Nevin Manimala

Curr Cancer Drug Targets. 2022 Aug 25. doi: 10.2174/1568009622666220825115528. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer stem-like cells in triple-negative breast cancer (TNBC-SLCs) are the tumorigenic core for malignancy. Aberrant expression of the RON receptor tyrosine kinase has been implication in TNBC tumorigenesis and malignancy.

OBJECTIVE: Here we identified the RON receptor as a pathogenic factor contributing to TNBC cell stemness and validated anti-RON antibody-drug conjugate Zt/g4-MMAE for eradication of RON-expressing TNBC-SLCs.

METHODS: Immunofluorescence and Western blotting were used for analyzing cellular marker expression. TNBC-SLCs were isolated by magnetic-immunofluorescence cell-sorting techniques. Spheroids were generated using the ultralow adhesion culture methods. Levels of TNBC-SLC chemosensitivity were determined by MTS assays. TNBC-SLC mediated tumor growth was determined in athymic nude mice. The effectiveness of Zt/g4-induced RON internalization was measured by immunofluorescence analysis. Efficacies of Zt/g4-MMAE in killing TNBC-SLCs in vitro and in eradicating TNBC-SLC-mediated tumors were determined in mouse models. All data were statistically analyzed using the GraphPad Prism 7 software.

RESULTS: Increased RON expression existed in TNBC-SLCs with CD44+/CD24- phenotypes and ALDH activities and facilitates epithelial to mesenchymal transition. RON-positive TNBC-SLCs had enhanced spheroid-formatting capability compared with RON-negative TNBC-SLCs, which was sensitive to small molecule kinase inhibitor BMS-777607. Increased RON expression also promoted TNBC-SLC chemoresistance and facilitated tumor growth at an accelerated rate. In vitro, Zt/g4-MMAE caused massive TNBC-SLC death with an average IC50 value of ~1.56 µg per/ml and impaired TNBC cell spheroid formation. In mice, Zt/g4-MMAE effectively inhibited and/or eradicated TNBC-SLC mediated tumors in a single agent regimen.

CONCLUSIONS: Sustained RON expression contributes to TNBC-SLC tumorigenesis. Zt/g4-MMAE is effective in vivo in killing TNBC-SLC-mediated xenograft tumors. Our findings highlight the feasibility of Zt/g4-MMAE for eradication of TNBC-SLCs in the future.

PMID:36028965 | DOI:10.2174/1568009622666220825115528

J Am Psychiatr Nurses Assoc. 2022 Aug 26:10783903221120828. doi: 10.1177/10783903221120828. Online ahead of print.

ABSTRACT

BACKGROUND: Residential treatment is among the most intensive and expensive settings for children with behavioral health challenges; yet, the extent to which evidence-based practices are used in these settings is unknown.

AIM: The purpose of this study was to describe the extent which family therapy, case management, telehealth, peer support, and family psychoeducation are provided in residential treatment using data from the National Mental Health Services Survey (N-MHSS). Organizational factors-region, ownership, payment, licensing/accreditation, and facility size-were examined in relation to evidence-based practices to understand disparities in care.

METHODS: This was a secondary analysis of publicly available data from the 2018 N-MHSS. A subpopulation was created consisting of residential facilities that served children (N = 576). Descriptive statistics were used to describe the sample, and Cohen’s h was calculated to determine patterns of evidence-based practice utilization.

RESULTS: Evidence-based practices from most to least prevalent were family therapy (76%), family psychoeducation (74%), case management (71.1%), telehealth (17.2%), and peer support (8.7%). The provision of evidence-based practices was not evenly distributed. There were primarily small to moderate differences by organizational factors, including region (i.e., Northeast, Midwest), ownership status (i.e., for-profit), payment type (i.e., self-pay, private insurance), licensing/accreditation (Department of Family and Children Services), and facility capacity (>251 clients served per year).

CONCLUSION: Findings demonstrate a need for research-practice partnerships to determine the barriers that prevent effective evidence-based practices from being implemented in the residential treatment setting.

PMID:36028952 | DOI:10.1177/10783903221120828

Biol Res Nurs. 2022 Aug 26:10998004221123288. doi: 10.1177/10998004221123288. Online ahead of print.

ABSTRACT

Background: Unplanned transfer to intensive care unit (ICU) lead to reduced trust of patients and their families in medical staff and challenge medical staff to allocate scarce ICU resources. This study aimed to explore the incidence and risk factors of unplanned transfer to ICU during emergence from general anesthesia after cerebral surgery, and to provide guidelines for preventing unplanned transfer from post-anesthesia care unit (PACU) to ICU following cerebral surgery. Methods: This was a retrospective case-control study and included patients with unplanned transfer from PACU to ICU following cerebral surgery between January 2016 and December 2020. The control group comprised patients matched (2:1) for age (±5 years), sex, and operation date (±48 hours) as those in the case group. Stata14.0 was used for statistical analysis, and p < .05 indicated statistical significance. Results: A total of 11,807 patients following cerebral surgery operations were cared in PACU during the study period. Of the 11,807 operations, 81 unscheduled ICU transfer occurred (0.686%). Finally, 76 patients were included in the case group, and 152 in the control group. The following factors were identified as independent risk factors for unplanned ICU admission after neurosurgery: low mean blood oxygen (OR = 1.57, 95%CI: 1.20-2.04), low mean albumin (OR = 1.14, 95%CI: 1.03-1.25), slow mean heart rate (OR = 1.04, 95%CI: 1.00-1.08), blood transfusion (OR = 2.78, 95%CI: 1.02-7.58), emergency surgery (OR = 3.08, 95%CI: 1.07-8.87), lung disease (OR = 2.64, 95%CI: 1.06-6.60), and high mean blood glucose (OR = 1.71, 95%CI: 1.21-2.41). Conclusion: We identified independent risk factors for unplanned transfer from PACU to ICU after cerebral surgery based on electronic medical records. Early identification of patients who may undergo unplanned ICU transfer after cerebral surgery is important to provide guidance for accurately implementing a patient’s level of care.

PMID:36028934 | DOI:10.1177/10998004221123288

Cancer Control. 2022 Jan-Dec;29:10732748221124440. doi: 10.1177/10732748221124440.

NO ABSTRACT

PMID:36028925 | DOI:10.1177/10732748221124440

J Int AIDS Soc. 2022 Aug;25(8):e25989. doi: 10.1002/jia2.25989.

ABSTRACT

INTRODUCTION: Viral load (VL) testing is still challenging to monitor treatment responses of antiretroviral therapy (ART) for HIV treatment programme in Asia. We assessed the association between routine VL testing and virological failure (VF) and determine factors associated with switching to second-line regimen.

METHODS: Among 21 sites from the TREAT Asia HIV Observational Database (TAHOD), people living with HIV (PLHIV) aged ≥18 years initiating ART from 2003 to 2021 were included. We calculated the average number of VL tests per patient per year between the date of ART initiation and the most recent visit. If the median average number of VL tests was ≥ 0.80 per patient per year, the site was classified as a routine VL site. A site with a median < 0.80 was classified into the non-routine VL sites. VF was defined as VL ≥1000 copies/ml during first-line therapy. Factors associated with VF were analysed using generalized estimating equations with Poisson distribution.

RESULTS: Of 6277 PLHIV starting ART after 2003, 3030 (48%) were from 11 routine VL testing sites and 3247 (52%) were from 10 non-routine VL testing sites. The median follow-up was 9 years (IQR 5-13). The median age was 35 (30-42) years; 68% were male and 5729 (91%) started non-nucleoside reverse-transcriptase inhibitor-based regimen. The median pre-ART CD4 count in PLHIV from routine VL sites was lower compared to non-routine VL sites (144 vs. 156 cells/mm³ , p <0.001). Overall, 1021 subsequent VF at a rate of 2.15 (95% CI 2.02-2.29) per 100 person-years (PY). VF was more frequent at non-routine VL sites (adjusted incidence rate ratio 2.85 [95% CI 2.27-3.59]) compared to routine VL sites. Other factors associated with an increased rate of VF were age <50 years and CD4 count <350 cells/mm³ . A total of 817 (13%) patients switched to second-line regimen at a rate of 1.44 (95% CI 1.35-1.54) per 100 PY. PLHIV at routine VL monitoring sites were at higher risk of switching than those at non-routine VL sites (adjusted sub-hazard ratio 1.78 95% CI [1.17-2.71]).

CONCLUSIONS: PLHIV from non-routine VL sites had a higher incidence of persistent VF and a low switching regimen rate, reflecting possible under-utilized VL testing.

PMID:36028921 | DOI:10.1002/jia2.25989

J Int AIDS Soc. 2022 Aug;25(8):e25998. doi: 10.1002/jia2.25998.

ABSTRACT

INTRODUCTION: Most Zimbabweans access medical care through tiered health systems. In 2013, HIV care was decentralized to primary care clinics; while oncology care remained centralized. Most persons in Zimbabwe with Kaposi sarcoma (KS) are diagnosed late in their disease, and the prognosis is poor. Little is known about whether educational interventions could improve KS outcomes in these settings.

METHODS: Interventions to improve KS detection and management were evaluated at eight Zimbabwe primary care sites (four rural/four urban) that provided HIV care. Interventions included a standardized KS clinical evaluation tool, palliative care integration, standardized treatment and improved consultative services. Interventions were implemented between February 2013 and January 2016 using a randomized stepped-wedge cluster design. Sites were monitored for KS diagnosis rates and KS outcomes, including early diagnosis (T0 vs. T1 tumour stage), participant retention and mortality. Analyses controlled for within-clinic correlations.

RESULTS: A total of 1102 persons with suspected KS (96% HIV positive) were enrolled: 47% incident (new diagnosis), 20% prevalent (previous diagnosis) and 33% determined as not KS. Early (T0) diagnosis increased post-intervention, though not significant statistically (adjusted odds ratio [aOR] = 1.48 [95% confidence interval (95% CI): 0.66-3.79], p = 0.37). New KS diagnosis rates increased 103% (95% CI: 11-273%), p = 0.02) post-intervention; although paired with an increased odds of incorrectly diagnosing KS (aOR = 2.08 [95% CI: 0.33-3.24], p = 0.001). Post-intervention, non-significant decreases in 90-day return rates (adjusted hazard ratio [aHR] = 0.69 [95% CI: 0.38-1.45], p = 0.21) and survival (aHR = 1.36 [95% CI: 0.85-2.20], p = 0.20) were estimated.

CONCLUSIONS: KS training interventions at urban and rural Zimbabwe decentralized primary care clinics significantly increased overall and incorrect KS diagnosis rates, but not early KS diagnosis rates, 90-day return rates or survival.

PMID:36028920 | DOI:10.1002/jia2.25998

Asthma Res Pract. 2022 Aug 27;8(1):5. doi: 10.1186/s40733-022-00087-3.

ABSTRACT

BACKGROUND: Asthma is a major public health challenge and is characterized by recurrent attacks of breathlessness and wheezing that vary in severity and frequency from person to person. Asthma control is an important measure of health outcomes of the patients with asthma and reflecting the impact of an illness and its treatment from the patient’s perspective. Therefore, this study assessed the asthma control levels and their determinants among adults living with asthma in selected public referral hospitals in northwestern Ethiopia.

MATERIALS AND METHOD: A multicenter institutional-based cross-sectional study was conducted in North-western Ethiopia, from October to December 2021. A systematic random sampling technique was employed to recruit the study participants. Bi-variable and multivariable ordinal logistic regression was used to determine the independent predictors of asthma control levels. A p-value of < 0.05 was considered as statistically significant.

RESULT: A total of 409 patients were included in the final analysis. Asthma was controlled by 28.9% with 95%CI (24.7, 33.5) people who have asthma. Regarding the potential predictor of asthma control level, being male (AOR = 6.5, 95%CI (1.28, 32.44), Married (AOR = 3.62, 95%CI (1.28, 10.27), healthcare provider adherence to guideline usage (AOR = 8.4,95%CI (2.7, 26) and non-fuel users (AOR = 6.0, 95%CI (1.5, 22.5) were variables that increase asthma control. However, non-adherent to medication (AOR = 0.16, 95%CI (0.059, 0.48), low level of patient enablement (AOR = 0.19, (95%CI) (0.08, 0.49) and poor relationship with healthcare provider (AOR = 0.024,95%CI (0.02, 0.23) were variables that significantly decreased asthma control level.

CONCLUSION: The findings indicated that asthma control remains suboptimal in a large proportion of patients with asthma in the study setting. Socio-demographic, clinical, healthcare-related, and medication-related variables were significantly associated with asthma control. Therefore, our study highlights multifaceted interventions, including comprehensive asthma education along with an integrated treatment plan to improve asthma control and quality of life.

PMID:36028919 | DOI:10.1186/s40733-022-00087-3

Int J Retina Vitreous. 2022 Aug 26;8(1):59. doi: 10.1186/s40942-022-00410-3.

ABSTRACT

PURPOSE: To correlate the structural-vascular-functional changes in type 2 non-proliferative macular telangiectasia (MacTel) using optical coherence tomography (OCT) angiography (OCTA).

METHODS: In this retrospective study, OCTA and enface OCT image analysis of eyes with confirmed diagnosis of non-proliferative type 2 MacTel was performed. The ‘MacTel area’ was calculated by marking the outer boundary of an area affected by MacTel on superficial (SCP) and deep capillary plexus (DCP) on OCTA images and photoreceptor layer (PRL) on enface OCT scan. At every follow-up OCTA scan visit, best-corrected visual acuity, MacTel area and stage of disease was documented. Analyses between disease stage, MacTel area and logMAR visual acuity was carried out.

RESULTS: In total, 38 single-visit OCTA scans of 22 patients were included. The mean age was 58.9 ± 10.98 years. An increase in disease severity stage correlated positively with MacTel area in SCP segmentations slab (r = 0.334; p = 0.04) and logMAR visual acuity (r = 0.338; p = 0.038). No correlation in the DCP area or PRL area (p > 0.05) was noted with disease stage. A statistically significant positive correlation was noted between the structural changes in PRL layer with vascular changes in SCP (p = 0.021) but not in DCP (p = 0.199). No correlation of visual acuity with changes in SCP, DCP or PRL was noted (p > 0.05).

CONCLUSION: OCTA is a useful adjunct for determining disease severity in type 2 non-proliferative MacTel by assessing the structural-vascular changes. Further longitudinal studies need to be considered in future for understanding the pathomechanism of retinal damage in type 2 MacTel.

PMID:36028918 | DOI:10.1186/s40942-022-00410-3

Trials. 2022 Aug 26;23(1):715. doi: 10.1186/s13063-022-06574-5.

ABSTRACT

INTRODUCTION: To date, there is no consensus on which anterior surgical technique is more cost-effective in treating cervical degenerative disc disease (CDDD). The most commonly used surgical treatment for patients with single- or multi-level symptomatic CDDD is anterior cervical discectomy with fusion (ACDF). However, new complaints of radiculopathy and/or myelopathy commonly develop at adjacent levels, also known as clinical adjacent segment pathology (CASP). The extent to which kinematics, surgery-induced fusion, natural history, and progression of disease play a role in the development of CASP remains unclear. Anterior cervical discectomy with arthroplasty (ACDA) is another treatment option that is thought to reduce the incidence of CASP by preserving motion in the operated segment. While ACDA is often discouraged, as the implant costs are higher while the clinical outcomes are similar to ACDF, preventing CASP might be a reason for ACDA to be a more cost-effective technique in the long term.

METHODS AND ANALYSIS: In this randomized controlled trial, patients will be randomized to receive ACDF or ACDA in a 1:1 ratio. Adult patients with single- or multi-level CDDD and symptoms of radiculopathy and/or myelopathy will be included. The primary outcome is cost-effectiveness and cost-utility of both techniques from a healthcare and societal perspective. Secondary objectives are the differences in clinical and radiological outcomes between the two techniques, as well as the qualitative process surrounding anterior decompression surgery. All outcomes will be measured at baseline and every 6 months until 4 years post-surgery.

DISCUSSION: High-quality evidence regarding the cost-effectiveness of both ACDA and ACDF is lacking; to date, there are no prospective trials from a societal perspective. Considering the aging of the population and the rising healthcare costs, there is an urgent need for a solid clinical cost-effectiveness trial addressing this question.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04623593. Registered on 29 September 2020.

PMID:36028916 | DOI:10.1186/s13063-022-06574-5

Pilot Feasibility Stud. 2022 Aug 26;8(1):191. doi: 10.1186/s40814-022-01154-5.

ABSTRACT

BACKGROUND: Local politicians can serve as enablers or barriers for health and social organizations to implement evidence, impacting the context of health and social service organizations. Increasing local politicians’ knowledge about, and support for, evidence-based practice (EBP) could be a way to strengthen the conditions in social service organizations for EBP. The aim of the study was to describe the development and assess the perceived feasibility, acceptability, and appropriateness of an intervention to enable local political committees to support the implementation of EBP. Furthermore, the achievement of the learning outcomes was examined.

METHODS: Workshops and interviews were used to co-create the intervention with social service representatives (n = 8) and local politicians (n = 6). A single-arm, non-blinded feasibility study was conducted in a social welfare committee with local politicians (n = 14) and representatives from social services (n = 4). Interviews and pre-post questionnaires were used to assess the intervention’s feasibility, acceptability, appropriateness, and learning outcomes. Progression criteria was set to > 80% of respondents judging the intervention to be feasible, acceptable, and appropriate. Thematic analysis and descriptive statistics were used for analysis.

RESULTS: The quantitative and qualitative results indicate that the intervention was perceived as acceptable and appropriate. However, the progression criteria for feasibility were not fully met. Qualitative findings show that the intervention was perceived as interesting, fun, and created curiosity to learn more about EBP. The discussions between the committee and the representatives from the social services department were much valued.

CONCLUSIONS: Careful anchoring of the intervention and comprehensive local adaptation regarding delivery format will be central to the delivery of this intervention if offered elsewhere. Furthermore, we recommend that skills training during the intervention should be included. The collaboration between local politicians and representatives from the social services department was a vital aspect of the intervention and should not be excluded. Collaboration between these actors will be of significance in further developing support for EBP implementation, as expressed by the interview participants.

PMID:36028906 | DOI:10.1186/s40814-022-01154-5