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1.
Emerg Med Clin North Am ; 42(3): 653-666, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38925780

ABSTRACT

Envenomations are the 23rd most common reason for calls to US poison control centers, with over 35,000 incidents reported annually. Snake bites account for over 20% of those calls, while marine envenomations are likely underreported at 3% to 4%.1 While these types of envenomations may not be encountered on a daily basis for many physicians, the different types of envenomations warrant unique management strategies based on the offending creature and symptom presentation. This text serves as a review of the epidemiology, clinical presentations, and management of endemic North American species of snakes and marine vertebrate and invertebrate envenomations.


Subject(s)
Antivenins , Snake Bites , Humans , Snake Bites/therapy , Snake Bites/epidemiology , Snake Bites/diagnosis , Animals , Antivenins/therapeutic use , Bites and Stings/therapy , Bites and Stings/epidemiology , Bites and Stings/diagnosis , North America/epidemiology , Snakes
2.
Curr Sports Med Rep ; 23(5): 199-206, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38709946

ABSTRACT

ABSTRACT: Breath-hold divers, also known as freedivers, are at risk of specific injuries that are unique from those of surface swimmers and compressed air divers. Using peer-reviewed scientific research and expert opinion, we created a guide for medical providers managing breath-hold diving injuries in the field. Hypoxia induced by prolonged apnea and increased oxygen uptake can result in an impaired mental state that can manifest as involuntary movements or full loss of consciousness. Negative pressure barotrauma secondary to airspace collapse can lead to edema and/or hemorrhage. Positive pressure barotrauma secondary to overexpansion of airspaces can result in gas embolism or air entry into tissues and organs. Inert gas loading into tissues from prolonged deep dives or repetitive shallow dives with short surface intervals can lead to decompression sickness. Inert gas narcosis at depth is commonly described as an altered state similar to that experienced by compressed air divers. Asymptomatic cardiac arrhythmias are common during apnea, normally reversing shortly after normal ventilation resumes. The methods of glossopharyngeal breathing (insufflation and exsufflation) can add to the risk of pulmonary overinflation barotrauma or loss of consciousness from decreased cardiac preload. This guide also includes information for medical providers who are tasked with providing medical support at an organized breath-hold diving event with a list of suggested equipment to facilitate diagnosis and treatment outside of the hospital setting.


Subject(s)
Barotrauma , Breath Holding , Decompression Sickness , Diving , Humans , Diving/injuries , Diving/adverse effects , Barotrauma/etiology , Barotrauma/diagnosis , Decompression Sickness/therapy , Decompression Sickness/etiology , Decompression Sickness/diagnosis , Hypoxia/etiology , Inert Gas Narcosis/etiology , Inert Gas Narcosis/diagnosis
4.
J Bone Miner Res ; 39(5): 517-530, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38590141

ABSTRACT

Using race and ethnicity in clinical algorithms potentially contributes to health inequities. The American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee convened the ASBMR Task Force on Clinical Algorithms for Fracture Risk to determine the impact of race and ethnicity adjustment in the US Fracture Risk Assessment Tool (US-FRAX). The Task Force engaged the University of Minnesota Evidence-based Practice Core to conduct a systematic review investigating the performance of US-FRAX for predicting incident fractures over 10 years in Asian, Black, Hispanic, and White individuals. Six studies from the Women's Health Initiative (WHI) and Study of Osteoporotic Fractures (SOF) were eligible; cohorts only included women and were predominantly White (WHI > 80% and SOF > 99%), data were not consistently stratified by race and ethnicity, and when stratified there were far fewer fractures in Black and Hispanic women vs White women rendering area under the curve (AUC) estimates less stable. In the younger WHI cohort (n = 64 739), US-FRAX without bone mineral density (BMD) had limited discrimination for major osteoporotic fracture (MOF) (AUC 0.53 (Black), 0.57 (Hispanic), and 0.57 (White)); somewhat better discrimination for hip fracture in White women only (AUC 0.54 (Black), 0.53 (Hispanic), and 0.66 (White)). In a subset of the older WHI cohort (n = 23 918), US-FRAX without BMD overestimated MOF. The Task Force concluded that there is little justification for estimating fracture risk while incorporating race and ethnicity adjustments and recommends that fracture prediction models not include race or ethnicity adjustment but instead be population-based and reflective of US demographics, and inclusive of key clinical, behavioral, and social determinants (where applicable). Research cohorts should be representative vis-à-vis race, ethnicity, gender, and age. There should be standardized collection of race and ethnicity; collection of social determinants of health to investigate impact on fracture risk; and measurement of fracture rates and BMD in cohorts inclusive of those historically underrepresented in osteoporosis research.


Using race or ethnicity when calculating disease risk may contribute to health disparities. The ASBMR Task Force on Clinical Algorithms for Fracture Risk was created to understand the impact of the US Fracture Risk Assessment Tool (US-FRAX) race and ethnicity adjustments. The Task Force reviewed the historical development of FRAX, including the assumptions underlying selection of race and ethnicity adjustment factors. Furthermore, a systematic review of literature was conducted, which revealed an overall paucity of data evaluating the performance of US-FRAX in racially and ethnically diverse groups. While acknowledging the existence of racial and ethnic differences in fracture epidemiology, the Task Force determined that currently there is limited evidence to support the use of race and ethnicity­specific adjustments in US-FRAX. The Task Force also concluded that research is needed to create generalizable fracture risk calculators broadly applicable to current US demographics, which do not include race and ethnicity adjustments. Until such population­based fracture calculators are available, clinicians should consider providing fracture risk ranges for Asian, Black, and/or Hispanic patients and should engage in shared decision-making with patients about fracture risk interpretation. Future studies are required to evaluate fracture risk tools in populations inclusive of those historically underrepresented in research.


Subject(s)
Algorithms , Humans , Female , Risk Assessment , United States/epidemiology , Advisory Committees , Fractures, Bone/epidemiology , Bone Density , Societies, Medical , Risk Factors , Osteoporotic Fractures/epidemiology , Male , Aged
5.
JBMR Plus ; 8(2): ziae003, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38505529

ABSTRACT

Diabetes, a disease marked by consistent high blood glucose levels, is associated with various complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Notably, skeletal fragility has emerged as a significant complication in both type 1 (T1D) and type 2 (T2D) diabetic patients. This review examines noninvasive imaging studies that evaluate skeletal outcomes in adults with T1D and T2D, emphasizing distinct skeletal phenotypes linked with each condition and pinpointing gaps in understanding bone health in diabetes. Although traditional DXA-BMD does not fully capture the increased fracture risk in diabetes, recent techniques such as quantitative computed tomography, peripheral quantitative computed tomography, high-resolution quantitative computed tomography, and MRI provide insights into 3D bone density, microstructure, and strength. Notably, existing studies present heterogeneous results possibly due to variations in design, outcome measures, and potential misclassification between T1D and T2D. Thus, the true nature of diabetic skeletal fragility is yet to be fully understood. As T1D and T2D are diverse conditions with heterogeneous subtypes, future research should delve deeper into skeletal fragility by diabetic phenotypes and focus on longitudinal studies in larger, diverse cohorts to elucidate the complex influence of T1D and T2D on bone health and fracture outcomes.

6.
AEM Educ Train ; 8(2): e10962, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38525360

ABSTRACT

Background: Mass casualty incident (MCI) triage simulation is an increasingly useful tool for teaching triage systems to medical students, trainees, and hospital staff. MCI simulation in the prehospital setting has not yet been studied in this population. Objectives/Aims: We aimed to assess the effectiveness of a prehospital MCI simulation in medical students, residents, and fellows. Our primary outcome was knowledge of the components of the triage algorithms used in MCI response. Our secondary outcome was each participant's confidence level if required to assist with or lead a MCI response. Methods: This was an observational study with pre-post surveys. We recruited 30 medical students, 14 emergency medicine (EM) residents, and four pediatric EM fellows to fill out a survey before and after a 3-h simulation session practicing the START and JumpSTART algorithms on two prehospital MCI scenarios. Results: Overall, all groups demonstrated significant improvement in knowledge of triage colors, information needed to assign a triage color, pediatric airway management during a MCI, and indications for breaths-first CPR. They also demonstrated significant increase in confidence both in assisting with and in leading a MCI response. Conclusions: Simulated practice triaging patients in prehospital MCI scenarios improves knowledge of triage algorithms and increases confidence in assisting with or leading a MCI response in medical trainees.

7.
AJPM Focus ; 3(2): 100186, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38304025

ABSTRACT

Introduction: Cardiometabolic diseases are associated with greater COVID-19 severity; however, the influences of cardiometabolic health on SARS-CoV-2 infections after vaccination remain unclear. Our objective was to investigate the associations between temporal blood pressure and total cholesterol patterns and incident SARS-CoV-2 infections among those with serologic evidence of vaccination. Methods: In this prospective cohort of blood donors, blood samples were collected in 2020-2021 and assayed for binding antibodies of SARS-CoV-2 nucleocapsid protein antibody seropositivity. We categorized participants into intraindividual pattern subgroups of blood pressure and total cholesterol (persistently, intermittently, or not elevated [systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg, total cholesterol <200 mg/dL]) across the study time points. Results: Among 13,930 donors with 39,736 donations representing 1,127,071 person-days, there were 221 incident SARS-CoV-2 infections among those with serologic evidence of vaccination (1.6%). Intermittent hypertension was associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination risk (adjusted incidence rate ratio=2.07; 95% CI=1.44, 2.96; p<0.01) than among participants with consistent normotension on the basis of a multivariable Poisson regression. Among men, intermittently elevated total cholesterol (adjusted incidence rate ratio=1.90; 95% CI=1.32, 2.74; p<0.01) and higher BMI at baseline (adjusted hazard ratio=1.44; 95% CI=1.07, 1.93; p=0.01; per 10 units) were associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination probability; these associations were null among women (both p>0.05). Conclusions: Our findings underscore that the benefits of cardiometabolic health, particularly blood pressure, include a lower risk of SARS-CoV-2 infection after vaccination.

8.
Oncologist ; 29(6): 534-542, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38417095

ABSTRACT

BACKGROUND: A recent real-world study observed that 24% of patients with advanced non-small cell lung cancer (aNSCLC) with actionable driver oncogenes (ADOs) initiated nontargeted therapies before biomarker test results became available. This study assessed the clinical impact of the timing of first-line (1L) targeted therapies (TTs) in aNSCLC. MATERIALS AND METHODS: This retrospective analysis of a nationwide electronic health record-derived deidentified database included patients aged ≥18 years diagnosed with aNSCLC with ADOs (ALK, BRAF, EGFR, RET, MET, ROS-1, and NTRK) from January 1, 2015, to October 18, 2022, by biomarker testing within 90 days after advanced diagnosis and received 1L treatment. Cohorts were defined by treatment patterns ≤42 days after test results: "Upfront TT" received 1L TT ≤42 days; "Switchers" initiated 1L non-TT before or after testing but switched to TT ≤42 days; and "Non-switchers" initiated non-TT before or after testing and did not switch at any time. Adjusted multivariate Cox regression evaluated real-world progression-free survival, real-world time to next treatment or death, and real-world overall survival. RESULTS: A total of 3540 patients met the study criteria; 78% were treated in a community setting, and 50% underwent next-generation sequencing (NGS). There was no significant difference in outcomes between Switchers and Upfront TT; inferior outcomes were observed in Non-switchers versus Upfront TT. CONCLUSION: Our findings demonstrated improved outcomes with upfront 1L TT versus non-TT in patients with aNSCLC with ADOs and observed timely switching to TT after biomarker test result had similar outcomes to Upfront TT. Opportunities remain to improve the use of NGS for early ADO identification and determination of 1L TT.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Molecular Targeted Therapy , Oncogenes , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/mortality , Female , Male , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/mortality , Middle Aged , Retrospective Studies , Molecular Targeted Therapy/methods , Aged , Adult , Biomarkers, Tumor/genetics , Aged, 80 and over
9.
JCO Oncol Pract ; 20(3): 370-377, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38194619

ABSTRACT

PURPOSE: Racial/ethnic inequities in next-generation sequencing (NGS) were examined for patients with advanced non-small-cell lung cancer (aNSCLC) at the practice and physician levels to inform policies to improve equitable quality of care. METHODS: This retrospective study used a nationwide electronic health record-derived deidentified database for patients with aNSCLC diagnosed between April 2018 and March 2022 in the community setting. Timely NGS was an NGS result between initial diagnosis and ≤60 days after advanced diagnosis. We studied how inequities were driven by (1) non-Latinx Black (Black) and Latinx patient under-representation at high testing practices versus (2) Black and Latinx patients being tested at lower rates than non-Latinx White (White) patients, even at the same practice. We defined these two concepts as across inequity and within inequity, respectively, with total inequity as their summation. Mean percentage point inequities were estimated using a Bayesian approach. RESULTS: A total of 12,045 patients (9,981 White; 1,528 Black; 536 Latinx) met study criteria. At the practice level, versus White patients, the mean percentage point difference in NGS testing total inequity was 7.49 for Black and 8.26 for Latinx. Within- and across-practice inequities contributed to total inequity in NGS testing for Black (48% v 52%) and Latinx patients (60% v 40%). At the physician level, versus White patients, the mean percentage point difference in total inequity was 7.73 for Black and 8.81 for Latinx patients. Within- versus across-physician inequities contributed to total inequity for Black and Latinx patients (77% v 23% and 67% v 33%). CONCLUSION: Within-practice, across-practice, and across-physician inequities were main contributors to total inequity in NGS testing, requiring a suite of interventions to effectively address inequities.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Physicians , Humans , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Bayes Theorem , Retrospective Studies , Lung Neoplasms/genetics , Lung Neoplasms/therapy , High-Throughput Nucleotide Sequencing
10.
Front Clin Diabetes Healthc ; 4: 1272804, 2023.
Article in English | MEDLINE | ID: mdl-37867730

ABSTRACT

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.

11.
Endocrinol Metab Clin North Am ; 52(4): 629-641, 2023 12.
Article in English | MEDLINE | ID: mdl-37865478

ABSTRACT

Racial and ethnic disparities exist in the prevalence and management of osteoporosis, metastatic cancer, and sickle cell disease. Despite being the most common metabolic bone disease, osteoporosis remains underscreened and undertreated among Black women. Skeletal-related events in metastatic cancer include bone pain, pathologic fractures, and spinal cord compression. Disparities in screening for and treating skeletal-related events disproportionately affect Black patients. Metabolic bone disease contributes significantly to morbidity in sickle cell disease; however, clinical guidelines for screening and treatment do not currently exist. Clinical care recommendations are provided to raise awareness, close health care gaps, and guide future research efforts.


Subject(s)
Anemia, Sickle Cell , Neoplasms , Osteoporosis , Humans , Female , Osteoporosis/etiology , Osteoporosis/therapy , Osteoporosis/diagnosis , Delivery of Health Care , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/therapy
12.
Front Sports Act Living ; 5: 1224581, 2023.
Article in English | MEDLINE | ID: mdl-37601165

ABSTRACT

Background: Non-professional climbers are increasingly attempting long routes in a single day. Many suffer injury or rely on search and rescue teams when they become too fatigued to finish. Predicting fatigue is difficult, and existing studies have only studied climbers over durations less than an hour, while many outdoor multipitch climbs require more than an hour of climbing. Objectives: To determine how strength, endurance, and dexterity reflect fatigue after 24 h of continuous climbing. Methods: Volunteer competitors completed measurements of grip strength, static hang time to failure, and time to tie a figure-eight follow-through knot. Measurements were taken during the registration period before the competition and again within an hour after the competition ended. Measurements were compared using the paired t-test. Subgroup analysis was applied to competitors by division. Linear regression was applied to determine the relationship between vertical feet climbed and the number of routes climbed during the competition on each metric. Results: Thirty-six total climbers (average age 29.4 years old) completed pre- and post-competition measurements. After 24 h of climbing (n = 36), mean grip strength decreased by 14.3-15 lbs or 14.7%-15.1% (p < 0.001) and static hang time decreased by 54.2 s or 71.2% (p < 0.001). There was no significant change in time to tie a figure-eight-follow-through knot. Grip strength and hang time decreases were significant in climbers with outdoor redpoints of 5.10a and above. Hang time decreased by 5.4 s per 1,000 vertical feet climbed (p = 0.044). Conclusion: Climbers can expect to experience a 14.7%-15.1% decrease in grip strength and 71.2% decrease in static hang time after 24 h of continuous climbing. These changes may make it difficult to climb consistently over a long objective, and climbers can use these measures at home to train for longer climbing routes. Future studies on shorter climbing intervals can help determine rates of decline in performance measures.

13.
JCEM Case Rep ; 1(4): luad085, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37457635

ABSTRACT

We report a case of isolated cutaneous small vessel vasculitis (SVV) occurring after zoledronic acid (Zol) infusion in a 58-year-old postmenopausal woman with a history of sleeve gastrectomy. This was the patient's first exposure to a bisphosphonate medication. Within minutes of the Zol infusion, she developed an episode of diffuse watery diarrhea. Although the diarrheal symptoms resolved quickly, she experienced nonsteroidal anti-inflammatory drug-responsive generalized myalgias and skin tenderness in her abdomen and extremities within a few hours. These symptoms progressed in severity over the next 5 days, and she developed nonblanching, palpable purpura extending from the ankles to the knees. Prior to Zol, labs showed sufficient 25-hydroxyvitamin D and calcium as well as normal renal and liver function. On day 10, laboratory tests revealed aspartate transaminase twice and alanine transaminase thrice the upper limit of normal. The patient was diagnosed with cutaneous SVV, with a timeline highly suggestive of an idiosyncratic reaction to Zol. She was successfully treated with a prednisone taper. No prior cases of Zol-induced cutaneous vasculitis have been reported, although there are a handful of reported cases of giant cell arteritis and urticarial vasculitis after bisphosphonate therapy. Clinicians should be aware that isolated cutaneous SVV may be a rare complication of Zol.

14.
Adv Nutr ; 14(5): 1145-1158, 2023 09.
Article in English | MEDLINE | ID: mdl-37302794

ABSTRACT

Cardiometabolic diseases and abnormalities have recently emerged as independent risk factors of coronavirus disease 2019 (COVID-19) severity, including hospitalizations, invasive mechanical ventilation, and mortality. Determining whether and how this observation translates to more effective long-term pandemic mitigation strategies remains a challenge due to key research gaps. Specific pathways by which cardiometabolic pathophysiology affects humoral immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and vice versa, remain unclear. This review summarizes current evidence of the bidirectional influences between cardiometabolic diseases (diabetes, adiposity, hypertension, CVDs) and SARS-CoV-2 antibodies induced from infection and vaccination based on human studies. Ninety-two studies among >408,000 participants in 37 countries on 5 continents (Europe, Asia, Africa, and North and South America) were included in this review. Obesity was associated with higher neutralizing antibody titers following SARS-CoV-2 infection. Most studies conducted prior to vaccinations found positive or null associations between binding antibodies (levels, seropositivity) and diabetes; after vaccinations, antibody responses did not differ by diabetes. Hypertension and CVDs were not associated with SARS-CoV-2 antibodies. Findings underscore the importance of elucidating the extent that tailored recommendations for COVID-19 prevention, vaccination effectiveness, screening, and diagnoses among people with obesity could reduce disease burden caused by SARS-CoV-2.


Subject(s)
COVID-19 , Cardiovascular Diseases , Hypertension , Humans , Immunity, Humoral , SARS-CoV-2 , Obesity/complications
15.
Future Oncol ; 19(20): 1397-1414, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37318757

ABSTRACT

Aim: Biomarker testing detects actionable driver mutations to inform first-line treatment in advanced non-small-cell lung cancer (aNSCLC) and metastatic colorectal cancer (mCRC). This study evaluated biomarker testing in a nationwide database (NAT) versus the OneOncology (OneOnc) community network. Patients & methods: Patients with aNSCLC or mCRC with ≥1 biomarker test in a de-identified electronic health record-derived database were evaluated. OneOnc oncologists were surveyed. Results: Biomarker testing rates were high and comparable between OneOnc and NAT; next-generation sequencing (NGS) rates were higher at OneOnc. Patients with NGS versus other biomarker testing were more likely to receive targeted treatment. Operational challenges and insufficient tissue were barriers to NGS testing. Conclusion: Community cancer centers delivered personalized healthcare through biomarker testing.


What is this article about? Cancer therapies often work better in certain subgroups of patients. Tumors may have characteristics that can predict which therapies may be more likely to work. These cancer biomarkers may be identified by special testing, such as next-generation sequencing (NGS). If a biomarker is detected, the patient can potentially be treated with medicine that targets that biomarker. This study looked at biomarker testing of lung and colon cancers in two community cancer practices (OneOncology [OneOnc] and nationwide database [NAT]). What were the results? The biomarker testing rates were high (≥81%) and similar between OneOnc and NAT. NGS testing rates were higher at OneOnc than at NAT (58 vs 49% for non-small-cell lung cancer, 55 vs 42% for metastatic colorectal cancer [mCRC]), suggesting the success of OneOnc's networkwide educational, pathway and operational programs. NGS testing was lower in community practices due to operational challenges and insufficient tissue collection. Patients who had NGS versus other biomarker testing were more likely to receive treatment specifically for that biomarker. However, some patients started treatment before their biomarker results were reported, usually because of their disease and a long wait time for biomarker test results. What do the results of the study mean? Community cancer centers can treat patients with targeted medicine based on biomarker testing results. There are opportunities to increase the number of patients getting NGS testing, shorten turnaround times and reduce the number of patients who start treatment before getting their biomarker test results.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Colorectal Neoplasms , Lung Neoplasms , Humans , United States/epidemiology , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/epidemiology , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/therapy , Community Networks , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , Colorectal Neoplasms/therapy , High-Throughput Nucleotide Sequencing , Mutation
16.
J Pharm Sci ; 112(6): 1625-1634, 2023 06.
Article in English | MEDLINE | ID: mdl-36627053

ABSTRACT

The drying time of lyophilization and resultant cake microstructure are dependent on each other as water and solvent leave a lyophilized cake. The drying rate affects the size, distribution, and tortuosity of the pores as these macropores evolve during the primary drying phase, which in return impact the further removal of water and solvent from the cake throughout the drying period. This interplay results in a microstructure that determines the reconstitution time for a given formulation. The current study employs advanced X-ray Microscopy (XRM) coupled with mathematical models to correlate the microstructure with the drying kinetics and the reconstitution time. The normalized diffusion coefficients, derived from the reconstructed 3D microstructure of the cake, correlate with the solid content of the pre-lyophilization solution and agree with the mass transfer coefficients from a semi-empirical drying model built with lyophilization process data. Specifically, a solution with less solid content leads to a lyophilized cake with larger pores, thinner walls, and a greater pore volume compared to a solution with more solid content. Consequently, models from the microstructure and drying experiments reveals faster mass transfer independently. While the mass transfer models from the cake structure and the lyophilization process data accurately represents the drying kinetics, both models are inadequate to describe the reconstitution process due to the significant impact from formulation ingredients that alter the mass transfer mechanism via solubility and wettability. In summary, X-ray microscopy imaging and mathematical models are powerful tools that provide insights into the lyophilization process from a new angle.


Subject(s)
Microscopy , Water , Kinetics , X-Rays , Temperature , Freeze Drying/methods , Solvents
17.
JCO Oncol Pract ; 19(1): e125-e137, 2023 01.
Article in English | MEDLINE | ID: mdl-36178937

ABSTRACT

PURPOSE: Delivering cancer care by high-functioning multidisciplinary teams promises to address care fragmentation, which threatens care quality, affects patient outcomes, and strains the oncology workforce. We assessed whether the 4R Oncology model for team-based interdependent care delivery and patient self-management affected team functioning in a large community-based health system. METHODS: 4R was deployed at four locations in breast and lung cancers and assessed along four characteristics of high-functioning teams: recognition as a team internally and externally; commitment to an explicit shared goal; enablement of interdependent work to achieve the goal; and engagement in regular reflection to adapt objectives and processes. RESULTS: We formed an internally and externally recognized team of 24 specialties committed to a shared goal of delivering multidisciplinary care at the optimal time and sequence from a patient-centric viewpoint. The team conducted 40 optimizations of interdependent care (22 for breast, seven for lung, and 11 for both cancers) at four points in the care continuum and established an ongoing teamwork adaptation process. Half of the optimizations entailed low effort, while 30% required high level of effort; 78% resulted in improved process efficiency. CONCLUSION: 4R facilitated development of a large high-functioning team and enabled 40 optimizations of interdependent care along the cancer care continuum in a feasible way. 4R may be an effective approach for fostering high-functioning teams, which could contribute to improving viability of the oncology workforce. Our intervention and taxonomy of results serve as a blueprint for other institutions motivated to strengthen teamwork to improve patient-centered care.


Subject(s)
Medical Oncology , Neoplasms , Humans , Delivery of Health Care , Patient-Centered Care , Breast , Continuity of Patient Care , Neoplasms/therapy
18.
J Trauma Stress ; 36(1): 167-179, 2023 02.
Article in English | MEDLINE | ID: mdl-36463566

ABSTRACT

Older adults, particularly those with trauma histories, may be vulnerable to adverse psychosocial outcomes during the COVID-19 pandemic. We tested associations between prepandemic childhood abuse or intimate partner violence (IPV) and elevated depressive, anxiety, conflict, and sleep symptoms during the pandemic among aging women. Women (N = 582, age: 65-77 years) from three U.S. sites (Pittsburgh, Boston, Newark) of the longitudinal Study of Women's Health Across the Nation (SWAN) reported pandemic-related psychosocial impacts from June 2020-March 2021. Prepandemic childhood abuse; physical/emotional IPV; social functioning; physical comorbidities; and depressive, anxiety, and sleep symptoms were drawn from SWAN assessments between 2009 and 2017. There were no measures of prepandemic conflict. In total, 47.7% and 35.3% of women, respectively, reported childhood abuse or IPV. Using logistic regression models adjusted for age; race/ethnicity; education; site; prepandemic social functioning and physical comorbidities; and, in respective models, prepandemic depressive, anxiety, or sleep symptoms, childhood abuse predicted elevated anxiety symptoms, OR = 1.67, 95% CI [1.10, 2.54]; household conflict, OR = 2.19, 95% CI [1.32, 3.61]; and nonhousehold family conflict, OR = 2.14, 95% CI [1.29, 3.55]. IPV predicted elevated sleep problems, OR = 1.63, 95% CI [1.07, 2.46], and household conflict, OR = 1.96, 95% CI [1.20, 3.21]. No associations emerged for depressive symptoms after adjusting for prepandemic depression. Aging women with interpersonal trauma histories reported worse anxiety, sleep, and conflict during the COVID-19 pandemic than those without. Women's trauma histories and prepandemic symptoms are critical to understanding the psychosocial impacts of the pandemic.


Subject(s)
COVID-19 , Intimate Partner Violence , Stress Disorders, Post-Traumatic , Female , Humans , Child , Aged , Pandemics , Longitudinal Studies , Women's Health , Intimate Partner Violence/psychology
19.
J Oral Maxillofac Surg ; 81(2): 232-237, 2023 02.
Article in English | MEDLINE | ID: mdl-36442534

ABSTRACT

PURPOSE: Osteonecrosis of the jaws (ONJ) occurs in patients on antiresorptive drugs for osteoporosis with the risk with oral bisphosphonates being known to be of the order of 0.1 to 0.3% while the risk for patients on denosumab for osteoporosis is not known. The aim of this study was to determine the risk of developing ONJ in a consecutive series of patients on denosumab for osteoporosis having dental extractions. MATERIAL AND METHODS: A prospective cohort study of patients on denosumab for osteoporosis having dental extractions in the period January 1, 2017 and June 30, 2021 were compared to a control group not on antiresorptives. Detailed demographic records including length of time on antiresorptives and CTX values were obtained. Comparison to further define risk factors was made between those patients developing ONJ to those who didn't. RESULTS: The treatment group included 427 patients who were on denosumab for osteoporosis; they collectively underwent 561 episodes of dental treatment involving extractions for a total of 1081 extractions, with 10 developing ONJ (risk 2.3%). The control group consisted of 299 patients who were not taking denosumab; they collectively underwent 315 episodes of dental treatment for a total of 669 extractions, and none of them developed ONJ. There were significant differences in age and sex, but not medical comorbidities between the treatment and control groups. Within the treatment group, there were no significant differences in any of these characteristics between those who did, and those who didn't, develop ONJ. Within the treatment group, the number of extractions modified the risk of developing ONJ (odds ratio, 1.35; confidence interval, 1.1-1.7). Of the 76 patients who had extractions between 6 and 7 months after the last denosumab injection, none developed ONJ. CONCLUSIONS: The risk of ONJ in patients on denosumab for osteoporosis is a magnitude greater than for patients on the oral bisphosphonates 2.3% v 0 - 0.3%, which is 7.7 times more likely. Number of extractions and early resumption of the next dose of denosumab increases the risk of ONJ.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Bone Density Conservation Agents , Osteonecrosis , Osteoporosis , Humans , Denosumab/adverse effects , Prospective Studies , Osteoporosis/drug therapy , Bone Density Conservation Agents/adverse effects , Osteonecrosis/chemically induced , Diphosphonates/adverse effects , Tooth Extraction/adverse effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology , Bisphosphonate-Associated Osteonecrosis of the Jaw/therapy
20.
J Pharm Sci ; 112(3): 859-867, 2023 03.
Article in English | MEDLINE | ID: mdl-36395899

ABSTRACT

Utilization of laser headspace and near-infrared (NIR) methods provides rapid and non-destructive approaches for moisture detection of lyophilized drug products to facilitate lyophilization formulation characterization and process development. In the present study, the NIR method was developed based on a partial least square regression (PLSR) model calibrated and validated with Karl Fisher (KF) data, whereas the laser headspace method was developed with aid of dynamic vapor sorption (DVS) method so that the water vapor pressure measured from the headspace of a lyophilized drug product vial can be converted directly to water content value through the water vapor sorption isotherm of the lyophilized drug product bypassing KF calibration. The water contents of lyophilized samples obtained from both methods agreed well with KF data, with a root mean squared error of prediction (RMSEP) of less than 0.15%. The pros and cons of NIR and laser headspace method were evaluated. The results suggest that traditional off-line KF method can be potentially replaced by at-line laser headspace method combined with water sorption isotherm data from DVS. Further studies may be needed to evaluate the quantitation limit and generality of this method to a variety of lyophilized formulations.


Subject(s)
Spectroscopy, Near-Infrared , Spectroscopy, Near-Infrared/methods , Freeze Drying , Calibration , Least-Squares Analysis
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