Prevalence of comorbid substance use disorders among people with opioid use disorder: A systematic review & meta-analysis.

BACKGROUND: Comorbid substance use disorders (SUDs) among people with opioid use disorder (OUD) contribute to poor clinical outcomes, including overdose and mortality. We present the first systematic review and meta-analysis to estimate the prevalence of specific non-opioid SUDs among people with OUD. METHODS: We searched Embase, PsycINFO, and MEDLINE from 1990 to 2022 for studies that used Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) criteria to assess the prevalence of non-opioid SUDs among individuals with OUD. We used random-effects meta-analyses with 95% Confidence Intervals (CIs) to pool current and lifetime prevalence estimates separately. Meta-regressions and stratified meta-analyses were used to examine differences in prevalence estimates by sample characteristics and methodological factors. RESULTS: Of the 36,971 publications identified, we included data from 194 studies and 77,212 participants with OUD. The prevalence of any comorbid SUD among people with OUD was 59.5% (95%CI 49.1-69.5%) for current non-opioid SUDs, with 72.0% (95%CI 52.5-87.9%) experiencing a comorbid SUD in their lifetime. Of the studies that examined current comorbid SUDs, cocaine use disorder (30.5%, 95%CI 23.0-38.7%) was most common, followed by alcohol (27.1%, 95%CI 24.4- 30.0%), cannabis (22.7%, 95%CI 19.0-26.6%), sedative (16.1%, 95%CI 13.1-19.3%), and methamphetamine (11.4%, 95%CI 6.8-17.1%) use disorders. Substantial heterogeneity (I2>90%) across estimates was observed. Substantial heterogeneity (I2>90%) was observed across estimates, with significant variations in prevalence identified across geographic locations, recruitment settings, and other study-level factors. CONCLUSION: Findings from this study emphasize the importance of comorbid SUD treatment access for people with OUD. Our estimates can inform the provision of treatment and harm reduction strategies for people with OUD and specific subpopulations.

Liquid-core polymer nanocapsules prepared using flash nanoprecipitation.

Hypothesis: Nanocapsules, consisting of a solid shell and a liquid core, are an interesting class of materials with numerous applications and various methods of synthesis. One common method for synthesis of nanoparticles is flash nanoprecipitation. For a multicomponent system consisting of a liquid (n-hexadecane) and solid (polystyrene), we hypothesize that nanocapsules will form from droplets created by the turbulent mixing in the nanoprecipitation process. We anticipate n-hexadecane molecules should phase-separate more rapidly from the non-solvent, thus becoming the core, while the more slowly diffusing polystyrene forms the shell. Additionally, we predict that the amount of both n-hexadecane and polystyrene used in creating these nanocapsules will influence capsule size. Experiments: Using flash nanoprecipitation, we synthesized nanocapsules of a polystyrene shell and liquid core of n-hexadecane. We varied the concentrations of both polystyrene and n-hexadecane and characterized the resulting dispersions using dynamic light scattering and scanning electron microscopy. Findings: Our experiments demonstrate that flash nanoprecipitation can be employed to create nanocapsules with radii ranging from 50 to 200 nm, with radii of the n-hexadecane cores between 35 and 175 nm and polystyrene shells with thickness ranging from 7 to 62 nm. We used various methods of analysis to confirm this core/shell morphology and applied a droplet model to explain the dependence of particle size on initial concentrations of n-hexadecane and polystyrene.

Aqueous Zn-Tetrazine Batteries with Cooperative Zn2+/H+ Insertion.

We present the investigation of 1,2,4,5-tetrazine derivatives as low-cost and synthetically modular organic electrode materials in rechargeable aqueous Zn-ion batteries (AZIBs). The substituents at the 3,6-positions of tetrazine were found to be critical for cycling stability. While heteroatom substituents (chloro, methoxy, and pyrazole) lead to the rapid decomposition of electrode materials in the electrolyte, the installation of phenyl groups enhances the cycling stability via π-π stacking. Spectroscopic characterization suggests a cooperative Zn2+ and H+ insertion mechanism. This unique cooperativity of Zn2+ and H+ leads to a steady discharge plateau in contrast to the undesirable sloping voltage profile typically observed in Zn-organic batteries.

"Sex Seems Less Important When You Are Worried About a Deadly Virus." A Content Analysis of Reported Reasons for Changes in Sexual Behavior and Satisfaction During the COVID-19 Pandemic.

The purpose of this study is to assess how the COVID-19 pandemic impacted various sexual behaviors and levels of sexual and relationship satisfaction by performing a content analysis of participants' (N = 1051 American adults) responses to open-ended survey questions. Results revealed a variety of impacts that increased, decreased, or otherwise qualitatively changed sexual behavior and satisfaction. Major themes included emotions and mental health, changes in routines, social distancing and fears related to COVID-19, and changes in romantic relationships. These findings are contextualized within the emerging quantitative research on COVID-19 and sexuality, and areas for future research based on these findings are discussed.

Mapping Critical Residues in ATG11's Coiled-Coil 2 Domain that Block Multiple Interactions and Disrupt Selective Autophagy.

Selective autophagy is a conserved subcellular process that maintains the health of eukaryotic cells by targeting damaged or toxic cytoplasmic components to the vacuole/lysosome for degradation. A key player in the initiation of selective autophagy in S. Cerevisiae (baker's yeast) is a large adapter protein called Atg11. Atg11 has multiple predicted coiled-coil domains and intrinsically disordered regions, is known to dimerize, and binds and organizes other essential components of the autophagosome formation machinery, including Atg1 and Atg9. We performed systematic directed mutagenesis on the coiled-coil 2 domain of Atg11 in order to map which residues were required for its structure and function. Using yeast-2-hybrid and coimmunoprecipitation, we found only three residues to be critical: I562, Y565, and I569. Mutation of any of these, but especially Y565, could interfere with Atg11 dimerization and block its interaction with Atg1 and Atg9, thereby inactivating selective autophagy.

Palliative care research centre's move into social media: constructing a framework for ethical research, a consensus paper.

BACKGROUND: Social media (SM) have altered the way we live and, for many, the way we die. The information available on even the rarest conditions is vast. Free from restrictions of mobility, time and distance, SM provides a space for people to share experiences of illness, death and dying, and potentially benefit from the emotional and practical support of others n similar positions. The communications that take place in these spaces also create large amounts of 'data' which, for any research centre, cannot be ignored. However, for a palliative care research centre the use of this 'data' comes with specific ethical dilemmas. METHODS: This paper details the process that we, as a research, went through in constructing a set of ethical guidelines by which to work. This involved conducting two consensus days; one with researchers from within the centre, and one with the inclusion of external researchers with a specific interest in SM. RESULTS: The primary themes that emerged from the consensus meetings includes; SM as a public or private space; the status of open and closed groups; the use of historical data; recruiting participants and obtaining informed consent and problems of anonymity associated with dissemination. CONCLUSIONS: These are the themes that this paper will focus on prior to setting out the guidelines that we subsequently constructed.

Improving the well-being of men by Evaluating and Addressing the Gastrointestinal Late Effects (EAGLE) of radical treatment for prostate cancer: study protocol for a mixed-method implementation project.

INTRODUCTION: Radiotherapy treatment for prostate cancer can cause bowel problems, which may lead to severe difficulties for cancer survivors including limiting travel, work or socialising. These symptoms can appear at any time following radiotherapy. This study focuses on the early identification and protocol-based management of effects known to cause long-term, or even permanent, changes to the well-being of prostate cancer survivors. The rationale of this study is to improve the care offered to men and their families following pelvic radiotherapy for prostate cancer. METHOD AND ANALYSIS: Implementation research methodology will be used to adopt a multicomponent intervention at three UK centres. The intervention package comprises a standardised clinical assessment of relevant symptoms in oncology outpatient clinics and rapid referral to an enhanced gastroenterological service for patients identified with bowel problems. Gastroenterology staff will be trained to use an expert-practice algorithm of targeted gastroenterology investigations and treatments. The evaluation of the intervention and its embedding within local practices will be conducted using a mixed-methods design. The effect of the new service will be measured in terms of the following outcomes: acceptability to staff and patients; quality of life; symptom control and cost-effectiveness. Data collection will take place at baseline, 6 months (±2 months), and 12 months (±2 months) after entry into the study. ETHICS AND DISSEMINATION: The study has ethical approval from the North West-Liverpool East Research Ethics Committee and the appropriate NHS governance clearance. All participants provide written informed consent. The study team aim to publish the results of the study in peer-reviewed journals as well as at national and international conferences. TRIAL REGISTRATION NUMBER: UKCRN16974.

The use of a pro forma to improve quality in clerking vascular surgery patients.

At our institution, a large tertiary referral centre for vascular surgery, patients are often admitted directly to the ward and clerked by foundation year one (FY1) doctors. We found that these clerkings frequently fell short of national record keeping standards, potentially leading to an increased risk for patients during their hospital stay. In addition, we found that junior doctors did not feel confident in clerking vascular surgery patients. A literature review found that high quality clerkings were strongly linked to improved patient safety, and that the use of a pro forma was one method to improve compliance with documentation guidelines. We devised a clerking pro forma based on national guidelines and introduced it to the department. We found that the use of a pro forma significantly improved documentation standards across a number of domains, including patient demographics, presenting complaint, and family and social histories (p <0.05). Examinations were significantly more comprehensive, with cardiac and vascular examination as well as peripheral pulses documented (p <0.05). In conclusion, we found that using a pro forma helped to aid junior doctors in clerking new patients, and significantly improved the quality of their history and examinations. This leads to a potential positive impact on patient safety during their inpatient stay, and should be rolled out more widely across the hospital.

Treatment of iron deficiency anemia: practical considerations.

Iron deficiency anemia is a common problem worldwide, and doctors of all specialties need to be competent in its treatment. While most patients respond well to oral iron preparations, a substantial minority have side effects that make them adhere poorly to their treatment. For oral iron­intolerant patients, those responding poorly despite good adherence, and those with severe and/or symptomatic anemia, intravenous iron is an excellent alternative. It is, however, more expensive and carries a very small but potentially life­threatening risk of severe infusion­related hypersensitivity reactions. After outlining the main features of iron metabolism, in this review we compare the indications for therapy with oral and intravenous iron, and then focus on how to maximize the efficacy and safety of the two different routes.

Unusual radiologic presentation of monostotic fibrous dysplasia.

Fibrous dysplasia is a benign fibro-osseous lesion that can occur as an isolated skeletal lesion (monostotic form) or affect multiple skeletal sites (polyostotic form). In addition, fibrous dysplasia may be associated with single or multiple endocrinopathies, or with precocious puberty and cutaneous hyperpigmentation in McCune-Albright syndrome. Fibrous dysplasia usually appears as a well-defined radiolucent medullary lesion that is irregular, mildly expansive, and with a hazy opacity classically described as "ground glass" in appearance. In the long tubular bones, fibrous dysplasia may cause expansion of the bone contour with cortical thinning and endosteal scalloping. The shaft is typically involved, but the metaphysis may also be affected. These changes are usually recognizable on plain radiographs, but in cases where the lesion is difficult to visualize computed tomography may be beneficial. However, fibrous dysplasia may present with radiographic features that may mimic other benign fibro-osseous lesions, may be associated with other lesions, and even be confused with certain types of malignancies. We present a case of monostotic fibrous dysplasia in the proximal tibia of an 11-year-old girl with the unusual radiologic features of multifocal lytic lesions and cortical disruption. While most often the clinical presentation, laboratory findings, and imaging studies permit the diagnosis of fibrous dysplasia, in certain cases this may pose a diagnostic challenge. The diagnosis was confirmed by open biopsy.

The posterior approach for low retrorectal tumors in adults.

BACKGROUND AND AIMS: Retrorectal tumors are uncommon in adults and arise in different tissues in the presacral space. The aim of this study is to evaluate early complete surgical resection by a perineal approach as the therapy-of-choice for tumors under the sacral promontory. PATIENTS AND METHODS: We evaluated the posterior approach, especially intersphincteric and parasacrococcygeal excisions, in terms of resectability, morbidity, risk of recurrence, and anal function. The records of all patients who underwent a posterior surgical procedure in our institution for low-lying retrorectal tumors between 1994 and 2003 were reviewed. RESULTS: Sixteen patients (13 women and three men) were included in this study. The age range was 21 to 57 years (median of 37 years). Pathological findings included ten tailgut cysts, three teratomas, one leiomyoma, one dermoid cyst, and one schwannoma. Complete tumor resection was obtained in 15 patients. There was one case with a microscopic residual tumor. No postoperative mortality was seen, and a minor complication occurred in one patient. There was no anal dysfunction. The postoperative course was uneventful, with only one tumor recurrence at 5 months. The median follow up was 60 months (ranging from 18 to 132 months). CONCLUSION: In this study, the posterior approach allows complete resection of low retrorectal tumors, with low morbidity, no incontinence, nearly no recurrence, and no mortality.

An illustrative case of Muir-Torre syndrome: contribution of immunohistochemical analysis in identifying indicator sebaceous lesions.

BACKGROUND: Muir-Torre syndrome (MTS) is an autosomal dominant genodermatosis characterized by the association of at least 1 cutaneous sebaceous tumor and 1 internal malignancy, often arising in the gastrointestinal tract. It is secondary to germline mutations in DNA mismatch repair genes, mainly MLH-1 and MSH-2. OBSERVATIONS: We report the case of a 54-year-old man with a 2-year history of skin-colored papules clinically reminiscent of large sebaceous hyperplasias on the nose and back, but histologically diagnosed as sebaceous adenomas and epitheliomas. His family history was positive for colon cancer in the mother and 2 brothers. A colonoscopy done during the hospitalization revealed 2 sessile polyps in the left colon, both showing a low-grade dysplasia on the biopsy specimen. Immunohistochemical staining performed on the cutaneous and colic biopsy specimens revealed a lack of expression of MSH-2 and MSH-6. Genetic testing revealed microsatellite instability in the colon and cutaneous tumors. CONCLUSION: The immunohistochemical testing for MSH-2, MSH-6, and MLH-1 is useful for rapid identification of an underlying mismatch repair defect and early diagnosis of MTS.

Assessment of the efficacy of different statins in murine collagen-induced arthritis.

OBJECTIVE: Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) are widely used lipid-lowering agents. In addition to their well-known effect on cholesterol levels, statins have been reported to display antiinflammatory activities both in vitro and in vivo. In this context, in vivo prophylactic and therapeutic effects of simvastatin were recently demonstrated in mouse collagen-induced arthritis, a well-described experimental model for human rheumatoid arthritis (RA). The aim of this study was to further investigate in vivo effects of 3 different statins, atorvastatin, rosuvastatin, and simvastatin, using the same experimental model. METHODS: Different doses and routes of administration were used for the various statins in an attempt to elicit antiarthritic activity in preventive and curative treatment protocols. RESULTS: Atorvastatin and rosuvastatin had no in vivo efficacy, as indicated by clinical, histologic (synovial hyperplasia, exudate, and cartilage damage), immunologic (anti-type II collagen IgG production), and biochemical (interleukin-6, serum amyloid A, and glucocorticoid production) parameters of inflammation and autoimmunity. The previously described beneficial effects of administration of intraperitoneal simvastatin were reproduced in our experiments, but could be accounted for by very severe side effects of the treatment, leading to increased glucocorticoid levels. CONCLUSION: This work shows that different statins have no effect in a murine model of arthritis, an unexpected observation given the previously described therapeutic effect of statins in immune-mediated inflammatory diseases. It is still unclear whether statins will have benefit in the treatment of RA.

Histologic grade, but not SYT-SSX fusion type, is an important prognostic factor in patients with synovial sarcoma: a multicenter, retrospective analysis.

PURPOSE: To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS). PATIENTS AND METHODS: Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Federation Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months). RESULTS: Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metastasis-free survivals (MFS) were 84 months and 54.2% for SYT-SSX1 versus 50 months and 47.6% for SYT-SSX2 (P = .76). Univariate analyses showed that high histologic grade (grade 3), high mitotic count (>/= 10 mitoses/10 high-power fields), stage III disease, size greater than 7 cm, tumor necrosis, and presence of areas of poorly differentiated morphology were significant adverse prognostic factors for DSS and MFS, whereas SYT-SSX fusion type, tumor histology (biphasic v monophasic), and patient sex were not. Age greater than 35 years adversely affected DSS but not MFS. In multivariate analyses, histologic grade was the most significant prognostic factor for both DSS and MFS. CONCLUSION: For patients with localized SS, histologic grade but not SYT-SSX fusion type is a strong predictor of survival.

An isolated vertebral metastasis of urachal adenocarcinoma.

We describe a case of urachal adenocarcinoma arising in a 30-year-old woman. The patient underwent partial cystectomy. Three years later, she presented with an isolated metastasis to a thoracic vertebra, which was treated by vertebral corporectomy. Histologic findings are described, and the clinical findings, management, and metastatic patterns of this rare tumor, as well as the differential diagnosis on a biopsy specimen, are discussed.

Are there any prognostic factors for small intestinal stromal tumors?

BACKGROUND: Stromal tumors of the digestive tract, or gastrointestinal stromal tumors (GIST), originate from an intestinal mesenchymal precursor cell. Criteria that predict the outcome of small intestinal stromal tumors (SIST) after surgical resection are not clearly established. The aim of the study was to define prognostic criteria for SIST. METHODS: All c-kit positive SIST treated in our center over a 10-year period were reviewed. RESULTS: Eighteen patients with SIST treated by surgical resection were included. Overall actuarial 5-year survival was 74% (median follow-up of 69 months). We developed a panel of five criteria (tumor size, mitotic rate, proliferation index, presence of necrosis, and invasion of mucosa or adjacent structures) that permitted distinction between low and high malignant potential SIST. Presence of any four of these five criteria defined a high malignant potential SIST, and was associated with disease recurrence and poor prognosis after surgical resection (P <0.01). Patients with low malignant potential SIST had a 5-year survival of 92%, compared with 0% for high malignant potential SIST (P <0.01). CONCLUSIONS: This study demonstrates that a panel of morphologic factors can reliably distinguish between low and high malignant potential SIST. Although patients with low malignant potential SIST have an excellent prognosis after surgical resection, the role of adjuvant treatment for high malignant potential SIST remains to be defined.