Features associated with suicide attempts in recurrent major depression

Sixty-seven individuals with recurrent major depression and a history of suicide attempts are compared with 163 individuals with recurrent major depression and no history of suicide attempts. The groups are contrasted on demographic features, clinical course, severity of depression, co-morbidity, and acute symptom profiles. Patients with a history of attempts are distinguished from non-attempters by suicidal ideation, marital isolation, neurovegetative signs, feelings of failure, and co-morbid alcoholism or bipolar II disorder. Logistic regression analysis using a model which included a portion of the significant variables correctly classified 77% of the cases. These findings are discussed with reference to prediction of suicide attempts in individuals with major affective disorder.     

A monoclonal blocking EIA for herpes simplex virus type 2 antibody: validation for seroepidemiological studies in Africa

A competitive type-specific enzyme-linked immunosorbent assay (ELISA) for herpes simplex virus type 2 (HSV-2) antibody was developed using an infected cell antigen and a monoclonal antibody to glycoprotein G-2. This assay has been validated for use for epidemiological studies using a large panel of sera collected in rural Uganda and a panel of 143 sera characterised previously by Western blotting, the 'gold standard' for HSV type-specific serology. This evaluation was found to have a sensitivity of 96% and a specificity of 91% in comparison with Western blot on 143 sera from clinic patients. The ELISA had a sensitivity of 93% and a specificity of 91% in comparison with Western blot on 495 sera collected in Uganda. The assay showed good reproducibility and a low percentage of sera gave equivocal results, indicating its suitability for epidemiological studies.     

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

Epidemiologic modeling using a microcomputer spreadsheet package

Epidemiologic modeling has provided both researchers and students with a means of studying complex disease processes as well as making intervention recommendations to decision makers. To develop more than the most elementary model, however, it has become necessary to be well versed in a computer programming language. While this has deterred many modelers in the past, with microcomputers it is now possible to develop even complex models without significant investment of time spent in learning a computer language. In addition to being affordable, many microcomputers offer "canned" spreadsheet packages which are readily adapted for epidemiologic modeling. To demonstrate this, two models were developed and run using a microcomputer spreadsheet package: 1) the classic Reed-Frost model, and 2) a modified Reed-Frost model with two intermixing subpopulations.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Burosumab for the Treatment of Tumor-Induced Osteomalacia

Tumor-induced osteomalacia (TIO) is caused by phosphaturic mesenchymal tumors producing fibroblast growth factor 23 (FGF23) and is characterized by impaired phosphate metabolism, skeletal health, and quality of life. UX023T-CL201 is an ongoing, open-label, phase 2 study investigating the safety and efficacy of burosumab, a fully human monoclonal antibody that inhibits FGF23, in adults with TIO or cutaneous skeletal hypophosphatemia syndrome (CSHS). Key endpoints were changes in serum phosphorus and osteomalacia assessed by transiliac bone biopsies at week 48. This report focuses on 14 patients with TIO, excluding two diagnosed with X-linked hypophosphatemia post-enrollment and one with CSHS. Serum phosphorus increased from baseline (0.52 mmol/L) and was maintained after dose titration from week 22 (0.91 mmol/L) to week 144 (0.82 mmol/L, p < 0.0001). Most measures of osteomalacia were improved at week 48: osteoid volume/bone, osteoid thickness, and mineralization lag time decreased; osteoid surface/bone surface showed no change. Of 249 fractures/pseudofractures detected across 14 patients at baseline, 33% were fully healed and 13% were partially healed at week 144. Patients reported a reduction in pain and fatigue and an increase in physical health. Two patients discontinued: one to treat an adverse event (AE) of neoplasm progression and one failed to meet dosing criteria (receiving minimal burosumab). Sixteen serious AEs occurred in seven patients, and there was one death; all serious AEs were considered unrelated to treatment. Nine patients had 16 treatment-related AEs; all were mild to moderate in severity. In adults with TIO, burosumab exhibited an acceptable safety profile and was associated with improvements in phosphate metabolism and osteomalacia. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..     

Predictors of clinical outcomes after non-operative management of symptomatic full-thickness rotator cuff tears

BACKGROUNDPrevious studies have shown that non-surgical management can be an effective treatment strategy for many patients with rotator cuff tears. Despite the prevalence of rotator cuff disease, few studies have examined the patient and tear related factors that predict outcomes of nonsurgical management in this cohort of patients.AIMTo identify factors that are associated with changes in patient reported outcomes over time in individuals with full-thickness rotator cuff tears treated without surgery. METHODSA cohort of 59 patients who underwent non-surgical management of full thickness rotator cuff tears with a minimum of 1-year follow-up were identified from our institutional registry. Patient demographics, comorbidities and tear characteristics were collected at initial presentation. Outcome measures were collected at baseline and at each clinical follow-up, which included Western Ontario Rotator Cuff (WORC) index, American Shoulder and Elbow Surgeons score, Visual Analog Scale for pain and Single Assessment Numerical Evaluation. Multi- and univariate regression analyses were used to determine the impact of each patient and tear related variable on final WORC scores and change in WORC scores throughout the study. RESULTSIn this non-surgical cohort, all patient-reported outcome measures significantly improved compared to baseline at 1 and 2-year follow-up. There was no significant difference in outcomes between 1 and 2 years. The average improvement surpassed the published minimal clinically important differences values for WORC, American Shoulder and Elbow Surgeons, Visual Analog Scale pain and Single Assessment Numerical Evaluation scores. Regression analysis identified female gender (β = - 19.88, P = 0.003), smoking (β = -29.98, P = 0.014) and significant subscapularis fatty infiltration (β = -15.35, P = 0.024) as predictors of less favorable WORC scores at 1 year, and female gender (β = -19.09, P = 0.015) alone as a predictor of lower WORC scores at 2 years. Patients with symptom duration greater than 1 year at presentation reported less improvement in WORC scores at 1-year follow-up (β = -14.63, P = 0.052) and patients with traumatic tears reported greater improvements in WORC scores at 2-year follow-up (β = 17.37, P = 0.031). CONCLUSIONPatients with full thickness rotator cuff tears can achieve and maintain clinically meaningful benefit from non-surgical management through 2-year follow-up. Female patients, smokers, and those with significant subscapularis fatty infiltration tend to have lower overall WORC scores at 1-year follow-up, and females also have lower WORC scores at 2-year follow-up. Patients presenting with symptoms greater than 1 year had less clinical improvement at 1-year follow-up, and those with traumatic tears had greater clinical improvement at 2-year follow-up.     

Timebanking and the co-production of preventive social care with adults; what can we learn from the challenges of implementing person-to-person timebanks in England?

This paper explores the potential contribution of timebanking, an innovative volunteering scheme, to the co-production of preventive social care with adults in England. Interest in volunteering in social care has increased as one proposed solution to the international crisis of a rising demand for services in juxtaposition with decreased resources. Volunteering has been particularly promoted in preventive services that prevent or delay care needs arising. Despite sustained interest in volunteering and co-production in social care, little is known about how theory translates into practice. Reporting implementation data from a Realistic Evaluation of six case studies in England, this paper explores one volunteering scheme, timebanking. The research explores how timebanks were working, what contribution they can make to adult social care, and whether they are an example of co-production. Data collected included interviews, focus groups or open question responses on surveys from 84 timebank members, and semi-structured interviews with 13 timebank staff. Each timebank was visited at least twice, and all timebank activity was analysed for a period of 12 months. Data were triangulated to improve reliability. The research found that in practice, timebanks were not working as described in theory, there were small numbers of person-to-person exchanges and some timebanks had abandoned this exchange model. Timebanks faced significant implementation challenges including managing risk and safeguarding and the associated bureaucracy, a paternalistic professional culture and the complexity of the timebank mechanism which required adequate resources. Lessons for timebanks are identified, as well as transferable lessons about co-production and volunteering in social care if such schemes are to be successful in the future.     

NCL-5D3: a new monoclonal antibody recognizing low molecular weight cytokeratins effective for immunohistochemistry using fixed paraffin-embedded tissue

Production of a new monoclonal antibody designated NCL-5D3 is described. The antibody recognizes several low molecular weight cytokeratins, in particular cytokeratin Moll number 8 as determined by immunoblotting studies, and is highly effective for immunocytochemistry using routinely processed paraffin-embedded material. Staining is enhanced by prior treatment of the sections with trypsin. Assessment using a wide variety of normal and neoplastic tissue indicates reactivity with all tissues of simple or glandular epithelial origin, and in addition with many squamous carcinomas. Thus the antibody should prove of value in diagnostic histopathology.