Tag: nevin manimala

Cancer Immunol Immunother. 2021 Aug 20. doi: 10.1007/s00262-021-03033-z. Online ahead of print.

ABSTRACT

Histiocytic sarcoma (HS) is a rare and aggressive tumor in humans with no universally agreed standard of care therapy. Spontaneous canine HS exhibits increased prevalence in specific breeds, shares key genetic and biologic similarities with the human disease, and occurs in an immunocompetent setting. Previous data allude to the immunogenicity of this disease in both species, highlighting the potential for their successful treatment with immunotherapy. Quantification of CD3 tumor-infiltrating lymphocytes (TIL) in five cases of human HS revealed variable intra-tumoral T cell infiltration. Due to the paucity of human cases and lack of current model systems in which to appraise associations between anti-tumor immunity and treatment-outcome in HS, we analyzed clinical data and quantified TIL in 18 dogs that were previously diagnosed with localized HS and treated with curative-intent tumor resection with or without adjuvant chemotherapy. As in humans, assessment of TIL in biopsy tissues taken at diagnosis reveal a spectrum of immunologically “cold” to “hot” tumors. Importantly, we show that increased CD3 and granzyme B TIL are positively associated with favorable outcomes in dogs following surgical resection. NanoString transcriptional analyses revealed increased T cell and antigen presentation transcripts associated with prolonged survival in canine pulmonary HS and a decreased tumor immunogenicity profile associated with shorter survivals in splenic HS. Based on these findings, we propose that spontaneous canine HS is an accessible and powerful novel model to study tumor immunology and will provide a unique platform to preclinically appraise the efficacy and tolerability of anti-cancer immunotherapies for HS.

PMID:34415404 | DOI:10.1007/s00262-021-03033-z

Environ Monit Assess. 2021 Aug 20;193(9):588. doi: 10.1007/s10661-021-09387-2.

ABSTRACT

Health of birds and heavy metal toxicity are growing concerns in Pakistan because of irresponsible industrial waste management and farming practices. Eight species of common wild birds were studied from three different study sites which varied in the type of environmental pollution (Kasur: industrial waste, Lahore city: traffic pollution and Shahdara: mixed pollution of traffic, sewerage, and industry which the Ravi River accumulates). Heavy metal analysis of six heavy metals in the various organs of birds showed that there was no evidence of organ preference for metal accumulation in birds. Shahdara and Kasur with numerous industries both showed chromium concentrations above toxicity levels in 54.16% tissues of Granivorous birds, 60% of omnivorous birds, and 33.33% in tissues of carnivorous species. Statistical analysis proved that there is no correlation between weight of birds and accumulation of metals; it depends on food preference of birds and properties of the metals as bioaccumulators or biomagnifiers.

PMID:34415417 | DOI:10.1007/s10661-021-09387-2

Occup Med (Lond). 2021 Aug 20:kqab108. doi: 10.1093/occmed/kqab108. Online ahead of print.

ABSTRACT

BACKGROUND: Comparative long-term trends in fatal accident rates in the UK’s most hazardous occupations have not been reported.

AIMS: To compare trends in fatal accident rates in six of the most hazardous occupations (the three armed forces, merchant shipping, sea fishing and coal mining) and the general British workforce during peacetime years since 1900.

METHODS: Examinations of annual mortality reports, returns, inquiry files and statistics. The main outcome measure was the fatal accident rate per 100 000 population employed.

RESULTS: These six occupations accounted for ~40% of all fatal accidents in the British workforce. Fatal accident rates were highest in merchant shipping to 1914 (400-600 per 100 000) and in the Royal Air Force and sea fishing by the early 1920s (around 300 per 100 000). Since the 1950s sea fishing has remained the most hazardous occupation (50-200). Widespread reductions in fatal accident rates for each occupation have been greatest in recent years in the three armed forces and merchant shipping. Compared with the general workforce, relative risks of fatalities have increased in recent decades in all these occupations except shipping.

CONCLUSIONS: All six occupations still have high fatal accident rates. The greatly increased fatalities in sea fishing generally and in the Royal Air Force during its early years reflect, for different reasons, cultures of extreme risk-taking in these two sectors. Reductions in fatality rates in the armed forces over the last 20 years are due largely to decreases in land transport accidents.

PMID:34415338 | DOI:10.1093/occmed/kqab108

Arch Gynecol Obstet. 2021 Aug 20. doi: 10.1007/s00404-021-06179-4. Online ahead of print.

ABSTRACT

AIMS: To compare current General Medical Practitioner treatment as usual (TAU) for the treatment of female urinary incontinence with a novel disposable home electro-stimulation device (Pelviva).

METHODS: Open label, Primary Care post-market evaluation. 86 women with urinary incontinence were randomly assigned to one of two 12-week treatments: TAU or Pelviva for 30 min every other day plus TAU. Outcome measures included ICIQ-UI (primary), PISQ-IR, PGI-S / PGI-I and FSFI (secondary) at recruitment and immediately after intervention, 1-h pad test at recruitment and usage diaries throughout.

RESULTS: Pelviva plus TAU produced significantly better outcome than TAU alone: 3 versus 1 point for ICIQ-UI (Difference – 1.8 95% CI: – 3.5 to – 0.1, P = 0.033). Significant differences were also observed for PGI-I at both 6 weeks (P = 0.001) and 12 weeks (P < 0.001). In the Pelviva group, 17% of women described themselves as feeling very much better and 54% a little or much better compared to 0% and 15% in the TAU. Overall PISQ-IR score reached statistical significance (P = 0.032) seemingly related to impact (P = 0.027). No other outcome measures reached statistical significance. Premature termination due to COVID-19 meant only 86 women were recruited from a sample size of 264. TAU did not reflect NICE guidelines.

CONCLUSIONS: This study suggests Pelviva is more successful than TAU in treating urinary incontinence in Primary Care. The study had reduced power due to early termination due to COVID-19 and suggests TAU does not follow NICE guidelines.

PMID:34415401 | DOI:10.1007/s00404-021-06179-4

JAMA Netw Open. 2021 Aug 2;4(8):e2121011. doi: 10.1001/jamanetworkopen.2021.21011.

ABSTRACT

IMPORTANCE: The management of coronary disease epitomizes the call to better engage patients in shared medical decision-making. Myocardial perfusion imaging (MPI) is the foundation of diagnosis, risk stratification, and subsequent therapy; however, MPI reports are currently interpretable by specialists but not patients.

OBJECTIVE: To design and test a patient-centered report for stress MPI test results.

DESIGN, SETTING, AND PARTICIPANTS: This qualitative study of outpatients who underwent an MPI stress test and clinicians used a mixed methods approach. Phase 1 (December 2018 to July 2019) used qualitative methods to design a patient-centered reporting tool, with 5 focus groups with 36 patients and 2 focus groups with 27 clinicians. Phase 2 (June to September 2019) consisted of pilot testing the reporting tool with feedback from a structured survey given to patients who received MPI reports before and after implementing the tool.

MAIN OUTCOMES AND MEASURES: Key themes around patient experiences with the current MPI reporting and their desire for a more useful report were identified, which led to a sample reporting tool after serial iterations with feedback. Differences in patient knowledge and engagement were assessed between patients before and after implementation of the new reporting tool using χ2 tests.

RESULTS: From patient focus groups (26 patients; mean [SD] age, 66.3 [9.6] years, 9 [35%] women), 3 themes on the inadequacies of current MPI reporting were identified: (1) inconsistent delivery of results, (2) use of medical jargon, and (3) unclear posttest course. We identified 5 themes for a more patient-centered MPI report: desire for written information, discussion of the report with medical personnel, presentation of results in simple language with use of visual graphics, comparisons with normal results, and personalized risk estimates. In a pilot survey with 123 patients split into a pre-implementation group (69 patients; mean [SD] age, 68.2 [8.5] years; 27 [51%] women) and a postimplementation group (54 patients; mean [SD] age, 66.4 [8.7] years; 30 [56%] women), the patient-centered report led to more patients reading the entire report (45 [83%] vs 46 [67%]; P = .04) and improved knowledge of future risk of cardiac events (41 [76%] vs 20 [29%]; P < .001). There was also a numerically higher percentage of patients who found the report easy to read (45 [83%] vs 44 [68%]; P = .05) and understand (42 [78%] vs 43 [66%]; P = .16), although these results were not statistically significant.

CONCLUSIONS AND RELEVANCE: This study identified key elements of a patient-centered report design for stress MPI test results, which improved patient engagement and knowledge. These preliminary data support further implementation and study of a more patient-centered MPI report.

PMID:34415313 | DOI:10.1001/jamanetworkopen.2021.21011

JAMA Netw Open. 2021 Aug 2;4(8):e2120951. doi: 10.1001/jamanetworkopen.2021.20951.

ABSTRACT

IMPORTANCE: A large proportion of extremity soft-tissue sarcomas (ESS) occur among young adults, yet this group is underrepresented in clinical trials, resulting in limited data on this population. Younger patients present many complex challenges that affect clinical management.

OBJECTIVE: To investigate variations in treatment management in young adults vs older adults with ESS.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter retrospective cohort study used the National Cancer Data Base (NCDB) to identify patients 18 years and older with ESS who received definitive treatment (ie, limb-sparing surgery [LSS] or amputation) between 2004 and 2014. Data analysis was conducted in November 2019.

EXPOSURES: Treatment regimen received among young adults (aged 18-39 years) and older adults (≥40 years) after diagnosis with ESS.

MAIN OUTCOMES AND MEASURES: To detect unique factors associated with treatment decisions in young adults with ESS, multivariable analyses used logistic regressions for patterns of treatment and their association with demographic factors and tumor characteristics.

RESULTS: Overall, 8953 patients were identified, and among these, 1280 (14.3%) were young adults. From the full cohort, 4796 patients (53.6%) identified as male and 6615 (73.9%) identified as non-Hispanic White. More young adults than older adults underwent amputation (age 18-39 years, 104 of 1280 [8.1%]; age 40-64 years, 217 of 3937 [5.5%]; aged ≥65 years, 199 of 3736 [5.3%]), but the association was not statistically significant (age ≥65 years, odds ratio [OR], 1.49; 95% CI, 1.00-2.23; P = .05). Young adults were more likely to receive chemotherapy than older patients (age 40-65 years, OR, 0.52; 95% CI, 0.45-0.60; P = .001; ≥65 years, OR, 0.16; 95% CI, 0.12-0.20; P = .001). Conversely, young adults were less likely to receive radiation therapy compared with older patients (age 40-65 years, OR, 1.40; 95% CI, 1.22-1.61; P = .001; ≥65 years, OR, 1.33; 95% CI, 1.10-1.61; P = .003). Unique to younger adults, clinical stage II disease vs stage I and positive surgical margins were not associated with use of radiation therapy (stage II disease: OR, 1.25; 95% CI, 0.81-1.91; P = .31; positive surgical margins: OR, 1.43; 95% CI, 0.93-2.22; P = .11). White Hispanic young adults were less likely than non-Hispanic White young adults to receive radiation therapy (OR, 0.53; 95% CI, 0.36-0.78; P = .002).

CONCLUSIONS AND RELEVANCE: In this study, young adults with ESS were more likely to receive chemotherapy and less likely to receive radiation therapy than older adults. Further study is warranted to identify the clinical outcomes of these practice disparities.

PMID:34415314 | DOI:10.1001/jamanetworkopen.2021.20951

Occup Med (Lond). 2021 Aug 20:kqab113. doi: 10.1093/occmed/kqab113. Online ahead of print.

ABSTRACT

BACKGROUND: The use of new psychoactive substances (NPS) in UK prisons is believed to have increased substantially. As well as posing a significant threat to prisoners’ health, NPS use can trigger violent, unpredictable and aggressive behaviour. Dealing with the direct and indirect effects of NPS therefore has the potential to compromise the physical and psychological safety of prison staff.

AIMS: This study investigates prison officers’ perceptions of NPS use in their workplace and their risk of exposure. Relationships between NPS exposure, the workplace safety climate and mental health were also examined.

METHODS: We assessed prison officers’ perceptions of the prevalence of NPS use among prisoners in their workplace, their personal exposure and the safety climate in their institution through an online survey. The General Health Questionnaire-12 measured mental health. Descriptive statistics were used to assess officers’ perceptions of NPS use in their workplace and their personal exposure and correlations examined relationships between variables.

RESULTS: The sample comprised 1956 prison officers (86% male). Most respondents (85%) highlighted NPS as a serious cause for concern in their institution. Two-thirds (66%) reported being personally exposed to NPS at least sometimes, with 22% being exposed once a day or more. Significant relationships were found between officers’ perceived NPS exposure, assessments of safety climate and self-reported mental health.

CONCLUSIONS: Our findings highlight the need for urgent action to reduce the use of NPS among prisoners. This is likely to improve the safety climate of UK prisons and the mental health of staff.

PMID:34415337 | DOI:10.1093/occmed/kqab113

Angle Orthod. 2021 Aug 20. doi: 10.2319/122820-1037.1. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess speech performance of adult patients undergoing orthodontic treatment with Invisalign.

MATERIALS AND METHODS: Twenty-four adult patients with Invisalign (Invisalign group: 6 men, 18 women; average age; 34.88 years) and 20 adult patients with fixed labial appliances (fixed group: 5 men, 15 women; average age; 38.85 years) were evaluated. Speech was recorded immediately before delivery of the first set of clear aligners or bonding of labial appliances (T0), immediately after delivery or bonding (T1), and 2 months after delivery or bonding (T2). Speech was evaluated via a combination of three auditory analyses: (1) objective acoustic analysis through digital sonography, (2) semiobjective assessment by six speech and language pathologists, and (3) subjective assessment patient questionnaire.

RESULTS: The objective acoustic analysis showed a statistically significant difference over time from T0 to T1, T1 to T2, and T0 to T2 for Invisalign patients. The semiobjective analysis revealed a significant speech alteration from T0 to T1 and T1 to T2 for both groups, and from T0 to T2 in the Invisalign group. The subjective analysis showed a significant difference between means of Invisalign and fixed group patient perception at both T1 and T2.

CONCLUSIONS: Invisalign treatment significantly affected speech, and although patients experience some level of adaptation, speech does not return to normal after 2 months of treatment.

PMID:34415296 | DOI:10.2319/122820-1037.1

Development. 2021 Aug 20:dev.199687. doi: 10.1242/dev.199687. Online ahead of print.

ABSTRACT

Sex differences in the brain are prevalent throughout the animal kingdom and particularly well appreciated in the nematode C. elegans, where male animals contain a little studied set of 93 male-specific neurons. To make these neurons amenable for future study, we describe here how a multicolor reporter transgene, NeuroPAL, is capable of visualizing the distinct identities of all male specific neurons. We used NeuroPAL to visualize and characterize a number of features of the male-specific nervous system. We provide several proofs of concept for using NeuroPAL to identify the sites of expression of gfp-tagged reporter genes and for cellular fate analysis by analyzing the effect of removal of several developmental patterning genes on neuronal identity acquisition. We use NeuroPAL and its intrinsic cohort of more than 40 distinct differentiation markers to show that, even though male-specific neurons are generated throughout all four larval stages, they execute their terminal differentiation program in a coordinated manner in the fourth larval stage. This coordinated wave of differentiation, which we call “just-in-time” differentiation, couples neuronal maturation programs with the appearance of sexual organs.

PMID:34415309 | DOI:10.1242/dev.199687

J Neuroophthalmol. 2021 Sep 1;41(3):342-350. doi: 10.1097/WNO.0000000000001220.

ABSTRACT

BACKGROUND: Tocilizumab (Actemra) is a humanized anti-interleukin-6 receptor antibody that has been used as a steroid-sparing agent in giant cell arteritis (GCA). Although the clinical effects are well described in GCA, the cost-effectiveness of the use of tocilizumab in GCA is ill defined. The purpose of this study was to determine the cost-effectiveness of tocilizumab in GCA compared with prednisone alone.

METHODS: A retrospective study of 32 patients with biopsy-proven GCA comparing prednisone alone (16 patients) and prednisone with tocilizumab (16 patients) was performed. The cost for tocilizumab therapy for 26 weeks with mild and severe side effects (Groups 1 and 2, respectively) and for 52 weeks with mild and severe side effects (Group 3 and 4, respectively) was compared with estimated costs of mild and severe steroid-induced side effects (Groups 5 and 6, respectively). Statistical analysis between groups was conducted using independent sample t tests.

RESULTS: Three out of the 4 group combinations of tocilizumab with prednisone demonstrated a statistically significant (P < 0.05) difference in cost compared with prednisone alone for GCA. Group 2 (26-week tocilizumab therapy with severe steroid-induced side effects), with no statically significant difference in price when compared with steroid therapy alone and far fewer side effects, demonstrated the potential use of tocilizumab in GCA therapy. As expected, longer treatment duration with tocilizumab was associated with greater cost. With respect to side effect severity, the number of side effects of steroid therapy was inversely associated with difference in cost between tocilizumab therapy and steroid side effect treatment.

CONCLUSION: This study demonstrates that combination therapy of tocilizumab and prednisone is significantly more expensive than steroids alone with or without accounting for the cost of steroid-induced side effects in treated GCA. The difference in cost between the 2 therapy types is directly related to tocilizumab therapy duration and inversely related to the number or severity of steroid side effects. Patients with GCA who require a shorter duration of steroid therapy and are at risk for a high number of side effects from steroid use may be potential candidates for tocilizumab therapy, from an economic perspective.

PMID:34415267 | DOI:10.1097/WNO.0000000000001220