Comprehensive identification of pathogenic microbes and antimicrobial resistance genes in food products using nanopore sequencing-based metagenomics.

Foodborne pathogens, particularly antimicrobial-resistant (AMR) bacteria, remain a significant threat to global health. Given the limitations of conventional culture-based approaches, which are limited in scope and time-consuming, metagenomic sequencing of food products emerges as a promising solution. This method provides a fast and comprehensive way to detect the presence of pathogenic microbes and antimicrobial resistance genes (ARGs). Notably, nanopore long-read sequencing provides more accurate bacterial taxonomic classification in comparison to short-read sequencing. Here, we revealed the impact of food types and attributes (origin, retail place, and food processing methods) on microbial communities and the AMR profile using nanopore metagenomic sequencing. We analyzed a total of 260 food products, including raw meat, sashimi, and ready-to-eat (RTE) vegetables. Clostridium botulinum, Acinetobacter baumannii, and Vibrio parahaemolyticus were identified as the top three foodborne pathogens in raw meat and sashimi. Importantly, even with low pathogen abundance, higher percentages of samples containing carbapenem and cephalosporin resistance genes were identified in chicken and RTE vegetables, respectively. In parallel, our results demonstrated that fresh, peeled, and minced foods exhibited higher levels of pathogenic bacteria. In conclusion, this comprehensive study offers invaluable data that can contribute to food safety assessments and serve as a basis for quality indicators.

Probable airborne transmission of Burkholderia pseudomallei causing an urban outbreak of melioidosis during typhoon season in Hong Kong, China.

Between January 2015 and October 2022, 38 patients with culture-confirmed melioidosis were identified in the Kowloon West (KW) Region, Hong Kong. Notably, 30 of them were clustered in the Sham Shui Po (SSP) district, which covers an estimated area of 2.5 km2. Between August and October 2022, 18 patients were identified in this district after heavy rainfall and typhoons. The sudden upsurge in cases prompted an environmental investigation, which involved collecting 20 air samples and 72 soil samples from residential areas near the patients. A viable isolate of Burkholderia pseudomallei was obtained from an air sample collected at a building site five days after a typhoon. B. pseudomallei DNA was also detected in 21 soil samples collected from the building site and adjacent gardening areas using full-length 16S rRNA gene sequencing, suggesting that B. psuedomallei is widely distributed in the soil environment surrounding the district. Core genome-multilocus sequence typing showed that the air sample isolate was phylogenetically clustered with the outbreak isolates in KW Region. Multispectral satellite imagery revealed a continuous reduction in vegetation region in SSP district by 162,255 m2 from 2016 to 2022, supporting the hypothesis of inhalation of aerosols from the contaminated soil as the transmission route of melioidosis during extreme weather events. This is because the bacteria in unvegetated soil are more easily spread by winds. In consistent with inhalational melioidosis, 24 (63.2%) patients had pneumonia. Clinicians should be aware of melioidosis during typhoon season and initiate appropriate investigation and treatment for patients with compatible symptoms.

The Burden of Health-Related Out-of-Pocket Cancer Costs in Canada: A Case-Control Study Using Linked Data.

BACKGROUND: The burden of out-of-pocket costs among cancer patients/survivors in Canada is not well understood. The objective of this study was to examine the health-related out-of-pocket cost burden experienced by households with a cancer patient/survivor compared to those without, examine the components of health-related costs and determine who experiences a greater burden. DATA AND METHODS: This study used a data linkage between the Survey of Household Spending and the Canadian Cancer Registry to identify households with a cancer patient/survivor (cases) and those without (controls). The out-of-pocket burden (out-of-pocket costs measured relative to household income) and mean costs were described and regression analyses examined the characteristics associated with the household out-of-pocket burden and annual out-of-pocket costs. RESULTS: The health-related out-of-pocket cost burden and annual costs measured in households with a cancer patient/survivor were 3.08% (95% CI: 2.55-3.62%) and CAD 1600 (95% CI: 1456-1759), respectively, compared to a burden of 2.84% (95% CI: 2.31-3.38) and annual costs of CAD 1511 (95% CI: 1377-1659) measured in control households, respectively. Households with a colorectal cancer patient/survivor had a significantly higher out-of-pocket burden compared to controls (mean difference: 1.0%, 95% CI: 0.18, 0.46). Among both cases and controls, the lowest income quintile households experienced the highest health-related out-of-pocket cost burden. INTERPRETATION: Within a universal health care system, it is still relevant to monitor health-related out-of-pocket spending that is not covered by existing insurance mechanisms; however, this is not routinely assessed in Canada. We demonstrate the feasibility of measuring such costs in households with a cancer patient/survivor using routinely collected data. While the burden and annual health-related out-of-pocket costs of households with a cancer patient/survivor were not significantly higher than control households in this study, the routine measurement of out-of-pocket costs in Canada could be systemized, providing a novel, system-level, equity-informed performance indicator, which is relevant for monitoring inequities in the burden of out-of-pocket costs.

Deep brain stimulation in a young child with GNAO1 mutation - Feasible and helpful.

Background: GNAO1 is an emerging disorder characterized with hypotonia, developmental delay, epilepsy, and movement disorder, which can be potentially life threatening during acute exacerbation. In the USA, deep brain stimulation (DBS) has been licensed for treating children with chronic, treatment-resistant primary dystonia, who are 7 years old or older. Case Description: A 4-year-old girl diagnosed to have GNAO1-related dyskinesia and severe global developmental delay. She had severe dyskinesia precipitated by intercurrent infection, requiring prolonged intensive care for heavy sedation and related complications. Her dyskinesia improved dramatically after DBS implantation. Technical difficulties and precautions of DBS in preschool children were discussed. Conclusion: DBS should be considered early in the treatment of drug-resistant movement disorders in young children with GNAO1, especially after dyskinetic crisis, as they tend to recur. Presurgical counseling to parents and close monitoring of complications is also important in the process.

Guillain-Barré syndrome in children - High occurrence of Miller Fisher syndrome in East Asian region.

BACKGROUND: Guillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed. METHODS: Paediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System. The collected data from medical health records were reviewed by paediatric neurologist from each department. Estimated incidence of paediatric GBS was calculated. We also compared our findings with other paediatric GBS studies in Asia. RESULTS: 63 subjects of paediatric GBS were identified, giving an estimated annual incidence of 0.62 per 100,000 population. Half of the subjects had acute inflammatory demyelinating polyneuropathy (AIDP) (n = 31; 49.2%), one quarter had Miller Fisher Syndrome (MFS) (n = 16; 25.4%), one-fifth had axonal types of GBS (n = 12; 19.0%), and four were unclassified. Paediatric subjects with axonal subtypes of GBS compared to the other 2 subtypes, had significantly higher intensive care unit (ICU) admission rates (p = 0.001) and longest length of stay (p = 0.009). With immunomodulating therapy, complete recovery was highest in those with MFS (100%), followed by AIDP (87.1%) and axonal GBS (75%). Our study also confirms a higher MFS rate for paediatric GBS in East Asia region and our study has the highest MFS rate (25.4%). CONCLUSION: Our population-based 10-year paediatric GBS study provides updated evidence on estimated incidence, healthcare burden and motor outcome of each subtype of paediatric GBS and confirmed a higher occurrence of paediatric MFS in East Asia.

Opportunistic salpingectomy between 2011 and 2016: a descriptive analysis.

BACKGROUND: Opportunistic salpingectomy (OS) is the removal of fallopian tubes during hysterectomy for benign indications or instead of tubal ligation, for the purpose of preventing ovarian cancer. We determined rates of OS at the time of hysterectomy and tubal sterilization and examined how they changed over the study period. METHODS: Using data from the Canadian Institute for Health Information's Discharge Abstract Database and National Ambulatory Care Reporting System for all Canadian provinces and territories (except Quebec) between the fiscal years 2011 and 2016, we conducted a descriptive analysis of all patients aged 15 years or older who underwent hysterectomy or tubal sterilization. We excluded those with diagnostic codes for any gynecologic cancer and those who underwent unilateral salpingectomy. We examined the proportion who had OS during their hysterectomy and compared the proportion of tubal sterilizations that were OS with the proportion that were tubal ligations. RESULTS: A total of 318 528 participants were included in the study (mean age 42.5 yr). The proportion of hysterectomies that included OS increased from 15.4% in 2011 to 35.5% by 2016. With respect to tubal sterilization, the rate of OS increased from 6.5% of all tubal sterilizations in 2011 to 22.0% in 2016. There was considerable variation across jurisdictions in 2016, with British Columbia having the highest rates (53.2% of all hysterectomies and 74.0% of tubal sterilizations involved OS). INTERPRETATION: The rates of OS increased between 2011 and 2016, but there was considerable variation across the included jurisdictions. Our study indicates room for rates of OS to increase across many of the included jurisdictions.

Risk factors and prognostic implications of diagnosis of cancer within 30 days after an emergency hospital admission (emergency presentation): an International Cancer Benchmarking Partnership (ICBP) population-based study.

BACKGROUND: Greater understanding of international cancer survival differences is needed. We aimed to identify predictors and consequences of cancer diagnosis through emergency presentation in different international jurisdictions in six high-income countries. METHODS: Using a federated analysis model, in this cross-sectional population-based study, we analysed cancer registration and linked hospital admissions data from 14 jurisdictions in six countries (Australia, Canada, Denmark, New Zealand, Norway, and the UK), including patients with primary diagnosis of invasive oesophageal, stomach, colon, rectal, liver, pancreatic, lung, or ovarian cancer during study periods from Jan 1, 2012, to Dec 31, 2017. Data were collected on cancer site, age group, sex, year of diagnosis, and stage at diagnosis. Emergency presentation was defined as diagnosis of cancer within 30 days after an emergency hospital admission. Using logistic regression, we examined variables associated with emergency presentation and associations between emergency presentation and short-term mortality. We meta-analysed estimates across jurisdictions and explored jurisdiction-level associations between cancer survival and the percentage of patients diagnosed as emergencies. FINDINGS: In 857 068 patients across 14 jurisdictions, considering all of the eight cancer sites together, the percentage of diagnoses through emergency presentation ranged from 24·0% (9165 of 38 212 patients) to 42·5% (12 238 of 28 794 patients). There was consistently large variation in the percentage of emergency presentations by cancer site across jurisdictions. Pancreatic cancer diagnoses had the highest percentage of emergency presentations on average overall (46·1% [30 972 of 67 173 patients]), with the jurisdictional range being 34·1% (1083 of 3172 patients) to 60·4% (1317 of 2182 patients). Rectal cancer had the lowest percentage of emergency presentations on average overall (12·1% [10 051 of 83 325 patients]), with a jurisdictional range of 9·1% (403 of 4438 patients) to 19·8% (643 of 3247 patients). Across the jurisdictions, older age (ie, 75-84 years and 85 years or older, compared with younger patients) and advanced stage at diagnosis compared with non-advanced stage were consistently associated with increased emergency presentation risk, with the percentage of emergency presentations being highest in the oldest age group (85 years or older) for 110 (98%) of 112 jurisdiction-cancer site strata, and in the most advanced (distant spread) stage category for 98 (97%) of 101 jurisdiction-cancer site strata with available information. Across the jurisdictions, and despite heterogeneity in association size (I2=93%), emergency presenters consistently had substantially greater risk of 12-month mortality than non-emergency presenters (odds ratio >1·9 for 112 [100%] of 112 jurisdiction-cancer site strata, with the minimum lower bound of the related 95% CIs being 1·26). There were negative associations between jurisdiction-level percentage of emergency presentations and jurisdiction-level 1-year survival for colon, stomach, lung, liver, pancreatic, and ovarian cancer, with a 10% increase in percentage of emergency presentations in a jurisdiction being associated with a decrease in 1-year net survival of between 2·5% (95% CI 0·28-4·7) and 7·0% (1·2-13·0). INTERPRETATION: Internationally, notable proportions of patients with cancer are diagnosed through emergency presentation. Specific types of cancer, older age, and advanced stage at diagnosis are consistently associated with an increased risk of emergency presentation, which strongly predicts worse prognosis and probably contributes to international differences in cancer survival. Monitoring emergency presentations, and identifying and acting on contributing behavioural and health-care factors, is a global priority for cancer control. FUNDING: Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; the Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Breast Density and Risk of Interval Cancers: The Effect of Annual Versus Biennial Screening Mammography Policies in Canada.

Regular screening mammography reduces breast cancer mortality. However, in women with dense breasts, the performance of screening mammography is reduced, which is reflected in higher interval cancer rates (ICR). In Canada, population-based screening mammography programs generally screen women biennially; however, some provinces and territories offer annual mammography for women with dense breast tissue routinely and/or on recommendation of the radiologist. This study compared the ICRs in those breast screening programs with a policy of annual vs. those with biennial screening for women with dense breasts. Among 148,575 women with dense breasts screened between 2008 to 2010, there were 288 invasive interval breast cancers; screening programs with policies offering annual screening for women with dense breasts had fewer interval cancers 63/70,814 (ICR 0.89/1000, 95% CI: 0.67-1.11) compared with those with policies of usual biennial screening 225/77,761 (ICR 1.45 /1000 (annualized), 95% CI: 1.19-1.72) i.e. 63% higher (p = 0.0016). In screening programs where radiologists' screening recommendations were able to be analyzed, a total of 76,103 women were screened, with 87 interval cancers; the ICR was lower for recommended annual (65/69,650, ICR 0.93/1000, 95% CI: 0.71, 1.16) versus recommended biennial screening (22/6,453, ICR 1.70/1000 (annualized), 95%CI: 0.70, 2.71)(p = 0.0605). Screening program policies of annual as compared with biennial screening in women with dense breasts had the greatest impact on reducing interval cancer rates. We review our results in the context of current dense breast notification in Canada.

Exome sequencing in paediatric patients with movement disorders.

BACKGROUND: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. RESULTS: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. CONCLUSIONS: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management. The study highlights the potential of implementing precision medicine in the patients.

Delineation of molecular findings by whole-exome sequencing for suspected cases of paediatric-onset mitochondrial diseases in the Southern Chinese population.

BACKGROUND: Mitochondrial diseases (MDs) are a group of clinically and genetically heterogeneous disorders characterized by defects in oxidative phosphorylation. Since clinical phenotypes of MDs may be non-specific, genetic diagnosis is crucial for guiding disease management. In the current study, whole-exome sequencing (WES) was performed for our paediatric-onset MD cohort of a Southern Chinese origin, with the aim of identifying key disease-causing variants in the Chinese patients with MDs. METHODS: We recruited Chinese patients who had paediatric-onset MDs and a minimum mitochondrial disease criteria (MDC) score of 3. Patients with positive target gene or mitochondrial DNA sequencing results were excluded. WES was performed, variants with population frequency ≤ 1% were analysed for pathogenicity on the basis of the American College of Medical Genetics and Genomics guidelines. RESULTS: Sixty-six patients with pre-biopsy MDC scores of 3-8 were recruited. The overall diagnostic yield was 35% (23/66). Eleven patients (17%) were found to have mutations in MD-related genes, with COQ4 having the highest mutation rate owing to the Chinese-specific founder mutation (4/66, 6%). Twelve patients (12/66, 18%) had mutations in non-MD-related genes: ATP1A3 (n = 3, two were siblings), ALDH5A1, ARX, FA2H, KCNT1, LDHD, NEFL, NKX2-2, TBCK, and WAC. CONCLUSIONS: We confirmed that the COQ4:c.370G>A, p.(Gly124Ser) variant, was a founder mutation among the Southern Chinese population. Screening for this mutation should therefore be considered while diagnosing Chinese patients suspected to have MDs. Furthermore, WES has proven to be useful in detecting variants in patients suspected to have MDs because it helps to obtain an unbiased and precise genetic diagnosis for these diseases, which are genetically heterogeneous.

The KLHL40 c.1516A>C is a Chinese-specific founder mutation causing nemaline myopathy 8: Report of six patients with pre- and postnatal phenotypes.

BACKGROUND: Autosomal recessive or compound heterozygous mutations in KLHL40 cause nemaline myopathy 8, which is one of the most severe forms of nemaline myopathy. The KLHL40 c.1516A>C variant has recently been reported as a founder mutation in southern Chinese. METHODS: We report six cases of nemaline myopathy 8 which involves the c.1516A>C variant, from five unrelated families of non-consanguineous southern Chinese. The pre- and postnatal phenotypes of these cases were reviewed with emphasis on prenatal clinical features. Genetic testing for the founder mutation was performed on three patients with homozygous mutations. RESULTS: Common prenatal features included reduced fetal movement, polyhydramnios, breech presentation, and clubfeet. Two pregnancies were terminated. Four live-born patients had postnatal features typical of nemaline myopathy 8. The length of survival ranged from 49 days to 17 months, with respiratory failure and infections being the principal causes of death. Haplotype analysis in three patients with homozygous mutation showed a shared haplotype block of 1.1727 cM spanning over the c.1516A>C variant, suggesting it is a southern Chinese-specific founder mutation. CONCLUSION: Analysis of the KLHL40 c.1516A>C variant should be considered in prenatal diagnosis of Chinese pregnant patients with suspected congenital neuromuscular disorders or with significant family history of congenital myopathies.

Anti-N-methyl-d-aspartate receptor encephalitis in children: Incidence and experience in Hong Kong.

AIM: The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl-d-aspartate receptor encephalitis in children from Hong Kong. METHOD: A retrospective study was carried out on paediatric patients diagnosed with anti-NMDAR encephalitis in Hong Kong from January 2009 to December 2015. RESULTS: Fifteen patients (67% female, 93% Chinese) were identified over seven years and the estimated incidence in Hong Kong was 2.2/million children per year (95% CI 1.2-3.6). The median age of presentation was 12 years (range 1-17 years). The most common symptom groups observed were abnormal psychiatric behavior or cognitive dysfunction (14/15, 93%) and seizures (14/15, 93%), followed by speech dysfunction (13/15, 87%), movement disorders (12/15, 80%), decreased level of consciousness (10/15, 67%) and autonomic dysfunction or central hypoventilation (5/15, 33%). The median number of symptom groups developed in each patient was 5 (range 3-6). All patients were treated with intravenous immunoglobulin and/or steroids. Three patients (20%) with more severe presentation required additional plasmapheresis and rituximab. Outcome was assessable in 14 patients. Among those eleven patients who had only received intravenous immunoglobulin and/or steroids, nine patients (82%) achieved full recovery. One patient (9%) had residual behavioral problem, while another one (9%) who developed anti-NMDAR encephalitis after herpes simplex virus encephalitis was complicated with dyskinetic cerebral palsy and epilepsy. Among those three patients who required plasmapheresis and rituximab, one (33%) had full recovery and two (66%) had substantial recovery. The median duration of follow up was 20.5 months (range 3-84 months). CONCLUSION: Anti-NMDAR encephalitis is an acquired, severe, but potentially treatable disorder. Ethnicity may play a role in the incidence of anti-NMDAR encephalitis and we have provided a local incidence with the majority of patients being Chinese. The diagnosis of anti-NMDAR encephalitis should be considered in children presenting with a constellation of symptoms including psychiatric and neurological manifestations. Patients may respond to first line immunotherapy. For those who do not, second line therapy is indicated in order to achieve a better outcome.

Predictors of radiotherapy induced bone injury (RIBI) after stereotactic lung radiotherapy.

BACKGROUND: The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy. METHODS: Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created. RESULTS: 46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 - 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 - 40 m). The mean maximum point dose in non-fractured ribs (n=1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n=41) 48.5 Gy ± 24.3 Gy (p<0.0001). On univariate analysis, age, dose to 0.5 cc of the ribs (D0.5), and the volume of the rib receiving at least 25 Gy (V25), were significantly associated with RIBI. As D0.5 and V25 were cross-correlated (Spearman correlation coefficient: 0.57, p<0.001), we selected D0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 - 1.21, p=0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 - 11.68, p=0.003), and rib D0.5 (odds ratio: 1.0009, 95% CI: 1.0007 - 1.001, p<0.0001) were significantly associated with rib fracture.Using D0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D0.5 of 60 Gy. CONCLUSIONS: Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.

Stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC): is FDG-PET a predictor of outcome?

BACKGROUND AND PURPOSE: Distant metastases are the dominant mode of failure after stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC). The primary study objective was to evaluate if the maximum standardized uptake value (SUV(max)) on pre-treatment FDG-PET/CT predicted clinical outcomes. Secondary objectives were to correlate 3-month post-SBRT SUV(max) and change in SUV(max) with outcomes. MATERIALS AND METHODS: Consecutive patients with medically inoperable early-stage NSCLC and an FDG-PET/CT scan before (n=82) and 3 months after (n=62) SBRT. RESULTS: Median follow up was 2 years. On univariate analysis baseline SUV(max) predicted for distant failure (p=0.0096), relapse free survival (RFS) (p=0.037) and local failure (p=0.044). On multivariate analysis baseline SUV(max) predicted for RFS (p=0.037). Baseline SUV(max) of above 5 was the most statistically significant cut off point for predicting distant failure (p=0.0002). Baseline SUV(max) ≥4.75 (median) was correlated with a higher risk of distant failure (p=0.012) and poorer RFS (p=0.04). Patients with a post-SBRT SUV(max) ≥2 and a reduction of <2.55 had a significantly higher rate of distant failure. CONCLUSIONS: Pre-SBRT SUV(max) on FDG-PET/CT correlated most strongly with distant failure. A cut off of ≥5 was the most significant. Post-SBRT SUV(max) ≥2 and a reduction of <2.55 were associated with a higher risk of distant failure.

Effect of topical anesthetics on needle insertion pain during botulinum toxin type A injections for limb spasticity.

OBJECTIVE: To compare pain perception using 3 anesthetics (eutectic mixture of local anesthetics [EMLA], vapocoolant spray, and ice) compared with a control (no anesthetic) during botulinum toxin type A (BTX-A) injections for lower limb spasticity. DESIGN: A placebo-controlled, single-blinded study where each study patient served as their own control. SETTING: Spasticity clinic. PARTICIPANTS: Subjects (N=30) with ankle spasticity who visited the clinic for BTX-A injections in the gastrocnemius muscle were consecutively sampled. INTERVENTION: The gastrocnemius muscle was divided into 4 quadrants and 1 of the 3 different anesthetic agents was applied to each quadrant with 1 quadrant using no anesthetic, control. MAIN OUTCOME MEASURES: Numerical Rating Scale (NRS) and the Wong-Baker FACES scale. RESULTS: Pain perception using the NRS and FACES scale was significantly lower using ice and EMLA compared with control and spray conditions (P<.05). Pain perception using EMLA and ice was similar. These results indicate that patients experience minimal to moderate pain during BTX-A injections. CONCLUSIONS: Pain relief offered by EMLA and ice was comparable, suggesting that ice is a more convenient option because of brief application time (compared with EMLA). Spray may have made the patients more sensitive to pain and alternative approaches for using vapocoolant should be considered.

Case-based online modules to teach graduate-level nursing students about complementary and alternative medical therapies.

We integrated complementary and alternative medicine (CAM)-related content into selected core courses in our master's-level curriculum. To facilitate students' application of the content, we developed evidence-based online case studies and evaluated their effectiveness by comparing students' pretest and posttest scores on multiple-choice quizzes. Findings suggest that evidence-based online case studies are an effective strategy for teaching graduate nursing students about the clinical issues surrounding patients' use of CAM therapies.

Stereotactic body radiotherapy for medically inoperable lung cancer: prospective, single-center study of 108 consecutive patients.

PURPOSE: To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. METHODS AND MATERIALS: Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy in 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. RESULTS: The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. CONCLUSIONS: Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.

Early aging in adult survivors of childhood medulloblastoma: long-term neurocognitive, functional, and physical outcomes.

Treatment for medulloblastoma during childhood impairs neurocognitive function in survivors. While those diagnosed at younger ages are most vulnerable, little is known about the long-term neurocognitive, functional, and physical outcomes in survivors as they approach middle age. In this retrospective cohort study, we assessed 20 adults who were treated with surgery and radiotherapy for medulloblastoma during childhood (median age at assessment, 21.9 years [range, 18-47 years]; median time since diagnosis, 15.5 years [range, 6.5-42.2 years]). Nine patients also underwent chemotherapy. Cross-sectional analyses of current neurocognitive, functional, and physical status were conducted. Data from prior neuropsychological assessments were available for 18 subjects; longitudinal analyses were used to model individual change over time for those subjects. The group was well below average across multiple neurocognitive domains, and 90% had required accommodations at school for learning disorders. Longer time since diagnosis, but not age at diagnosis, was associated with continued decline in working memory, a common sign of aging. Younger age at diagnosis was associated with lower intelligence quotient and academic achievement scores, even many years after treatment had been completed. The most common health complications in survivors were hearing impairment, second cancers, diabetes, hypertension, and endocrine deficiencies. Adult survivors of childhood medulloblastoma exhibit signs of early aging regardless of how young they were at diagnosis. As survival rates for brain tumors continue to improve, these neurocognitive and physical sequelae may become evident in survivors diagnosed at different ages across the lifespan. It will become increasingly important to identify factors that contribute to risk and resilience in this growing population.

Retrospective study of palliative radiotherapy in newly diagnosed head and neck carcinoma.

PURPOSE: To examine the patterns of care, outcomes, and prognostic factors for patients with head-and-neck cancer (HNC) treated with palliative radiotherapy (RT). METHODS AND MATERIALS: An institutional HNC anthology and electronic patient records were used to identify patients with previously untreated HNC of mucosal or salivary gland origin who underwent palliative RT at our institution between July 2003 and June 2008. Overall survival was determined from the start date of RT to either the date of death or the date of last follow-up for living patients. The data were censored if the subject was either lost to follow-up or had not been seen for follow-up at our institution for ≥4 months. RESULTS: We identified 148 eligible patients. The median age was 72 years (range, 19-94). Of the 148 patients, 12 had Stage II-III, 39 Stage IVA, 36 Stage IVB, and 54 Stage IVC; for 7 patients, the stage was unknown. Oropharyngeal primary cancer (40) was the most common primary site. The Eastern Cooperative Oncology Group performance status was 0 in 15, 1 in 69, 2 in 40, 3 in 19, and 4 in 5 patients. The Adult Co-morbidity Evaluation-27 scale was 0 in 33, 1 in 47, 2 in 44, and 3 in 21. The median radiation dose was 50 Gy (range, 2-70), the median fraction number was 20 (range, 1-40), and the median total treatment time (including breaks) was 29 days (range, 1-80). At analysis, 108 patients (73%) had died, 20 (13.5%) were alive, and 20 (13.5%) had been censored. The median follow-up was 4.8 months, and the median survival time was 5.2 months. Information on the treatment response was available for 103 patients (70%). On multivariate analysis, the radiation dose was an independent predictor of both overall survival (hazard ratio 0.97, 95% confidence interval 0.96-0.99, p <.01) and treatment response (odds ratio 1.05, 95% confidence interval 1.01-1.08, p <.01). CONCLUSION: For patients considered unsuitable for curative RT, the radiation dose might be an independent predictive factor for both overall survival and treatment response. Additional research is required to more effectively select those patients who might benefit from more aggressive treatment.

10-year experience with I-125 prostate brachytherapy at the Princess Margaret Hospital: results for 1,100 patients.

PURPOSE: To report outcomes for 1,111 men treated with iodine-125 brachytherapy (BT) at a single institution. METHODS AND MATERIALS: A total of 1,111 men (median age, 63) were treated with iodine-125 prostate BT for low- or intermediate-risk prostate cancer between March 1999 and November 2008. Median prostate-specific antigen (PSA) level was 5.4 ng/ml (range, 0.9-26.1). T stage was T1c in 66% and T2 in 34% of patients. Gleason score was 6 in 90.1% and 7 or 8 in 9.9% of patients. Neoadjuvant hormonal therapy (2-6 months course) was used in 10.1% of patients and combined external radiotherapy (45 Gy) with BT (110 Gy) in 4.1% (n = 46) of patients. Univariate and multivariate Cox proportional hazards were used to determine predictors of failure. RESULTS: Median follow-up was 42 months (range, 6-114), but for biochemical freedom from relapse, a minimum PSA test follow-up of 30 months was required (median 54; n = 776). There were 27 failures, yielding an actuarial 7-year disease-free survival rate of 95.2% (96 at risk beyond 84 months). All failures underwent repeat 12-core transrectal ultrasound -guided biopsies, confirming 8 local failures. On multivariate analysis, Gleason score was the only independent predictor of failure (p = 0.001; hazard ratio, 4.8 (1.9-12.4). Median International Prostate Symptom score from 12 to 108 months ranged between 3 and 9. Of the men reporting baseline potency, 82.8% retained satisfactory erectile function beyond 5 years. CONCLUSION: Iodine-125 prostate BT is a highly effective treatment option for favorable- and intermediate-risk prostate cancer and is associated with maintenance of good urinary and erectile functions.