Initial Course Of Treatment Research Articles

Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part III-Treatment and Prevention of Infections.

Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) and its subset, pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS), are emerging autoimmune encephalopathies of childhood. Management guidelines are needed. This article, from the PANS/PANDAS Consortium, presents a consensus management guideline for the infection components. Accompanying papers from the Consortium discuss psychiatric and immunomodulatory management. Methods: Literature was reviewed and integrated with the clinical experience of the authors to provide a set of practical guidelines. This article was submitted to all members of the PANS/PANDAS Consortium, and their additional comments were added. Results: The relationships between PANS and infections are reviewed. An approach to the retrospective diagnosis of group A streptococcal infection for an operational definition of PANDAS is proposed. An initial course of anti-streptococcal treatment is proposed for all newly diagnosed PANS cases. Chronic secondary antimicrobial prophylaxis is suggested for children with PANDAS who have severe neuropsychiatric symptoms or recurrent group A Streptococcus-associated exacerbations. Guidelines for children with non-streptococcal PANS include vigilance for streptococcal pharyngitis or dermatitis in the patient and close contacts. All patients with PANS or PANDAS should also be closely monitored for other intercurrent infections, including sinusitis and influenza. Intercurrent infections should be diagnosed and treated promptly according to current standard guidelines. A guideline for the assessment of infection at initial onset or during neuropsychiatric exacerbations is also presented. Standard immunizations and attention to vitamin D are encouraged. Data indicating limited utility of adenotonsillectomy and probiotics are presented. Conclusion: A working guideline for the management of infection issues in PANS and PANDAS, based on literature and expert opinion, is provided.

A Comparison of Veterans Who Repeat Versus Who Do Not Repeat a Course of Manualized, Cognitive-Behavioral Therapy for Posttraumatic Stress Disorder

Despite evidence that cognitive-behavioral therapy (CBT) for posttraumatic stress disorder (PTSD) is effective, some individuals do not experience clinically significant reduction or remission of their PTSD symptoms. These individuals may return for additional PTSD-focused psychotherapy. However, there is no research to know whether PTSD treatment repeaters have worse symptoms prior to the initial treatment episode or display differences in other pretreatment characteristics versus nonrepeaters. Research is also needed to explore whether treatment repeaters exhibit PTSD symptom changes during an initial or second course of treatment. The current study examines differences in pretreatment characteristics and treatment response among U.S. military veterans who participated in either a single course (n = 711) or in two separate courses (n = 87) of CBT for PTSD through an outpatient Veterans Affairs PTSD treatment program. Veterans completing two courses of CBT for PTSD were more likely to be married and employed and more likely to drop out of their initial course of treatment versus those who completed a single course. Hierarchical linear models showed that reductions in PTSD symptoms during treatment were not different for those who completed a second versus single course of CBT for PTSD. However, for those participating in two courses of CBT for PTSD, a relapse in PTSD symptoms was observed between the first and second course. These findings show that a second course of CBT may be viable for those with ongoing PTSD symptoms.

Evaluation of outcomes after stereotactic radiosurgery for pilocytic astrocytoma.

Pilocytic astrocytomas are rare intracranial gliomas that are typically treated with surgical extirpation. Our aim was to report the radiologic and clinical outcomes of patients treated with stereotactic radiosurgery (SRS) for pilocytic astrocytoma in the primary and salvage setting. Patients with pilocytic astrocytoma treated at a single institution with SRS from 1990 to 2015 were reviewed. Patient, disease, and treatment characteristics were collected and overall survival, local control, and toxicity were evaluated. Twenty-eight consecutive patients (12 females and 16 males) with a median age of 17.4 years at SRS were identified. Overall, 46% of patients were treated with SRS as part of the initial treatment course after biopsy or subtotal resection, and the remainder as a salvage therapy. The most common location was the cerebellum (28%) followed by brainstem and basal ganglia (21 and 18%, respectively). Four patients received prior external beam radiation therapy (14%). Median tumor volume was 1.84cc (0.19-15.94cc), and 39% had a cystic component at SRS. Prescription dose ranged from 4 to 20Gy (median 16Gy) to a median isodose line of 50% (range 30-100%). With a median follow-up of 5.2 years (0.3-17.1 years), all patients remained alive at last follow-up. Two patients demonstrated evidence of local radiographic progression at last follow-up (7%). No toxicity could be directly attributed to SRS. In this SRS series, durable tumor control was achieved in 93% of patients with pilocytic astrocytoma, although continued follow up will be important giving the natural history of this disease. As demonstrated, SRS is an appropriate technique in the primary and recurrent treatment of pilocytic astrocytoma that offers favorable disease control and infrequent clinical toxicity.

Family Discord After Completion of an Outpatient Community Treatment Program Predicts Greater Substance Use During Follow-up

ABSTRACTBackground: It is reasonable to consider family discord after treatment as a potential target for a next-step intervention, since family discord is often comorbid with substance use disorders. Objective: This study evaluated family discord after completing an initial course of treatment as a predictor of substance use and retention in the community treatment program during follow-up. Method: Patients were from two multisite randomized clinical trials implemented through the Clinical Trials Network of the National Institute on Drug Abuse. There were 315 participants from Study 1 (12-week posttreatment follow-up) and 295 participants from Study 2 (8-week posttreatment follow-up). Negative binomial and logistic regression were used to estimate days of substance use and odds of retention in the community treatment program at follow-up, respectively, from family discord status. Results: Family discord was significantly associated with more days of substance use during the posttreatment follow-up period than those without family discord in both Study 1 (9.12 vs. 2.89 days, p =.0001) and Study 2 (5.58 vs. 2.83 days, p =.0062). Family discord was significantly associated with lower retention in the community treatment program at follow-up than those not reporting family discord in Study 1 (47.6% vs. 60.6%; p =.03), but not in Study 2 (55.3% vs. 64.9%; p =.11). Conclusion: Family discord after an initial course of treatment might be a clinically relevant predictor of substance use. There is mixed support for a conclusion that family discord is associated with lower retention in the community treatment program at follow-up.

Evaluation of the Effectiveness of a Short-term Treatment and Repeat Treatment of Nocturnal Enuresis Using an Enuresis Alarm

To evaluate the effectiveness of a 3-month enuresis alarm (EA) treatment and repeat EA treatment among pediatric patients with nocturnal enuresis, and to compare patient characteristics among "responders" and "nonresponders" to treatment. Clinical outcomes were retrospectively evaluated for 137 children (94 boys and 43 girls, mean age, 10.1 years). Effectiveness was evaluated after an initial 3-month treatment, using the International Children's Continence Society criteria. Among children in the no-response group at 3 months, those who continued the EA treatment for ≥4 months were subclassified into group 1, whereas children who repeated the EA treatment at an interval ≥6 months were subclassified into group 2. Among our 137 cases, 19 achieved complete response and 47 achieved partial response at 3 months, for an overall treatment effectiveness rate of 48%. Among the no-response group, treatment was extended in 17 cases (group 1), with 3 (18%) achieving a successful outcome. Treatment was repeated in 18 cases (group 2). In group 2, 8 (44%) achieved successful outcome at 3-month time point. Daytime urinary incontinence did not modify treatment effectiveness. EA treatment should be given for a short period of time and should not be continued without a definite purpose or clear response. Suspending and then repeating this treatment after an appropriate interval is effective for patients who do not respond to the initial course of treatment.

Predictors of Hospital Readmission for Children with Psychiatric Illness who have Received an Initial Course of Treatment

Predictors of Hospital Readmission for Children with Psychiatric Illness who have Received an Initial Course of Treatment

Treatment outcome in children with nontuberculous mycobacterial lymphadenitis: A retrospective follow-up study.

Information on the long-term treatment outcome following nontuberculous mycobacterial (NTM) lymphadenitis is very limited. We performed a study to (a) compare cure rates following different initial treatment courses, (b) describe subsequent treatment courses and their outcomes, and (c) determine the occurrence of late sequelae in immunocompetent children with NTM lymphadenitis. In 2011, we conducted a retrospective follow-up study in 71 parents whose children had been hospitalized with NTM disease 2002-2005. A telephone survey was performed using a standardized questionnaire to collect information on the therapeutic management and treatment outcome. Of 61 children with NTM lymphadenitis, 33 (54%) children were cured after the initial treatment. We found no significant difference in cure rates following surgical intervention only (45%, 13/29 children) and a combination of surgical intervention and chemotherapy (61%, 19/31 children). In 7 out of 11 children, the cure rate following complete lymph node excision was 64%. Subsequent courses of treatment including repeated surgical intervention, combination therapy, chemotherapy only, and wait-and-see strategy in children where initial therapy failed resulted in the cure of all 61 children. In four children (7%), recurrences were observed up to 5 years later. Our study showed that recurrent NTM lymphadenitis might be observed several years after initial resolution of disease. The cure rate following complete lymph node excision was lower than reported in other studies. Subsequent treatment courses were necessary in half of the children. Physicians and parents need to be aware that NTM lymphadenitis in children requires careful choice of intervention and active follow-up.

Rationale and Design of a Phase III Single-Arm Multicenter Study of Dabigatran Etexilate for the Secondary Prevention of Venous Thromboembolism in Children

Background: In children, the incidence of venous thromboembolism (VTE) is increasing and is often associated with underlying diseases such as cancer, or risk factors such as thrombophilia. Following treatment for acute VTE, thrombosis or thromboembolic events can recur particularly if a clinical risk factor for VTE persists. The efficacy and safety of the oral anticoagulant dabigatran etexilate (DE) have been demonstrated in a number of thrombosis-related indications in adults, including for secondary VTE-prevention. There are, however, potential differences between adults and children related to developmental physiology and pharmacology and therefore trials to evaluate the pharmacokinetics (PK), pharmacodynamics (PD) and safety of DE in children are required. To date, all pediatric phase IIa studies conducted have shown a similar PK and PK/PD relationship of DE in comparison to adult studies.Objective: To describe the design of a study to evaluate the safety and PK-PD of DE for secondary prevention of VTE in children aged 0-<18 years.Methods: This phase III, open-label, single-arm, multicenter study will be conducted at ~100 sites worldwide (NCT02197416). Eligible patients will have completed a course of initial treatment for confirmed acute VTE (for ≥ 3 months) and be considered at high risk for VTE recurrence due to the remaining presence of a clinical risk factor. Approximately 100 subjects between 0-<18 years of age will be included. Treatment with DE will extend up to 12 months, or less if the clinical risk factor resolves, with a follow-up visit 28 days after the last dose. DE will be administered twice daily as capsules, pellets or oral liquid formulation, depending on subject age and their ability to swallow capsules or pellets. A dosing nomogram will be used to scale down an adult dose based on the child’s age and weight. Initial doses calculated using the nomogram should achieve steady-state trough concentrations of DE of between 50 and < 250 ng/ml, a range which is assumed to result in safe and effective use of DE in this pediatric population; after about 3 days, trough dabigatran plasma concentration will be measured and DE may be titrated up or down to achieve the target steady-state trough plasma concentration.Results: Demographic and medical history data will be collected for all participants. The primary outcomes to be evaluated are instances at 6 and 12 months of image-proven VTE recurrence; major and minor bleeding, including clinically relevant non-major bleeding; and overall and thrombotic/thromboembolic mortality. All elements of the primary endpoints will be evaluated by an independent adjudication committee that will confirm or refute outcome events. The secondary outcomes are rates of post-thrombotic syndrome at 6 and 12 months; PK and PD (e.g., activated partial thromboplastin time and ecarin clotting time); and the number of DE dose adjustments required during the treatment period. Data on the acceptability of the age-appropriate drug formulation, the tolerability of the study medication, adverse events, treatment discontinuations due to an adverse event, and laboratory and clinical parameters will also be collected during the study. Safety and tolerability will be monitored by the independent Data Monitoring Committee.Conclusion: This phase III study has been designed to provide data on the safety and PK-PD of DE for the secondary prevention of VTE in children aged 0-<18 years. DisclosuresLuciani:Boehringer Ingelheim: Other: Member of Pediatric Expert Working Group for Boehringer Ingelheim. Albisetti:Boehringer Ingelheim: Other: Pediatric Expert Working Group. Manastirski:Boehringer Ingelheim: Employment. Brueckmann:Boehringer Ingelheim: Employment. Gropper:Boehringer Ingelheim: Employment. Tartakovsky:Boehringer Ingelheim: Employment. Wang:Boehringer Ingelheim: Employment. Biss:Boehringer Ingelheim: Employment. Mitchell:Bristol Myers Squibb: Consultancy; Pfizer: Consultancy; Boehringer Ingelheim: Consultancy. Huang:Boehringer Ingelheim: Employment. Halton:Boehringer Ingelheim: Other: Pediatric Expert Working Group for Boehringer Ingelheim.

Evolving Risk of Myelodysplastic Syndromes Among Adolescents and Young Adults Following Radiation Treatment for First Cancers in the United States, 1973 - 2014

▪BackgroundAdolescents and young adults (AYA; aged 15-39) treated for first cancers are a demographic cohort that are uniquely predisposed to risk of second cancers. This is due to increased sensitivity of exposed tissues to cancer therapies and a longer latency for the development of second cancers due to longer survival resulting from advances in cancer treatments. Radiotherapy is a commonly used modality in several AYA cancers and has been associated with increased risk of subsequent neoplasms including myeloid malignancies. Myelodysplastic syndrome (MDS) is the most common myeloid malignancy in the US but very little is known regarding the risk of MDS in the AYA population. In this study, we analyzed the evolving risk of MDS in the AYA population spanning over 4 decades using the US Surveillance Epidemiology and End Results (SEER) registry.MethodsA novel R program, SEERaBomb (Leukemia. 2016;30(2):285-94) was developed to query all 18 SEER registries. We identified all AYA first cancer cases treated with radiation that subsequently developed MDS as second cancers. Diagnosis was derived from the International Classification of Diseases for Oncology Third Revision categories. SEER cancer registries collect information on the initial course of treatment and does not carry information on chemotherapy. SEERaBomb allows merging of all 18 SEER registries - a function not permitted by the NIH-developed SEER*Stat MP-SIR program that limits researchers to use either SEER 9 or SEER 13. This significantly increases the capture of MDS cases. AYA cancer survivor person yrs at risk for developing MDS was based on age at diagnosis of the first cancer, survival time, and age at diagnosis of MDS. Relative risks (RR) for developing MDS were based on observed/expected cases between the cohorts receiving no radiation (control) or radiation.ResultsIn total 569,681 AYA first cancer patients (pts) were identified, of whom 133,829 (23%) received radiation as initial part of their cancer treatment and 426,272 (75%) received no radiotherapy. Mean age at the time of first cancer diagnosis was similar in radiation treated and untreated cohorts (32 yrs vs. 31.2 yrs). Median yrs of follow up after first cancer diagnosis was 5.7 yrs (25-75 interquartile [IQR], 1.9-12.2) in pts receiving radiation and 9.1 yrs (25-75 IQR, 2.7-20.2) in those not treated with radiation. A total of 48 pts developed MDS; 21 in the radiation group and 27 in the cohort that did not receive radiation. Median time to development of MDS after first cancer diagnosis was 3.8 yrs (25-75 IQR, 2.0-6.1) in those who received radiation and 3.1 yrs (25-75 IQR, 1.1-4.2) in non-irradiated pts. MDS cases were classified as RA (n=5), RARS (n=4), RCMD (n=3), RAEB (n=8), MDS with 5q deletion syndrome (n=2), and MDS-U (n=26). Compared with the risk in general population, pts treated with radiotherapy and those who did not receive radiation had an elevated risk of developing MDS within the first 10 yrs (RR=33.3; 95% CI, 20.4-51.5 vs. RR=19.3; 95% CI, 12.6-28.2). The risk of MDS in both radiation-treated and untreated cohort peaked within the first two yrs. The risk of MDS in general was higher in the radiation-treated pts compared to non-radiated pts for up to 7 yrs from exposure and beyond 10 yrs, the risk for MDS steadily fell to baseline rates (Fig 1). The risk kinetics of developing MDS in AYA first cancer survivors mimics the kinetics of MDS development in adults > 40 yrs, whereas the magnitude of the RR is much higher in the first group (Fig 2). When the pooled occurrence of AML and MDS as second cancers was analyzed in AYA first cancer survivors, those who received radiation had a statistically significant increased risk of developing AML or MDS within the first 3 yrs of exposure compared with pts not treated with radiation (RR=22.5; 95% CI, 18.2-27.7 vs. RR=12.5; 95% CI,10.3-15.0; Fig 3).ConclusionAYA cancer pts have a strikingly increased risk of developing MDS in the first 10 yrs after first cancer diagnosis. AYA cancer pts undergoing radiotherapy for first cancers appear to have an even higher risk of developing MDS that can last up to 10 yrs following exposure. Considering the long latency of MDS seen in atomic bomb cohorts and relative young age of AYA pts, MDS rates are likely to continue to rise. [Display omitted] [Display omitted] [Display omitted] DisclosuresCarraway:Baxalta: Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding, Speakers Bureau. Maciejewski:Celgene: Consultancy, Honoraria, Speakers Bureau; Apellis Pharmaceuticals Inc: Membership on an entity's Board of Directors or advisory committees; Alexion Pharmaceuticals Inc: Consultancy, Honoraria, Speakers Bureau. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Novartis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding.

Supply and Demand for Radiation Oncology in the United States: Updated Projections for 2015 to 2025

Prior studies forecast demand for radiation therapy to grow 10 times faster than supply between 2010 and 2020. We updated these projections for 2015 to 2025 to determine whether this imbalance persists and to assess the accuracy of prior projections. Demand for radiation therapy between 2015 and 2025 was estimated by combining current radiation utilization rates determined by Surveillance, Epidemiology, and End Results data with population projections provided by the Census Bureau. Supply of radiation oncologists was forecast using workforce demographics and full-time equivalent (FTE) status provided by the American Society for Radiation Oncology (ASTRO), current resident class sizes, and expected survival per life tables from the Center for Disease Control. Between 2015 and 2025, the annual total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 19%, from 490,000 to 580,000. Assuming a graduating resident class size of 200, the number of FTE physicians is expected to increase by 27%, from 3,903 to 4,965. Compared to prior projections, the new projected demand for radiation therapy in 2020 dropped by 24,000 cases (a 4% relative decline). This decrease is attributable to an overall reduction in the utilization of radiation to treat cancer, from 28% of all newly diagnosed cancers in the prior projections down to 26% for the new projections. In contrast, the new projected supply of radiation oncologists in 2020 increased by 275 FTEs compared to the prior projection for 2020 (a 7% relative increase), attributable to rising residency class sizes. The supply of radiation oncologists is expected to grow more quickly than demand for radiation therapy from 2015 to 2025. Further research is needed to determine whether this is an appropriate correction or will result in excess capacity.

Minimally Invasive Spine Surgery for Unstable Thoracolumbar Burst Fractures: A Case Series

Introduction Traumatic thoracolumbar burst fracture is a common pathology without a clear consensus on best treatment approach. Minimally invasive approaches are being investigated due to potential benefits in recovery time and morbidity. We examine long-term resolution of symptoms of traumatic thoracolumbar burst fractures treated with percutaneous posterior pedicle screw fixation. Methods Retrospective clinical review of seven patients with spinal trauma who presented with thoracolumbar burst fracture from July 2012 to April 2013 and were treated with percutaneous pedicle screw fixation. Electronic patient charts and radiographic imaging were reviewed for initial presentation, fracture characteristics, operative treatment, and postoperative course. Results The patients had a median age of 29 years (range 18 to 57), and 57% were men. The median Thoracolumbar Injury Classification and Severity Scale score was 4 (range 2 to 9). All patients had proper screw placement and uneventful postoperative courses given the severity of their individual traumas. Five of seven patients were reached for long-term follow-up of greater than 28 months. Six of seven patients had excellent pain control and stability at their last follow-up. One patient required revision surgery for noncatastrophic hardware failure. Conclusion Percutaneous pedicle screw fixation for the treatment of unstable thoracolumbar burst fracture may provide patients with durable benefits and warrants further investigation.

The Safety and Efficacy of Weekly Paclitaxel Administration for Anaplastic Thyroid Cancer Patients: A Nationwide Prospective Study

Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive malignancy, with a median survival of less than 6 months due to rapid progression and resistance to multimodal therapies. Effective treatment strategies have not been identified. A prospective clinical study was performed to objectively evaluate outcomes of treatment with paclitaxel. An investigator-initiated, multicenter, nonrandomized, open-label, single-arm study to evaluate the feasibility and efficacy of weekly paclitaxel (80 mg/m(2)) administration for patients with pathologically confirmed ATC was conducted in a nationwide organization. Feasibility was analyzed in 56 patients. More than one course of treatment was performed in 52 (93%) patients retaining sufficient dose intensity (>84%). No patient had to terminate the treatment because of an adverse event. The median overall survival was 6.7 months [confidence interval 4.4-9.0]. The 6-month survival was 54%. Among the 42 patients with an evaluable lesion, none demonstrated complete remission, 9 (21%) showed partial remission, 22 (52%) achieved stable disease, and 8 (19%) exhibited progressive disease; 3 did not complete the initial treatment course. The objective response rate was 21%, and the clinical benefit rate was 73%. The median time to progression was 1.6 months. Statistically, no additional effect of concomitant radiation was demonstrated in 6 patients receiving combined therapy. Eight patients, in whom a complete post-treatment surgical removal of the tumor was feasible, survived significantly longer (median 7.6 months [CI 8.1-23.0]) than the other 34 patients in whom the tumor could not be completely removed after chemotherapy (5.4 months [CI 3.0-7.8], p = 0.018). The study demonstrates objective and accurate information concerning the feasibility and efficacy of a standardized treatment with weekly paclitaxel administration for ATC patients. Weekly paclitaxel administration for ATC patients can be of clinical benefit in a neo-adjuvant setting.

Non Surgical Management of Mini Guide Wire Embolism with Self Made Guide Wire Snare

A 5 3 years old male presented in emergency department of local hospital with acute inferior wall myocardial infarction During his initial course of treatment he dev eloped symptomatic bradycardia and 2:1 artioventricular block, for which he was tried for implantation of temporary pacing lead through right subclavian vein with 6 F venous sheath. During the procedure the operator embolized the J-tip mini guide wire in the heart, for which the patient was shifted to our hospital for the management of the embolised guide wire and coronary angiography. The patient was immediately brought to cardiac catheterization laboratory and the position of mini guide wire was located under fluoroscopy. Its upper end was lying near the junction of superior vena cava with right atrium and the lower end was in the right common iliac vein. ContinuedÂ

Supply and Demand for Radiation Oncology in the United States: Updated Projections for 2015 to 2025

Prior studies have forecasted demand for radiation therapy to grow 10 times faster than the supply between 2010 and 2020. We updated these projections for 2015 to 2025 to determine whether this imbalance persists and to assess the accuracy of prior projections. The demand for radiation therapy between 2015 and 2025 was estimated by combining current radiation utilization rates determined by the Surveillance, Epidemiology, and End Results data with population projections provided by the US Census Bureau. The supply of radiation oncologists was forecast by using workforce demographics and full-time equivalent (FTE) status provided by the American Society for Radiation Oncology (ASTRO), current resident class sizes, and expected survival per life tables from the US Centers for Disease Control. Between 2015 and 2025, the annual total number of patients receiving radiation therapy during their initial treatment course is expected to increase by 19%, from 490,000 to 580,000. Assuming a graduating resident class size of 200, the number of FTE physicians is expected to increase by 27%, from 3903 to 4965. In comparison with prior projections, the new projected demand for radiation therapy in 2020 dropped by 24,000 cases (a 4% relative decline). This decrease is attributable to an overall reduction in the use of radiation to treat cancer, from 28% of all newly diagnosed cancers in the prior projections down to 26% for the new projections. By contrast, the new projected supply of radiation oncologists in 2020 increased by 275 FTEs in comparison with the prior projection for 2020 (a 7% relative increase), attributable to rising residency class sizes. The supply of radiation oncologists is expected to grow more quickly than the demand for radiation therapy from 2015 to 2025. Further research is needed to determine whether this is an appropriate correction or will result in excess capacity.

Colon cancer care and survival: income and insurance are more predictive in the USA, community primary care physician supply more so in Canada.

BackgroundOur research group advanced a health insurance theory to explain Canada’s cancer care advantages over America. The late Barbara Starfield theorized that Canada’s greater primary care-orientation also plays a critically protective role. We tested the resultant Starfield-Gorey theory by examining the effects of poverty, health insurance and physician supplies, primary care and specialists, on colon cancer care in Ontario and California.MethodsWe analyzed registry data for people with non-metastasized colon cancer from Ontario (n = 2,060) and California (n = 4,574) diagnosed between 1996 and 2000 and followed to 2010. We obtained census tract-based socioeconomic data from population censuses and data on county-level physician supplies from national repositories: primary care physicians, gastroenterologists and other specialists. High poverty neighborhoods were oversampled and the criterion was 10 year survival. Hypotheses were explored with standardized rate ratios (RR) and tested with logistic regression models.ResultsSignificant inverse associations of poverty (RR = 0.79) and inadequate health insurance (RR = 0.80) with survival were observed in the California, while they were non-significant or non-existent in Ontario. The direct associations of primary care physician (RRs of 1.32 versus 1.11) and gastroenterologist (RRs of 1.56 versus 1.15) supplies with survival were both stronger in Ontario than California. The supply of primary care physicians took precedence. Probably mediated through the initial course of treatment, it largely explained the Canadian advantage.ConclusionsPoverty and health insurance were more predictive in the USA, community physician supplies more so in Canada. Canada’s primary care protections were greatest among the most socioeconomically vulnerable. The protective effects of Canadian health care prior to enactment of the Affordable Care Act (ACA) clearly suggested the following. Notwithstanding the importance of insuring all, strengthening America’s system of primary care will probably be the best way to ensure that the ACA’s full benefits are realized. Finally, Canada’s strong primary care system ought to be maintained.

Fecal Microbiota Transplantation in Refractory Clostridium difficile Infection in Children: Case Report and Review of the Literature

The human gastrointestinal tract evolves gradually from being sterile as neonates to being populated with trillions of bacterial species existing symbiotically for proper colonic function [1]. Disruption of homeostasis predisposes the gastrointestinal tract to increased incidence of enteric infections. Antibiotic use and immunocompromised states have been associated with an increased incidence of Clostridium difficile infection (CDI). Although approximately 35% of children's guts are colonized with CDI, it rarely causes symptoms [5]. Antibiotic therapy is considered first line for CDI; however, fecal microbiota transplantation (FMT) has recently gained favorable results for refractory and recurrent cases [6]. This involves reintroducing typical microbiota to reestablish balance of the gut flora [6,7]. We report a case of refractory CDI affecting half of an immunocompromised child's life that was cured with single FMT treatment. A 4-year-old male born via cesarean section at 37 weeks was diagnosed with a genetic disorder, Kabuki syndrome. His early life was complicated by recurrent infections, requiring several courses of antibiotics. As a result, he developed refractory CDI that lasted for 30 months, affecting his growth. His parents sought alternative options in which he was evaluated for FMT. He underwent FMT with his father as the stool donor. A 250mL aliquot of stool slurry was infused into the terminal ileum via colonoscopy, according to our institution's protocol. The child recovered from CDI with decreased bowel movements within 24 hours. He remained CDI negative and asymptomatic at 8 weeks after the procedure. Antibiotic use and immunocompromised states have been associated with an increased incidence of CDI [6]. CDI causes profuse diarrhea and may progress to colitis or complications including multi-organ failure and sepsis [6]. Recurrence after initial treatment course with antibiotics is noted to be as high as 20% [8]. In this case, Kabuki syndrome predisposed this patient to multiple infections requiring several courses of antibiotics. Each course of antibiotics caused an additional insult to the homeostasis of the gut microbiome, leading to refractory CDI. FMT has been reported to successfully treat patients with recurrent CDI in immunocompetent patients; however, there have been no reported cases of FMT in the immunocompromised pediatric population with Kabuki syndrome and CDI. The success in this case should prompt consideration of FMT in he pediatric population.

Ethics in orthodontics. A proud tradition of ethics in a proud specialty.

Ethics in orthodontics. A proud tradition of ethics in a proud specialty.

To Retreat or Not to Retreat? That is the Question

It is widely accepted that approximately half of all patients with a cancer diagnosis will require radiation therapy but, perhaps, less commonly known is that, of this 50%, approximately one-fifth of patients require a second or subsequent line of radiotherapy at some point along their disease trajectory. This may occur in the setting of persistent or recurrent disease in the previously treated volume; local/distant metastases arising subsequent to radical treatment; or when patients previously treated palliatively require additional radiation treatment. Curative dose and fractionation schemes may have delivered significant doses (near or at tolerance) to organs at risk (OARs) making retreatment difficult from both a technological and a clinical standpoint. Palliative doses, although typically lower, can still result in complexity for retreatment as the daily doses are often higher and structures like the spinal cord often have to be re-irradiated on multiple occasions. Factors like previous dose, interval between subsequent treatments, tumour histology, normal tissue tolerance, life expectancy, and response to prior radiotherapy need to be considered. A chart audit of palliative patients treated between January and December of 2013 was conducted at the Carlo Fidani Regional Cancer Centre (CFRCC) to determine local radiotherapy retreatment patterns. The number of retreatment episodes, first and subsequent radiotherapy dose/fractionation schemes, time interval between initial treatment and subsequent courses, diagnoses, and whether or not the same volume was retreated was determined using data extracted from the Aria™ software. This information was then analyzed to identify trends and to calculate averages and means. 1095 patients were treated with a palliative intent and 1784 courses of palliative treatment were delivered during the time period examined. 142, or 13%, of those patients treated palliatively in 2013 had received previous courses of treatment at our centre. 9% received treatment to the same/overlapping treatment volume. 30% of these patients had a lung diagnosis, 24% were breast, 22% were prostate, and the other 24% was made up of a variety of diagnoses. The average interval between subsequent courses was 11 months with a range of between 1 and 77 months. Dose prescriptions varied greatly between practitioners. A significant proportion of the patients treated with palliative radiation in the CFRCC have a prior history of radiation treatment and many have received more than one course of treatment to the same area resulting in more complex decision making for the radiation oncologist. As anti-neoplastic therapies improve, these numbers may increase further due to the ever more chronic nature of the disease. As a result, techniques like SRS and SBRT may prove more useful in the palliative setting in order to spare normal tissues that have been treated previously.

Risk of anaphylaxis with repeated courses of rasburicase: a Research on Adverse Drug Events and Reports (RADAR) project.

Rasburicase, a recombinant urate oxidase, is used to rapidly metabolize uric acid in patients with hyperuricaemia. Rasburicase is an immunogenic therapeutic protein, which has been shown to elicit antibody response in 64% of healthy volunteers within 1-6weeks after the initial course, with persistent antibodies for over 1year. Drug labelling indicates that anaphylaxis rarely occurs (in <1% of patients) after a single course of therapy with rasburicase, but there are no data available on the incidence of anaphylaxis in patients receiving a subsequent rasburicase course. The objective of this study was to determine the incidence of anaphylaxis after multiple treatment courses of rasburicase. A retrospective chart review was performed on 97 consecutively treated patients who received repeated courses of rasburicase for hyperuricaemia. None of the 97 patients who were reviewed experienced anaphylaxis during the first rasburicase course; however, six patients (6.2%) experienced anaphylaxis during a subsequent rasburicase treatment course (p=0.03). Anaphylaxis after a second course of rasburicase appears to occur more frequently than described in the US Food and Drug Administration-approved package insert for initial treatment courses. Given the serious nature of anaphylactic events, caution is advised when administering repeated courses of rasburicase.

Repeated treatment with bone marrow cell secretory products maintains long-term renoprotection in experimental chronic kidney disease: a placebo-controlled trial.

BackgroundBone marrow-derived early outgrowth cells (EOCs) secrete soluble factors that exert potent renoprotective effects, such that infusion of their conditioned medium recapitulates the affects of the cells themselves.ObjectivesThe objective of this study is to test whether the protective effect of conditioned medium infusion wanes with time and whether tachyphylaxis occurs with repeated administration.DesignThis is a placebo-controlled animal study.SettingThe study was conducted at St. Michael’s Hospital, Toronto, Ontario, Canada.SubjectsFischer 344 (F344) rats were used in this study.MeasurementsThe following were measured: (1) urinary protein:creatinine ratio, (2) glomerular filtration rate, (3) systolic blood pressure, (4) body weight, (5) glomerular endothelial cell density, and (6) glomerular and tubulointerstitial type IV collagen deposition.MethodsSubtotally nephrectomized F344 rats, a model of progressive chronic kidney disease, were randomized 4 weeks post-surgery to receive thrice-weekly intravenous injections of concentrated EOC-conditioned medium (EOC CM) or unconditioned medium (UCM) over 2 weeks. Three animal groups were studied, according to whether they were administered conditioned medium: once (Initial Therapy Only group), twice (Repeat Therapy group), or not at all (No Therapy group).ResultsFollowing initial therapy, EOC CM-treated animals excreted less urinary protein, a marker of renal injury, than their UCM-treated counterparts. At 10 weeks post-subtotal nephrectomy, however, mean urinary protein excretion in conditioned medium-treated animals was fourfold greater than at the completion of the initial treatment course. At this time point, conditioned medium-treated animals were randomized to receive a second course of either conditioned medium (Repeat Therapy group) or unconditioned medium (Initial Therapy Only group). At study end (14 weeks post-subtotal nephrectomy), Repeat Therapy animals demonstrated higher glomerular filtration rate, less proteinuria, preserved renal microvasculature, and diminished fibrosis when compared with the No Therapy group. Initial Therapy Only animals exhibited an intermediate effect.LimitationsTesting the effect of EOC-conditioned medium in a single model of chronic kidney disease (CKD) has limitations.ConclusionsThese findings suggest that early outgrowth cell-derived factors, while renoprotective, have a limited duration of action. Repeated administration of these factors, however, is able to extend the duration of efficacy and attenuate the progression of experimental chronic kidney disease.