A cost-utility study of elective haemorrhoidectomies in Canada.

AIM: The aim was to estimate the 10-year cost-utility of haemorrhoidectomy surgery with preference-based measures of health using Canadian health utility measures and costs. METHODS: Patients undergoing elective haemorrhoidectomies by general and colorectal surgeons in British Columbia, Vancouver, between September 2015 and November 2022, completed preoperatively and postoperatively the EuroQol five-dimension five-level health-related quality of life questionnaire (EQ-5D-5L). Quality-adjusted life years (QALYs) attributable to surgery were calculated by discounting preoperative and postoperative health utility values derived from the EQ-5D-5L. Costs were measured from a health system perspective which incorporated costs of hospital stay and specialists' fees. Results are presented in 2021 Canadian dollars. RESULTS: Of 94 (47%) patients who completed both the preoperative and postoperative questionnaires, the mean gain in QALYs 10 years after surgery was 1.0609, assuming a 3.5% annual discounting rate. The average cost of the surgery was $3166. The average cost per QALY was $2985 when benefits of the surgery were assumed to accrue for 10 years. The cost per QALY was higher for women ($3821) compared with men ($2485). Participants over the age of 70 had the highest cost per QALY ($8079/QALY). CONCLUSIONS: Haemorrhoidectomies have been associated with significant gains in health status and are inexpensive relative to the associated gains in quality of life based on patients' perspectives of their improvement in health and well-being.

Peer Activate: A Feasibility Trial of a Peer-Delivered Intervention to Decrease Disparities in Substance Use, Depression, and Linkage to Substance Use Treatment.

Although effective evidence-based interventions (EBIs) exist, racial/ethnic minority individuals with lower income are less likely to have access to these interventions and may experience greater stigma in the health care system, resulting in disproportionate rates of morbidity and mortality. Peer recovery specialists (PRSs) may be uniquely suited to address barriers faced by those from impoverished areas; however, peers have not traditionally been trained in implementing EBIs. The current open-label trial (N = 8) was performed to evaluate implementation and preliminary effectiveness of an adapted EBI supporting recovery, linkage to treatment, and reduced depression. Results suggest the intervention was feasible, acceptable, and appropriate for linking individuals from a community setting to substance use treatment and could be delivered with fidelity by a peer interventionist. Participants who completed the intervention demonstrated clinically reliable decreases in substance use and depressive symptoms. Findings provide initial support for PRS dissemination of EBIs to increase linkage to care and support recovery in traditionally underserved populations. [Journal of Psychosocial Nursing and Mental Health Services, 61(11), 23-31.].

Act Healthy: A Randomized Clinical Trial Evaluating a Behavioral Activation Intervention to Address Substance Use and Medication Adherence Among Low-Income, Black/African American Individuals Living with HIV/AIDS.

There is a need for parsimonious behavioral interventions to support HIV and substance use treatment outcomes for low-income, Black/African American individuals living with HIV. This randomized clinical trial (N = 61) evaluated Act Healthy (AH), an integrated behavioral intervention to reduce substance use and improve medication adherence, compared to supportive counseling (SC) plus Life-Steps medication adherence counseling on substance use, craving, adherence-related outcomes, and depression over one year. Participants in AH had significantly steeper decreases in cravings compared to SC, but no significant differences in substance use. Across both groups, there was a significant increase in probability of being on antiretroviral therapy (ART) (86% on ART at 12 months vs. 56% at baseline), and a significant decrease in medication nonadherence. Findings provide preliminary support for an intervention to reduce cravings and strategies to improve ART use in a hard-to-reach, vulnerable population at high risk for poor treatment outcomes and ongoing HIV transmission. TRIAL REGISTRATION: ClinicalTrials.gov trial registration number: identifier: NCT01351454. Retrospectively registered on May 10, 2011.

Surgical site infection in elective colonic and rectal resections: effect of oral antibiotics and mechanical bowel preparation compared with mechanical bowel preparation only.

AIM: Surgical site infections are disproportionately common after colorectal surgery and may be largely preventable. The objective of this retrospective cohort study was to determine the effect of oral antibiotics and mechanical bowel preparation on surgical site infections. METHOD: A retrospective study of a consecutive series of elective colonic and rectal resections following an Enhanced Recovery After Surgery pathway, which also included mechanical bowel preparation, from 1 September 2014 to 30 September 2017. The addition of oral antibiotics (neomycin and metronidazole) to the mechanical bowel preparation procedure was assessed. Development of surgical site infections within 30 days was the main outcome measured. The secondary outcome was assessment of possible surgical site infection predictors. RESULTS: Seven-hundred thirty-two patients were included: 313 (43%) preintervention (mechanical bowel preparation only); and 419 (57%) postintervention (mechanical bowel preparation plus oral antibiotics). Surgical site infection rates preintervention and. postintervention were: overall, 20.8% vs 10.5%, P < 0.001; superficial, 10.9% vs 4.3%, P < 0.001; and organ space, 9.9% vs 6.2%, P = 0.03. Subgroup analysis of colonic resections revealed a significant reduction in overall (17.1% vs 6.8%), superficial (10.7% vs 4.3%) and organ space (6.4% vs. 2.6%) infections. Rectal resections had significant reduction in overall (26.2% vs 15.3%) and superficial (11.1% vs 4.4%) infection rates but not in organ space infections (15.1% vs 10.9%). Multivariate regression analysis revealed open vs minimally invasive surgery (P < 0.001) and omission of oral antibiotics (P = 0.004) as independent predictors of surgical site infections. CONCLUSION: Administration of oral antibiotics resulted in significant reduction of superficial and organ space infections after colonic resection; after rectal resection, significant reduction only of superficial infections was found.

Health and quality of life among a cohort of patients having lateral internal sphincterotomy for anal fissures.

AIM: The aim of this study is to report changes in health-related quality of life attributable to lateral internal sphincterotomy for treatment of anal fissure. There is very little evidence on whether the overall health-related quality of life of patients is detrimentally affected by the condition, or which aspects of self-perceived health status improve after lateral internal sphincterotomy. This study will articulate which aspects of health tend to improve and guide postoperative expectations appropriately. Knowledge gained from this study may also identify gaps in an individual patient's episode of care. METHOD: Patients were prospectively identified when they consented to surgical treatment of their anal fissure and were contacted by phone to participate. Participants completed a number of patient-reported outcomes preoperatively and 6 months postoperatively. Faecal incontinence-related quality of life, pain and depression were measured at both time points. The severity of faecal incontinence was measured at both times. RESULTS: Participants reported high levels of pain preoperatively. Postoperatively, improvement in pain exceeded the threshold of clinical relevance (P < 0.01). Thirty-five per cent of participants reported significant effects of faecal incontinence preoperatively, while 26% did so postoperatively. Participants with multiple comorbidities were more likely to report faecal incontinence postoperatively than preoperatively. CONCLUSION: This study reports that lateral internal sphincterotomy improved pain symptoms without adverse effects on continence. Not all domains of health-related quality of life were similarly positively affected by anal fissure repair.

Prediction model and web-based risk calculator for postoperative ileus after loop ileostomy closure.

BACKGROUND: Postoperative ileus (POI) is a significant complication after loop ileostomy closure given both its frequency and impact on the patient. The purpose of this study was to develop and externally validate a prediction model for POI after loop ileostomy closure. METHODS: The model was developed and validated according to the TRIPOD checklist for prediction model development and validation. The development cohort included consecutive patients who underwent loop ileostomy closure in two teaching hospitals in Montreal, Canada. Candidate variables considered for inclusion in the model were chosen a priori based on subject knowledge. The final prediction model, which modelled the 30-day cumulative incidence of POI using logistic regression, was selected using the highest area under the receiver operating characteristic curve (AUC) criterion. Model calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. The model was then validated externally in an independent cohort of similar patients from the University of British Columbia. RESULTS: The development cohort included 531 patients, in whom the incidence of POI was 16·8 per cent. The final model included five variables: age, ASA fitness grade, underlying pathology/treatment, interval between ileostomy creation and closure, and duration of surgery for ileostomy closure (AUC 0·68, 95 per cent c.i. 0·61 to 0·74). The model demonstrated good calibration (P = 0·142). The validation cohort consisted of 216 patients, and the incidence of POI was 15·7 per cent. On external validation, the model maintained good discrimination (AUC 0·72, 0·63 to 0·81) and calibration (P = 0·538). CONCLUSION: A prediction model was developed for POI after loop ileostomy closure and included five variables. The model maintained good performance on external validation.

ANTECEDENTES: El íleo postoperatorio (postoperative ileus, POI) es una complicación importante tras el cierre de la ileostomía en asa, dada su frecuencia e impacto en el paciente. El propósito de este estudio fue desarrollar y validar externamente un modelo de predicción para el POI después del cierre de la ileostomía en asa. MÉTODOS: El modelo fue desarrollado y validado de acuerdo con la lista de verificación TRIPOD para el desarrollo y validación de un modelo de predicción. La cohorte de desarrollo incluyó pacientes consecutivos en los que se realizó el cierre de la ileostomía en asa en dos hospitales universitarios en Montreal, Canadá. Las variables candidatas consideradas para su inclusión en el modelo se seleccionaron a priori en función del conocimiento del problema. El modelo de predicción final, que modeló la incidencia acumulada a 30 días de POI mediante regresión logística, se seleccionó según el criterio del área más alta bajo la curva operativa del receptor (area under the receiver operating curve, AUC). La calibración del modelo se evaluó utilizando la prueba de bondad de ajuste de Hosmer-Lemeshow. El modelo fue posteriormente validado externamente en una cohorte independiente de pacientes similares de la Universidad de British Columbia. RESULTADOS: La cohorte de desarrollo incluyó a 531 pacientes, y la incidencia de POI fue de 16,7%. El modelo final incluyó cinco variables: edad, clasificación ASA (American Society of Anaesthesiologists), patología inicial y tratamiento, tiempo entre las dos intervenciones quirúrgicas y tiempo operatorio del cierre de ileostomía (AUC = 0,68; i.c. del 95%: 0,61 a 0,74). El modelo demostró buena calibración (P = 0,142). La cohorte de validación consistió en 216 pacientes, y la incidencia de POI fue de 15,7%. En la validación externa, el modelo mantuvo una buena discriminación (AUC = 0,72; i.c. del 95%: 0,63 a 0,81) y calibración (P = 0,538). CONCLUSIÓN: Se ha desarrollado un modelo de predicción de POI después del cierre de la ileostomía en asa que incluía cinco variables. El modelo mantuvo un buen funcionamiento en la validación externa.

A multi-centre randomized controlled trial of open vs closed management of the rectal defect after transanal endoscopic microsurgery.

AIM: Transanal endoscopic microsurgery (TEM) is a technically challenging strategy that allows expanded indications for local excision of rectal lesions. Transluminal suturing is difficult, so open management of the resultant defect is appealing. Expert opinion suggests there is more pain when the defect is left open. The aim of this study was to determine if closure of the defect created during full thickness excision of rectal lesions with TEM leads to less postoperative pain compared to leaving the defect open. METHOD: At the time of surgery, patients undergoing a full thickness TEM were randomized to sutured (TEM-S) or open (TEM-O) management of the rectal defect. At five Canadian academic colorectal surgery centres, experienced TEM surgeons enrolled patients ≥ 18 years treated by full thickness TEM. The primary outcome was postoperative pain measured by the visual analogue scale. Secondary outcomes included postoperative pain medication use and 30-day postoperative complications, including bleeding, infection and hospital readmission. RESULTS: Between March 2012 and October 2013, 50 patients were enrolled and randomized to sutured (TEM-S, n = 28) or open (TEM-O, n = 22) management of the rectal defect. There was no difference between the two study groups in postoperative pain on postoperative day 1 (2.8 vs 2.6, P = 0.76), day 3 (2.8 vs 2.1, P = 0.23) and day 7 (2.8 vs 1.7, P = 0.10). CONCLUSION: In this multicentre randomized controlled trial, there was no difference in postoperative pain between sutured or open defect management in patients having a full thickness excision with TEM.

Avoided emissions and conservation of scrub mangroves: potential for a Blue Carbon project in the Gulf of California, Mexico.

Mangroves are considered ideal ecosystems for Blue Carbon projects. However, because of their short stature, some mangroves ('scrub' mangroves, less than 2 m) do not fulfil the current definition of 'forests', which makes them ineligible for emission reduction programmes such as REDD+. Short stature mangroves can be the dominant form of mangroves in arid and nutrient-poor landscapes, and emissions from their deforestation and degradation could be substantial. Here, we describe a Blue Carbon project in the Gulf of California, Mexico, to illustrate that projects that avoid emissions from deforestation and degradation could provide financial resources to protect mangroves that cannot be included in other emission reduction programmes. The goal of the project is to protect 16 058 ha of mangroves through conservation concessions from the Mexican Federal Government. The cumulative avoided emissions of the project are 2.84 million Mg CO2 over 100 years, valued at $US 426 000 per year (US$15 per Mg CO2 in the California market). The funds could be used for community-based projects that will improve mangrove management, such as surveillance, eradication of invasive species, rehabilitation after tropical storms and environmental education. The strong institutional support, secure financial status, community engagement and clear project boundaries provide favourable conditions to implement this Blue Carbon project. Financial resources from Blue Carbon projects, even in mangroves of short stature, can provide substantial resources to enhance community resilience and mangrove protection.

Transanal endoscopic microsurgery as day surgery - a single-centre experience with 500 patients.

AIM: Transanal endoscopic microsurgery (TEM) is the current treatment of choice for rectal adenomas and early rectal cancer. Postoperative admission to hospital is common but possibly unnecessary. Our objective was to analyse predictors and outcomes of TEM patients having same day discharge (TEM-D) compared with those who were admitted to hospital (TEM-A). METHOD: At St Paul's Hospital (SPH), demographic, surgical, pathological and follow-up data have been collected prospectively since TEM was started in 2007. Trends in admission and readmission rates were analysed using the Cochran-Armitage trend test, and predictors of admission were analysed using univariate and multivariate logistic regressions. RESULTS: Between 2007 and 2016, 500 patients were treated by TEM at SPH. The overall admission rate was 29% (145/500), but this decreased to 19% in the last 3 years of the study (P < 0.001). The readmission rate was 5.2% (n = 26/500) and did not change significantly over the study period (P = 0.30). Reasons for admission included the following: surgeon discretion/monitoring (35%), urinary retention (26%), haemorrhage (10%), breach of peritoneal cavity (7%), infection (7%) and other (15%). The most common reasons for readmission were haemorrhage (54%, n = 14), pain (19%, n = 5) and infection (12%, n = 3). Factors associated with admission were as follows: tumour height (OR 1.09, 1.02-1.17), prolonged operative time (OR 1.25, 1.14-1.37), unsutured surgical defect (OR 1.99, 1.22-3.25) and surgeon experience (OR 4.62, 2.75-7.77). CONCLUSION: Outpatient TEM is safe and carries a low risk of readmission. In centres with an outpatient TEM strategy, predictors of hospital admission include proximal tumours, prolonged surgical time and open management of the surgical defect.

Salvage TME following TEM: a possible indication for TaTME.

BACKGROUND: Salvage surgery after transanal endoscopic microsurgery (TEM) has shown mixed results. Transanal total mesorectal excision (TaTME) might be advantageous in this population. The aim of this study was to assess the short-term oncologic and operative outcomes of salvage surgery after TEM, comparing TaTME to conventional salavge TME (sTME). METHODS: Consecutive patients treated with salvage surgery after TEM were identified. Patients who underwent TaTME were compared to those who had conventional sTME. The primary outcome was the ability to perform an appropriate oncologic procedure defined by a composite outcome (negative distal margins, negative radial margins and complete or near complete mesorectum specimen). RESULTS: During the study period, 41 patients had salvage surgery after TEM. Of those, 11 patients had TaTME while 30 patients had sTME. All patients in the TaTME group met the composite outcome of appropriate oncologic procedure compared to 76.7% for the conventional sTME group (p = 0.19). TaTME was associated with significantly higher rates of sphincter preservation (100 vs. 50%, p = 0.01), higher rates of laparoscopic surgery (100 vs. 23.3%, p < 0.001) and lower rates of conversion to open surgery (9.1 vs. 57%, p < 0.001). No difference was found in postoperative morbidity (36.3 vs. 36.7%, p = 0.77). CONCLUSIONS: The present study demonstrates that for patients requiring salvage surgery after TEM, TaTME is associated with significantly higher rates of sphincter-sparing surgery when compared to conventional transabdominal TME while producing adequate short-term oncologic outcomes. Salvage surgery after TEM might be a clear indication for TaTME rather than conventional surgery.

Coordination of radiologic and clinical care reduces the wait time to breast cancer diagnosis.

BACKGROUND: In 2009, a Rapid Access Breast Clinic (rabc) was opened at our urban hospital. Compared with the traditional system (ts), the navigated care through the clinic was associated with a significantly shorter time to surgical consultation. Since 2009, many radiology facilities have introduced facilitated-care pathways for patients with breast pathology. Our objective was to determine if that change in diagnostic imaging pathways had eliminated the advantage in time to care previously shown for the rabc. METHODS: All patients seen in the rabc and the office-based ts in November-December 2012 were included in the analysis. A retrospective chart review tabulated demographic, surgeon, pathology, and radiologic data, including time intervals to care for all patients. The results were compared with data from 2009. RESULTS: In 2012, time from presentation to surgical consultation was less for the rabc group than for the ts group (36 days vs. 73 days, p < 0.001) for both malignant (31 days vs. 55 days, p = 0.008) and benign diagnoses (43 days vs. 79 days, p < 0.001). Comparing the 2012 results with results from 2009, a decline in mean wait time was observed for the ts group (86 days vs. 73 days, p = 0.02). Compared with patients having investigations in the ts, rabc patients with cancer were more likely to undergo surgery within 60 days of presentation (33% vs. 15%, p = 0.04). CONCLUSIONS: The coordination of radiology and clinical care reduces wait times for diagnosis and surgery in breast cancer. To achieve recommended targets, we recommend implementation of more systematic coordination of care for a breast cancer diagnosis and of navigation to surgeons for patients needing surgical care.

Randomized double-blind trial comparing the cosmetic outcome of cutting diathermy versus scalpel for skin incisions.

BACKGROUND: Controversy exists about whether cutting diathermy for skin incisions leads to a cosmetically inferior scar. Cosmetic outcomes were compared between skin incisions created with cutting diathermy versus scalpel. Wound infection rates and postoperative incisional pain were also compared. METHODS: This was a randomized double-blind trial comparing cutting diathermy and scalpel in patients undergoing bowel resection. Scar cosmesis was assessed at 6 months after surgery by a plastic surgeon and a research associate using the Vancouver Scar Scale (VSS) and the Patient and Observer Scar Assessment Scale (POSAS). Patients also used POSAS to self-evaluate their scars. Wound infections within 30 days were recorded, and incision pain scores were measured on the first 5 days after operation. RESULTS: A total of 66 patients were randomized to cutting diathermy (31) or scalpel (35). At 6 months, there was no significant difference between the diathermy and scalpel groups in mean(s.d.) VSS scores (4·9(2·6) versus 5·0(1·9); P = 0·837), mean POSAS total scores (19·2(8·0) versus 20·0(7·4); P = 0·684) or subjective POSAS total scores (20·2(12·1) versus 21·3(10·4); P = 0·725). Neither were there significant differences in wound infection rates between the groups (5 of 30 versus 5 of 32; P = 1·000). Pain scores on day 1 after operation were significantly lower in the diathermy group (mean 1·68 versus 3·13; P = 0·018), but were not significantly different on days 2-5. CONCLUSION: Cutting diathermy is a cosmetically acceptable technique for abdominal skin incisions. There is no increased risk of wound infection, and diathermy may convey benefit in terms of early postoperative wound pain. REGISTRATION NUMBER: NCT01496404 ( http://www.clinicaltrials.gov).

Can behavioral theory inform the understanding of depression and medication nonadherence among HIV-positive substance users?

Medication adherence is highly predictive of health outcomes across chronic conditions, particularly HIV/AIDS. Depression is consistently associated with worse adherence, yet few studies have sought to understand how depression relates to adherence. This study tested three components of behavioral depression theory--goal-directed activation, positive reinforcement, and environmental punishment--as potential indirect effects in the relation between depressive symptoms and medication nonadherence among low-income, predominantly African American substance users (n = 83). Medication nonadherence was assessed as frequency of doses missed across common reasons for nonadherence. Non-parametric bootstrapping was used to evaluate the indirect effects. Of the three intermediary variables, there was only an indirect effect of environmental punishment; depressive symptoms were associated with greater nonadherence through greater environmental punishment. Goal-directed activation and positive reinforcement were unrelated to adherence. Findings suggest the importance of environmental punishment in the relation between depression and medication adherence and may inform future intervention efforts for this population.

Implementing Behavioral Activation and Life-Steps for Depression and HIV Medication Adherence in a Community Health Center.

Antiretroviral therapy to treat HIV/AIDS has substantially improved clinical outcomes among patients living with HIV/AIDS, but only in the presence of very consistent adherence. One of the most prevalent and impactful individual-level predictors of poor adherence is depressive symptoms, even at subthreshold levels. Evidence-based cognitive behavioral interventions exist to address improvements in depressive symptoms and adherence in this population, yet these techniques have largely been designed and tested as individual treatments for delivery in mental health settings. This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits) and few hands-on resources exist to guide this process. As such, primary aims of this study were to adapt and implement evidence-based cognitive behavioral techniques for depression (behavioral activation; BA) and HIV medication adherence (Life-Steps) that have potential for dissemination in an outpatient community health center. The intervention incorporated feedback from health center staff and utilized a modular, group format that did not rely on sequential session attendance. Feasibility was examined over 8 weeks (n = 13). Preliminary effects on depression, health-related quality of life, and medication adherence were examined and exit interviews were conducted with a subset of participants (n = 4) to inform future modifications. Treatment descriptions and recommendations for effective clinical implementation based on patient and clinician feedback are provided along with case material of two individual patients and an example group session. Current efforts are an important next step for disseminating evidence-based techniques for depression and HIV medication adherence to community health center or AIDS service organization settings.

Novel Ameloblastin Variants, Contrasting Amelogenesis Imperfecta Phenotypes.

Amelogenesis imperfecta (AI) comprises a group of rare, inherited disorders with abnormal enamel formation. Ameloblastin (AMBN), the second most abundant enamel matrix protein (EMP), plays a critical role in amelogenesis. Pathogenic biallelic loss-of-function AMBN variants are known to cause recessive hypoplastic AI. A report of a family with dominant hypoplastic AI attributed to AMBN missense change p.Pro357Ser, together with data from animal models, suggests that the consequences of AMBN variants in human AI remain incompletely characterized. Here we describe 5 new pathogenic AMBN variants in 11 individuals with AI. These fall within 3 groups by phenotype. Group 1, consisting of 6 families biallelic for combinations of 4 different variants, have yellow hypoplastic AI with poor-quality enamel, consistent with previous reports. Group 2, with 2 families, appears monoallelic for a variant shared with group 1 and has hypomaturation AI of near-normal enamel volume with pitting. Group 3 includes 3 families, all monoallelic for a fifth variant, which are affected by white hypoplastic AI with a thin intact enamel layer. Three variants, c.209C>G; p.(Ser70*) (groups 1 and 2), c.295T>C; p.(Tyr99His) (group 1), and c.76G>A; p.(Ala26Thr) (group 3) were identified in multiple families. Long-read AMBN locus sequencing revealed these variants are on the same conserved haplotype, implying they originate from a common ancestor. Data presented therefore provide further support for possible dominant as well as recessive inheritance for AMBN-related AI and for multiple contrasting phenotypes. In conclusion, our findings suggest pathogenic AMBN variants have a more complex impact on human AI than previously reported.

Novel mRNA isoforms and mutations of uridine monophosphate synthetase and 5-fluorouracil resistance in colorectal cancer.

The drug fluorouracil (5-FU) is a widely used antimetabolite chemotherapy in the treatment of colorectal cancer. The gene uridine monophosphate synthetase (UMPS) is thought to be primarily responsible for conversion of 5-FU to active anticancer metabolites in tumor cells. Mutation or aberrant expression of UMPS may contribute to 5-FU resistance during treatment. We undertook a characterization of UMPS mRNA isoform expression and sequence variation in 5-FU-resistant cell lines and drug-naive or -exposed primary and metastatic tumors. We observed reciprocal differential expression of two UMPS isoforms in a colorectal cancer cell line with acquired 5-FU resistance relative to the 5-FU-sensitive cell line from which it was derived. A novel isoform arising as a consequence of exon skipping was increased in abundance in resistant cells. The underlying mechanism responsible for this shift in isoform expression was determined to be a heterozygous splice site mutation acquired in the resistant cell line. We developed sequencing and expression assays to specifically detect alternative UMPS isoforms and used these to determine that UMPS was recurrently disrupted by mutations and aberrant splicing in additional 5-FU-resistant colorectal cancer cell lines and colorectal tumors. The observed mutations, aberrant splicing and downregulation of UMPS represent novel mechanisms for acquired 5-FU resistance in colorectal cancer.

The role of gender and race in the relation between adolescent distress tolerance and externalizing and internalizing psychopathology.

Distress tolerance (DT) is an established construct contributing to the onset and maintenance of psychopathology in adulthood; however, few studies have examined the role of DT in older adolescent psychopathology. Emerging data suggest that gender and race may influence this relation. Therefore, the current study examined the relation between gender, race, and DT on parent-reported internalizing and externalizing DSM-oriented symptoms among a community sample of 128, 14-18 year old adolescents. Results indicated a moderating effect of gender on affective problems, such that females with low DT, but not males, displayed significantly greater affective problems. Findings also indicated a significant moderating effect of race, such that Caucasians with low DT, but not African Americans, displayed significantly higher somatic, oppositional defiant, and conduct problems. These findings suggest that DT is an important clinical variable in older adolescence, particularly among Caucasians and females.

Patient experiences of COVID-19-induced changes to methadone treatment in a large community-based opioid treatment program in Baltimore.

INTRODUCTION: Following the March 2020 federal declaration of a COVID-19 public health emergency, in line with recommendations for social distancing and decreased congregation, federal agencies issued sweeping regulation changes to facilitate access to medications for opioid use disorder (MOUD) treatment. These changes allowed patients new to treatment to receive multiple days of take-home medications (THM) and to use remote technology for treatment encounters-allowances that previously had been reserved exclusively for "stable" patients who met minimum adherence and time-in-treatment criteria. The impact of these changes on low-income, minoritized patients (frequently the largest recipients of opioid treatment program [OTP]-based addiction care), however, is not well characterized. We aimed to explore the experiences of patients who were enrolled in treatment prior to COVID-19 OTP regulation changes, with the goal of understanding patients' perceptions of the impact of these changes on treatment. METHODS: This study included semistructured, qualitative interviews with 28 patients. We used a purposeful sampling method to recruit individuals who were active in treatment just before COVID-19-related policy changes went into effect, and who were still in treatment several months later. To ensure a diverse array of perspectives, we interviewed individuals who either had or had not experienced challenges with methadone medication adherence from 3/24/21 to 6/8/21, approximately 12-15 months following the onset of COVID-19. Interviews were transcribed and coded using thematic analysis. RESULTS: Participants were majority male (57 %), Black/African American (57 %), with a mean age of 50.1 (SD = 9.3). Fifty percent received THM prior to COVID-19, which increased to 93 % during the pandemic. COVID-19 program changes had mixed effects on treatment and recovery experiences. Themes identified convenience, safety, and employment as reasons for preferring THM. Challenges included difficulty with managing/storing medications, experiencing isolation, and concern about relapse. Furthermore, some participants reported that telebehavioral health encounters felt less personal. CONCLUSIONS: Policymakers should consider patients' perspectives to foster a more patient-centered approach to methadone dosing that is safe, flexible, and accommodating to a diverse array of patients' needs. Additionally, technical support should be provided to OTPs to ensure interpersonal connections are maintained in the patient-provider relationship beyond the pandemic.

Substance Use Outcomes Among Sexual and Gender Minority Individuals Living with HIV Following Residential Substance Use Treatment in Washington, DC.

This study explored how sexual or gender minority (SGM) status influenced substance use (SU) treatment outcomes in a predominantly African American and unemployed sample of people with HIV. N = 60 participants were enrolled in an abstinence-focused inpatient SU treatment center, followed by outpatient treatment sessions. At 12-months follow-up, the survival rate (i.e. those who did not reuse substances) was 37.6% (non-SGM group) vs. 4.8% (SGM group). The impact of SGM status on reuse was .54 log odds, p = .11, which translates to a 71.8% increase in the hazard of reusing substances for SGM vs. non-SGM individuals. For both groups, frequency of reuse remained stable and problems associated with SU decreased over time. Results suggest a potentially clinically relevant finding that SGM individuals have possible heigh-tened risk of SU after a mixed inpatient-outpatient program. ClinicalTrials.gov trial registration number: NCT01351454.