Tag: nevin manimala

Cancer. 2023 May 9. doi: 10.1002/cncr.34808. Online ahead of print.

ABSTRACT

BACKGROUND: United States cancer death rates have been steadily declining since the early 1990s, but information on disparities in progress against cancer mortality across congressional districts is lacking. This study examined trends in cancer death rates, overall and for lung, colorectal, female breast, and prostate cancer by congressional district.

METHODS: County level cancer death counts and population data from the National Center for Health Statistics were used to estimate relative change in age-standardized cancer death rates from 1996-2003 to 2012-2020 by sex and congressional district.

RESULTS: From 1996-2003 to 2012-2020, overall cancer death rates declined in every congressional district, with most congressional districts showing a 20%-45% decline among males and a 10%-40% decline among females. In general, the smallest percent of relative declines were found in the Midwest and Appalachia, whereas the largest declines were found in the South along the East Coast and the southern border. As a result, the highest cancer death rates generally shifted from congressional districts across the South in 1996-2003 to districts in the Midwest and central divisions of the South (including Appalachia) in 2012-2020. Death rates for lung, colorectal, female breast, and prostate cancers also declined in almost all congressional districts, although with some variation in relative changes and geographical patterns.

CONCLUSIONS: Progress in reducing cancer death rates during the past 25 years considerably vary by congressional district, underscoring the need for strengthening existing and implementing new public health policies for broad and equitable application of proven interventions such as raising tax on tobacco and Medicaid expansion.

PMID:37159301 | DOI:10.1002/cncr.34808

Clin Orthop Relat Res. 2023 May 9. doi: 10.1097/CORR.0000000000002697. Online ahead of print.

ABSTRACT

BACKGROUND: The Stopping Opioids After Surgery (SOS) score is a validated tool that was developed to determine the risk of sustained opioid use after surgical interventions, including orthopaedic procedures. Despite prior investigations validating the SOS score in diverse contexts, its performance across racial, ethnic, and socioeconomic subgroups has not been assessed.

QUESTIONS/PURPOSES: In a large, urban, academic health network, did the performance of the SOS score differ depending on (1) race and ethnicity or (2) socioeconomic status?

METHODS: This retrospective investigation was conducted using data from an internal, longitudinally maintained registry of a large, urban, academic health system in the Northeastern United States. Between January 1, 2018, and March 31, 2022, we treated 26,732 adult patients via rotator cuff repair, lumbar discectomy, lumbar fusion, TKA, THA, ankle or distal radius open reduction and internal fixation, or ACL reconstruction. We excluded 1% of patients (274 of 26,732) because of missing length of stay information, 0.06% (15) for missing discharge information, 1% (310) for missing medication information related to loss to follow-up, and 0.07% (19) who died during their hospital stay. Based on these inclusion and exclusion criteria, 26,114 adult patients were left for analysis. The median age in our cohort was 63 years (IQR 52 to 71), and most patients were women (52% [13,462 of 26,114]). Most patients self-reported their race and ethnicity as non-Hispanic White (78% [20,408 of 26,114]), but the cohort also included non-Hispanic Black (4% [939]), non-Hispanic Asian (2% [638]), and Hispanic (1% [365]) patients. Five percent (1295) of patients were of low socioeconomic status, defined by prior SOS score investigations as patients with Medicaid insurance. Components of the SOS score and the observed frequency of sustained postoperative opioid prescriptions were abstracted. The performance of the SOS score was compared across racial, ethnic, and socioeconomic subgroups using the c-statistic, which measures the capacity of the model to differentiate between patients with and without sustained opioid use. This measure should be interpreted on a scale between 0 and 1, where 0 represents a model that perfectly predicts the wrong classification, 0.5 represents performance no better than chance, and 1.0 represents perfect discrimination. Scores less than 0.7 are generally considered poor. The baseline performance of the SOS score in past investigations has ranged from 0.76 to 0.80.

RESULTS: The c-statistic for non-Hispanic White patients was 0.79 (95% CI 0.78 to 0.81), which fell within the range of past investigations. The SOS score performed worse for Hispanic patients (c-statistic 0.66 [95% CI 0.52 to 0.79]; p < 0.001), where it tended to overestimate patients’ risks of sustained opioid use. The SOS score for non-Hispanic Asian patients did not perform worse than in the White patient population (c-statistic 0.79 [95% CI 0.67 to 0.90]; p = 0.65). Similarly, the degree of overlapping CIs suggests that the SOS score did not perform worse in the non-Hispanic Black population (c-statistic 0.75 [95% CI 0.69 to 0.81]; p = 0.003). There was no difference in score performance among socioeconomic groups (c-statistic 0.79 [95% CI 0.74 to 0.83] for socioeconomically disadvantaged patients; 0.78 [95% CI 0.77 to 0.80] for patients who were not socioeconomically disadvantaged; p = 0.92).

CONCLUSION: The SOS score performed adequately for non-Hispanic White patients but performed worse for Hispanic patients, where the 95% CI nearly included an area under the curve value of 0.5, suggesting that the tool is no better than chance at predicting sustained opioid use for Hispanic patients. In the Hispanic population, it commonly overestimated the risk of opioid dependence. Its performance did not differ among patients of different sociodemographic backgrounds. Future studies might seek to contextualize why the SOS score overestimates expected opioid prescriptions for Hispanic patients and how the utility performs among more specific Hispanic subgroups.

CLINICAL RELEVANCE: The SOS score is a valuable tool in ongoing efforts to combat the opioid epidemic; however, disparities exist in terms of its clinical applicability. Based on this analysis, the SOS score should not be used for Hispanic patients. Additionally, we provide a framework for how other predictive models should be tested in various lesser-represented populations before implementation.

PMID:37159263 | DOI:10.1097/CORR.0000000000002697

JCI Insight. 2023 May 9:e170270. doi: 10.1172/jci.insight.170270. Online ahead of print.

ABSTRACT

Respiration can positively impact cerebrospinal fluid (CSF) flow in the brain, yet its effects on central nervous system (CNS) fluid homeostasis including waste clearance function via the glymphatic and meningeal lymphatic systems remain unclear. Here, we investigated the effect of supporting respiratory function via continuous positive airway pressure (CPAP) on glymphatic-lymphatic function in spontaneously breathing anesthetized rodents. To do this, we used a systems approach combining engineering, magnetic resonance imaging, computational fluid dynamics analysis, and physiological testing. We first designed a nasal CPAP device for use in the rat and demonstrated that it functioned similar to clinical devices as evidenced by its ability to open the upper airway, augment end-expiratory lung volume, and improve arterial oxygenation. We further showed that CPAP increased CSF flow speed at the skull base and augmented glymphatic transport regionally. The CPAP-induced augmented CSF flow speed was associated with an increase in intracranial pressure (ICP), including the ICP waveform pulse amplitude. We suggest that the augmented pulse amplitude with CPAP underlies the increase in CSF bulk flow and glymphatic transport. Our results provide new insights into the functional crosstalk at the pulmonary-CSF interface and suggest that CPAP might have therapeutic benefit for sustaining glymphatic-lymphatic function.

PMID:37159262 | DOI:10.1172/jci.insight.170270

JMIR Res Protoc. 2023 May 9;12:e38487. doi: 10.2196/38487.

ABSTRACT

BACKGROUND: Maintaining a sufficiently high systolic blood pressure is essential for free flap perfusion after microsurgical breast reconstruction. Yet, many women undergoing these procedures have low postoperative systolic blood pressure. Intravenous volume administration or vasopressors may be needed to maintain systolic blood pressure above a predefined threshold. However, excessive volume administration may lead to volume overload and flap stasis, and the postoperative use of vasopressors may be limited depending on institutional standards. Additional nonpharmacological measures to raise blood pressure might be beneficial. Evidence suggests that the Red Bull energy drink could raise blood pressure. It has been shown to increase systolic and diastolic blood pressure in healthy volunteers and athletes.

OBJECTIVE: The primary objective of this study is to determine the difference in systolic blood pressure between an intervention group receiving Red Bull and a control group receiving still water after microsurgical breast reconstruction. Secondary objectives include postoperative heart rate, 24-hour fluid balance, pain level, or necessity for revision surgery due to flap complications.

METHODS: The Red Bull study is a prospective, multicenter randomized controlled trial comparing the effect of postoperative ingestion of Red Bull energy drink against still water in female patients undergoing unilateral microsurgical breast reconstruction. A total of 250 mL of Red Bull (intervention group) or 250 mL of still water (control group) will be administered to the study participants 2 hours postoperatively as well as for breakfast and lunch on postoperative day 1, amounting to a total volume of 750 mL per 24 hours. Female patients between 18 and 70 years of age undergoing unilateral microsurgical breast reconstruction will be included. Exclusion criteria are a history of arterial hypertension, cardiac rhythm disorder, diabetes mellitus, gastric or duodenal ulcer, thyroid disease, and current use of antihypertensive or antiarrhythmic drugs or thyroid hormones, as well as intolerance to Red Bull.

RESULTS: Recruitment for the study started in June 2020 and was completed in December 2022. There is evidence that the Red Bull energy drink increases blood pressure in healthy volunteers and athletes. We hypothesize that postoperative ingestion of Red Bull will increase systolic blood pressure in women after microsurgical breast reconstruction. Red Bull could hence be used as a nonpharmacological adjunct to vasopressors or volume administration in women with hypotensive blood pressure after microsurgical breast reconstruction.

CONCLUSIONS: This paper describes the Red Bull study trial protocol and analysis plan. The information will increase the transparency of the data analysis for the Red Bull study.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04397419; https://clinicaltrials.gov/ct2/show/NCT04397419.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38487.

PMID:37159251 | DOI:10.2196/38487

Am Surg. 2023 May 9:31348231175495. doi: 10.1177/00031348231175495. Online ahead of print.

ABSTRACT

BACKGROUND: The American Association for the Surgery of Trauma (AAST) Organ Injury Scale (OIS) for the spleen (and other organs) was created in 1989. It has been validated to predict mortality, need for operation, length of stay (LOS), and intensive care unit (ICU) LOS.

PURPOSE: We aimed to determine if the Spleen OIS is applied equally to blunt and penetrating trauma.

RESEARCH DESIGN/STUDY SAMPLE: We analyzed the Trauma Quality Improvement Program (TQIP) database from 2017-2019, including patients with spleen injuries.

DATA COLLECTION: Outcomes included the rates of mortality, operation, spleen-specific operation, splenectomy, and splenic embolization.

RESULTS: 60900 patients had a spleen injury with an OIS grade. Mortality rates increased in Grades IV and V for both blunt and penetrating trauma. In blunt trauma, the odds for any operation, spleen-specific operation, and splenectomy increased, for each increase in grade. Penetrating trauma showed similar trends in grades up to grade IV, but were statistically similar between grade IV and V. Splenectomy was higher in penetrating trauma for all grades. Splenic embolization peaked at 25% of grade IV trauma before decreasing in grade V. Rates in penetrating trauma were significantly lower in all grades, peaking at 2.5% of Grade III injuries.

CONCLUSIONS: The mechanism of trauma is a significant factor for all outcomes, independent of AAST-OIS. Hemostasis is predominantly surgical in penetrating trauma, achieved with angioembolization more frequently in blunt trauma. Penetrating trauma management is influenced by the potential for injury to peri-splenic organs.

PMID:37159228 | DOI:10.1177/00031348231175495

J Oral Rehabil. 2023 May 9. doi: 10.1111/joor.13486. Online ahead of print.

ABSTRACT

BACKGROUND: Oral health may be associated with cognitive disorders such as mild cognitive impairment or dementia.

OBJECTIVE: This study elucidates the effects of oral health conditions on the progression of cognitive disorders.

METHODS: Data were collected from 153 participants of the Korean Longitudinal Study on Cognitive Aging and Dementia cohort who completed the longitudinal dental examinations and cognitive function assessments using the three-wave biannual survey. We analyzed the relationship between dental factors and the conversion of cognitive function.

RESULTS: The ratio of maxillary removable partial denture use (p = 0.03) was high in the converter and mild cognitive impairment/dementia groups. The low-grade ratio of posterior masticatory performance increased in the converter and mild cognitive impairment/dementia groups (modified Eichner index 2, p = 0.04). The mild cognitive impairment/dementia group had a higher rate of complete mandibular denture use (p < 0.001). The converter and mild cognitive impairment/dementia groups had fewer remaining teeth (p < 0.05) or removable prostheses (p < 0.01) than the normal group.

CONCLUSIONS: Masticatory performance is associated with the conversion of cognitive disorders. Our findings suggest that oral health management can help delay the progression of cognitive disorders.

PMID:37159220 | DOI:10.1111/joor.13486

Clin Cancer Res. 2023 May 9:CCR-22-3217. doi: 10.1158/1078-0432.CCR-22-3217. Online ahead of print.

ABSTRACT

PURPOSE: To determine the role of CD49d for response to Bruton’s tyrosine kinase inhibitors (BTKis) in patients with chronic lymphocytic leukemia (CLL).

METHODS: In patients treated with acalabrutinib (n=48), CD49d expression, VLA-4 integrin activation, and tumor transcriptomes of CLL cells were assessed. Clinical responses to BTKis were investigated in acalabrutinib (n=48; NCT02337829), and ibrutinib (n=73; NCT01500733) treated patients.

RESULTS: In patients treated with acalabrutinib, treatment induced lymphocytosis was comparable for both subgroups but resolved more rapidly for CD49d+ cases. Acalabrutinib inhibited constitutive VLA-4 activation but was insufficient to block BCR and CXCR4 mediated inside-out activation. Transcriptomes of CD49d+ and CD49d- cases were compared using RNA sequencing at baseline and at 1 and 6 months on treatment. Gene set enrichment analysis revealed increased constitutive NF-кB and JAK-STAT signaling, enhanced survival, adhesion, and migratory capacity in CD49d+ over CD49d- CLL that was maintained during therapy. In the combined cohorts of 121 BTKi treated patients, 48 (39.7%) progressed on treatment with BTK and/or PLCG2 mutations detected in 87% of CLL progressions. Consistent with a recent report, homogeneous and bimodal CD49d positive cases (the latter having concurrent CD49d+ and CD49d- CLL subpopulations, irrespective of the traditional 30% cutoff), had a shorter time to progression of 6.6 years, while 90% of cases homogenously CD49d negative were estimated progression-free at 8 years (P = .0004).

CONCLUSIONS: CD49d/VLA-4 emerges as a microenvironmental factor that contributes to BTKi resistance in CLL. The prognostic value of CD49d is improved by considering bimodal CD49d expression.

PMID:37159219 | DOI:10.1158/1078-0432.CCR-22-3217

J Vis. 2023 May 2;23(5):8. doi: 10.1167/jov.23.5.8.

ABSTRACT

“The function of painting is to make poetry visible… to render thought visible.” René Magritte Pictorial art reveals some of the visual brain’s “neural rules” and processing hierarchy. This article examines one salient exemplar drawn from the vast oeuvre of the great Belgian surrealist, René Magritte (1898-1967). The painting Le Blanc-Seing (1965) is a virtual course in perception, with many elements illustrating figure-ground segregation, object identification, cues for depth perception, Gestalt Laws of occlusion-continuation, and visual scene organization. Le Blanc-Seing is visually stunning, beautifully rendered, and, at first glance, otherwise unremarkable. However, Magritte has embedded several jarring surreal effects in the painting that provide clues about the visual brain’s visual processing hierarchy in scene construction. This includes elements whose alternation between two incompatible percepts cannot be explained in terms of local spatiochromatic statistics (Ritchie & van Buren, 2020). Finally, I provide a plausible pictorial inspiration (never before demonstrated) for the painting in a brief scene from a 1924 German silent film.

PMID:37159206 | DOI:10.1167/jov.23.5.8

JAMA Netw Open. 2023 May 1;6(5):e2312538. doi: 10.1001/jamanetworkopen.2023.12538.

NO ABSTRACT

PMID:37159201 | DOI:10.1001/jamanetworkopen.2023.12538

JAMA Netw Open. 2023 May 1;6(5):e2310223. doi: 10.1001/jamanetworkopen.2023.10223.

ABSTRACT

IMPORTANCE: To date, no psychopharmacologic treatment has been found to be uniformly effective in veterans with posttraumatic stress disorder (PTSD); novel targets and approaches are needed to treat this disabling disorder.

OBJECTIVE: To examine whether treatment with the glucocorticoid receptor antagonist mifepristone yields a signal for clinical efficacy in male veterans with PTSD.

DESIGN, SETTING, AND PARTICIPANTS: This phase 2a, double-blind, parallel-group randomized clinical trial was conducted from November 19, 2012 (accrual started), through November 16, 2016 (final follow-up), within the US Department of Veterans Affairs. Participants were male veterans with chronic PTSD and a screening Clinician-Administered PTSD Scale score of 50 or higher. A total of 181 veterans consented to participation. Statistical analysis was conducted between August 2014 and May 2017.

INTERVENTIONS: Participants were randomized in a 1:1 ratio to mifepristone (600 mg) or matched placebo taken orally for 7 days.

MAIN OUTCOMES AND MEASURES: The clinical outcome was whether a veteran achieved a clinical response status (a reduction of ≥30% of total Clinician-Administered PTSD Scale score from baseline) at 4- and 12-week follow-up. On the basis of a binary statistical selection rule, a difference in the proportion of treatment vs control group responders of 15% would be a clinically relevant difference. Self-report measures of PTSD and associated symptoms were also obtained. Neuroendocrine outcomes and plasma levels of mifepristone were measured. Safety was assessed throughout the study. The primary analysis was based on a multiple imputation technique to address missing outcome data; thus, some participant numbers may not appear as whole numbers.

RESULTS: A total of 81 veterans were enrolled and randomized. Excluding 1 participant randomized in error, 80 were included in the modified intention-to-treat analysis (41 randomized to mifepristone and 39 to placebo). The mean (SD) age was 43.1 (13.7) years. A total of 15.6 (38.1%) in the mifepristone group and 12.1 (31.1%) in the placebo group were clinical responders at 4 weeks in the analysis using the multiple imputation technique. The group difference in the proportion of clinical responders (7.0%) was less than the predefined margin of 15% indicating signal for clinical efficacy. In an exploratory analysis, the difference in response to mifepristone vs placebo in the subgroup with no lifetime history of traumatic brain injury (TBI) (7.0 [50.0%] vs 3.0 [27.3%]; difference, 22.7%) exceeded the efficacy margin at 4 weeks and was sustained at 12 weeks. In contrast, in veterans with PTSD and lifetime TBI, the response rate to mifepristone was lower than placebo at 12 weeks (7.4 [27.4%] vs 13.5 [48.3%]; difference, -20.9%).

CONCLUSIONS AND RELEVANCE: This study did not detect a signal for efficacy for mifepristone at 600 mg/d for 1 week in male veterans with chronic PTSD. Thus, this study does not support a phase 3 trial in this population. Future studies of mifepristone for the treatment of PTSD may be of interest in those without a history of TBI or in samples with a low base rate of lifetime head trauma.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01946685.

PMID:37159200 | DOI:10.1001/jamanetworkopen.2023.10223