Central Endocrine Complications Among Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: Children who receive cranial radiation therapy (RT) as a component of treatment for malignancy are often at risk of long-term central endocrine toxicity secondary to radiation to the hypothalamic-pituitary axis (HPA). A comprehensive analysis was performed of central endocrine late effects in survivors of childhood cancer treated with RT as part of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium. METHODS AND MATERIALS: A systematic review of the risk of RT-related central endocrine effects was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 4629 publications were identified, of which 16 met criteria for inclusion in dose modeling analysis, with a total of 570 patients in 19 cohorts. Eighteen cohorts reported outcomes for growth hormone deficiency (GHD), 7 reported outcomes for central hypothyroidism (HT), and 6 reported outcomes for adrenocorticotropic hormone (ACTH) deficiency. RESULTS: Normal tissue complication probability modeling for GHD (18 cohorts, 545 patients) yielded D50 = 24.9 Gy (95% CI, 20.9-28.0) and γ50 = 0.5 (95% CI, 0.27-0.78). The normal tissue complication probability model fit for whole brain irradiation in children with a median age of >5 years indicated a 20% risk of GHD for patients who receive a mean dose of 21 Gy in 2-Gy fractions to the HPA. For HT, among 7 cohorts (250 patients), D50 = 39 Gy (95% CI, 34.1-53.2) and γ50 = 0.81 (95% CI, 0.46-1.35), with a 20% risk of HT in children who receive a mean dose of 22 Gy in 2-Gy fractions to the HPA. For ACTH deficiency (6 cohorts, 230 patients), D50 = 61 Gy (95% CI, 44.7-119.4) and γ50 = 0.76 (95% CI, 0.5-1.19); there is a 20% risk of ACTH deficiency in children who receive a mean dose of 34 Gy in 2-Gy fractions to the HPA. CONCLUSIONS: RT dose to the HPA increases the risk of central endocrine toxicity, including GHD, HT, and ACTH deficiency. In some clinical situations, these toxicities may be difficult to avoid, and counseling of patients and families with respect to anticipated outcomes is important.

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma

Background and purpose To predict treatment-related cardiovascular disease (CVD) and second cancer 30-yea. absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. Material and methods This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016–2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose–response relationships. Results Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4–6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2–23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. Conclusion For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects (AU)

Predicted cardiac and second cancer risks for patients undergoing VMAT for mediastinal Hodgkin lymphoma.

BACKGROUND AND PURPOSE: To predict treatment-related cardiovascular disease (CVD) and second cancer 30-year absolute mortality risks (AMR30) for patients with mediastinal Hodgkin lymphoma in a large multicentre radiation oncology network in Ireland. MATERIAL AND METHODS: This study includes consecutive patients treated for mediastinal lymphoma using chemotherapy and involved site radiotherapy (RT) 2016-2019. Radiation doses to heart, left ventricle, cardiac valves, lungs, oesophagus, carotid arteries and female breasts were calculated. Individual CVD and second cancer AMR30 were predicted using Irish background population rates and dose-response relationships. RESULTS: Forty-four patients with Hodgkin lymphoma were identified, 23 females, median age 28 years. Ninety-eight percent received anthracycline, 80% received 4-6 cycles ABVD. Volumetric modulated arc therapy (VMAT) ± deep inspiration breath hold (DIBH) was delivered, median total prescribed dose 30 Gy. Average mean heart dose 9.8 Gy (range 0.2-23.8 Gy). Excess treatment-related mean AMR30 from CVD was 2.18% (0.79, 0.90, 0.01, 0.13 and 0.35% for coronary disease, heart failure, valvular disease, stroke and other cardiac diseases), 1.07% due to chemotherapy and a further 1.11% from RT. Excess mean AMR30 for second cancers following RT were: lung cancer 2.20%, breast cancer in females 0.34%, and oesophageal cancer 0.28%. CONCLUSION: For patients with mediastinal lymphoma excess mortality risks from CVD and second cancers remain clinically significant despite contemporary chemotherapy and photon-RT. Efforts to reduce the toxicity of combined modality treatment, for example, using DIBH, reduced margins and advanced RT, e.g. proton beam therapy, should be continued to further reduce potentially fatal treatment effects.

Recruiting bereaved family and friends left behind after a suicide loss to participate in research.

BACKGROUND: Although understanding bereavement experiences following a suicide is necessary for development of better interventions to support and provide mental health care services for friends and family members, recruiting suicide loss survivors (friends and family members left behind following a suicide) to participate in research presents challenges. Expanding recruitment to include previously underrepresented male and rural participants can further complicate recruitment. PURPOSE: In this paper, the author describes the methods used for recruiting suicide loss survivors (the friends and family members left behind following loss of a loved one to suicide) to participate in this qualitative research study. CONCLUSION: Facebook, Twitter, and Instagram were useful social media platforms used to recruit 28 participants for telephone interviews. Participants in this study reported an interest in research in hopes they could help others with suicide bereavement.

Experiences With Suicide Loss: A Qualitative Study.

To better understand suicide loss survivors' experiences and barriers to accessing support and mental health care, 28 (21 women and 7 men) suicide loss survivors were interviewed. Using qualitative analysis of 28 in-depth, semi-structured phone interviews data, three categories emerged: Life before Suicide, Life after Suicide, and Meaning of Life. This deeper understanding of suicide loss survivors along with inclusion of experiences of male and rural participants' suicide loss, fill previously identified research gaps. Our findings suggest importance in providing emotional support and mental health resources to those with suicide intent or experiences with suicide loss. Most importantly, the recognition of suicide loss survivors extends beyond the immediate family and includes cousins, friends, and work associates. Recognition of extended suicide loss survivors' bereavement will provide additional opportunities for healthcare providers to effectively intervene with this vulnerable population.

Ambulance waiting and associated work flow improvement strategies: a pilot study to improve door-in-door-out time for thrombectomy patients in a primary stroke center.

BACKGROUND: Rapid access to thrombectomy for patients with large vessel occlusion (LVO) acute ischemic stroke (AIS) is critical for improving outcome. A major challenge for the 'drip and ship' model is reducing the door-in-door-out time (DIDO). We propose a new protocol with the aim of reducing DIDO, without adversely affecting emergency service usage time. METHODS: Consecutive patients with suspected LVO AIS admitted to a Primary Stroke Center (PSC) from October 2018 to January 2021 were included. On arrival, the ambulance crew remained with the patient. Following immediate clinical and radiological evaluation, patients were transferred to the Comprehensive Stroke Center (CSC) by the same waiting crew. Key time metrics were collected and compared with historical data prior to the new protocol. RESULTS: 27 patients had an LVO amenable for mechanical thrombectomy during the time period. There was a significant reduction in the DIDO times compared with the historical group (median 45 min vs 96 min; p<0.0001). There was no significant difference in ambulance usage time between the two time periods (median 53 min vs 45 min; p=0.530). There was an increase in ambulance usage time in FAST-positive patients not for transfer in the pilot group compared with FAST-positive patients not for transfer in the historical group (27 min vs 58 min; p<0.001). In addition, door-to-needle times (24 min vs 40 min; p=0.018) and door-to-CT times (11 min vs 25 min; p<0.0001) improved between the two groups. CONCLUSION: Our data show a significant reduction in the DIDO for patients transferred for thrombectomy, with no adverse effects on ambulance usage time.

Infection control, occupational and public health measures including mRNA-based vaccination against SARS-CoV-2 infections to protect healthcare workers from variants of concern: A 14-month observational study using surveillance data.

BACKGROUND: We evaluated measures to protect healthcare workers (HCWs) in Vancouver, Canada, where variants of concern (VOC) went from <1% VOC in February 2021 to >92% in mid-May. Canada has amongst the longest periods between vaccine doses worldwide, despite Vancouver having the highest P.1 variant rate outside Brazil. METHODS: With surveillance data since the pandemic began, we tracked laboratory-confirmed SARS-CoV-2 infections, positivity rates, and vaccine uptake in all 25,558 HCWs in Vancouver Coastal Health, by occupation and subsector, and compared to the general population. Cox regression modelling adjusted for age and calendar-time calculated vaccine effectiveness (VE) against SARS-CoV-2 in fully vaccinated (≥ 7 days post-second dose), partially vaccinated infection (after 14 days) and unvaccinated HCWs; we also compared with unvaccinated community members of the same age-range. FINDINGS: Only 3.3% of our HCWs became infected, mirroring community rates, with peak positivity of 9.1%, compared to 11.8% in the community. As vaccine coverage increased, SARS-CoV-2 infections declined significantly in HCWs, despite a surge with predominantly VOC; unvaccinated HCWs had an infection rate of 1.3/10,000 person-days compared to 0.89 for HCWs post first dose, and 0.30 for fully vaccinated HCWs. VE compared to unvaccinated HCWs was 37.2% (95% CI: 16.6-52.7%) 14 days post-first dose, 79.2% (CI: 64.6-87.8%) 7 days post-second dose; one dose provided significant protection against infection until at least day 42. Compared with community infection rates, VE after one dose was 54.7% (CI: 44.8-62.9%); and 84.8% (CI: 75.2-90.7%) when fully vaccinated. INTERPRETATION: Rigorous droplet-contact precautions with N95s for aerosol-generating procedures are effective in preventing occupational infection in HCWs, with one dose of mRNA vaccination further reducing infection risk despite VOC and transmissibility concerns. Delaying second doses to allow more widespread vaccination against severe disease, with strict public health, occupational health and infection control measures, has been effective in protecting the healthcare workforce.

Deep inspiration breath hold versus free breathing technique in mediastinal radiotherapy for lymphoma.

OBJECTIVE: Radiotherapy plays an important role in the management of lymphoma and many patients with lymphoma are cured with treatment. Risk of secondary malignancy and long-term cardiac and pulmonary toxicity from mediastinal radiotherapy exists. Delivery of radiotherapy using a deep inspiration breath-hold (DIBH) technique increases lung volume and has the potential to reduce dose to heart and lungs. We undertook a prospective study to assess the dosimetric differences in DIBH and free breathing (FB) plans in patients requiring mediastinal radiotherapy in clinical practice. METHODS: We performed both FB and DIBH planning scans on 35 consecutive patients with mediastinal lymphoma needing radiotherapy. Contours and plans were generated for both data sets and dosimetric data were compared. All patients were planned using volumetric modulated arc therapy (VMAT). Data were compared for FB and DIBH plans with each patient acting as their own control using the related-samples Wilcoxon signed rank test. RESULTS: DIBH significantly reduced lung doses (mean 10.6 vs 11.4Gy, p < 0.0005; V20 16.8 vs 18.3%, p = 0.001) and spinal cord maximum dose (20.6 vs 22.8Gy, p = 0.001). DIBH increased breast V4 (38.5% vs 31.8%, p = 0.006) and mean right breast dose (4.2 vs 3.6Gy, p = 0.010). There was no significant difference in heart doses when the entire study cohort was considered, however, mean heart dose tended to be lower with DIBH for upper mediastinal (UM) tumours (4.3 vs 4.9Gy, p = 0.05). CONCLUSION: Our study describes the potential benefit of DIBH in a population reflective of clinical practice. DIBH can decrease radiation dose to lungs, heart and spinal cord, however, may increase dose to breasts. DIBH is not always superior to FB, and the clinical significance of differences in dose to organs at risk in addition to the time required to treat patients with DIBH must be considered when deciding the most appropriate radiotherapy technique for each patient. ADVANCES IN KNOWLEDGE: To our knowledge, this is the largest study comparing DIBH and FB planning for patients with lymphoma receiving mediastinal radiotherapy in clinical practice. It demonstrates the impact of an increasingly common radiotherapy technique on dose to organs at risk and the subsequent potential for long-term radiotherapy side-effects.

Endoscopic extended transsphenoidal surgery for newly diagnosed paediatric craniopharyngiomas.

PURPOSE: Endoscopic extended transsphenoidal surgery (EETSS) has gained popularity for treatment of craniopharyngiomas. The aim of this study is to assess the outcome of endoscopic extended transsphenoidal surgery (EETSS) for newly diagnosed paediatric craniopharyngiomas. METHODS: Patient details were obtained from a prospective database of all endoscopic transnasal operations performed by a single surgeon. Outcomes including visual function, pituitary function, body mass index (BMI), postoperative neurological deficit, extent of resection and recurrence on follow-up were obtained. Obesity was defined as BMI percentile of equal to or greater than 95%. RESULTS: Between January 2011 and January 2020, 15 of 16 children (5-18 years old) with newly diagnosed craniopharyngiomas underwent EETSS. Four patients had a conchal-type sphenoid sinus. Gross total resection (GTR) was achieved in 4 patients and near total resection (NTR) in 5 patients. The remaining 6 had subtotal resection (STR). Postoperative radiotherapy was used in 6 patients (4 with STR, 2 with NTR). There were no postoperative deaths, strokes or CSF leaks. Normalisation of visual fields (VF) occurred in 9/13 patients with preoperative VF defects. One patient developed a new visual field defect. During a median follow-up period of 74 (8-104) months, 2 patients have required further surgery for tumour progression following initial STR, where a tumour remnant was left in situ to preserve the pituitary stalk. 6/11 patients developed new anterior pituitary dysfunction as a result of surgery and 9/12 developed new diabetes insipidus (DI). At the time of last follow-up, 14/15 children had anterior panhypopituitarism, 13/15 had DI and 1 patient developed new onset obesity. Two patients, who were obese preoperatively, were no longer obese at last follow-up. CONCLUSIONS: EETSS can be performed as the first option in the majority of children with newly diagnosed craniopharyngioma, despite factors such as small nose, non-pneumatised sphenoid sinus, small sella or purely suprasellar tumour location. Preservation of the pituitary stalk at the expense of leaving residual tumour may not be in the best interests of the patient.

Evaluation of a multisectoral intervention to mitigate the risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission in long-term care facilities.

OBJECTIVE: A Canadian health authority implemented a multisectoral intervention designed to control severe acute respiratory coronavirus virus 2 (SARS-CoV-2) transmission during long-term care facility (LTCF) outbreaks. The primary objective was to evaluate the effectiveness of the intervention 14 days after implementation. DESIGN: Quasi-experimental, segmented regression analysis. INTERVENTION: A series of outbreak measures classified into 4 categories: case and contact management, proactive case detection, rigorous infection control practices and resource prioritization and stewardship. METHODS: A mixed-effects segmented Poisson regression model was fitted to the incidence rate of coronavirus disease 2019 (COVID-19), calculated every 2 days, within each facility and case type (staff vs residents). For each facility, the outbreak time period was segmented into an early outbreak period (within 14 days of the intervention) and postintervention period (beyond 14 days following the intervention). Model outputs quantified COVID-19 incidence trend and rate changes between these 2 periods. A secondary model was constructed to identify effect modification by case type. RESULTS: The significant upward trend in COVID-19 incidence rate during the early outbreak period (rate ratio [RR], 1.07; 95% confidence interval [CI], 1.03-1.11; P < .001) reversed during the postintervention period (RR, 0.73; 95% CI, 0.67-0.80; P < .001). The average trend did not differ by case type during the early outbreak period (P > .05) or the postintervention period (P > .05). However, staff had a 70% larger decrease in the average rate of COVID-19 during the postintervention period than residents (RR, 0.30; 95% CI, 0.10-0.88; P < .05). CONCLUSIONS: Our study provides evidence for the effectiveness of this intervention to reduce the transmission of COVID-19 in LTCFs. This intervention can be adapted and utilized by other jurisdictions to protect the vulnerable individuals in LTCFs.

Serological survey following SARS-COV-2 outbreaks at long-term care facilities in metro Vancouver, British Columbia: Implications for outbreak management and infection control policies.

A cross-sectional serological survey was carried out in two long-term care facilities that experienced COVID-19 outbreaks in order to evaluate current clinical COVID-19 case definitions. Among individuals with a negative or no previous COVID-19 diagnostic test, myalgias, headache, and loss of appetite were associated with serological reactivity. The US CDC probable case definition was also associated with seropositivity. Public health and infection control practitioners should consider these findings for case exclusion in outbreak settings.

Environmental detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from medical equipment in long-term care facilities undergoing COVID-19 outbreaks.

Environmental sampling was conducted at long-term care facilities to determine the extent of surface contamination with severe acute respiratory syndrome coronavirus 2 virus. Medical equipment used throughout the facility was determined to be contaminated.

Routine HIV testing in acute care hospitals: Changing practice to curb a local HIV epidemic in Vancouver, BC.

Early treatment of HIV infection increases life expectancy and reduces infectivity; however, delayed HIV diagnosis remains common. Implementation and sustainability of hospital-based routine HIV testing in Vancouver, British Columbia, was evaluated to address a local HIV epidemic by facilitating earlier diagnosis and treatment. Public health issued a recommendation in 2011 to offer HIV testing to all patients presenting to three Vancouver hospitals as part of routine care, including all patients admitted to medical/surgical units with expansion to emergency departments (ED). We evaluated acceptability, feasibility, and effectiveness from 2011 to 2014 and continued monitoring through 2016 for sustainability. Between October 2011-December 2016, 114,803 HIV tests were administered at the three hospitals; an 11-fold increase following implementation of routine testing. The rate of testing was sustained and remained high through 2018. Of those tested, 151 patients were diagnosed with HIV for a testing yield of 0.13%. Review of 12,996 charts demonstrated 4935/5876 (96·9%) of admitted patients agreed to have an HIV test when offered. People diagnosed in hospital were significantly more likely to be diagnosed with acute stage (aOR 1·96, 95% CI 1·19, 3·23) infection, particularly those diagnosed in the ED. This study provides practice-based evidence of the feasibility, acceptability, and effectiveness of implementing a recommendation for routine HIV testing among inpatient and emergency department admissions, as well as the ability to normalize and sustain this change. Routine hospital-based HIV testing can increase diagnoses of acute HIV infection and facilitate earlier initiation of antiretroviral treatment.

Reconciling randomized trial evidence on proximal versus distal outcomes, with application to trials of influenza vaccination for healthcare workers.

When synthesizing the body of evidence concerning a clinical intervention, impacts on both proximal and distal outcome variables may be relevant. Assessments will be more defensible if results concerning a proximal outcome align with those concerning a corresponding distal outcome. We present a method to assess the coherence of empirical clinical trial results with biologic and mathematical first principles in situations where the intervention can only plausibly impact the distal outcome indirectly via the proximal outcome. The method comprises a probabilistic sensitivity analysis, where plausible ranges for key parameters are specified, resulting in a constellation of plausible pairs of estimated intervention effects, for the proximal and distal outcomes, respectively. Both outcome misclassification and sampling variability are reflected in the method. We apply our methodology in the context of cluster randomized trials to evaluate the impacts of vaccinating healthcare workers on the health of elderly patients, where the proximal outcome is suspected influenza and the distal outcome is death. However, there is scope to apply the method for other interventions in other disease areas.

Declining rates of health problems associated with crack smoking during the expansion of crack pipe distribution in Vancouver, Canada.

BACKGROUND: Crack cocaine smoking is associated with an array of negative health consequences, including cuts and burns from unsafe pipes, and infectious diseases such as HIV. Despite the well-established and researched harm reduction programs for injection drug users, little is known regarding the potential for harm reduction programs targeting crack smoking to reduce health problems from crack smoking. In the wake of recent crack pipe distribution services expansion, we utilized data from long running cohort studies to estimate the impact of crack pipe distribution services on the rates of health problems associated with crack smoking in Vancouver, Canada. METHODS: Data were derived from two prospective cohort studies of community-recruited people who inject drugs in Vancouver between December 2005 and November 2014. We employed multivariable generalized estimating equations to examine the relationship between crack pipe acquisition sources and self-reported health problems associated with crack smoking (e.g., cut fingers/sores, coughing blood) among people reported smoking crack. RESULTS: Among 1718 eligible participants, proportions of those obtaining crack pipes only through health service points have significantly increased from 7.2% in 2005 to 62.3% in 2014 (p < 0.001), while the rates of reporting health problems associated with crack smoking have significantly declined (p < 0.001). In multivariable analysis, compared to those obtaining pipes only through other sources (e.g., on the street, self-made), those acquiring pipes through health service points only were significantly less likely to report health problems from smoking crack (adjusted odds ratio: 0.82; 95% confidence interval: 0.73-0.93). CONCLUSIONS: These findings suggest that the expansion of crack pipe distribution services has likely served to reduce health problems from smoking crack in this setting. They provide evidence supporting crack pipe distribution programs as a harm reduction service for crack smokers.

High prevalence of adenomatous colorectal polyps in young cancer survivors treated with abdominal radiation therapy: results of a prospective trial.

OBJECTIVE: Cancer survivors treated with abdominal/pelvic radiation therapy (ART) have increased the risks of colorectal cancer (CRC), although evidence supporting early CRC screening for these patients is lacking. We sought to determine whether there is an elevated prevalence of adenomatous colorectal polyps in young survivors prior to the age when screening would be routinely recommended. DESIGN: We conducted a prospective study of early colonoscopic screening in cancer survivors aged 35-49 who had received ART ≥10 years previously. The planned sample size was based on prior studies reporting a prevalence of adenomatous polyps of approximately 20% among the average-risk population ≥50 years of age, in contrast to ≤10% among those average-risk people aged 40-50 years, for whom screening is not routinely recommended. RESULTS: Colonoscopy was performed in 54 survivors, at a median age of 45 years (range 36-49) and after median interval from radiation treatment of 19 years (10.6-43.5). Forty-nine polyps were detected in 24 patients, with 15 patients (27.8%; 95% CI 17.6% to 40.9%) having potentially precancerous polyps. Fifty-three per cent of polyps were within or at the edge of the prior ART fields. CONCLUSIONS: Young survivors treated with ART have a polyp prevalence comparable with the average-risk population aged ≥50 years and substantially higher than previously reported for the average-risk population aged 40-50 years. These findings lend support to the early initiation of screening in these survivors. CLINICAL TRIAL REGISTRATION NUMBER: NCT00982059; results.

Compromized DNA repair as a basis for identification of cancer radiotherapy patients with extreme radiosensitivity.

A small percentage of cancer radiotherapy patients develop abnormally severe side effects as a consequence of intrinsic radiosensitivity. We analysed the γ-H2AX response to ex-vivo irradiation of peripheral blood lymphocytes (PBL) and plucked eyebrow hair follicles from 16 patients who developed severe late radiation toxicity following radiotherapy, and 12 matched control patients. Longer retention of the γ-H2AX signal and lower colocalization efficiency of repair factors in over-responding patients confirmed that DNA repair in these individuals was compromised. Five of the radiosensitive patients harboured LoF mutations in DNA repair genes. An extensive range of quantitative parameters of the γ-H2AX response were studied with the objective to establish a predictor for radiosensitivity status. The most powerful predictor was the combination of the fraction of the unrepairable component of γ-H2AX foci and repair rate in PBL, both derived from non-linear regression analysis of foci repair kinetics. We introduce a visual representation of radiosensitivity status that allocates a position for each patient on a two-dimensional "radiosensitivity map". This analytical approach provides the basis for larger prospective studies to further refine the algorithm, ultimately to triage capability.

A mindful eating intervention: A theory-guided randomized anti-obesity feasibility study with adolescent Latino females.

UNLABELLED: While pediatric anti-obesity lifestyle interventions have received considerable attention, few show sustained impact on body mass index (BMI). Using the Information-Motivation-Behavioral Skills Theory as a framework, we examined the effects of a satiety-focused mindful eating intervention (MEI) on BMI, weight and mindful awareness. DESIGN AND SETTING: Utilizing a two-group, repeated measures design, 37 adolescent females with a BMI >90th percentile, recruited from a public high school in a Latino community in the Southwestern United States, were randomized 2:1, one third to the group receiving a 6-week MEI and two thirds to the comparison group (CG) receiving the usual care (nutrition and exercise information). INTERVENTION: During six weekly 90-min after school MEI group sessions, the behavioral skills of slow intentional eating were practiced with foci on satiety cues and triggers to overeat. OUTCOMES: Feasibility and acceptability were measured as participant retention (goal ≥55%) and evaluative comments from those in the MEI group, respectively. BMI and mindful awareness were measured on site at baseline, immediately post intervention, and at 4-week follow-up (week 10). RESULTS: Fifty-seven and 65% of those in the MEI and CG were retained throughout the study, respectively. MEI participants showed significantly lowered BMI compared with CG participants, whose weight increased (p<0.001). At six weeks, the MEI group BMI decreased by 1.1kg/m(2) (BMI continued to decline to 1.4kg/m(2) by week 10); while CG BMI increased by 0.7kg/m(2) (consistent with BMI >90th percentile standard growth projections). CONCLUSIONS: Initial and sustained decline of BMI in the MEI group supports further study of this theory-guided approach, and the value of practicing satiety-focused mindful eating behavioral skills to facilitate health behavior change.

Protocol of the impact of alternative social assistance disbursement on drug-related harm (TASA) study: a randomized controlled trial to evaluate changes to payment timing and frequency among people who use illicit drugs.

BACKGROUND: Government social assistance payments seek to alleviate poverty and address survival needs, but their monthly disbursement may cue increases in illicit drug use. This cue may be magnified when assistance is disbursed simultaneously across the population. Synchronized payments have been linked to escalations in drug use and unintended but severe drug-related harms, including overdose, as well as spikes in demand for health, social, financial and police services. METHODS/DESIGN: The TASA study examines whether changing payment timing and frequency can mitigate drug-related harm associated with synchronized social assistance disbursement. The study is a parallel arm multi-group randomized controlled trial in which 273 participants are randomly allocated for six assistance cycles to a control or one of two intervention arms on a 1:1:1 basis. Intervention arm participants receive their payments: (1) monthly; or (2) semi-monthly, in each case on days that are not during the week when cheques are normally issued. The study partners with a community-based credit union that has developed a system to vary social assistance payment timing. The primary outcome is a 40 % increase in drug use during the 3 days beginning with cheque issue day compared to other days of the month. Bi-weekly follow-up interviews collect participant information on this and secondary outcomes of interest, including drug-related harm (e.g. non-fatal overdose), exposure to violence and health service utilization. Self-reported data will be supplemented with participant information from health, financial, police and government administrative databases. A longitudinal, nested, qualitative parallel process evaluation explores participant experiences, and a cost-effectiveness evaluation of different disbursement scenarios will be undertaken. Outcomes will be compared between control and intervention arms to identify the impacts of alternative disbursement schedules on drug-related harm resulting from synchronized income assistance. DISCUSSION: This structural RCT benefits from strong community partnerships, highly detailed outcome measurement, robust methods of randomization and data triangulation with third party administrative databases. The study will provide evidence regarding the potential importance of social assistance program design as a lever to support population health outcomes and service provision for populations with a high prevalence of substance use. TRIAL REGISTRATION: NCT02457949 Registered 13 May 2015.

Near real-time monitoring of HIV transmission hotspots from routine HIV genotyping: an implementation case study.

BACKGROUND: HIV evolves rapidly and therefore infections with similar genetic sequences are likely linked by recent transmission events. Clusters of related infections can represent subpopulations with high rates of transmission. We describe the implementation of an automated near real-time system to monitor and characterise HIV transmission hotspots in British Columbia, Canada. METHODS: In this implementation case study, we applied a monitoring system to the British Columbia drug treatment database, which holds more than 32 000 anonymised HIV genotypes for nearly 9000 residents of British Columbia living with HIV. On average, five to six new HIV genotypes are deposited in the database every day, which triggers an automated reanalysis of the entire database. We extracted clusters of five or more individuals with short phylogenetic distances between their respective HIV sequences. The system generated monthly reports of the growth and characteristics of clusters that were distributed to public health officers. FINDINGS: In June, 2014, the monitoring system detected the expansion of a cluster by 11 new cases during 3 months, including eight cases with transmitted drug resistance. This cluster generally comprised young men who have sex with men. The subsequent report precipitated an enhanced public health follow-up to ensure linkage to care and treatment initiation in the affected subpopulation. Of the nine cases associated with this follow-up, all had already been linked to care and five cases had started treatment. Subsequent to the follow-up, three additional cases started treatment and most cases achieved suppressed viral loads. During the next 12 months, we detected 12 new cases in this cluster with reduction in the onward transmission of drug resistance. INTERPRETATION: Our findings show the first application of an automated phylogenetic system monitoring a clinical database to detect a recent HIV outbreak and support the ensuing public health response. By making secondary use of routinely collected HIV genotypes, this approach is cost-effective, attains near real-time monitoring of new cases, and can be implemented in all settings in which HIV genotyping is the standard of care. FUNDING: BC Centre for Excellence in HIV/AIDS, the Canadian Institutes for Health Research, the Genome Canada-CIHR Partnership in Genomics and Personalized Health, and the US National Institute on Drug Abuse.