weeks postmenstrual age. Weight and head circumference (HC) were expressed as standard deviation score (SDS), growth between birth and discharge as SDS gain (SDSG), and illness severity and breast milk exposure as the number of days of level 1 (full) intensive care (%L1IC) and the number of days on which breast milk was received (%BM) as a percentage of days from birth to discharge. RESULTS: Infants showed poor postnatal weight gain but accelerated head growth. There was a highly significant fall in mean (SD) weight SDS between birth and discharge (-0.31 (0.96) and -1.32 (1.02) respectively, p<0.001) and a highly significant increase in HC SDS (-0.52 (0.95) and -0.03 (1.25) respectively, p = 0.003). %L1IC had a highly significant negative impact on weight SDSG (p = 0.006), and %BM had a significant positive impact on HC SDSG (p = 0.043). CONCLUSIONS: Accelerated postnatal head growth suggests catch up after antenatal restraint. This raises the possibility that poor neurocognitive outcomes after extremely preterm birth may in part be consequent on poor intrauterine brain growth. As postnatal head growth may be facilitated by breast milk, there is an urgent need to evaluate the optimal use of breast milk in preterm neonates. Illness severity is a significant determinant of poor postnatal weight gain.