The Ross-Konno Procedure With or Without Mitral Valve Surgery: A Systematic Review With Individual Data Pooling.

Background: The Ross-Konno procedure is a technically demanding surgical option to treat multilevel left ventricular outflow tract obstruction. Methods: A systematic review with pooled analyses was conducted according to PRISMA criteria on studies published between January 2000 and May 2022 that assessed outcomes following the Ross-Konno intervention in children. Individual patient data were extracted from published Kaplan-Meier curves using digitalization software. Overall survival and freedom from reintervention were assessed by time-to-event approaches. Determinants of one-year survival were investigated by meta-regression analyses. Results: Ten studies with a total population of 274 patients were included. The overall pooled early (≤30 days) survival rate was 86.9% (95% CI [87.6%-78.4%]). Five-year survival rates in patients without and with (N = 50 [18.2%] of 274 total patients) concomitant mitral valve surgery were 82.5% (95% CI [87.6%-77.4%]) versus 56.1% (95% CI [74.1%-38.1%]), hazard ratio 2.67, 95% CI (1.44-4.93), P < .0001. Five- and ten-year freedom from pulmonary autograft reoperation rates were 93.5% and 90.9%, respectively. Five- and ten-year freedom from right ventricular outflow tract reoperation rates were 74.3% and 57.3%, respectively. By meta-regression analysis, resection of endocardial fibroelastosis (N = 32 [11.7%] of 274 total patients) was associated with superior one-year survival (P = .027). Conclusion: The Ross-Konno procedure is associated with substantial early mortality and gradual attrition thereafter. Mortality is higher in patients with concomitant mitral valve surgery. Resection of endocardial fibroelastosis is associated with superior survival. Right ventricular outflow tract reinterventions are common.

Effect of red blood cell storage time in pediatric cardiac surgery patients: A subgroup analysis of a randomized controlled trial.

Objective: This study aimed to determine whether or not transfusion of fresh red blood cells (RBCs) reduced the incidence of new or progressive multiple organ dysfunction syndrome compared with standard-issue RBCs in pediatric patients undergoing cardiac surgery. Methods: Preplanned secondary analysis of the Age of Blood in Children in Pediatric Intensive Care Unit study, an international randomized controlled trial. This study included children enrolled in the Age of Blood in Children in Pediatric Intensive Care Unit trial and admitted to a pediatric intensive care unit after cardiac surgery with cardiopulmonary bypass. Patients were randomized to receive either fresh (stored ≤7 days) or standard-issue RBCs. The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured up to 28 days postrandomization or at pediatric intensive care unit discharge, or death. Results: One hundred seventy-eight patients (median age, 0.6 years; interquartile range, 0.3-2.6 years) were included with 89 patients randomized to the fresh RBCs group (median length of storage, 5 days; interquartile range, 4-6 days) and 89 to the standard-issue RBCs group (median length of storage, 18 days; interquartile range, 13-22 days). There were no statistically significant differences in new or progressive multiple organ dysfunction syndrome between fresh (43 out of 89 [48.3%]) and standard-issue RBCs groups (38 out of 88 [43.2%]), with a relative risk of 1.12 (95% CI, 0.81 to 1.54; P = .49) and an unadjusted absolute risk difference of 5.1% (95% CI, -9.5% to 19.8%; P = .49). Conclusions: In neonates and children undergoing cardiac surgery with cardiopulmonary bypass, the use of fresh RBCs did not reduce the incidence of new or progressive multiple organ dysfunction syndrome compared with the standard-issue RBCs. A larger trial is needed to confirm these results.

Indocyanine green fluorescence angiography in pediatric intestinal resections: A first prospective mixed methods clinical trial.

BACKGROUND: The aim of this study was to establish the feasibility and safety of the use of indocyanine green technology during pediatric intestinal resections. While indocyanine green fluorescence angiography (ICG-FA) has been advocated as an imaging technique to assess bowel perfusion in adults, few studies have evaluated this technology in a pediatric context. METHODS: A prospective clinical trial was conducted. Patients 16 years old or younger undergoing a surgery potentially requiring an intestinal resection were eligible. Patients received a standardized intravenous injection of indocyanine green and intestinal perfusion was evaluated. The study endpoints included safety, impact on bowel resection and feasibility and acceptance of ICG-FA in this population. RESULTS: From May 2020 to March 2021, 30 consecutive patients were included in this trial. Final analysis was done on 28 patients with a median age of 15.00 [6.36,85.00] weeks and weight of 5.58 [3.64,11.70] kg at surgery. Adequate fluorescence was achieved in less than one minute for all cases with an average dose of 0.14 mg/kg. No adverse event related to indocyanine green occurred. ICG-FA versus standard assessment of potential resection sites differed in 62% (95% IC 0.41-0.82) of our cases. Qualitative analysis demonstrated that 95% of the surgical team agreed that ICG-FA was safe. CONCLUSIONS: The use of ICG-FA is feasible and safe for pediatric intestinal resections. Introduction of ICG-FA was simple and acceptance rates were high within the surgical team. This fluorescence imaging may be a valuable imaging technology for intestinal resections in pediatric surgery.

Is Busulfan Clearance Different in Patients With Sickle Cell Disease? Let's Clear Up That Case With Some Controls.

In busulfan-based conditioning regimen for hematopoietic stem cell transplantation in children, accurate a priori determination of the first dose is important because of its narrow therapeutic window. Sickle cell disease (SCD) influences pharmacokinetics of the commonly used drugs by affecting organs responsible for drug metabolism and elimination. This pharmacokinetics study assesses the influence of SCD on the metabolic pathway of busulfan that is mainly metabolized in the liver. In this retrospective cross-sectional case-control study, 16 patients with SCD were matched to 50 patients without SCD on known busulfan clearance's covariates (glutathione-S-transferase alpha1 polymorphisms, age, weight). Clearance of the first dose of busulfan was not significantly different independently of genetic or anthropometric factors in patients with or without SCD.

YKL-40 as a clinical biomarker in adult patients with CF: Implications of a CHI3L1 single nucleotide polymorphism in disease severity.

BACKGROUND: YKL-40 (chitinase 3-like 1 gene; CHI3L1) is an inflammatory marker that is increased in the blood of patients with inflammatory diseases, including cystic fibrosis (CF). The objective of our study was to explore the relationship between circulating levels of YKL-40, selected CHI3L1 single nucleotide polymorphisms (SNPs) and the severity of CF disease. METHODS: A prospective cohort of 188 adult patients with CF was established in 2015. Blood samples and clinical data were collected over 2 years to analyze the circulating levels of YKL-40 and to genotype selected CHI3L1 SNPs. We also looked for an association between these factors and clinical parameters. RESULTS: We found that according to the serum YKL-40 concentration, the patients could be categorized into two distinct groups: low and high YKL-40. Compared to the patients in the low YKL-40 group, the patients in the high YKL-40 group had lower lung function (P < 0.001), a higher proportion of delF508 homozygote mutations (P= 0.027) and dysglycemia (P= 0.015). They were also more colonized with Pseudomonas aeruginosa (P= 0.003) and required more frequent antibiotic intravenous courses (P < 0.001). We also observed that patients expressing the C/C-rs4950928 genotype had higher levels of YKL-40 in their blood and were more frequently dysglycemic. CONCLUSION: Our study suggests that YKL-40 could be a potential biomarker of CF disease severity. Furthermore, the CHI3L1 rs4950928 SNP could be a susceptible gene that could be used by CF health professionals to identify patients who are the most at risk of having a severe clinical profile.

Clinical relevance of membrane attack complex deposition in children with IgA nephropathy and Henoch-Schönlein purpura.

BACKGROUND: IgA nephropathy (IgAN) and Henoch-Schönlein purpura are common glomerular disorders in children sharing the same histopathologic pattern of IgA deposits within the mesangium, even if their physiopathology may be different. Repeated exposure to pathogens induces the production of abnormal IgA1. The immune complex deposition in the renal mesangium in IgAN or potentially in small vessels in Henoch-Schönlein purpura induces complement activation via the alternative and lectin pathways. Recent studies suggest that levels of membrane attack complex (MAC) in the urine might be a useful indicator of renal injury. Because of the emerging availability of therapies that selectively block complement activation, the aim of the present study is to investigate whether MAC immunostaining might be a useful marker of IgA-mediated renal injury. METHODS: We conducted immunohistochemistry analysis of the MAC on renal biopsies from 67 pediatric patients with IgAN and Henoch-Schönlein purpura. We classified their renal biopsies according to the Oxford classification, retrieved symptoms, biological parameters, treatment, and follow-up. RESULTS: We found MAC expression was significantly related to impaired renal function and patients whose clinical course required therapy. MAC deposits tend to be more abundant in patients with decreased glomerular filtration rate (p = 0.02), patients with proteinuria > 0.750 g/day/1.73 m2, and with nephrotic syndrome. No correlation with histological alterations was observed. CONCLUSIONS: We conclude that MAC deposition could be a useful additional indicator of renal injury in patients with IgAN and Henoch-Schönlein purpura, independent of other indicators.

Clinical Use of an Order Protocol for Distress in Pediatric Palliative Care.

Several children receiving palliative care experience dyspnea and pain. An order protocol for distress (OPD) is available at Sainte-Justine Hospital, aimed at alleviating respiratory distress, pain and anxiety in pediatric palliative care patients. This study evaluates the clinical use of the OPD at Sainte-Justine Hospital, through a retrospective chart review of all patients for whom the OPD was prescribed between September 2009 and September 2012. Effectiveness of the OPD was assessed using chart documentation of the patient's symptoms, or the modified Borg scale. Safety of the OPD was evaluated by measuring the time between administration of the first medication and the patient's death, and clinical evolution of the patient as recorded in the chart. One hundred and four (104) patients were included in the study. The OPD was administered at least once to 78 (75%) patients. A total of 350 episodes of administration occurred, mainly for respiratory distress (89%). Relief was provided in 90% of cases. The interval between administration of the first protocol and death was 17 h; the interval was longer in children with cancer compared to other illnesses (p = 0.02). Data from this study support the effectiveness and safety of using an OPD for children receiving palliative care.

Red Blood Cell Transfusion in the Postoperative Care of Pediatric Cardiac Surgery: Survey on Stated Practice.

The optimal red blood cell transfusion threshold for postoperative pediatric cardiac surgery patients is unknown. This study describes the stated red blood cell transfusion practice of physicians who treat postoperative pediatric cardiac surgery patients in intensive care units. A scenario-based survey was sent to physicians involved in postoperative intensive care of pediatric cardiac surgery patients in all Canadian centers that perform such surgery. Respondents reported their red blood cell transfusion practice in four postoperative scenarios: acyanotic or cyanotic cardiac lesion, in a neonate or an infant. In part A of each scenario, the patient was critically ill, but stabilized; in part B, the patient became unstable. Response rate was 58 % (71 of 123), with 45 respondents indicating direct involvement in postoperative intensive care. There was a wide variability in stated transfusion threshold, ranging from <7.0-14.0 g/dL for stabilized cases. There was no significant difference between neonates and infants in stated transfusion threshold. The mean hemoglobin level below which respondents would transfuse a stabilized patient was 9 g/dL for acyanotic and 11.2 g/dL for cyanotic patients, a statistically significant difference (2.2 ± 0.9 g/dL, p < 0.001). All clinical determinants of instability significantly increased transfusion threshold. Hemodynamic instability increased transfusion threshold by 2.3 ± 1.3 g/dL in acyanotic patients and by 1.3 ± 1.1 g/dL in cyanotic patients. Cyanotic lesion and clinical instability, but not patient age, increased stated red blood cell transfusion threshold. Significant variation in reported red blood cell transfusion practice exists among physicians treating pediatric patients in intensive care following cardiac surgery.

Platelet Transfusions in Pediatric Intensive Care.

OBJECTIVES: To characterize the determinants of platelet transfusion in a PICU and determine whether there exists an association between platelet transfusion and adverse outcomes. DESIGN: Prospective observational single center study, combined with a self-administered survey. SETTING: PICU of Sainte-Justine Hospital, a university-affiliated tertiary care institution. PATIENTS: All children admitted to the PICU from April 2009 to April 2010. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Among 842 consecutive PICU admissions, 60 patients (7.1%) received at least one platelet transfusion while in PICU. In the univariate analysis, significant determinants for platelet transfusion were admission Pediatric Risk of Mortality Score greater than 10 (odds ratio, 6.80; 95% CI, 2.5-18.3; p < 0.01) and Pediatric Logistic Organ Dysfunction scores greater than 20 (odds ratio, 26.9; 95% CI, 8.88-81.5; p < 0.01), history of malignancy (odds ratio, 5.08; 95% CI, 2.43-10.68; p < 0.01), thrombocytopenia (platelet count, < 50 × 10/L or < 50,000/mm) (odds ratio, 141; 95% CI, 50.4-394.5; p < 0.01), use of heparin (odds ratio, 3.03; 95% CI, 1.40-6.37; p < 0.01), shock (odds ratio, 5.73; 95% CI, 2.85-11.5; p < 0.01), and multiple organ dysfunction syndrome (odds ratio, 10.41; 95% CI, 5.89-10.40; p < 0.01). In the multivariate analysis, platelet count less than 50 × 10/L (odds ratio, 138; 95% CI, 42.6-449; p < 0.01) and age less than 12 months (odds ratio, 3.06; 95% CI, 1.03-9.10; p = 0.02) remained statistically significant determinants. The attending physicians were asked why they gave a platelet transfusion; the most frequent justification was prophylactic platelet transfusion in presence of thrombocytopenia with an average pretransfusion platelet count of 32 ± 27 × 10/L (median, 21), followed by active bleeding with an average pretransfusion platelet count of 76 ± 39 × 10/L (median, 72). Platelet transfusions were associated with the subsequent development of multiple organ dysfunction syndrome (odds ratio, 2.53; 95% CI, 1.18-5.43; p = 0.03) and mortality (odds ratio, 10.1; 95% CI, 4.48-22.7; p < 0.01). CONCLUSIONS: Among children, 7.1% received at least one platelet transfusion while in PICU. Thrombocytopenia and active bleeding were significant determinants of platelet transfusion. Platelet transfusions were associated with the development of multiple organ dysfunction syndrome and increased mortality.

Clonidine as a First-Line Sedative Agent After Neonatal Cardiac Surgery: Retrospective Cohort Study.

OBJECTIVES: To determine the cardiovascular tolerance of clonidine used as a first-line sedative after cardiac surgery in small infants. DESIGN: Retrospective chart review. SETTING: A tertiary and quaternary referral cardiac PICU. PATIENTS: All infants younger than 2 months who received a clonidine infusion for sedation after cardiac surgery from October 2011 to July 2013. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Heart rate, blood pressure, central venous and left atrial pressure, vasoactive inotropic score, volume of fluid bolus, and lactate and central mixed venous saturation were assessed. Preinfusion values were compared with postinfusion values. Of 224 potentially eligible patients, only 23 infants met inclusion criteria, as most patients only received high doses of morphine and some received midazolam instead of clonidine. Clonidine administration was started at a median of 12 hours after surgery (Q1-Q3, 5-23), and infusion rate was 0.5-2 µg/kg/hr for a median duration of 30 hours (Q1-Q3, 12-54). Heart rate decreased (maximal mean decrease: 12% [149 beats/min (SD, 17) to 131 beats/min (SD, 17)]; p < 0.0001). Apart from a transient and limited drop in diastolic blood pressure of 13% (maximal mean decrease: from 42.8 mm Hg [SD, 5.9] to 37.1 mm Hg [SD, 4.0]; p = 0.018), all other cardiovascular variables were stable or improved. A contemporaneous cohort of patients who received midazolam, did so sooner after surgery, stayed longer in the PICU and showed less favorable hemodynamics. CONCLUSIONS: IV clonidine as sedative added to morphine in selected patients seems hemodynamically safe. The observed decrease in heart rate and diastolic blood pressure seems of minimal clinical importance as all other hemodynamic variables remained stable or improved. The safety of clonidine given early after cardiac surgery as alternative to midazolam merits further study.

An Order Protocol for Respiratory Distress/Acute Pain Crisis in Pediatric Palliative Care Patients: Medical and Nursing Staff Perceptions.

BACKGROUND: An order protocol for distress (OPD), including respiratory distress and acute pain crisis, has been established for pediatric palliative care patients at Sainte-Justine Hospital (SJH). After discussion with the patient/his or her family, the OPD is prescribed by the attending physician whenever judged appropriate. The OPD can then be initiated by the bedside nurse when necessary; the physician is notified after the first dose is administered. OBJECTIVES: The study objectives were to evaluate the perceptions and experience of the medical/nursing staff towards the use of the OPD. METHODS: A survey was distributed to all physicians/nurses working on wards with pediatric palliative care patients. Answers to the survey were anonymous, done on a voluntary basis, and after consent of the participant. RESULTS: Surveys (258/548) were answered corresponding to a response rate of 47%. According to the respondents, the most important motivations in using the OPD were the desire to relieve patient's distress and the speed of relief of distress by the OPD; the most important obstacles were going against the patient's/his or her family's wishes and fear of hastening death. The respondents reported that the OPD was frequently (56%) or always (36%) effective in relieving the patient's distress. The respondents felt sometimes (16%), frequently (34%), or always (41%) comfortable in giving the OPD. They thought the OPD could never (12%), rarely (32%), sometimes (46%), frequently (8%), or always (1%) hasten death. Physicians were less favorable than nurses with the autonomy of bedside nurses to initiate the OPD before notifying the physician (p = 0.04). Overall, 95% of respondents considered that they would use the OPD in the future. CONCLUSIONS: Data from this survey shows that respondents are in favor of using the OPD at SJH and find it effective. Further training as well as support for health care professionals are mandatory in such palliative care settings.

Revisiting Pathological Criteria for Earlier Diagnosis of Coeliac Disease.

OBJECTIVES: The diagnosis of coeliac disease (CD) remains sometimes difficult because the histological criteria are not fully met. The aim of this study was to refine histological diagnostic criteria of CD. METHODS: One hundred seventy-five duodenal bulb D1 (n = 79) and duodenal D2 (n = 96) biopsies of 96 patients with CD (58 girls, mean age 7 years), 135 normal D2 biopsies (69 girls, mean age 12 years), and 64 D2 biopsies of other digestive disorders (DDs) (39 girls, mean age 13 years) obtained from children during a period of 4 years were reviewed. RESULTS: Interobserver agreement was greater for the classification of Corazza-Villanacci than for Marsh-Oberhuber (κ = 0.812 vs κ = 0.409, respectively). Between 40 and 70 intraepithelial lymphocytes (IELs) per 100 epithelial cells (ECs), 32% of patients were CD, whereas 50% had other DD. Above 70 IELs per 100 EC, 53% were CD, and only 6% had other DD. In CD, IELs were significantly located above EC nuclei compared with other DD, (12 IELs/100 EC vs 2 IELs/100 EC, respectively). In 21% of CD cases, D2 were normal and the diagnosis could only be made on D1. Finally, 6% of CD cases showed isolated increase of IELs in D1 without architectural modification. CONCLUSIONS: D1 allowed diagnosis of CD in 21% of cases and IEL >70 per 100 EC correlated strongly with CD. Between 40 and 70 IELs per 100 EC, CD is very likely but other DD must be considered. Finally, the preferential localisation of IELs above EC nuclei favours CD, and increased IEL in D1 may be the sole abnormality.

Blood Transfusions After Pediatric Cardiac Operations: A North American Multicenter Prospective Study.

BACKGROUND: Red blood cell transfusion is an important supportive measure after pediatric cardiac operations. However, no clear hemoglobin threshold has been established. This study characterized anemia development and red blood cell transfusions in the pediatric intensive care unit (PICU) after cardiac operations. METHODS: A prospective, multicenter, 6-month cohort study on the management of anemia in critically ill pediatric patients was conducted in 30 North American PICUs. This observational study enrolled 977 consecutive children (aged <18 years) who stayed in the PICU for 48 hours or more. We analyzed a subgroup of postcardiac surgical patients from this study. RESULTS: Included were 175 cardiac patients, 56% of whom had cyanotic heart disease. The mean Pediatric Risk of Mortality (PRISM III) score was 6.4 ± 5.4. Fifty-four percent of children were anemic in the PICU (20% on admission, 34% during PICU stay). Most patients (79%) received at least one red blood cell transfusion in the PICU. Patients who received a transfusion had a significantly longer PICU stay (9.3 ± 6.3 vs 6.1 ± 5.4 days, p = 0.01). Pretransfusion hemoglobin was different in acyanotic and cyanotic patients (mean ± standard deviation: 11.1 ± 2.2 g/dL and 11.8 ± 2.1 g/dL, respectively). According to the attending physician, a low hemoglobin level was the primary indication for transfusion in only 17% of cases. CONCLUSIONS: Pediatric cardiac surgical patients are at high risk of receiving red blood cell transfusions. This study, which showed great variability in transfusion practices across North American PICUs, highlights the need for clearer transfusion guidelines in this specific population.

ABO Group as a Thrombotic Risk Factor in Children With Acute Lymphoblastic Leukemia: A Retrospective Study of 523 Patients.

Children with acute lymphoblastic leukemia (ALL) are at high risk of thrombotic complications, resulting from multiple risk factors (malignancy, chemotherapy, central venous access devices, and inherent host characteristics). Non-O blood groups have been associated with an increased risk of venous thromboembolism (VTE) in adults, with a compounding effect in the presence of thrombophilia or cancer. We hypothesized that among children with ALL receiving a standardized protocol, there would be an increased risk of thrombotic events in non-O compared with O blood group patients. In a retrospective study of 523 children with ALL from June 1995 to April 2013, there were 56 (10.7%) thromboembolic events. Patients with VTE were compared with the whole cohort, based on blood group, age, sex, leukemia phenotype, and clinical risk category. Among children with VTE, 42 (75%) had non-O and 14 (25%) had O blood group, compared with 302 (57.7%) non-O and 221 (42.3%) O blood groups in the cohort. Non-O blood group was confirmed as an independent risk factor for VTE in multivariate analysis. This is the first study to report a significant association between non-O blood groups and VTE in children with cancer.

Assessment of correlation between p16INK4a staining, specific subtype of human papillomavirus, and progression of LSIL/CIN1 lesions: first comparative study.

OBJECTIVES: To study and compare the effectiveness of p16(INK4a) staining and specific human papillomavirus (HPV) subtypes as a prognostic marker in cervical intraepithelial neoplasia grade 1 (CIN1; low-grade squamous intraepithelial lesions). METHODS: Sixty-four cervical samples diagnosed as CIN1 and stained with p16(INK4a), with HPV status assessed by polymerase chain reaction-direct sequencing. RESULTS: Of the 34 p16(INK4a)-negative biopsy specimens, 26 regressed, seven persisted, and one progressed. Of the 20 p16(INK4a) diffusely positive biopsy specimens, seven regressed, eight persisted, and five progressed. Ten biopsy specimens stained positive only in the lower one-third of the sample, of which seven regressed and three persisted. p16(INK4a) diffusely positive CIN1 lesions were associated with only high-risk HPV subtypes, with the exception of one HPV-negative biopsy specimen. Three different high-risk HPV subtypes and one low-risk HPV subtype (HPV66) were identified in the six CIN1 lesions that progressed. CONCLUSIONS: There is a significant relationship between p16(INK4a) immunostaining and follow-up (P = .002). p16(INK4a)-negative specimens or positivity in the lower one-third of CIN1 lesions seldom progress to a CIN2-3 lesion.

Smoked cannabis for chronic neuropathic pain: a randomized controlled trial.

BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. RESULTS: We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. CONCLUSION: A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).

Red blood cell transfusion threshold in postsurgical pediatric intensive care patients: a randomized clinical trial.

BACKGROUND: The optimal transfusion threshold after surgery in children is unknown. We analyzed the general surgery subgroup of the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study to determine the impact of a restrictive versus a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome (MODS). METHODS: The TRIPICU study, a prospective randomized controlled trial conducted in 17 centers, enrolled a total of 648 critically ill children with a hemoglobin equal to or below 9.5 g/dL within 7 days of pediatric intensive care unit (PICU) admission to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped below either 7.0 g/dL (restrictive) or 9.5 g/dL (liberal). A subgroup of 124 postoperative patients (60 randomized to restrictive and 64 to the liberal group) were analyzed. This study was registered at http://www.controlled-trials.com and carries the following ID ISRCTN37246456. RESULTS: Participants in the restrictive and liberal groups were similar at randomization in age (restrictive vs. liberal: 53.5 +/- 51.8 vs. 73.7 +/- 61.8 months), severity of illness (pediatric risk of mortality [PRISM] score: 3.5 +/- 4.0 vs. 4.4 +/- 4.0), MODS (35% vs. 29%), need for mechanical ventilation (77% vs. 74%), and hemoglobin level (7.7 +/- 1.1 vs. 7.9 +/- 1.0 g/dL). The mean hemoglobin level remained 2.3 g/dL lower in the restrictive group after randomization. No significant differences were found for new or progressive MODS (8% vs. 9%; P = 0.83) or for 28-day mortality (2% vs. 2%; P = 0.96) in the restrictive versus liberal group. However, there was a statistically significant difference between groups for PICU length of stay (7.7 +/- 6.6 days for the restrictive group vs. 11.6 +/- 10.2 days for the liberal group; P = 0.03). CONCLUSIONS: In this subgroup analysis of pediatric general surgery patients, we found no conclusive evidence that a restrictive red-cell transfusion strategy, as compared with a liberal one, increased the rate of new or progressive MODS or mortality.

Comparison of two red-cell transfusion strategies after pediatric cardiac surgery: a subgroup analysis.

OBJECTIVE: To determine the impact of a restrictive vs. a liberal transfusion strategy on new or progressive multiple organ dysfunction syndrome in children post cardiac surgery. The optimal transfusion threshold after cardiac surgery in children is unknown. DESIGN: Randomized, controlled trial. SETTING: Tertiary pediatric intensive care units. PATIENTS: Participants are a subgroup of pediatric patients post cardiac surgery from the TRIPICU (Transfusion Requirements in Pediatric Intensive Care Units) study. Exclusion criteria specific to the cardiac surgery subgroup included: age <28 days and patients remaining cyanotic. INTERVENTION: Critically ill children with a hemoglobin < or = 95 g/L within 7 days of pediatric intensive care unit admission were randomized to receive prestorage leukocyte-reduced red-cell transfusion if their hemoglobin dropped either <70 g/L (restrictive) or 95 g/L (liberal). MEASUREMENTS AND MAIN RESULTS: Postoperative cardiac patients (n = 125) from seven centers were enrolled. The restrictive (n = 63) and liberal (n = 62) groups were similar at baseline in age (mean +/- standard deviation = 31.4 +/- 38.1 mos vs. 26.4 +/- 39.1 mos), surgical procedure, severity of illness (Pediatric Risk of Mortality score = 3.4 +/- 3.2 vs. 3.2 +/- 3.2), multiple organ dysfunction syndrome (46% vs. 44%), mechanical ventilation (62% vs. 60%), and hemoglobin (83 vs. 80 g/L). Mean hemoglobin remained 21 g/L lower in the restrictive group after randomization. No significant difference was found in new or progressive multiple organ dysfunction syndrome (primary outcome) in the restrictive group vs. liberal group (12.7% vs. 6.5%; p = .36), pediatric intensive care unit length of stay (7.0 +/- 5.0 days vs. 7.4 +/- 6.4 days) or 28-day mortality (3.2% vs. 3.2%). CONCLUSION: In this subgroup analysis of cardiac surgery patients, a restrictive red-cell transfusion strategy, as compared with a liberal one, was not associated with any significant difference in new or progressive multiple organ dysfunction syndrome, but this evidence is not definitive.

Risk of hypogonadism from scatter radiation during pelvic radiation in male patients with rectal cancer.

PURPOSE: Recent studies have reported fluctuations in sex hormones during pelvic irradiation. The objective of this study was to observe the effects of radiation on hormonal profiles for two treatment modalities: conventional external beam radiotherapy (EBRT) and high-dose-rate brachytherapy (HDRBT) given neoadjuvantly for patients with rectal cancer. METHODS AND MATERIALS: Routine serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were collected from 119 consecutive male patients receiving either EBRT, using 45.0-50.4 Gy in 25-28 fractions with concurrent 5-fluorouracil chemotherapy or HDRBT using 26 Gy in 4 fractions. RESULTS: Thirty patients with initially abnormal profiles were excluded. Profiles included in this study were collected from 51 patients treated with EBRT and 38 patients treated with HDRBT, all of whom had normal hormonal profiles before treatment. Mean follow-up times were 17 months for the entire patient cohort-14 and 20 months, respectively-for the EBRT and HDRBT arms. Dosimetry results revealed a mean cumulative testicular dose of 1.24 Gy received in EBRT patients compared with 0.27 Gy in the HDRBT group. After treatment, FSH and LH were elevated in all patients but were more pronounced in the EBRT group. The testosterone-to-LH ratio was significantly lower (p = 0.0036) in EBRT patients for tumors in the lower third of the rectum. The 2-year hypogonadism rate observed was 2.6% for HDRBT compared with 17.6% for EBRT (p = 0.09) for tumors in the lower two thirds of the rectum. CONCLUSION: HDRBT allows better hormonal sparing than EBRT during neoadjuvant treatment of patients with rectal cancer.

Economic impact of non-persistence to antidepressant therapy in the Quebec community-dwelling elderly population.

BACKGROUND: In a real-life setting, differences across newer antidepressants in patterns of use remain poorly explored, particularly in the older patients despite the high prevalence of late-life depression. METHODS: An observational retrospective cohort study was conducted in the community-dwelling elderly population of Quebec using health databases to compare the newer antidepressants with respect to non-persistence, associated health care costs and cost/persistence ratio. A random sample of 12,825 outpatients who initiated an antidepressant treatment in 2000 were followed for 12 months. Non-persistence was defined as treatment duration of less than 180 days. Economic variables included direct costs of prescribed medications, medical services and hospitalizations assessed through RAMQ claims databases and Med-Echo hospitalization database. Cost/persistence ratio and incremental cost/persistence ratio were obtained for each antidepressant product; persistence being considered as an indicator of effectiveness. RESULTS: 55.6% of antidepressant treatments were non-persistent. Products associated with low antidepressant costs were often associated with high costs of other medications and health care services, and vice versa. Paroxetine was associated with the lowest non-persistence (50.5%; 95%CI 48.5-52.5) and one of the most favourable cost/persistence ratios (CDN$4869 per persistent treatment). Fluoxetine was associated with the most favourable incremental cost/persistence ratio. LIMITATIONS: Some services and hospitalizations are not included in the administrative databases. No data on indication for treatment were available. These were likely to be non-differential across newer antidepressants. CONCLUSION: As found in other populations, non-persistence with antidepressant treatment is very frequent in the Quebec elderly population. Products associated with poor persistence result in increased health care costs. Hence, intervention programs aimed at improving persistence would optimize the use of health care resources and result in economic advantages.