Variations In Treatment Protocols Research Articles

Systematic review of clinical prediction tools and prognostic factors in aneurysmal subarachnoid hemorrhage.

Background:Clinical prediction tools assist in clinical outcome prediction. They quantify the relative contributions of certain variables and condense information that identifies important indicators or predictors to a targeted condition. This systematic review synthesizes and critically appraises the methodologic quality of studies that derive both clinical predictors and clinical predictor tools used to determine outcome prognosis in patients suffering from aneurysmal subarachnoid hemorrhage (SAH).Methods:This systematic review included prospective and retrospective cohort studies, and randomized controlled trials (RCTs) investigating prognostic factors and clinical prediction tools associated with determining the neurologic outcome in adult patients with aneurysmal SAH.Results:Twenty-two studies were included in this systemic review. Independent, confounding, and outcome variables were studied. Methodologic quality of individual studies was also analyzed. Included were 3 studies analyzing databases from RCTs, 8 prospective cohort studies, and 11 retrospective cohort studies. The most frequently retained significant clinical prognostic factors for long-term neurologic outcome prediction include age, neurological grade, blood clot thickness, and aneurysm size.Conclusions:Systematic reviews for clinical prognostic factors and clinical prediction tools in aneurysmal SAH face a number of methodological challenges. These include within and between study patient heterogeneity, regional variations in treatment protocols, patient referral biases, and differences in treatment, and prognosis viewpoints across different cultures.

Management of Pediatric Migraine in a Tertiary Care Versus Community Based Emergency Department: An Observational Pilot Study

BackgroundBecause of a lack of guidelines for the management of pediatric migraine in the emergency department setting, marked variations in treatment protocols exist between institutions. We aimed to characterize differences in management strategies for pediatric migraine treatment between a community-based and a tertiary care emergency department. MethodsA retrospective cohort study was performed to include pediatric patients presenting with headache fulfilling the International Classification of Headache Disorders-2 migraine criteria in a tertiary care (site 1) and a community based (site 2) emergency department. The two sites were compared with respect to patient demographics and approach to treatment. ResultsA total of 158 patients at site 1 (mean age 13.6 years, 70% female, 68% African-American) and 63 patients at site 2 (mean age 16.7 years, 71% female, 100% Caucasian) were analyzed. Opiate use (7.6% vs. 33%), imaging (6.3% vs. 20.6%), use of nonsteroidal anti-inflammatory drugs/serotonin agonists at discharge (72.7% vs. 22.2%), and admission rates to hospital (22% vs. 0%) were significantly different. Logistic regression analysis indicated that the main predictors of hospital admission were use of opiates and intravenous combination abortive therapy. ConclusionLow rates of intravenous combination therapy, antidopaminergic agent, and serotonin agonist use were noted across both hospital settings. Community-based physicians used opiates and obtained neuro-imaging more than those in the academic setting. Standardization of care in the emergency setting coupled with reliable acute care plans that are based on evidenced-based guidelines can allow for better control of episodic migraine and reduce emergency department visits.

BCG immunotherapy for bladder cancer—the effects of substrain differences

Genetic mutations have been progressively introduced to BCG by repeated serial passage over many decades of its culture and global dissemination. Thus, marked differences exist in the phenotype, antigenicity, reactogenicity, and clinical characteristics of the numerous substrains of BCG currently in use for bladder cancer immunotherapy. These differences influence proposed mycobacterial antitumour mechanisms and toxicity, potentially resulting in variations in clinical efficacy and adverse effects. However, although there is evidence of substrain-related differences in the clinical efficacy of BCG as a tuberculosis vaccine, evidence of an effect on bladder cancer immunotherapy remains elusive, owing to the lack of appropriately powered head-to-head comparative clinical trials, the nonstandardization of BCG manufacture, and variation in treatment protocols--possibly itself a response to underlying substrain differences. Advances in our understanding of mycobacterial genetics, structure and function, and host-pathogen interactions might explain differences in clinical practice and outcomes. These advances are guiding the identification of biomarkers for reactogenicity and efficacy, and the rational design of immunotherapeutic strategies to eliminate the use of live bacilli for bladder cancer therapy.

Reply to "Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study" by Redmond et al.

Dear Editor: In a recent article in Neuro-Oncology, “Association between radiation dose to neuronal progenitor cell niches and temporal lobes and performance on neuropsychological testing in children: a prospective study,”1 the connection between radiation dose and cognitive outcomes was evaluated. This is an interesting and important area of research that is inherently difficult to study because of the wide variation in treatment protocols. There are several methodological observations that may be important to consider when interpreting the findings of this study. First, the reported relationship between radiation dose and neurocognitive outcomes is difficult to interpret. For example, 74% of the patients were treated with 50–60 Gy radiation, with an overall mean dosage of 42.9 Gy. Only 3 patients (16% of the sample) were treated with 21–49 Gy radiation, and only 2 patients (11% of the sample) were treated with 0–20 Gy radiation. Because of these uneven and small individual sample sizes, it is very difficult to make comparisons among groups in neurocognitive functioning. In addition, there does not appear to be adequate variance within the patient sample (74% of patients were in the highest dose group) to draw conclusions regarding dose effects, particularly for those receiving <50–60 Gy radiation. Second, findings are very difficult to generalize because of the heterogeneity of the sample. Patients ranged in age from 1 to 18 years at the time of radiation, with a standard deviation of 1.1–18.6 years of age. To address this wide age range, the authors state in the Discussion that “Because we used standardized, age-adjusted scores for our analysis of the neurocognitive tests, we would not expect this difference to have an impact on our results.” The authors appear to have used raw scores instead of normative data and standardized scores and controlled for age in the regression analysis. Controlling for age at the time of radiation dose is not equivalent to using normative standardized scores. It is not stated in the manuscript why this method was chosen. Moreover, it appears that controlling for age at the time of radiation is counterintuitive because age at time of radiation moderates cognitive functioning and brain maturational trajectories.2 In other words, age at time of radiation and neurocognitive performance is not random but likely strongly correlated and contributory. The same argument might be made for controlling for presence or absence of chemotherapy; controlling for a variable that is likely to affect an outcome measure in one group but not the other (ie, patient group but not control group) may be artificially masking important and significant variance. On a similar note, neurocognitive testing was attempted at baseline (1–18 years of age) and at around 6, 15, and 27 months after completion of radiation treatment. The time between diagnosis and baseline testing ranged from 14 to 2284 days. It is theoretically and conceptually problematic that some patients received baseline testing years after diagnosis, whereas others were tested 2 weeks after diagnosis. There are many variables that may account for differences in neurocognitive functioning (eg, health status, time away from school, age differences, and chemotherapy effects) beyond radiation dose. This weakens the interpretation of the independent and dependent variables and overall results of the study. The study would be improved by clearly defined and more homogenous groups, to provide more ecologically valid information. The use of statistical covariates likely to affect outcome measures should also be clarified if indeed the results are to inform clinical practice and ongoing research. Conflict of interest. None declared.

Pharmacogenomic variations in treatment protocols for childhood acute lymphoblastic leukemia

This retrospective study evaluates the role of pharmacogenomic determinants in the treatment of childhood acute lymphoblastic leukemia (ALL) in the Taiwanese population. A total of 105 childhood ALL patients received combined chemotherapy of different intensities based on risk-directed Taiwan Pediatric Oncology Group (TPOG)-ALL-93 protocols. Seventeen genetic polymorphisms in 13 pharmacogenomic targets were analyzed by PCR-based restriction fragment length polymorphism (RFLP) and sequence-specific oligonucleotide (SSO) probe hybridization. Pharmacogenomic polymorphisms were correlated with event-free survival (EFS) of patients, with confounding effects adjusted by multivariate regression. Three polymorphic alleles in the multi-drug resistance 1 (MDR1) ABCB1 gene, and homozygotic MDR1 2677GG, 3435CC, and 2677G-3435C genotypes were highly associated with a significant reduction in EFS in those patients treated by the standard risk (SR) protocol (TPOG-ALL-93-SR). The hazard ratios were 6.8 (p = 0.01), 21.7 (p = 0.009), and 6.8 (p = 0.01), respectively. Independent pharmacogenomic determinants associated with treatment outcome were identified in subsets of Taiwanese ALL patients.

Genomics of Childhood Leukemias: The Virtue of Complexity

Genomics of Childhood Leukemias: The Virtue of Complexity

Wilms' tumor and neuroblastoma

Significant differences exist between the European and North American treatment protocols for Wilms' tumor and neuroblastoma. There are variations in biopsy technique, timing and extent of initial surgery, chemotherapy protocols and dosage routines, as well as the type of salvage therapy. With the consolidation of the two major North American study groups into a single entity (Children's Oncology Group), the European and North American study groups represent the only remaining large-scale venues for treatment comparison. It is important to study and understand the variation in treatment protocols in order to maintain an open forum of scientific investigation that will lead to improving the care and outcome of children with cancer. It is anticipated that the unification of the North American groups will lead to greater interest and scientific cooperation with the European study group. This paper will serve as a forum for such a discussion at a local level.

Treatment strategies for early presenting acetaminophen overdose: a survey of medical directors of poison centers in North America and Europe

Acetaminophen is frequently used in self-poisoning in Western countries. Although treatment with N-acetylcysteine (NAC) reduces liver injury, no consensus exists on the preferred management of acetaminophen toxicity. To describe the approach taken by toxicologists in North America and Europe toward the management of acetaminophen toxicity. Medical directors of poison centers in the US, Canada, and Europe were surveyed by means of a questionnaire presenting two clinical scenarios of acetaminophen overdose: a healthy adolescent with no risk factors who had an acute ingestion of acetaminophen, and an adult with both acute ingestion and possible risk factors. For each case, several questions about the management of these patients were asked. Questionnaires were sent to medical directors of 76 poison centers in North America and 48 in Europe, with response rates of 62% and 44%, respectively. Forty percent of responders suggested using charcoal 4 hours after ingestion of a potential toxic dose of acetaminophen, and 90% recommended treatment with NAC when levels were above 150 microg/mL but below 200 microg/mL 4 hours after ingestion. Duration of treatment with oral NAC ranged from 24 to 96 hours; 38 responders suggested a duration of 72 hours. Of 49 centers recommending oral NAC, 18 (36.7%) said they might consider treatment for less than 72 hours. Eleven of 29 (37.9%) responders suggested treatment with intravenous NAC for more than 20 hours as their usual protocol or a protocol for specific circumstances. Our study showed large variability in the management of acetaminophen overdose. Variations in treatment protocols should be addressed in clinical trials to optimize the treatment for this common problem.