The Effectiveness and Perceptions of Three Moderate Intensity Walking Cadence Aids and their Effects on Affective States: A Mixed Methods Study.

Substantial health benefits can be derived from walking at a moderate intensity cadence. To help regulate this cadence, three distinct aids exist 1) self-perception; 2) cadence prescription; 3) auditory cues. This study aimed to compare the effectiveness and explore perceptions of these aids to promote moderate intensity walking and effects on affective states, thereby addressing an important research gap. Individualised moderate relative intensity waking cadence was determined for participants (n = 23, Mage = 26.35, SD = 10.11). A convergent mixed-methods design was employed. A within-persons repeated measures design was used to explore the effectiveness of three aids (general guidelines, cadence prescription, and music) on promoting moderate intensity physical activity and positive affective states. Perceptions of these aids were elicited through qualitative interviews and thematic content analysis. Main effects for condition on relative physical activity intensity (η2 = .72) and positive affect (η2 = .25) were observed. Music evoked significantly higher relative physical activity intensity than other conditions (p values < .01), and higher positive affect compared to the general guidelines condition (p = .038). A significantly greater proportion of participants achieved moderate relative intensity physical activity during the music compared to general guidelines condition (p = .03). Congruently, qualitative findings suggested that participants predominantly perceived music as most effective for promoting a moderate intensity cadence and positive affect. However, individual variability existed in ability to utilise this aid. Implications of the findings for practitioners seeking to promote a moderate intensity cadence and positive affect during walking are discussed.

Does Long-Term Bowel Function Change After Colectomy for Colon Malignancy?

INTRODUCTION: Current understanding of bowel function after colectomy for colon cancer is informed by conflicting data, making preoperative patient counseling difficult. Our previous work demonstrates bowel movement frequency increases by postoperative follow-up, while overall function does not change. Long-term changes are unknown. We aimed to evaluate changes to patient-reported bowel function after colectomy for colon malignancy. METHODS: This is an observational study of patients that underwent colectomy for colon malignancy and completed the Colorectal Functional Outcome (COREFO) questionnaire at preoperative and 30-d postoperative clinic visits. Long-term bowel function was assessed using the same questionnaire via telephone or surveillance clinic visit. Mean domain and Total COREFO scores were compared baseline to long-term using paired t-tests. Quality of life analysis was obtained using the Patient Reported Outcome Measurement Information System-10 Global Health questionnaire for patients who completed this measure at surveillance visits or via telephone. RESULTS: Sixty-six patients met inclusion criteria. Median time between baseline and long-term questionnaire completion was 16 mo (interquartile range 11-30). Stool-related aspects (pain and bleeding with bowel movements, anal skin irritation) improved significantly from baseline to long-term. There were no other differences in any domain or Total COREFO score. Patient Reported Outcome Measurement Information System-10 scores demonstrated quality of life equivalent to the general US population. CONCLUSIONS: Over the long-term, after colectomy for colon cancer, patients report improvements in stool-related aspects (pain and bleeding with bowel movements, anal skin irritation). Evidence-based preoperative patient counseling should include these findings.

Effective alcohol policies are associated with reduced consumption among demographic groups who drink heavily.

BACKGROUND: Alcohol policies stand out among other noncommunicable disease-relevant policies for the lack of uptake. Composite indicators have been developed to measure the effects of alcohol control policy. We investigated whether drinking patterns among demographic groups from general population samples of drinkers from diverse countries are associated with alcohol control policy as measured by the International Alcohol Control (IAC) Policy Index. METHODS: Representative samples of adult drinkers from 10 countries (five high-income and five middle-income) were surveyed about alcohol consumption, using beverage and location-specific questions. MEASUREMENTS: The IAC Policy Index was analyzed with frequency, typical occasion quantity, and volume consumed. Analyses used mixed models that included interactions between country IAC Policy Index score and age group, gender, and education level. FINDINGS: Each increase in IAC policy index score (reflecting more effective alcohol policy) was associated with a 13.9% decrease in drinking frequency (p = 0.006) and a 16.5% decrease in volume (p = 0.001). With each increase in IAC Policy Index score, both genders decreased for all three measures, but men less so than women. Women decreased their typical occasion quantity by 1.2% (p = 0.006), frequency by 3.1% (p < 0.001), and total volume by 4.2% (p < 0.001) compared to men. Low and mid-education groups decreased their typical occasion quantity by 2.6% (p < 0.001) and 1.6% (p = 0.001), respectively, compared to high education, while for drinking frequency the low education group increased by 7.0% (p < 0.001). There was an overall effect of age (F = 19.27, p < 0.0001), with 18-19 and 20-24-year-olds showing the largest decreases in typical occasion quantity with increasing IAC policy index score. CONCLUSIONS: The IAC Policy Index, reflecting four effective policies, was associated with volume and frequency of drinking across 10 diverse countries. Each increase in the IAC Policy Index was associated with lower typical quantities consumed among groups reporting heavy drinking: young adults and less well-educated. There is value in implementing such alcohol policies and a need to accelerate their uptake globally.

Extreme Elevation of Baseline Intraoperative Parathyroid Hormone Measurements: Should Usual Protocols Apply?

INTRODUCTION: Intraoperative parathyroid hormone (IOPTH) monitoring is routinely used to facilitate minimally invasive parathyroidectomy. Many IOPTH protocols exist for predicting biochemical cure. Some patients are found to have extremely high baseline IOPTH levels (defined in this study as >500 pg/mL), which may affect the likelihood of satisfying certain final IOPTH criteria. We aimed to discover whether clinically significant differences exist in patients with extremely high baseline IOPTH and which IOPTH protocols are most appropriately applied to these patients. MATERIALS AND METHODS: This is a retrospective review of 237 patients who underwent parathyroidectomy with IOPTH monitoring for primary hyperparathyroidism (pHPT) from 2016 to 2020. Baseline IOPTH levels, drawn prior to manipulation of parathyroid glands, were grouped into categories labeled "elevated" (>65-500 pg/mL) and "extremely elevated" (>500 pg/mL). Final IOPTH levels were analyzed to determine whether there was a >50% decrease from baseline and whether a normal IOPTH value was achieved. 6-wk postoperative calcium levels were also examined. RESULTS: Of the patients in this cohort, 76% were in the elevated group and 24% in the extremely elevated group. Male sex and higher preoperative PTH levels were correlated with higher baseline IOPTH levels. Patients with extremely elevated baseline IOPTH were less likely to have IOPTH fall into normal range at the conclusion of the case (P = 0.019), and final IOPTH levels were higher (P < 0.001), but the IOPTH was equally likely to decrease >50% from baseline. There was no difference in the mean postoperative calcium levels between the two groups at 6-wk or at longer term follow-up (mean 525 d). CONCLUSIONS: Detection of baseline IOPTH levels >500 pg/mL during parathyroidectomy performed for pHPT is not uncommon. IOPTH in patients with extremely elevated baseline levels were less likely to fall into normal range, but follow-up calcium levels were equal, suggesting that applying more stringent IOPTH criteria for predicting biochemical cure may not be appropriate for this population.

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches. Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis. Design, Setting, and Participants: This prognostic study analyzed patients with MIBC pooled from 6 prospective phase I/II, II, or III trials of trimodality therapy (Radiation Therapy Oncology Group [RTOG] 8802, 8903, 9506, 9706, 9906, and 0233) across 37 participating institutions in North America from 1988 to 2007. Eligible patients had nonmetastatic MIBC and were enrolled in 1 of the 6 trimodality therapy clinical trials. Analyses were completed August 2020. Exposures: Trimodality therapy with transurethral bladder tumor resection and cisplatin-based chemoradiation therapy. Main Outcomes and Measures: MRE11 expression and association with disease-specific (bladder cancer) mortality (DSM), defined as death from bladder cancer. Pretreatment tumor tissues were processed for immunofluorescence with anti-MRE11 antibody and analyzed using automated quantitative image analysis to calculate a normalized score for MRE11 based on nuclear-to-cytoplasmic (NC) signal ratio. Results: Of 465 patients from 6 trials, 168 patients had available tissue, of which 135 were analyzable for MRE11 expression (median age of 65 years [minimum-maximum, 34-90 years]; 111 [82.2%] men). Median (minimum-maximum) follow-up for alive patients was 5.0 (0.6-11.7) years. Median (Q1-Q3) MRE11 NC signal ratio was 2.41 (1.49-3.34). Patients with an MRE11 NC ratio above 1.49 (ie, above first quartile) had a significantly lower DSM (HR, 0.50; 95% CI, 0.26-0.93; P = .03). The 4-year DSM was 41.0% (95% CI, 23.2%-58.0%) for patients with an MRE11 NC signal ratio of 1.49 or lower vs 21.0% (95% CI, 13.4%-29.8%) for a ratio above 1.49. MRE11 NC signal ratio was not significantly associated with overall survival (HR, 0.84; 95% CI, 0.49-1.44). Conclusions and Relevance: Higher MRE11 NC signal ratios were associated with better DSM after trimodality therapy. Lower MRE11 NC signal ratios identified a poor prognosis subgroup that may benefit from intensification of therapy.

Serial changes in liquid biopsy-derived variant allele frequency predict immune checkpoint inhibitor responsiveness in the pan-cancer setting.

Major immunotherapy challenges include a limited number of predictive biomarkers and the unusual imaging features post-therapy, such as pseudo-progression, which denote immune infiltrate-mediated tumor enlargement. Such phenomena confound clinical decision-making, since the cancer may eventually regress, and the patient should stay on treatment. We prospectively evaluated serial, blood-derived cell-free DNA (cfDNA) (baseline and 2-3 weeks post-immune checkpoint inhibitors [ICIs]) for variant allele frequency (VAF) and blood tumor mutation burden (bTMB) changes (next-generation sequencing) (N = 84 evaluable patients, diverse cancers). Low vs. high cfDNA-derived average adjusted ΔVAF (calculated by a machine-learning model) was an independent predictor of higher clinical benefit rate (stable disease ≥6 months/complete/partial response) (69.2% vs. 22.5%), and longer median progression-free (10.1 vs. 2.25 months) and overall survival (not reached vs. 6.1 months) (all P < .001, multivariate). bTMB changes did not correlate with outcomes. Therefore, early dynamic changes in cfDNA-derived VAF were a powerful predictor of pan-cancer immunotherapy outcomes.

What Are the Long-Term Changes to Bowel Function Patient-reported Outcomes After Elective Sigmoidectomy for Diverticular Disease?: Observational Study of Patients Undergoing Elective Sigmoidectomy for Diverticular Disease.

Objective: To evaluate long-term changes to bowel function after elective sigmoidectomy for diverticular disease. Background: For patients with diverticular disease, choosing surgery is often based on the presumption of improvement in preoperative symptoms. Our group previously reported bowel function does not change in the early perioperative period; however, studies of long-term outcomes are limited. Methods: This is an observational study of patients that underwent elective sigmoidectomy for diverticular disease and completed the Colorectal Functional Outcome (COREFO) questionnaire before surgery. Patients were stratified into two groups based on presence or absence of a preoperative symptomatic score (i.e., total COREFO ≥ 15). Long-term bowel function (>1 year from surgery) was assessed using the COREFO questionnaire via telephone or subsequent clinic visit. Paired t-tests compared mean preoperative scores to mean long-term scores. Results: Fifty-one patients met inclusion criteria (21 symptomatic, 30 asymptomatic). All symptomatic patients had uncomplicated disease, whereas 90% of asymptomatic patients had complicated disease. Median time from operation to questionnaire completion was 23 months (IQR = 13-34). Asymptomatic patients demonstrated impaired bowel function, predominantly driven by changes in the social impact domain. Symptomatic patients demonstrated improved bowel function, driven by changes in the incontinence, social impact, stool-related aspects, and need for medication domains. Conclusions: In the long-term after elective sigmoidectomy for diverticular disease, patients with symptomatic bowel function preoperatively improve substantially, while those with asymptomatic preoperative scores demonstrate statistically significant impairment. Patients determined to be symptomatic with patient-reported outcomes likely benefit long-term from sigmoid resection.Mini-Abstract: In this manuscript, long-term changes to patient-reported bowel function were assessed using a validated questionnaire after sigmoidectomy for diverticular disease. We found that in patients with symptomatic preoperative bowel function, long-term bowel function improved after elective resection. Alternatively, patients with asymptomatic preoperative bowel function demonstrated long-term impairment in bowel function.

Molecular Profiling of Exceptional Responders to Cancer Therapy.

BACKGROUND: The vast majority of metastatic cancers cannot be cured. Palliative treatment may relieve disease symptoms by stopping or slowing cancer growth and may prolong patients' lives, but almost all patients will inevitably develop disease progression after initial response. However, for reasons that are not fully understood, a very few patients will have extraordinary durable responses to standard anticancer treatments. MATERIALS AND METHODS: We analyzed exceptional responders treated at Fox Chase Cancer Center between September 2009 and November 2017. An exceptional response was defined as a complete response lasting more than 1 year or a partial response or stable disease for more than 2 years. Tumor samples were analyzed using an Ambry Genetics test kit with a 142-gene panel. Messenger RNA expression was evaluated using NanoString's nCounter PanCancer Pathways Panel and Immune Profiling Panel and compared with matched controls for gender, age, and cancer type. RESULTS: Twenty-six exceptional responders with metastatic bladder, kidney, breast, lung, ovarian, uterine, and colon cancers were enrolled. Mutations were identified in 45 genes. The most common mutation was an EPHA5 nonsynonymous mutation detected in 87.5% of patients. Mutations in DNA damage repair pathway genes were also frequent, suggesting increased genome instability. We also found varying expression of 73 genes in the Pathways panel and 85 genes in the Immune Profiling panel, many of them responsible for improvement in tumor recognition and antitumor immune response. CONCLUSIONS: The genomic instability detected in our exceptional responders, plus treatment with DNA damage compounds combined with favorable anticancer immunity, may have contributed to exceptional responses to standard anticancer therapies in the patients studied. IMPLICATIONS FOR PRACTICE: With recent advances in the treatment of cancer, there is increased emphasis on the importance of identifying molecular markers to predict treatment outcomes, thereby allowing precision oncology. In this study, it was hypothesized that there is a "specific biologic signature" in the biology of the cancer in long-term survivors that allows sensitivity to systemic therapy and durability of response. Results showed that DNA damage repair pathway alterations, combined with favorable anticancer immunity, may have contributed to exceptional responses. It is very likely that an in-depth examination of outlier responses will become a standard component of drug development in the future.

Does Bowel Function Change After Colectomy for Colon Malignancy?

BACKGROUND: Colon cancer patients often ask how surgery will affect bowel function. Current understanding is informed by conflicting data, making preoperative patient counseling difficult. We aimed to evaluate patient-reported bowel function changes after colectomy for colon malignancy. MATERIAL AND METHODS: This was a retrospective analysis of a prospectively collected institutional database from July 2015 to June 2019. The included patients underwent colectomy for adenocarcinoma of the colon, and completed the Colorectal Functional Outcome (COREFO) questionnaire at preoperative presentation and postoperative followup. Preoperative and postoperative scores were compared using paired t-tests. Multivariable analysis was performed using domains demonstrating statistical significance on bivariate analysis, assessing the factors that were associated with symptomatic bowel function. RESULTS: We identified 117 patients with a mean age of 64 ± 13 y. The median time between preoperative and postoperative questionnaire completion was 52 d (interquartile range 45-70). Bowel movement frequency increased significantly from a mean preoperative score of 9.72 to a mean postoperative score of 14.2 (P = 0.003). There were no significant differences in the remaining four domains of bowel function or global function. Multivariable analysis demonstrated higher likelihood of symptomatic postoperative frequency scores in male patients (OR 3.85, 95% CI 1.44-11.11, P = 0.007) and patients with symptomatic preoperative frequency (OR 5.56, 95% CI 1.62-19.02, P = 0.006). CONCLUSIONS: Patient-reported bowel movement frequency worsens at postoperative follow-up after colectomy for colon cancer, while overall bowel function does not change. Men and patients with preoperative symptomatic frequency have an increased likelihood of reporting symptomatic postoperative frequency. These findings should guide more personalized and evidence-based preoperative patient counseling.

It sounds like a good handover but can I trust it: the correlation between perceived quality and accuracy?

This article was migrated. The article was marked as recommended. Background Safe handover is crucial in healthcare and is taught in undergraduate and pre-vocational training curricula. It is now considered an Entrustable Professional Activity (EPA). Handover assessment tools have been developed but the correlation between the perceived quality of a handover and its accuracy has not been studied. Aims This paper aims to determine the correlation between the perceived quality and the accuracy and safety of handover. Methods This descriptive, quantitative study looked at medical students on long-term rural clinical placements who gave clinical handovers to supervisors. The supervisors scored the handovers using the Clinical Handover Assessment Tool (CHAT) and assessed the accuracy and safety of the handover, after seeing the patient. The correlation between handover scores, accuracy and safety was calculated using Cramer's V coefficient. Results 114 handovers from 25 students were assessed. The correlation coefficient for a global assessment of quality and accuracy was 0.585 and for safety was 0.583, considered large effects (>0.35). This also held using a checklist quality assessment but less strongly: 0.419, 0.363 respectively. Conclusion These findings suggest that handovers that sound 'good' are likely to be accurate: clinicians can 'trust their gut-feeling'. A high quality handover reflects more than the trainee'. clinical reasoning, communication and organisational skills: it suggests that they can provide accurate and safe handover. This supports the use of global assessments of handover as an important part of the multi-source feedback required for summative entrustment decision-making.

Paired tumor sequencing and germline testing in breast cancer management: An experience of a single academic center.

BACKGROUND: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. AIM: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. METHODS AND RESULTS: Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. CONCLUSIONS: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.

Comprehensive Paired Tumor/Germline Testing for Lynch Syndrome: Bringing Resolution to the Diagnostic Process.

PURPOSE: The current diagnostic testing algorithm for Lynch syndrome (LS) is complex and often involves multiple follow-up germline and somatic tests. We aimed to describe the results of paired tumor/germline testing performed on a large cohort of patients with colorectal cancer (CRC) and endometrial cancer (EC) to better determine the utility of this novel testing methodology. MATERIALS AND METHODS: We retrospectively reviewed a consecutive series of patients with CRC and EC undergoing paired tumor/germline analysis of the LS genes at a clinical diagnostic laboratory (N = 702). Microsatellite instability, MLH1 promoter hypermethylation, and germline testing of additional genes were performed if ordered. Patients were assigned to one of five groups on the basis of prior tumor screening and germline testing outcomes. Results for each group are described. RESULTS: Overall results were informative regarding an LS diagnosis for 76.1% and 60.8% of patients with mismatch-repair-deficient (MMRd) CRC and EC without and with prior germline testing, respectively. LS germline mutations were identified in 24.8% of patients in the group without prior germline testing, and interestingly, in 9.5% of patients with previous germline testing; four of these were discordant with prior tumor screening. Upon excluding patients with MLH1 promoter hypermethylation and germline mutations, biallelic somatic inactivation was seen in approximately 50% of patients with MMRd tumors across groups. CONCLUSION: Paired testing identified a cause for MMRd tumors in 76% and 61% of patients without and with prior LS germline testing, respectively. Findings support inclusion of tumor sequencing as well as comprehensive LS germline testing in the LS testing algorithm. Paired testing offers a complete, convenient evaluation for LS with high diagnostic resolution.

Correction: DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.

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DNA breakpoint assay reveals a majority of gross duplications occur in tandem reducing VUS classifications in breast cancer predisposition genes.

PURPOSE: Gross duplications are ambiguous in terms of clinical interpretation due to the limitations of the detection methods that cannot infer their context, namely, whether they occur in tandem or are duplicated and inserted elsewhere in the genome. We investigated the proportion of gross duplications occurring in tandem in breast cancer predisposition genes with the intent of informing their classifications. METHODS: The DNA breakpoint assay (DBA) is a custom, paired-end, next-generation sequencing (NGS) method designed to capture and detect deep-intronic DNA breakpoints in gross duplications in BRCA1, BRCA2, ATM, CDH1, PALB2, and CHEK2. RESULTS: DBA allowed us to ascertain breakpoints for 44 unique gross duplications from 147 probands. We determined that the duplications occurred in tandem in 114 (78%) carriers from this cohort, while the remainder have unknown tandem status. Among the tandem gross duplications that were eligible for reclassification, 95% of them were upgraded to pathogenic. CONCLUSION: DBA is a novel, high-throughput, NGS-based method that informs the tandem status, and thereby the classification of, gross duplications. This method revealed that most gross duplications in the investigated genes occurred in tandem and resulted in a pathogenic classification, which helps to secure the necessary treatment options for their carriers.

Perception of harm and benefits of cannabis use among adolescents from Latin America and Caribe / Percepción de daños y beneficios del uso de cannabis entre adolescentes de América Latina y Caribe / Percepção de danos e benefícios do uso de cannabis entre adolescentes da América Latina e Caribe

ABSTRACT Objective: to investigate the perception of harms and benefits associated with cannabis use among adolescents and how regulatory changes might affect their intention to use marijuana. Method: this multi-centric cross-sectional survey study. participants included 2717 students aged 15-17 from 10 cities in Belize, Brazil, Chile, Colombia, Dominican Republic, Jamaica, Mexico, St. Kitts and Nevis, and Trinidad and Tobago. Results: an average lifetime prevalence of cannabis use of 30.6% (25.8% past year, 15.8% past 30 days). Most participants reported that their closest friends use cannabis (60%); many (55%) stated that they would not use marijuana, even if it were legally available. Conclusion: statistics revealed that a strong perception of benefits, a low perception of risk, and friends' use of cannabis were associated with individual use as well as intention to use within a hypothetical context of regulatory change.

RESUMEN Objetivo: investigar la percepción de daños y beneficios asociados al uso de marihuana en adolescentes y cómo los cambios regulatorios pueden afectar la intención de uso. Método: estudio multicéntrico, cuantitativo y transversal tipo encuesta. los participantes fueron 2,717 estudiantes entre 15 y 17 años de 10 ciudades de Belice, Brasil. Chile, Colombia, República Dominicana, Jamaica, México, San Cristóbal y Nieves, y Trinidad y Tobago. Resultados: prevalencia de alguna vez en la vida de 30.6% (25.8% ultimo año, 15.8% últimos 30 días). Los adolescentes refieren que amigos cercanos consumen marihuana (60%). Los participantes (55%) declaran que no usarían marihuana, incluso si estuviera disponible legalmente. Conclusión: las estadísticas revelan que la alta percepción de los beneficios, baja percepción de daño y amigos que consumen marihuana, está asociado con el consumo y la intención de uso en el contexto hipotético de cambios regulatorios.

RESUMO Objetivo: investigar a percepção de danos e benefícios associados ao uso de maconha entre os adolescentes e como as mudanças regulatórias podem afetar a intenção de usar maconha. Método: estudo multicêntrico de corte transversal. Os participantes foram 2.717 alunos com idades entre 15 e 17 anos de 10 cidades em Belize, Brasil, Chile, Colômbia, República Dominicana, Jamaica, México, São Cristóvão e Nevis e Trinidad e Tobago. Resultados: prevalência de uso de maconha na vida de 30,6% (25,8% no ano passado, 15,8% nos últimos 30 dias). Os participantes relataram que os amigos mais próximos usam maconha (60%); e metade (55%) afirmou que não usariam maconha, mesmo se ela estivesse legalmente disponível. Conclusão: as estatísticas revelaram que percepção elevada de benefícios, percepção de baixo risco e uso de maconha por parte de amigos estavam associados ao uso individual, bem como à intenção de usar a maconha em um contexto hipotético de mudanças regulatórias.

Perception of harms and benefits associated with marijuana use among adolescents in st kitts-nevis - caribe / Percepção de danos e benefícios associados ao uso de maconha entre adolescentes em st kitts-nevis-caribe / Percepción de daños y beneficios relacionados al uso de la marihuana entre adolescentes en st kitts-nevis en el caribe

ABSTRACT Objective: this investigation examined adolescents' perception of the harms and benefits of marijuana use and how regulatory changes may affect their intent to use marijuana. Method: this cross-sectional survey gathered data from 268 15 to 17 years old students who were enrolled in public secondary schools in St Kitts-Nevis - Caribe. Results: forty five percent of the students perceive that there is no risk if marijuana is smoked once or twice. One out of every 4 students felt that there is great risk if marijuana is used regularly. About half of the students felt that marijuana helps persons their age to cope with emotional difficulties. Students who have used marijuana have a low perception of the risks associated with marijuana use and are seven times more likely to continue using marijuana, if it were legal and they were 18 years of age. Conclusion: most of the students perceive that there is no personal harm associated with smoking marijuana. Students are not sure whether the benefits of using marijuana are greater than the risks. A noticeable proportion of students were unsure of the harms and benefits associated with marijuana use. It is recommended that suitable educational and preventative programmes be implemented in schools.

RESUMO Objetivo: esta investigação analisou a percepção dos adolescentes sobre os danos e benefícios do uso de maconha e como as mudanças regulatórias podem afetar sua intenção de usar maconha. Método: este estudo de levantamento transversal reuniu dados de 268 alunos de 15 a 17 anos matriculados em escolas públicas de ensino médio em St. Kitts-Nevis - Caribe. Resultados: quarenta e cinco por cento dos estudantes afirmaram que não há risco se a maconha for consumida uma ou duas vezes. Um em cada quatro estudantes sentiu que há um grande risco se a maconha for usada regularmente. Cerca de metade dos alunos relatou que a maconha ajuda as pessoas da sua idade a lidar com dificuldades emocionais. Os estudantes que usaram maconha têm uma baixa percepção dos riscos associados ao uso de maconha e são sete vezes mais propensos a continuar usando maconha, se fosse legalizada e se tivessem 18 anos de idade. Conclusão: a maioria dos estudantes percebe que não há danos pessoais associados ao consumo de maconha. Os estudantes não têm certeza se os benefícios do uso da maconha são maiores que os riscos. Uma proporção notável de estudantes não tinha certeza dos danos e benefícios associados ao uso de maconha. Recomenda-se que sejam implementados programas educativos e preventivos adequados nas escolas.

RESUMEN Objetivo: esta investigación analizó las percepciones de los adolescentes sobre los daños y beneficios del uso de la marihuana y cómo los cambios regulatorios pueden afectar su intención de consumirla. Método: este estudio transversal recolectó datos de 268 estudiantes de 15 a 17 años inscritos en escuelas secundarias públicas en St. Kitts-Nevis en el Caribe. Resultados: el 45% de los estudiantes dijeron que no había riesgo si la marihuana se consumía una o dos veces. Uno de cada cuatro estudiantes sintió que existe un gran riesgo si la marihuana se usa de forma regular. Alrededor de la mitad de los estudiantes informó que la marihuana ayuda a las personas de su edad a enfrentar dificultades emocionales. Los estudiantes que consumieron marihuana tienen una baja percepción de los riesgos asociados al uso de la misma y siete veces más probabilidades de seguir consumiendo marihuana si esta estuviera legalizada y si tuvieran 18 años. Conclusión: la mayoría de los estudiantes se da cuenta de que no hay lesiones personales asociadas con el consumo de la marihuana. Los estudiantes no están seguros de si los beneficios del consumo de la marihuana son mayores que los riesgos. Un número notable de los estudiantes no estaba seguro de los daños y beneficios asociados al uso de la marihuana. Se recomienda que se implementen programas educativos y preventivos apropiados en las escuelas.

Quantitative Analysis of BRCA1 and BRCA2 Germline Splicing Variants Using a Novel RNA-Massively Parallel Sequencing Assay.

Clinical genetic testing for hereditary breast and ovarian cancer (HBOC) is becoming widespread. However, the interpretation of variants of unknown significance (VUS) in HBOC genes, such as the clinically actionable genes BRCA1 and BRCA2, remain a challenge. Among the variants that are frequently classified as VUS are those with unclear effects on splicing. In order to address this issue we developed a high-throughput RNA-massively parallel sequencing assay-CloneSeq-capable to perform quantitative and qualitative analysis of transcripts in cell lines and HBOC patients. This assay is based on cloning of RT-PCR products followed by massive parallel sequencing of the cloned transcripts. To validate this assay we compared it to the RNA splicing assays recommended by members of the ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) consortium. This comparison was performed using well-characterized lymphoblastoid cell lines (LCLs) generated from carriers of the BRCA1 or BRCA2 germline variants that have been previously described to be associated with splicing defects. CloneSeq was able to replicate the ENIGMA results, in addition to providing quantitative characterization of BRCA1 and BRCA2 germline splicing alterations in a high-throughput fashion. Furthermore, CloneSeq was used to analyze blood samples obtained from carriers of BRCA1 or BRCA2 germline sequence variants, including the novel uncharacterized alteration BRCA1 c.5152+5G>T, which was identified in a HBOC family. CloneSeq provided a high-resolution picture of all the transcripts induced by BRCA1 c.5152+5G>T, indicating it results in significant levels of exon skipping. This analysis proved to be important for the classification of BRCA1 c.5152+5G>T as a clinically actionable likely pathogenic variant. Reclassifications such as these are fundamental in order to offer preventive measures, targeted treatment, and pre-symptomatic screening to the correct individuals.

Drinking patterns vary by gender, age and country-level income: Cross-country analysis of the International Alcohol Control Study.

INTRODUCTION AND AIMS: Gender and age patterns of drinking are important in guiding country responses to harmful use of alcohol. This study undertook cross-country analysis of drinking across gender, age groups in some high-and middle-income countries. DESIGN AND METHODS: Surveys of drinkers were conducted in Australia, England, Scotland, New Zealand, St Kitts and Nevis (high-income), Thailand, South Africa, Mongolia and Vietnam (middle-income) as part of the International Alcohol Control Study. Drinking pattern measures were high-frequency, heavier-typical quantity and higher-risk drinking. Differences in the drinking patterns across age and gender groups were calculated. Logistic regression models were applied including a measure of country-level income. RESULTS: Percentages of high-frequency, heavier-typical quantity and higher-risk drinking were greater among men than in women in all countries. Older age was associated with drinking more frequently but smaller typical quantities especially in high-income countries. Middle-income countries overall showed less frequent but heavier typical quantities; however, the lower frequencies meant the percentages of higher risk drinkers were lower overall compared with high-income countries (with the exception of South Africa). DISCUSSION AND CONCLUSIONS: High-frequency drinking was greater in high-income countries, particularly in older age groups. Middle-income countries overall showed less frequent drinking but heavier typical quantities. As alcohol use becomes more normalised as a result of the expansion of commercial alcohol it is likely frequency of drinking will increase with a likelihood of greater numbers drinking at higher risk levels.

TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2, MSH6, MLH1, PMS2 and EPCAM. Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.

PURPOSE: There is increasing demand from the public for direct-to-consumer (DTC) genetic tests, and the US Food and Drug Administration limits the type of health-related claims DTC tests can market. Some DTC companies provide raw genotyping data to customers if requested, and these raw data may include variants occurring in genes recommended by the American College of Medical Genetics and Genomics to be reported as incidental/secondary findings. The purpose of this study was to review the outcome of requests for clinical confirmation of DTC results that were received by our laboratory and to analyze variant classification concordance. METHODS: We identified 49 patient samples received for further testing that had previously identified genetic variants reported in DTC raw data. For each case identified, information pertaining to the outcome of clinical confirmation testing as well as classification of the DTC variant was collected and analyzed. RESULTS: Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the "increased risk" classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases. CONCLUSION: Our results demonstrate the importance of confirming DTC raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.