Daily opioid and stimulant co-use and nonfatal overdoses in the context of social disadvantage: Findings on marginalized populations.

OBJECTIVE: Opioids and stimulants are increasingly implicated in overdose deaths, particularly among minoritized groups. We examined daily opioid and cocaine co-use, nonfatal overdoses, and naloxone carrying among minoritized people who inject drugs (PWID). METHODS: The study derived data from 499 PWID in Baltimore City, MD, recruited using street-based outreach between 2016 and 2019. Participants reported overdoses; sociodemographic characteristics; and use of nonmedical prescription opioids, heroin, cocaine, and naloxone. RESULTS: Among the participants, the mean age was 46, 34 % were female, 64 % self-identified as Black, and 53 % experienced recent homelessness. Black PWID, compared to White PWID, were as likely to use opioids and cocaine daily but were 61 % less likely to have naloxone. After controlling for sociodemographic characteristics, women (aOR:1.88, 95%CI: 1.14, 3.11), persons experiencing homelessness (aOR:3.07, 95%CI: 1.79, 5.24), and those who experienced a recent overdose (aOR:2.14, 95%CI: 1.29, 3.58) were significantly more likely to use opioids and any form of cocaine every day. In a subanalysis of only female PWID, females engaged in sex work (aOR:2.27, 95%CI: 1.02, 5.07) and females experiencing recent homelessness (aOR:5.82, 95%CI: 2.50, 13.52) were significantly more likely to use opioids and cocaine daily. Furthermore, females (aOR:1.69, 95%CI:1.03, 2.77), persons experiencing homelessness (aOR:1.94, 95%CI:1.16, 3.24), and those with higher educational attainment (aOR:2.06, 95%CI:1.09, 3.91) were more likely to often/always carry naloxone, while Black PWID were less likely to have naloxone (aOR:0.39, 95%CI:0.22, 0.69). CONCLUSIONS: These findings highlight the need for targeted naloxone distribution and other harm-reduction interventions among minoritized groups in urban areas.

Osteoporotic fracture admissions compared to other major medical admissions in Irish public hospitals.

Multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis. Hospital care represents the costliest portion of health services. We found public hospital bed days for fragility fractures in Ireland increased by 43% between 2008 and 2017 which exceeded those for other common diseases. INTRODUCTION: Recent multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis, manifesting clinically as fragility fractures (FF). International reports show that FF incidence, rate of hospital admission and cost are similar or greater than those for breast cancer, myocardial infarction and stroke. Studies addressing the illness burden of osteoporosis in Ireland are few, and none compares fragility fractures to other common chronic diseases. METHODS: A retrospective analysis of national administrative data for all public hospital admissions was performed on adults aged 50 years and older from January 2008 to December 2017. RESULTS: In 2017, public hospital bed days for FF totalled 249,887 outnumbering Chronic Obstructive Pulmonary Disease (COPD): 131,897; 6 solid cancers (CA): 118,098; myocardial infarction (MI): 83,477; and diabetes mellitus (DM): 31,044. Bed days for FF increased by 43% between 2008 and 2017, in contrast to a 32%, 28% and 31% reduction for CA, MI and DM, respectively, and a 12% increase for COPD. Public hospital bed days for FF in 2016 were greater than MI, stroke, atrial fibrillation and chest pain combined but less than a combination of COPD, pneumonia and lower respiratory tract infection. CONCLUSION: Osteoporotic fractures represent a large and rapidly increasing illness burden amongst older Irish adults, with substantial care requirements and the resulting onus on our healthcare system. Urgent action is needed to address this public health issue and the services for those at risk of fracture.

Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis.

OBJECTIVE: The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS: Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS: In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 ± 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD3 and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. CONCLUSION: Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.

Seroprevalence of SARS-CoV-2 antibodies, associated epidemiological factors and antibody kinetics among healthcare workers in Connecticut.

BACKGROUND: Healthcare workers (HCWs) are at the front line of the ongoing coronavirus 2019 (COVID-19) pandemic. Comprehensive evaluation of the seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) among HCWs in a large healthcare system could help to identify the impact of epidemiological factors and the presence of symptoms on the immune response to the infection over time. AIM: To determine the seroprevalence of SARS-CoV-2-specific antibodies among HCWs, identify associated epidemiological factors and study antibody kinetics. METHODS: A longitudinal evaluation of the seroprevalence and epidemiology of SARS-CoV-2-specific antibodies was undertaken in approximately 30,000 HCWs in the largest healthcare system in Connecticut, USA. FINDINGS: At baseline, the prevalence of SARS-CoV-2 antibody among 6863 HCWs was 6.3% [95% confidence interval (CI) 5.7-6.9%], and was highest among patient care support (16.7%), medical assistants (9.1%) and nurses (8.2%), and lower for physicians (3.8%) and advanced practice providers (4.5%). Seroprevalence was significantly higher among African Americans [odds ratio (OR) 3.26 compared with Caucasians, 95% CI 1.77-5.99], in participants with at least one symptom of COVID-19 (OR 3.00, 95% CI 1.92-4.68), and in those reporting prior quarantine (OR 3.83, 95% CI 2.57-5.70). No symptoms were reported in 24% of seropositive participants. Among the 47% of participants who returned for a follow-up serological test, the seroreversion rate was 39.5% and the seroconversion rate was 2.2%. The incidence of re-infection in the seropositive group was zero. CONCLUSION: Although there is a decline in the immunoglobulin G antibody signal over time, 60.5% of seropositive HCWs had maintained their seroconversion status after a median of 5.5 months.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.

Flow-induced concentration gradients in shear-banding of branched wormlike micellar solutions.

HYPOTHESIS: Shear-banding of branched wormlike solutions is a topic of active investigation which has not been fully elucidated. Here, we surmise that flow-induced microstructuring in the shear banding regime is associated with spatial concentration gradients. EXPERIMENTS: The experiments focus on the flow-induced behavior of a CTAB/NaSal wormlike micellar system. A unique approach based on a microfluidic-spitter geometry, combined with particle-image velocimetry and high-speed video microscopy, is used to separate the streams flowing out from the core and the near wall zones of the microchannel. FINDINGS: Here, we present the first direct experimental evidence of the correlation between phase separation and shear banding. By increasing the pressure-drop across a microcapillary, the onset of a grainy texture close to the wall, showing a flow-induced demixing effect, is observed. We use a splitter to measure effluent streams from the center and the near-wall zones in terms of viscosity, conductance and dry mass. We observe that phase-separation induced by the flow correlates with chemical concentration gradients. This confirms our hypothesis that shear-induced local de-mixing of the system is strongly related to chemical concentration gradients.

Contributions of biogenic material to the atmospheric ice-nucleating particle population in North Western Europe.

A minute fraction of atmospheric particles exert a disproportionate effect on the phase of mixed-phase clouds by acting as ice-nucleating particles (INPs). To understand the effects of these particles on weather and climate, both now and into the future, we must first develop a quantitative understanding of the major INP sources worldwide. Previous work has demonstrated that aerosols such as desert dusts are globally important INPs, but the role of biogenic INPs is unclear, with conflicting evidence for their importance. Here, we show that at a temperate site all INPs active above -18 °C at concentrations >0.1 L-1 are destroyed on heating, consistent with these INPs being of biological origin. Furthermore, we show that a global model of desert dust INPs dramatically underestimates the measured INP concentrations, but is consistent with the thermally-stable component. Notably, the heat sensitive INPs are active at temperatures where shallow cloud layers in Northern Europe are frequently observed to glaciate. Hence, we suggest that biogenic material is important for primary ice production in this region. The prevalence of heat sensitive, most likely biogenic, INPs in this region highlights that, as a community, we need to quantify the sources and transport of these particles as well as determine their atmospheric abundance across the globe and at cloud altitudes.

Immobilization of whole cells of Lactococcus lactis containing high levels of a hyperthermostable ß-galactosidase enzyme in chitosan beads for efficient galacto-oligosaccharide production.

Galacto-oligosaccharides (GOS) are prebiotic food ingredients that are proposed to stimulate the growth of beneficial gut microorganisms, particularly bifidobacteria. Previously, we developed a method for efficient GOS production using whole cells of Lactococcus lactis containing high levels of a hyper-thermostable ß-galactosidase enzyme from Sulfolobus solfataricus. In this study, a recombinant DNA removal and whole-cell enzyme immobilization process was developed to produce GOS from lactose before removal of the immobilized whole-cell enzyme, which could be reused for subsequent applications. Chitosan was found to be a superior immobilization material compared with alginate, as it retained its bead structure during the high temperature (90°C) used here for GOS production. Prior to immobilization, the recombinant DNA was degraded in the whole cells using UV treatment, resulting in an immobilized whole-cell enzyme that was free of recombinant DNA and with minimum effect on the efficiency of the enzyme. The optimum pH and temperature for GOS synthesis using the chitosan beads was pH = 5.5 and 90°C. The highest GOS production using the chitosan beads occurred with 40% initial lactose resulting in 150 g/L of GOS (tri-oligosaccharides and tetra-oligosaccharides) in addition to di-oligosaccharide GOS products that were not quantified. Notably, the highest lactose conversion rate was found using lower starting lactose concentrations, with more than 60% conversion into tri-oligosaccharides and tetra-oligosaccharides. The immobilized enzyme retained ∼50% activity after 2 cycles of GOS production. In conclusion, the chitosan-immobilized whole-cell enzyme can be used for efficient GOS production that is free of the whole-cell enzyme as well as detectable recombinant DNA.

Analysis of head impacts during sub-elite hurling practice sessions.

The reported incidence of head and neck injuries in hurling is 0.12 per 1000 hours, but no previous research has quantified head impact characteristics in this sport. Here, a wireless accelerometer and gyroscope captured head impacts, in 20 senior club level hurling players. Peak linear and rotational acceleration and impact location were recorded during three hurling training sessions, each player participating once. A mean of 27.9 impacts (linear acceleration >10g) per player, per session were recorded; 1314 impacts during a total exposure time of 247 minutes. Only 2.6% impacts had peak linear acceleration of >70g and 6.2% had peak rotational acceleration >7900 rad/s2. There were significant differences in the number and magnitude of impacts, quantified by the accelerometer, between three training sessions of differing intensity (ŋ2 0.03-0.09, p < 0.001). This study represents a first step in quantifying head impacts during hurling, demonstrating the feasibility of this technology in the field. The sensors were able to discriminate between sessions of varying intensity. These data can be used to develop athlete monitoring protocols and may be useful in developing innovative helmet-testing standards for hurling. The potential for this technology to provide feedback has clinical utility for team medical personnel.

Dynamic sentinel node biopsy for penile cancer: an initial experience in an Irish Hospital.

BACKGROUND: The presence of nodal metastases is the single most important prognostic factor in penile cancer. However, reliable assessment of nodal status in clinically node-negative (cN0) patients poses a challenge. Approximately 20% of these patients harbour occult nodal metastases. Currently available non-invasive radiological investigations are unreliable in excluding micrometastatic disease. AIM: Dynamic sentinel node biopsy (DSNB) is a minimally invasive procedure for assessing lymph node involvement. We report our initial experience with DSNB in assessing the status of regional lymph nodes in cN0 penile cancer patients. METHODS: DSNB was performed in penile cancer patients with at least one cN0 groin. All patients undergoing DSNB at our institution were included. Lymphoscintigraphic images were obtained from all patients, after intradermal, peritumoral injection of a Technetium-99m nanocolloid. The sentinel nodes were defined as the nodes identified on lymphoscintigraphy, which were also radioactive intraoperatively using a gamma probe. RESULTS: In total, 18 groins from 11 patients underwent DSNB. Of these, 11 patients underwent bilateral DSNB and 4 had unilateral DSNB. The mean (range) age of patients at the time of presentation of their primary tumour was 63 (39-78) years. A mean of 1.2 nodes per groin was retrieved. One lymph node was positive in one patient, who subsequently underwent a bilateral inguinal lymph node dissection. Overall, the median (range) follow-up was 12.8 (2.7-31.3) months with no local or regional recurrences. CONCLUSION: Further cases and longer follow-up will define the accuracy of this technique in the Irish population.

Heterogeneous Ice Nucleation by Soufriere Hills Volcanic Ash Immersed in Water Droplets.

Fine particles of ash emitted during volcanic eruptions may sporadically influence cloud properties on a regional or global scale as well as influencing the dynamics of volcanic clouds and the subsequent dispersion of volcanic aerosol and gases. It has been shown that volcanic ash can trigger ice nucleation, but ash from relatively few volcanoes has been studied for its ice nucleating ability. In this study we quantify the efficiency with which ash from the Soufriere Hills volcano on Montserrat nucleates ice when immersed in supercooled water droplets. Using an ash sample from the 11th February 2010 eruption, we report ice nucleating efficiencies from 246 to 265 K. This wide range of temperatures was achieved using two separate droplet freezing instruments, one employing nanolitre droplets, the other using microlitre droplets. Soufriere Hills volcanic ash was significantly more efficient than all other ash samples that have been previously examined. At present the reasons for these differences are not understood, but may be related to mineralogy, amorphous content and surface chemistry.

Phenotype-driven molecular autopsy for sudden cardiac death.

A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths.

Late effects of chemotherapeutic agents on renal function in childhood cancer survivors: a review of the literature.

BACKGROUND: Survival outcomes for childhood cancers have significantly improved. As more children are now surviving into adulthood, knowledge of the long-term effects of childhood cancer treatments has become the focus of research. AIM: To determine what is known about the incidence of renal function impairment in childhood cancer survivors and to determine what is known about risk factors for developing renal function impairment following childhood cancer treatment. METHODS: A comprehensive literature search was preformed to identify studies that investigated renal dysfunction in patients who were diagnosed with childhood cancer and treated with potentially nephrotoxic chemotherapeutic agents. Potentially nephrotoxic chemotherapeutic agents identified in the selection criteria include ifosfamide, cisplatin, carboplatin and methotrexate. RESULTS: 15 papers met the inclusion criteria. Renal function impairment was reported in 15 of 15 studies included in this literature review. The incidence of ifosfamide induced nephrotoxicity varied from 1 to 50 %. This variation may be due to the heterogeneity of reported outcome measurements. Treatment with cisplatin and carboplatin was associated with hypomagnesemia. The prevalence of hypomagnesemia varied from 7 to 29 %. This variation may be due to diversity of treatment protocols. The incidence of renal dysfunction following treatment with methotrexate was reported as 1.8 % and completely reversible. CONCLUSION: As more childhood cancer survivors are reaching adulthood, a new niche of cancer research has emerged. Researchers are now investigating the late effects due to cytotoxic treatments. Renal function impairment is a potential late effect of treatment with nephrotoxic chemotherapeutic agents including ifosfamide, cisplatin, carboplatin and methotrexate.

Anticholinergic burden in schizophrenia and ability to benefit from psychosocial treatment programmes: a 3-year prospective cohort study.

BACKGROUND: Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown. METHOD: Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS: Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by -0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for. CONCLUSIONS: Anticholinergic burden has a significant impact on patients' ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.

An introduction to standard setting methods in dentistry.

The aim of this paper is to give readers an overview of contemporary standard setting methods used within dental education, and to provide a better understanding of the subject. We hope that it will be of benefit not just to those in academic dentistry, but all practitioners involved with both undergraduate and postgraduate assessment.