Association Between Time From Surgery to Radiation Therapy and Multimodality Treatment Outcomes in HPV+ Head and Neck Cancer: A Multi-Institutional Cohort Experience.

Purpose: Oropharyngeal squamous cell cancers (OPSCCs) are traditionally managed with surgery and, if indicated, adjuvant radiation therapy (RT) with or without chemotherapy. NCCN recommends keeping the time from surgery to the start of RT (TSRT) within 6 weeks to avoid possibly compromising patient outcomes. HPV+ OPSCCs behave more favorably than HPV- OPSCCs. We hypothesized that TSRT beyond 6 weeks may not portend poorer outcomes for the former. Methods: We identified nonmetastatic, high-risk HPV+ OPSCCs treated with multimodal therapy at 2 institutions. Prolonged TSRT was defined as >6 weeks and was evaluated for association with recurrence-free survival (RFS). Radiation treatment time (RTT; time from the first to the last day of RT), total treatment package time (TTPT; time from surgery to the end of adjuvant treatments), de-escalated RT (dose ≤56 Gy), concurrent chemotherapy, smoking history, and treatment institution were evaluated as possible confounders. Results: In total, 96 patients were included. The median follow-up time was 62 months (4-123 months); 69 patients underwent transoral robotic surgeries, and 27 received open surgeries. The median postoperative RT dose was 60 Gy (50-70.8 Gy). The median TSRT, RTT, and TTPT were 38 days (11-208), 43 days (26-56 days), and 81 days (40-255 days), respectively. Ten patients failed treatment at a median of 8 months (4-64 months). Two locoregional and 4 distant failures occurred in the group without prolonged TSRT, whereas 2 locoregional and 2 distant failures were recorded in the prolonged TSRT group. Prolonged TTPT, de-escalated RT, chemotherapy, smoking history, and treatment institution were not associated with treatment failure. RTT was dropped from our analyses as no events appeared in the prolonged RTT group, and no reliable hazard ratio could be computed. Conclusions: TSRT > 6 weeks was not significantly associated with inferior outcomes in the postoperative management of HPV+ OPSCCs. Longer TSRT may facilitate better recovery from surgical toxicity, as needed, without compromising oncologic outcomes. The TSRT goal for these cancers should be investigated in future studies.

Community Culture Survey - Revised: Measuring neighborhood culture and exploring geographic, socioeconomic, and cultural determinants of health in samples across the United States and in Thailand.

Objectives: Research on links between social, geographic, and cultural determinants of health has been thwarted by inadequate measures of culture. The purpose of this study was to improve the measurement of community culture, defined as shared patterns of attitudes and behaviors among people within a neighborhood that distinguish it from others, and to examine dimensions of culture, independent of socioeconomic and demographic factors, and their relationships with health. Study design: A survey research design with correlational analyses was used. Methods: A survey packet including the Community Culture Survey - Revised (CCS-R), demographic, health, and other individual-level measures was administered through convenience sampling across the United States (US) and to a sample in Thailand from 2016 to 2018. US county-level variables were obtained from zip codes. Results: 1930 participants from 49 US states (n = 1592) and Thailand (n = 338) completed all CCS-R items, from which 12 subscales were derived: Social Support & Connectedness, Responsibility for Self & Others, Family Ties & Duties, Social Distress, Urban Diversity, Discontinuity, Church-Engaged, External Resource-Seeking, Locally Owned Business-Active, Power Deference, Next Generation Focus, and Self-Reliance. Neighborhood culture subscale scores varied more by geography than by participant's demographics. All subscales predicted one or more health indicator, and some of these relationships were significant after adjusting for participant age and county-level socioeconomic variables. Most of the significant differences on subscales by race/ethnicity were no longer significant after adjusting for participant's age and county-level socioeconomic variables. Most rural/urban and regional differences in culture within the US persisted after these adjustments. Based on correlational analyses, Social Support & Connectedness and Responsibility for Self & Others were the best predictors of participants' overall health and quality of life, and Responsibility for Self & Others was the best predictor (inversely) of the CDC's measures of social vulnerability. Conclusions: Neighborhood culture is measurable, multi-dimensional, distinct from race/ethnicity, and related to health even after controlling for age and socioeconomic factors. The CCS-R is useful for advancing research and practice addressing the complex interactions between individuals, their neighborhood communities, and health outcomes.

The EORTC QLQ43 and FACT H&N questionnaires of quality of life at 1 and 5 years after treatment and dental care in head and neck cancer patients: a pilot study.

PURPOSE: This study aimed to examine health-related quality of life (HRQoL) in head and neck cancer patients at 1 and 5 years after successful treatment of their tumors, and to explore the usefulness of 2 instruments for assessing the need of dental care services. METHODS: This cross-sectional pilot study included 20 adult patients with head and neck cancer who completed the Functional Assessment of Cancer Therapy-Head and Neck (FACT H&N) Symptom Index and the European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-H&N43) after 1 and 5 years of treatment. RESULTS: Mean (standard deviation, SD) scores of the FACT H&N Symptom Index were higher (better HRQoL) at 5 years than at 1 year (24.1 [4.4] vs. 21.1 [6.4]; p = 0.236). Only three of the ten items of FACT H&N (swallow, pain in mouth/throat or neck, and solid foods) evaluated oral health. In the EORTC QLQ-H&N43 questionnaire, scores were lower at 5 years (better HRQoL) in almost all multi- and single-item symptoms. This questionnaire includes four multi-item scales (pain in the mouth, social eating, swallowing, and problems with teeth) measuring dental and orthodontic needs. CONCLUSION: HRQoL in patients with head and neck cancer improved with the length of follow-up. The EORTC QLQ-H&N43 has more items addressing oral health compared to the FACT H&N Symptom Index and may be more adequate to assess the need of dental therapy in clinical practice.

Adalimumab for the Treatment of Non-Infectious Uveitis: A Real Life Experience.

OBJECTIVE: To describe the efficacy and safety of adalimumab for the treatment of non-infectious uveitis (NIU) in four Uveitis Units from tertiary Spanish hospitals. METHODS: Multicenter and retrospective clinical cohort study including all patients with NIU treated with adalimumab from January 2012 to October 2022 in four uveitis units was performed. Efficacy was measured with the number of relapses, ocular inflammation and reduction in immunosuppression and corticosteroid dosage before and after adalimumab use. We collected data regarding adverse effects and examined the immunogenicity of adalimumab. RESULTS: One hundred and twenty-two patients (59% females), with a mean age of 48.6 years (SD = 14.8) accounting for 217 eyes were included. The majority (92.6%) were Caucasian. Uveitis analyzed were predominantly panuveitis (34.7%), bilateral (77.9%), acute (41.5%), and non-granulomatous (90%). Most of them were immune mediated (42.6%), and the main reason to initiate adalimumab was refractory disease (96.7%). The analysis was statistically significant due to the reduction in the number of immunosuppressive drugs as well as the dose of oral corticosteroids and the number of relapses during follow-up (p < 0.001). The decrease in ocular inflammation parameters and the improvement in visual acuity (p < 0.05) were also significant. There were no deaths due to the drug and only one reported case of serious infection. In total, 10.9% of 73 patients tested developed anti-adalimumab antibodies and 4.1% lupus-like. CONCLUSIONS: We consider adalimumab as a leading drug in the treatment of NIU with high safety and efficacy.

Study of late toxicity biomarkers of locally advanced head and neck cancer patients treated with radiotherapy plus cisplatin or cetuximab points to the relevance of skin macrophages (TOX-TTCC-2015-01).

PURPOSE: Radiotherapy (RT) with concomitant cisplatin (CRT) or cetuximab (ERT) are accepted treatment options for locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). Long-term adverse events (AEs) have a vast impact on patients' quality of life. This study explored tissue biomarkers which could help predict late toxicity. METHODS/PATIENTS: Single-institution prospective study including patients aged ≥ 18 with histologically confirmed newly diagnosed LA-SCCHN treated with RT and either concomitant cisplatin q3w or weekly cetuximab, according to institutional protocols. All patients underwent pre- and post-treatment skin biopsies of neck regions included in the clinical target volume. Angiogenesis, macrophages, and extracellular matrix (ECM) markers were evaluated by immunohistochemistry (IHC). RESULTS: From April 15, 2016, to December 11, 2017; 31 patients were evaluated [CRT = 12 (38.7%) and ERT = 19 (61.3%)]. 27 patients (87%) had received induction chemotherapy. All patients finished RT as planned. IHC expression of vasculature (CD34) and collagen (Masson's Trichrome) did not differ significantly between and within CRT and ERT arms. Conversely, an increased CD68 and CD163 macrophage infiltration expression was observed after treatment, without significant impact of treatment modality. Patients with higher late toxicity showed lower expression of macrophage markers in pre-treatment samples compared with those with lower late toxicity, with statistically significant differences for CD68. CONCLUSIONS: Angiogenesis and ECM biomarkers did not differ significantly between CRT and ERT. Macrophage markers increased after both treatments and deserve further investigation as predictors of late toxicity in LA-SCCHN patients. [Protocol code: TOX-TTCC-2015-01/Spanish registry of clinical studies (REec): 2015-003012-21/Date of registration: 27/01/2016].

Prospective evaluation of patient-reported outcomes of invisible ink tattoos for the delivery of external beam radiation therapy: the PREFER trial.

Introduction: Invisible ink tattoos (IITs) avoid cosmetic permanence of visible ink tattoos (VITs) while serving as more reliable landmarks for radiation setup than tattooless setups. This trial evaluated patient-reported preference and feasibility of IIT implementation. Methods and materials: In an IRB-approved, single institution, prospective trial, patients receiving proton therapy underwent IIT-based treatment setup. A survey tool assessed patient preference on tattoos using a Likert scale. Matched patients treated using our institutional standard tattooless setup were identified; treatment times and image guidance requirements were evaluated between tattooless and IIT-based alignment approaches. Distribution differences were estimated using Wilcoxon rank-sum tests or Chi-square tests. Results: Of 94 eligible patients enrolled, median age was 58 years, and 58.5% were female. Most common treatment sites were breast (18.1%), lung (17.0%) and pelvic (14.9%). Patients preferred to receive IITs versus VITs (79.8% pre-treatment and 75.5% post-treatment, respectively). Patients were willing to travel farther from home to avoid VITs versus IITs (p<0.01). Females were willing to travel (45.5% vs. 23.1%; p=0.04) and pay additional money to avoid VITs (34.5% vs. 5.1%; p<0.01). Per-fraction average +treatment time and time from on table/in room to first beam were shorter with IIT-based vs. tattooless setup (12.3min vs. 14.1min; p=0.04 and 24.1min vs. 26.2min; p=0.02, respectively). Discussion: In the largest prospective trial on IIT-based radiotherapy setup to date, we found that patients prefer IITs to VITs. Additionally, IIT-based alignment is an effective and efficient strategy in comparison with tattooless setup. Standard incorporation of IITs for patient setup should be strongly considered.

Association of chronotropic incompetence with reduced cardiorespiratory fitness in older adults with HIV.

OBJECTIVE: Understanding the physiological drivers of reduced cardiorespiratory fitness in people with HIV (PWH) will inform strategies to optimize healthspan. Chronotropic incompetence is common in heart failure and associated with low cardiorespiratory fitness yet is understudied in PWH. The objective was to determine the prevalence of chronotropic incompetence and its relationship with cardiorespiratory fitness. DESIGN: Participants were PWH at least 50 years of age with no prior history of heart failure or coronary heart disease who were enrolled in a randomized exercise trial. Baseline cardiopulmonary exercise testing (CPET) was used to measure cardiorespiratory fitness as peak oxygen consumption (VO2peak) and calculate the chronotropic index from heart rate values. Chronotropic incompetence was defined as an index less than 80%. RESULTS: The 74 participants were on average 61 years old, 80% Black or African American, and 93% men. Chronotropic incompetence was present in 31.1%. VO2peak was significantly lower among participants with chronotropic incompetence compared with participants without chronotropic incompetence [mean (SD) ml/min/kg: 20.9 (5.1) vs. 25.0 (4.5), P = 0.001]. Linear regression showed that chronotropic incompetence and age were independent predictors of VO2peak, but smoking and comorbidity were not. The chronotropic index correlated with VO2peak (r = 0.48, P < 0.001). CONCLUSION: Among older PWH without heart failure or coronary heart disease, chronotropic incompetence was present in approximately one-third of individuals and was associated with clinically relevant impaired cardiorespiratory fitness. Investigation of chronotropic incompetence in large cohorts which includes PWH and heart failure may contribute to strategies that promote healthy aging with HIV infection and offer a preclinical window for intervention.

Social vulnerability and traumatic brain injury hospitalizations from sports and recreation among pediatric patients in the United States.

PURPOSE: This study examined the associations between individual as well as neighborhood social vulnerability and sports and recreation-related traumatic brain injury (SR-TBI) hospitalizations among pediatric patients in the U.S. METHODS: We obtained 2009, 2010 and 2011 hospitalization data in the U.S. from the National Inpatient Sample (NIS) database, linked it to 2010 neighborhood social vulnerability index (SVI) data from the Centers for Disease Prevention and Control (CDC), and assigned U.S. hospitals to one of four SVI quartiles. SR-TBI outcomes studied include: odds of hospitalization, length of stay (LOS), and discharge to post-acute care (DTPAC). RESULTS: We found associations between race/ethnicity and all SR-TBI outcomes; however, sex, primary payer, and neighborhood overall SVI were only associated with LOS. Compared to White children, Native American children had almost three times higher odds of hospitalization for SR-TBI (OR: 2.82, 95% CI: 1.30, 6.14), 27% longer LOS (ß: 27.06, 95% CI: 16.56, 38.51), but 99.9% lower odds of DTPAC (OR: 0.001, 95% CI: 0.00, 0.01). Compared to children with private insurance, children with public insurance had 11% longer LOS (ß: 10.83, 95% CI: 8.65, 13.05). Hospitalization in neighborhood with higher overall SVI was associated with longer LOS (p < 0.0001). CONCLUSIONS: These findings suggest that individual and neighborhood social vulnerability can have a significant impact on the health outcomes of children, especially in the context of SR-TBI.

A Randomized Trial of Healthy Weight Gain in Athletic Individuals.

PURPOSE: The purpose of this study is to evaluate the outcomes of a 10-wk diet and exercise regimen designed to promote healthy weight gain with excess energy from peanut-containing or high-carbohydrate foods. METHODS: Nineteen male and 13 female athletes were randomly assigned to receive an additional 500 kcal·d -1 above typical intake through provision of either peanut-based whole foods/snacks (PNT group) or a similar, high-carbohydrate, peanut-free snack (CHO group) along with supervised, whole-body RT (3 d·wk -1 for 60-120 min). Body composition was assessed by dual-energyx-ray absorptiometry at baseline and postintervention. RESULTS: Total body mass (TBM) increased 2.2 ± 1.3 kg with 1.5 ± 1.1 kg as LBM after week 10. The PNT group ( n = 16; 27 ± 7 yr; 10 men, 6 women) gained less TBM than the CHO group ( n = 16; 23 ± 3 yr; 9 men, 7 women) (1.6 ± 1.1 kg vs 2.7 ± 1.2 kg, respectively, P = 0.007) with no differences in LBM (1.2 ± 1.1 kg vs 1.9 ± 1.0 kg, P = 0.136). CONCLUSIONS: These results suggest that the addition of 500 kcal·d -1 from whole foods/snacks in combination with a rigorous RT program promotes a similar weight gain of ~0.22 kg·wk -1 , primarily as LBM, over 10 wk in both male and female athletes. However, snack macronutrient content may impact the effectiveness of this regimen.

Comparative Evaluation of Proton Therapy and Volumetric Modulated Arc Therapy for Brachial Plexus Sparing in the Comprehensive Reirradiation of High-Risk Recurrent Breast Cancer.

Purpose: Recurrent or new primary breast cancer requiring comprehensive regional nodal irradiation after prior radiation therapy (RT) to the supraclavicular area and upper axilla is challenging due to cumulative brachial plexus (BP) dose tolerance. We assessed BP dose sparing achieved with pencil beam scanning proton therapy (PBS-PT) and photon volumetric modulated arc therapy (VMAT). Methods and Materials: In an institutional review board-approved planning study, all patients with ipsilateral recurrent breast cancer treated with PBS-PT re-RT (PBT1) with at least partial BP overlap from prior photon RT were identified. Comparative VMAT plans (XRT1) using matched BP dose constraints were developed. A second pair of proton (PBT2) and VMAT (XRT2) plans using standardized target volumes were created, applying uniform prescription dose of 50.4 per 1.8 Gy and a maximum BP constraint <25 Gy. Incidence of brachial plexopathy was also assessed. Results: Ten consecutive patients were identified. Median time between RT courses was 48 months (15-276). Median first, second, and cumulative RT doses were 50.4 Gy (range, 42.6-60.0), 50.4 Gy relative biologic effectiveness (RBE) (45.0-64.4), and 102.4 Gy (RBE) (95.0-120.0), respectively. Median follow-up was 15 months (5-33) and 18 months for living patients (11-33) Mean BP max was 37.5 Gy (RBE) for PBT1 and 36.9 Gy for XRT1. Target volume coverage of V85% (volume receiving 85% of prescription dose), V90%, and V95% were numerically lower for XRT1 versus PBT1. Similarly, axilla I-III and supraclavicular area coverage were significantly higher for PBT2 than XRT2 at dose levels of V55%, V65%, V75%, V85%, and V95%. Only axilla I V55% did not reach significance (P = .06) favoring PBS-PT. Two patients with high cumulative BPmax (95.2 Gy [RBE], 101.6 Gy [RBE]) developed brachial plexopathy symptoms with ulnar nerve distribution neuropathy without pain or weakness (1 of 2 had symptom resolution after 6 months without intervention). Conclusions: PBS-PT improved BP sparing and target volume coverage versus VMAT. For patients requiring comprehensive re-RT for high-risk, nonmetastatic breast cancer recurrence with BP overlap and reasonable expectation for prolonged life expectancy, PBT may be the preferred treatment modality.

Periodontal Pocket Therapy Using a Class IV Dental Diode Laser in Dogs: A Retrospective Analysis.

Class IV dental diode lasers have been introduced as a nonsurgical therapy for periodontal pockets in veterinary and human dentistry. This retrospective case series evaluates the use of Class IV dental diode laser therapy for abnormal periodontal pockets in a specialty veterinary dental practice. A hypothesis that the Class IV diode dental laser is a useful adjuvant modality in canine periodontal pocket therapy in the reduction of clinical pocket depth was made. This article discusses and demonstrates diode laser use in periodontal pocket therapy in a specialty veterinary dental practice and reviews the current literature. Inclusion in this study was limited to client-owned dogs with noted periodontal pocketing on any tooth type between 3 and 6 mm, which were treated with closed root planing (RP/C) and laser therapy who returned in 6 to 7 months for recheck of the pockets from the years 2017 to 2020. Twelve patients met the inclusion criteria. A total of 128 periodontal pockets were included in the study. Each periodontal pocket was a case receiving therapy. The mean periodontal pocket depth before the treatment is measured as 3.35 mm. The mean pocket depth of the periodontal pockets following treatment was 0.59 mm. The mean improvement in periodontal pocket depths after diode laser therapy when considering patient and tooth number using linear mixed-effects modeling was 2.63 mm (95% confidence interval [CI]: 1.81-3.46, P < .0001). No statistically significant results were observed for pocket type, as P values were greater than .05.

Real life results of direct-acting oral anticoagulants recommended-dose in obese vs normal-weight patients with venous thromboembolism.

BACKGROUND: There is scarce evidence on the effectiveness and safety of recommended-dose direct acting oral anticoagulants (DOACs) in obese patients with venous thromboembolism (VTE). MATERIAL AND METHODS: We used the data in the RIETE registry to compare the rates of VTE recurrences and major bleeding during long-term therapy with DOACs at recommended doses in patients with body mass index ≥30 kg/m2 (obese) vs. those with BMI 18.5-24.9 kg/m2 (normal weight). We performed regression models with competing risks for death. RESULTS: From January 2013 through October 2022, 2885 obese patients and 2676 with normal weight in RIETE received rivaroxaban (n = 3020), apixaban (n = 1754), edoxaban (n = 636) or dabigatran (n = 151). Median age was 63 years and 52 % were female. At baseline, obese patients were more likely to have diabetes (18.6 % vs. 8.4 %), hypertension (51.9 % vs. 31.4 %) or pulmonary embolism (67.7 % vs. 61 %), and less likely to have renal insufficiency (5.3 % vs. 16 %) or anaemia (21.8 % vs. 28 %%). During anticoagulation (median, 147 vs. 101 days), the obese had a similar rate of VTE recurrences (1.71 vs. 2.14 events per 100 patients-years; hazard ratio (HR): 0.81; 95 % CI: 0.49-1.34) or major bleeding (1.45 vs. 1.76 per 100 patients-years; HR: 0.91; 95 % CI: 0.52-1.59) than those with normal weight. These findings persisted after multivariable analysis (recurrent VTE, HR: 0.80; 95 % CI: 0.48-1.32; major bleeding, HR: 1.11; 95 % CI: 0.60-2.07). CONCLUSION: The use of DOACs at recommended doses in obese patients with VTE was associated with similar rates of VTE recurrences or major bleeding than in patients with normal weight.

Multidisciplinary Inflammatory Bowel Disease Conference: The Impact of the Expert Pathologist on Patient Care.

BACKGROUND: Multidisciplinary teams (MDT) aid the diagnosis and management of patients with inflammatory bowel disease (IBD) and improve patient outcomes. The direct impact of a gastrointestinal expert pathologist on MDT care of IBD patients is unknown. METHODS: A retrospective chart review was conducted evaluating all cases (N = 289) discussed at the IBD MDT conference at Carilion Roanoke Memorial Hospital from June 1, 2013, through December 31, 2019. Cases were discussed between 1 and 6 times at the conference. Data collected included demographics, diagnosis before and after conference, reason for diagnostic change, endoscopy findings, medications, surgeries, and clinical follow-up. RESULTS: Approximately 15% to 42% of patients had a change in diagnosis after the first 3 conferences. The majority of diagnostic changes after the first (84%), second (73%), and third (67%) conferences were due to expert pathologist interpretation. Indeterminate colitis was the most frequently changed diagnosis, and Crohn's disease was the most common new diagnosis after conference. Among patients with a diagnostic change, 28.6% to 38.5% of patients had a change in their IBD medication regimen, and 7.7% to 10.9% had a surgical intervention after the first 2 conferences. Approximately 54.2% to 60% of patients reported clinical improvement or remission within 6 months of the first 3 conferences. CONCLUSION: The majority of diagnostic changes made at the multidisciplinary IBD conference were due to histopathologic re-interpretation. A change in diagnosis at times led to significant modifications in medical or surgical management. An expert gastrointestinal pathologist is an essential MDT member for IBD management.

An expert gastrointestinal pathologist plays a critical role in the diagnosis of patients presented at multidisciplinary team inflammatory bowel disease conferences. Their input at these conferences significantly impacts patients' medical and surgical management and clinical outcomes.

Advances and Challenges in Conducting Clinical Trials With Proton Beam Therapy.

Advances in proton therapy have garnered much attention and speculation in recent years as the indications for proton therapy have grown beyond pediatric, prostate, spine, and ocular tumors. To achieve and maintain consistent access to this cancer treatment and to ensure the future viability and availability of proton centers in the United States, a call for evidence has been heard and answered by proton radiation oncologists. Answers provided in this review include the evolution of proton therapy research, rationale for proton clinical trial design, challenges in and barriers to the conduct of proton therapy research, and other unique considerations for the study of proton therapy.

Extracellular Perinexal Separation Is a Principal Determinant of Cardiac Conduction.

BACKGROUND: Cardiac conduction is understood to occur through gap junctions. Recent evidence supports ephaptic coupling as another mechanism of electrical communication in the heart. Conduction via gap junctions predicts a direct relationship between conduction velocity (CV) and bulk extracellular resistance. By contrast, ephaptic theory is premised on the existence of a biphasic relationship between CV and the volume of specialized extracellular clefts within intercalated discs such as the perinexus. Our objective was to determine the relationship between ventricular CV and structural changes to micro- and nanoscale extracellular spaces. METHODS: Conduction and Cx43 (connexin43) protein expression were quantified from optically mapped guinea pig whole-heart preparations perfused with the osmotic agents albumin, mannitol, dextran 70 kDa, or dextran 2 MDa. Peak sodium current was quantified in isolated guinea pig ventricular myocytes. Extracellular resistance was quantified by impedance spectroscopy. Intercellular communication was assessed in a heterologous expression system with fluorescence recovery after photobleaching. Perinexal width was quantified from transmission electron micrographs. RESULTS: CV primarily in the transverse direction of propagation was significantly reduced by mannitol and increased by albumin and both dextrans. The combination of albumin and dextran 70 kDa decreased CV relative to albumin alone. Extracellular resistance was reduced by mannitol, unchanged by albumin, and increased by both dextrans. Cx43 expression and conductance and peak sodium currents were not significantly altered by the osmotic agents. In response to osmotic agents, perinexal width, in order of narrowest to widest, was albumin with dextran 70 kDa; albumin or dextran 2 MDa; dextran 70 kDa or no osmotic agent, and mannitol. When compared in the same order, CV was biphasically related to perinexal width. CONCLUSIONS: Cardiac conduction does not correlate with extracellular resistance but is biphasically related to perinexal separation, providing evidence that the relationship between CV and extracellular volume is determined by ephaptic mechanisms under conditions of normal gap junctional coupling.

Noninferiority Clinical Trial of Adapted START NOW Psychotherapy for Outpatient Opioid Treatment.

Background: Medications for opioid use disorder (MOUD) such as buprenorphine is effective for treating opioid use disorder (OUD). START NOW (SN) is a manualized, skills-based group psychotherapy originally developed and validated for the correctional population and has been shown to result in reduced risk of disciplinary infractions and future psychiatric inpatient days with a dose response effect. We investigate whether adapted START NOW is effective for treating OUD in a MOUD office-based opioid treatment (OBOT) setting in this non-inferiority clinical trial. Methods: Patients enrolled in once weekly buprenorphine/suboxone MOUD OBOT were eligible for enrollment in this study. Participants were cluster-randomized, individually-randomized, or not randomized into either START NOW psychotherapy or treatment-as-usual (TAU) for 32 weeks of therapy. Treatment effectiveness was measured as the number of groups attended, treatment duration, intensity of attendance, and overall drug use as determined by drug screens. Results: 137 participants were quasi-randomized to participate in SN (n = 79) or TAU (n = 58). Participants receiving START NOW psychotherapy, when compared to TAU, had comparable number of groups attended (16.5 vs. 16.7, p = 0.80), treatment duration in weeks (24.1 vs. 23.8, p = 0.62), and intensity defined by number of groups attended divided by the number of weeks to last group (0.71 vs. 0.71, p = 0.90). SN compared to TAU also had similar rates of any positive drug screen result (81.0% vs. 91.4%, p = 0.16). This suggests that adapted START NOW is noninferior to TAU, or the standard of care at our institution, for treating opioid use disorder. Conclusion: Adapted START NOW is an effective psychotherapy for treating OUD when paired with buprenorphine/naloxone in the outpatient group therapy setting. Always free and publicly available, START NOW psychotherapy, along with its clinician manual and training materials, are easily accessible and distributable and may be especially useful for low-resource settings in need of evidence-based psychotherapy.

Manejo de la pandemia de COVID-19 en hospitalización domiciliaria en dos hospitales comarcales españoles: qué significó, quiénes atendimos, quién falleció y como evolucionó la asistencia a lo largo del tiempo / Management of COVID-19 pandemic in hospital at home in two regional Spanish hospitals. what it meant, who we cared for, who died and how assistance has evolved over time

Introducción. La Hospitalización a Domicilio (HAD) es una modalidad de ingreso alternativa que puede resultar de gran utilidad en momentos de estrés sanitario como la pandemia de COVID-19. En el presente trabajo se recoge el manejo de los pacientes ingresados con COVID-19 en HAD en dos hospitales comarcales españoles durante dos años.Métodos. Se realizó un estudio descriptivo, observacional y retrospectivo de los pacientes ingresados en HAD con COVID-19. Posteriormente se realizó un análisis para caracterizar a los pacientes que fallecieron en HAD o a 30 días del alta y otro para comparar el manejo entre la primera fase del estudio (2020) y la segunda (2021 y parte de 2022).Resultados. Se reclutaron 167 pacientes. Un 52,1% se trasladaron para vigilar que continuaban mejorando frente a un 40,7% en los que se hizo para vigilar que no empeoraran. Los pacientes que fallecieron en HAD resultaron más ancianos (87,5 años de media), más comórbidos y con mayor probabilidad de ser no reanimables en caso de paro cardiaco (No RCP) (85%). En la segunda fase del estudio se ingresaron pacientes más ancianos, más comórbidos y en mayor grado No RCP que los ingresados en 2020.Conclusiones. La HAD es un recurso útil para aumentar la resiliencia de los sistemas sanitarios en casos de estrés como supuso la enfermedad por COVID-19. El desarrollo y crecimiento de las unidades ya existentes, así como la creación de otras nuevas allá donde no existan, puede ser una herramienta básica para la medicina del futuro (AU)

Introduction. Home Hospitalization (HH) is an alternative hospitalization modality that can be very useful in times of health stress such as the COVID-19 pandemic. This paper includes the management of patients admitted with COVID-19 in HH in two county spanish hospitals for two years.Methods. A descriptive, observational and retrospective study of all patients admitted at HH with a diagnosis of COVID-19 disease was carried out. Subsequently, further analysis was carried out to characterize the patients who died in HH or 30 days after discharge and another to compare the management between the first phase of the study (2020) and the second one (2021 and part of 2022).Results. A total of 167 patients were recruited. A 52.1% moved to watch that the recovery continued compared to 40.7% in which it was done to watch that they did not worsen. The patients who died in HAD were older (mean 87.5 years), more comorbid and more likely to have do-not resucitate orders (DNR) in case of cardiac arrest (85%). In the second phase of the study, older patients, more comorbid patients and with a greater degree of DNR orders were admitted than those admitted throughout 2020.Conclusions. HAD is a useful resource to increase the resilience of health systems in cases of stress such as the disease caused by COVID-19. The development and growth of existing units, as well as the creation of new ones where they do not exist, could be a basic tool for the medicine of the future (AU)

Validation of a prognostic model for predicting larynx preservation outcome (TALK score) in a Southern European population

Objective Larynx preservation is the current standard for locally advanced (LA) laryngeal/hypopharyngeal tumors, but not all patients respond as expected. TALK score model measures four variables (T-staging, albumin levels, liquor consumption and Karnofsky score) to determine which cases are best suited to preservation treatment scheme. We aimed to validate this prognostic model in a Southern European population. Methods We retrospectively evaluated 175 patients diagnosed from July 2008 to December 2015 with LA laryngeal/hypopharyngeal carcinoma and treated with a laryngeal preservation scheme comprising induction chemotherapy followed by concomitant chemotherapy and radiotherapy. We applied the TALK score model to predict larynx preservation rate. Results Of the 175 patients evaluated, 96.6% were men, 98.3% were smokers and 77.1% misused alcohol. Tumors were laryngeal 66.3% vs 33.7% in hypopharynx, and all were either stage III (37.7%) or stage IV (62.3%). TALK prognostic subgroups were: good risk 40.0%; intermediate risk 52.5%; and poor risk 7.5%. With a median follow-up of 40.1 months, larynx preservation rate, laryngectomy-free survival and overall survival at 3 years was 84.5%, 63.7% and 68.2%, respectively. Although TALK score was not predictive of 3-year larynx preservation rate (good risk 85.5%; intermediate risk 83.1%; poor risk 91.6%), it was predictive of 3-year overall survival (good risk 81.9%; intermediate risk 62.9%; poor risk 33.5%) and 3-year laryngectomy-free survival (good risk 75.6%; intermediate risk 59.6%; poor risk 30.7%) Conclusion TALK model could predict OS and laryngectomy-free survival, helping clinicians to decide which patients should avoid laryngeal preservation and undergo laryngectomy after diagnosis (AU)