A Feasibility Study on Re-establishing the Bioavailability/Bioequivalence Unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila.

Objectives: The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. Methods: The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. Results: The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. Conclusion: Based on the SWOT analysis and market, technical, financial, and organizational considerations, re-establishing the BA/BE Unit as a bioequivalence testing center is feasible.

Fecal Immunochemical Test Screening and Risk of Colorectal Cancer Death.

Importance: The fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening, but evidence of its effectiveness is limited. Objective: To evaluate whether FIT screening is associated with a lower risk of dying from CRC overall, according to cancer location, and within demographic groups. Design, Setting, and Participants: This nested case-control study in a cohort of screening-eligible people was conducted in 2 large, integrated health systems of racially, ethnically, and socioeconomically diverse members with long-term programs of mailed FIT screening outreach. Eligible participants included people aged 52 to 85 years who died from colorectal adenocarcinoma between 2011 and 2017 (cases); cases were matched in a 1:8 ratio based on age, sex, health-plan membership duration, and geographic area to randomly selected persons who were alive and CRC-free on case's diagnosis date (controls). Data analysis was conducted from January 2002 to December 2017. Exposures: Completing 1 or more FIT screenings in the 5-year period prior to the CRC diagnosis date among cases or the corresponding date among controls; in secondary analyses, 2- to 10-year intervals were evaluated. Main Outcomes and Measures: The primary study outcome was CRC death overall and by tumor location. Secondary analyses were performed to assess CRC death by race and ethnicity. Results: From a cohort of 2 127 128 people, a total of 10 711 participants (3529 aged 60-69 years [32.9%]; 5587 male [52.1%] and 5124 female [47.8%]; 1254 non-Hispanic Asian [11.7%]; 973 non-Hispanic Black [9.1%]; 1929 Hispanic or Latino [18.0%]; 6345 non-Hispanic White [59.2%]) was identified, including 1103 cases and 9608 controls. Among controls during the 10-year period prior to the reference date, 6101 (63.5%) completed 1 or more FITs with a cumulative 12.6% positivity rate (768 controls), of whom 610 (79.4%) had a colonoscopy within 1 year. During the 5-year period, 494 cases (44.8%) and 5345 controls (55.6%) completed 1 or more FITs. In regression analysis, completing 1 or more FIT screening was associated with a 33% lower risk of death from CRC (adjusted odds ratio [aOR], 0.67; 95% CI, 0.59-0.76) and 42% lower risk in the left colon and rectum (aOR, 0.58; 95% CI, 0.48-0.71). There was no association with right colon cancers (aOR, 0.83; 95% CI, 0.69-1.01) but the difference in the estimates between the right colon and left colon or rectum was statistically significant (P = .01). FIT screening was associated with lower CRC mortality risk among non-Hispanic Asian (aOR, 0.37; 95% CI, 0.23-0.59), non-Hispanic Black (aOR, 0.58; 95% CI, 0.39-0.85) and non-Hispanic White individuals (aOR, 0.70; 95% CI, 0.57-0.86) (P for homogeneity = .04 for homogeneity). Conclusions and Relevance: In this nested case-control study, completing FIT was associated with a lower risk of overall death from CRC, particularly in the left colon, and the associations were observed across racial and ethnic groups. These findings support the use of FIT in population-based screening strategies.

Visual Outcomes and Complications of Intraocular Lens Placement in the Absence of Capsular Support in a Philippine Tertiary Hospital.

Background: Surgical correction of aphakia without capsular support continues to be a challenge. Improvements in the technology of cataract surgery have provided advancements in techniques in surgical management of aphakia. Locally, we have limited data on the outcomes of the different intraocular lenses used in aphakia. Objective: This study aimed to determine visual outcomes and complications associated with different techniques of intraocular lens implantation in the absence of capsular support. Methods: We reviewed the medical charts of 207 patients who underwent intraocular lens implantation without capsular support. Excluded were patients with incomplete follow up, pediatric patients, and lost records. Best corrected visual acuity at day 1, 1st month, 3rd month and 6th month postoperatively, and the complications were noted. Results: Mean age was 60 and 51% (n=105) were females. The mean follow-up time was 9.33 ± 0.71 months. Loss of capsular support was most frequently caused by intraoperative complication (n=146, 70%) and trauma. Retropupillary fixation iris claw intraocular lens was frequently used (n=93, 44.9%). Across all patients, visual acuities showed excellent outcomes with 20/50 or better. Across IOL types, the most frequent postoperative complication was increase in IOP. Statistically significant results were set at P <0.05. Conclusion: There is a notable preference towards iris claw retropupillary lenses through time. Iris claw lenses showed the shortest operative time. All intraocular lenses used in aphakia showed comparably good postoperative visual acuities, except for the superior visual acuity trend seen among retropupillary iris claw and anterior chamber IOL groups. Complications included elevated intraocular pressures, corneal edema, and pigment dispersion.

Predictors of Disease Activity in Patients With Juvenile Idiopathic Arthritis at 12 and 24 Months After Diagnosis.

OBJECTIVE: Identification of characteristics associated with active disease in juvenile idiopathic arthritis (JIA) could inform early disease treatment strategies. This study evaluated characteristics associated with active disease at 12 and 24 months after JIA diagnosis in the era in which biologic disease-modifying antirheumatic drugs (DMARDs) became available for JIA. METHODS: This single-center retrospective study from 2004 through 2018 assessed characteristics associated with active nonsystemic categories of JIA at 12 and 24 months after diagnosis. Relative prevalence (RP) of disease activity was evaluated in relation to prespecified characteristics. Using RP, the effect of increasing biologic DMARD availability on these predictors was assessed at 12 months. RESULTS: A total of 1,151 patients with JIA were included. At 12 months, a 40% to 45% higher point prevalence of active disease was noted in older children (>5 years). Patients with active disease at 3 months had a greater prevalence of active disease at 12 months (RP 1.5, 95% confidence interval [CI] 1.2-1.8) and 24 months (RP 1.3, 95% CI 1-1.6). Compared to oligoarticular JIA, polyarticular RF-negative, psoriatic, and enthesitis-related JIA had a greater prevalence of active disease at 12 and 24 months. At 24 months, a greater prevalence of active disease was observed in children ≥10 years. RP of active disease was 25% lower in the late cohort (2013-2018) than in the earliest cohort (2004-2008; RP 0.75, 95% CI 0.62-0.92) when more biologic medications were available, but disease activity predictors were broadly similar over time. CONCLUSION: Patients with JIA with active disease at 12 and 24 months were older at diagnosis, categorized as polyarticular RF-negative, psoriatic, or enthesitis-related JIA. Active disease at 3 months after diagnosis was associated with worse outcomes at 12 and 24 months.

Colorectal Cancer Screening After Sequential Outreach Components in a Demographically Diverse Cohort.

Importance: Organized screening outreach can reduce differences in colorectal cancer (CRC) incidence and mortality between demographic subgroups. Outcomes associated with additional outreach, beyond universal outreach, are not well known. Objective: To compare CRC screening completion by race and ethnicity, age, and sex after universal automated outreach and additional personalized outreach. Design, Setting, and Participants: This observational cohort study included screening-eligible individuals aged 50 to 75 years assessed during 2019 in a community-based organized CRC screening program within the Kaiser Permanente Northern California (KPNC) integrated health care delivery setting. For KPNC members who are not up to date with screening by colonoscopy, each year the program first uses automated outreach (mailed prescreening notification postcards and fecal immunochemical test [FIT] kits, automated telephone calls, and postcard reminders), followed by personalized components for nonresponders (telephone calls, electronic messaging, and screening offers during office visits). Data analyses were performed between November 2021 and February 2023 and completed on February 5, 2023. Exposures: Completed CRC screening via colonoscopy, sigmoidoscopy, or FIT. Main Outcomes and Measures: The primary outcome was the proportion of participants completing an FIT or colonoscopy after each component of the screening process. Differences across subgroups were assessed using the χ2 test. Results: This study included 1 046 745 KPNC members. Their mean (SD) age was 61.1 (6.9) years, and more than half (53.2%) were women. A total of 0.4% of members were American Indian or Alaska Native, 18.5% were Asian, 7.2% were Black, 16.2% were Hispanic, 0.8% were Native Hawaiian or Other Pacific Islander, and 56.5% were White. Automated outreach significantly increased screening participation by 31.1%, 38.1%, 29.5%, 31.9%, 31.8%, and 34.5% among these groups, respectively; follow-up personalized outreach further significantly increased participation by absolute additional increases of 12.5%, 12.4%, 13.3%, 14.4%, 14.7%, and 11.2%, respectively (all differences P < .05 compared with White members). Overall screening coverage at the end of the yearly program differed significantly among members who were American Indian or Alaska Native (74.1%), Asian (83.5%), Black (77.7%), Hispanic (76.4%), or Native Hawaiian or Other Pacific Islander (74.4%) compared with White members (82.2%) (all differences P < .05 compared with White members). Screening completion was similar by sex; older members were substantially more likely to be up to date with CRC screening both before and at the end of the screening process. Conclusions and Relevance: In this cohort study of a CRC screening program, sequential automated and personalized strategies each contributed to substantial increases in screening completion in all demographic groups. These findings suggest that such programs may potentially reduce differences in CRC screening completion across demographic groups.

Comparing Functional Efficacy of Transforaminal vs Interlaminar Epidural Steroid Injection for Lumbar Disc Disease!! Do We Really Need Transforaminal Epidural Route Injections?

This study compared the functional efficacy of therapeutic transforaminal versus interlaminar epidural steroid injection. Adult patients were selected and randomized using an online research randomizer website and assigned into two groups and were given epidural injection either via transforaminal route or interlaminar route. The outcome was measured based on the Modified Japanese Orthopedic Association back index score (mJOA), Oswestry disability index (ODI), and visual analog scale (VAS) over a follow-up on 1st, 3rd, and 6th month postinjection period. It was found that there was no significant difference seen in m JOA, ODI, and VAS score at 1 month, 3 months, and 6 months between transforaminal and interlaminar epidural steroid injection. Pain management in the epidural route was comparable to the interlaminar route. Even though the transforaminal epidural route has the advantage of being a selective nerve route block, it has similar results as the interlaminar route at 6 months follow-up.

Randomized trials of multicancer screening tests: augmenting their ability to identify a genuine mortality benefit.

Randomized trials of the efficacy of multicancer early detection, by means of measurement of cell-free DNA and/or protein biomarkers in peripheral blood specimens, will attempt to document a difference in cancer mortality between persons assigned to intervention and control arms. Their ability to do so is limited by the relatively low rate of death from individual forms of cancer, the relatively low sensitivity of the tests currently being used, and the use of other cancer screening modalities among trial participants. However, if those same blood specimens also could be obtained from control arm participants in a given trial and then tested for the same markers, with results not known (or not made available) until the conclusion of follow-up for cancer mortality, it would be possible to compare mortality from given forms of cancer between test-positive individuals whose results were known and not known during the course of the trial. Such an analysis addresses the impact of a stimulus to offer targeted diagnostic testing, potentially leading to early treatment, against cancer mortality. Among persons who screen as positive, it should provide a relatively more sensitive means of gauging a possible mortality benefit resulting from multicancer screening.

Effectiveness of Endoscopic Screening on Esophageal Cancer Incidence and Mortality: A 9-Year Report of the Endoscopic Screening for Esophageal Cancer in China (ESECC) Randomized Trial.

PURPOSE: To evaluate the effectiveness of endoscopic screening against incidence of and mortality from esophageal squamous cell carcinoma (ESCC). METHODS: From January 2012 to September 2016, we conducted a community-based cluster randomized controlled trial involving permanent residents age 45-69 years in a high-risk region for ESCC in northern China. A total of 668 targeted villages were randomly assigned in a 1:1 ratio to the screening group (offered Lugol's chromoendoscopy) or control group (no screening). Intention-to-treat and per-protocol analyses were performed to compare esophageal cancer (EC) incidence and mortality between the two groups. The per-protocol analysis adjusted for nonadherence to the screening procedure. RESULTS: A total of 33,847 participants were included in the analysis: 17,104 in the screening group, 15,165 (88.7%) of whom underwent screening, and 16,743 in the control group. During a maximum follow-up of 9 years, EC incidence in the screening and control groups were 60.9 and 72.5 per 100,000 person-years, respectively; mortality in the screening and control groups were 29.7 and 32.4 per 100,000 person-years, respectively. Compared with the control group, the incidence and mortality of the screening group reduced by 19% (adjusted hazard ratio [aHR], 0.81 [95% CI, 0.60 to 1.09]) and 18% (aHR, 0.82 [95% CI, 0.53 to 1.26]), respectively, in the intention-to-treat analysis; and by 22% (aHR, 0.78 [95% CI, 0.56 to 1.10]) and 21% (aHR, 0.79 [95% CI, 0.49 to 1.30]), respectively, in the per-protocol analysis. CONCLUSION: With a 9-year follow-up, our trial suggests that chromoendoscopic screening induces modest reductions in EC incidence and mortality. A more efficient strategy for EC screening and subsequent patient management should be established to guarantee the effectiveness of endoscopic screening.

Effects of bleaching on oxygen dynamics and energy metabolism of two Caribbean coral species.

As mass coral bleaching events become more frequent, it is increasingly important to elucidate the factors underlying coral susceptibility and survival. We measured photosynthesis, respiration, and O2 concentration at the coral tissue surface, Symbiodiniaceae genotypes, and energy metabolic enzyme activities in Agaricia agaricites and Orbicella franksi throughout experimentally-induced thermal bleaching (+3 °C). A. agaricites colonies started to bleach two days into the thermal treatment and were fully bleached between Days 19-31. In contrast, O. franksi colonies only started to bleach on Day 12 and five colonies fully bleached between Days 24-38 while the remining three colonies took up 55 days. Both species experienced decreased photosynthesis and respiration rates as bleaching progressed. As a result, daytime O2 concentration at the coral surface shifted from hyperoxia in unbleached corals to normoxia in partially bleached corals, and to near hypoxia in fully bleached corals. Additionally, nighttime tissue surface O2 concentration shifted from hypoxia to normoxia, likely resulting from decreased symbiotic algae density, respiration, and photosynthates that fuel coral aerobic respiration. Genetic profiling of internal transcribed spacer 2 (ITS2) revealed differences in Symbiodiniaceae clade proportions between control and bleached colonies. Activity levels of energy metabolic enzymes did not significantly vary between control and bleached A. agaricites, but malate dehydrogenase and strombine dehydrogenase activities were significantly higher in bleached O. franksi colonies compared to controls. These differences were driven by the three O. franksi colonies that took the longest to bleach and contained >98 % Durusdinium sp. D1. The shifts in O2 dynamics within the microhabitat of bleached corals may have important implications for the metabolism of the coral holobiont while the changes in Symbiodiniaceae ITS2 profile and the upregulation of energy metabolic enzymes identify a potential factor contributing to bleaching dynamics.

Factors Associated with Costly Hospital Care among Patients with Dementia and Acute Respiratory Failure.

Rationale: Understanding contributors to costly and potentially burdensome care for patients with dementia is of interest to healthcare systems and may facilitate efforts to promote goal-concordant care. Objective: To identify risk factors, in particular whether an early goals-of-care discussion (GOCD) took place, for high-cost hospitalization among patients with dementia and acute respiratory failure. Methods: We conducted an electronic health record-based retrospective cohort study of 298 adults with dementia hospitalized with respiratory failure (receiving ⩾48 h of mechanical ventilation) within an academic healthcare system. We collected demographic and clinical characteristics, including clinical markers of advanced dementia (weight loss, pressure ulcers, hypernatremia, mobility limitations) and intensive care unit (ICU) service (medical, surgical, neurologic). We ascertained whether a GOCD was documented within 48 hours of ICU admission. We used logistic regression to identify patient characteristics associated with high-cost hospitalization measured using the hospital system accounting database and defined as total cost in the top third of the sample (⩾$145,000). We examined a path model that included hospital length of stay as a final mediator between exposure variables and high-cost hospitalization. Results: Patients in the sample had a median age of 71 (IQR, 62-79) years. Approximately half (49%) were admitted to a medical ICU, 29% to a surgical ICU, and 22% to a neurologic ICU. More than half (59%) had a clinical indicator of advanced dementia. A minority (31%) had a GOCD documented within 48 hours of ICU admission; those who did had a 50% lower risk of a high-cost hospitalization (risk ratio, 0.50; 95% confidence interval, 0.2-0.8). Older age, limited English proficiency, and nursing home residence were associated with a lower likelihood of high-cost hospitalization, whereas greater comorbidity burden and admission to a surgical or neurologic ICU compared with a medical ICU were associated with a higher likelihood of high-cost hospitalization. Conclusions: Early GOCDs for patients with dementia and respiratory failure may promote high-value care by ensuring aggressive and costly life support interventions are aligned with patients' goals. Future work should focus on increasing early palliative care delivery for patients with dementia and respiratory failure, in particular in surgical and neurologic ICU settings.

The effects of spirituality on the quality of life among cancer patients enrolled in the out patient chemotherapy clinic of a Tertiary Hospital: An analytical cross-sectional study

Introduction@#Spirituality was defined as a way individual seek and express meaning and purpose and the way they experience their connectedness to the moment. Studies showed that spiritual beliefs provided comfort to cancer patients and that different dimensions were related with the different aspects of health.@*Objectives@#The aim of the study is to determine the correlation on effects of spirituality and the quality of life among patients enrolled in the outpatient chemotherapy clinic.@*Methodology@#An analytical cross-sectional study using a non-probability convenience sampling was done of which validated questionnaires on the Spirituality and Quality of Life were the research instruments of the study. The Pearson’s correlation coefficient/Spearman rho computed on the relationship between the dimensions of spirituality and subscales of the quality of life among cancer patients. Chi Square/Fisher’s test was used to determine the correlation among the types and stages of cancer with the quality of life and spirituality of the respondents.@*Results@#A total of 105 cancer patients participated in this study, with ages ranging from 21 to 76 years and a mean age of 51 +/- 11 years, 2/5 were married females and 4/5 were Roman Catholic. Fifty-six percent of the cancer patients have Invasive Ductal Carcinoma (Breast Cancer). Most of the respondents are at stages 2 and 3 with equal percentages of 41%. This study revealed that most of the cancer patients enrolled in the outpatient chemotherapy clinic had a mean score of 3.56 + 0.35 indicating moderate to high level of spirituality. It also showed a mean score of 5.41 +.53 indicating high QOLs. Dimensions of spirituality which were found to have significant association with QOL domains (p < 0.05) were Mindfulness and Feeling of Security which were both found to have positive correlation with Emotional Wellbeing and Social Status.@*Conclusion@#Spiritual care should be included as one of the non-pharmacological modalities in the comprehensive management and palliative care for the Filipino cancer patients in order to improve the over-all well-being, healthcare outcomes and quality of life of patients and their families.

A feasibility study on re-establishing the Bioavailability/Bioequivalence unit of the Department of Pharmacology and Toxicology, College of Medicine-University of the Philippines Manila

Objectives@#The Bioavailability/Bioequivalence Unit (BA/BE Unit) of the Department of Pharmacology and Toxicology, College of Medicine, University of the Philippines Manila which has not been operational since 2012, is due for renewal of its accreditation. To date, there are only three Philippine Food and Drug Administration-accredited laboratories that perform bioequivalence studies in the Philippines. One of the prerequisites of registering specific generic medicines is the conduct of Bioequivalence (BE) studies which are performed to ensure that the generic drug is at par with the innovator drug. Thus, this study aimed to determine the feasibility of re-establishing the BA/BE Unit as a bioequivalence testing center. @*Methods@#The feasibility study done is a qualitative descriptive analysis based on expansive literature review and performance of SWOT analysis within the BA/BE unit. Literatures were selected based on its assessed relevance to the study. The databases checked were PubMed and Google Scholar. The terms used were from the Medical Subject Heading (MeSH) including feasibility studies, therapeutic equivalency, and generic drugs. Literature review was performed on the factors affecting the four types of feasibility studies (market, technical, financial, and organizational). A SWOT analysis of the BA/BE Unit was done through the review of records and documents of previous BE studies and focus group discussion among the BA/BE Unit team members. @*Results@#The BA/BE Unit conducted 24 bioequivalence studies from 2006-2009 and still receives inquiries from drug companies. It implements its QMS throughout the pre-analytical, analytical, and post-analytical stages of the workflow. Its organizational structure consists of qualified professionals with updated GCP and GLP certificates. Because of the adequately equipped facility, lower honoraria for government-employed personnel, and lower expenses for laboratories and in-patient admissions, the cost of conducting a bioequivalence study in the BA/BE Unit will be lower than in other BE centers. @*Conclusion@#Based on the SWOT analysis and market, technical, financial, and organizational considerations, reestablishing the BA/BE Unit as a bioequivalence testing center is feasible.

Visual outcomes and complications of intraocular lens placement in the absence of capsular support in a Philippine Tertiary Hospital

Background@#Surgical correction of aphakia without capsular support continues to be a challenge. Improvements in the technology of cataract surgery have provided advancements in techniques in surgical management of aphakia. Locally, we have limited data on the outcomes of the different intraocular lenses used in aphakia.@*Objective@#This study aimed to determine visual outcomes and complications associated with different techniques of intraocular lens implantation in the absence of capsular support.@*Methods@#We reviewed the medical charts of 207 patients who underwent intraocular lens implantation without capsular support. Excluded were patients with incomplete follow up, pediatric patients, and lost records. Best corrected visual acuity at day 1, 1st month, 3rd month and 6th month postoperatively, and the complications were noted.@*Results@#Mean age was 60 and 51% (n=105) were females. The mean follow-up time was 9.33 ± 0.71 months. Loss of capsular support was most frequently caused by intraoperative complication (n=146, 70%) and trauma. Retropupillary fixation iris claw intraocular lens was frequently used (n=93, 44.9%). Across all patients, visual acuities showed excellent outcomes with 20/50 or better. Across IOL types, the most frequent postoperative complication was increase in IOP. Statistically significant results were set at P <0.05. @*Conclusion@#There is a notable preference towards iris claw retropupillary lenses through time. Iris claw lenses showed the shortest operative time. All intraocular lenses used in aphakia showed comparably good postoperative visual acuities, except for the superior visual acuity trend seen among retropupillary iris claw and anterior chamber IOL groups. Complications included elevated intraocular pressures, corneal edema, and pigment dispersion.

Risk of Colorectal Cancer and Colorectal Cancer Mortality Beginning One Year after a Negative Fecal Occult Blood Test, among Screen-Eligible 76- to 85-Year-Olds.

BACKGROUND: Colorectal cancer screening is universally recommended for adults ages 45 to 75 years. Noninvasive fecal occult blood tests are effective screening tests recommended by guidelines. However, empirical evidence to inform older adults' decisions about whether to continue screening is sparse, especially for individuals with prior screening. METHODS: This study used a retrospective cohort of older adults at three Kaiser Permanente integrated healthcare systems (Northern California, Southern California, Washington) and Parkland Health. Beginning 1 year following a negative stool-based screening test, cumulative risks of colorectal cancer incidence, colorectal cancer mortality (accounting for deaths from other causes), and non-colorectal cancer mortality were estimated. RESULTS: Cumulative incidence of colorectal cancer in screen-eligible adults ages 76 to 85 with a negative fecal occult blood test 1 year ago (N = 118,269) was 0.23% [95% confidence interval (CI), 0.20%-0.26%] after 2 years and 1.21% (95% CI, 1.13%-1.30%) after 8 years. Cumulative colorectal cancer mortality was 0.03% (95% CI, 0.02%-0.04%) after 2 years and 0.33% (95% CI, 0.28%-0.39%) after 8 years. Cumulative risk of death from non-colorectal cancer causes was 4.81% (95% CI, 4.68%-4.96%) after 2 years and 28.40% (95% CI, 27.95%-28.85%) after 8 years. CONCLUSIONS: Among 76- to 85-year-olds with a recent negative stool-based test, cumulative colorectal cancer incidence and mortality estimates were low, especially within 2 years; death from other causes was over 100 times more likely than death from colorectal cancer. IMPACT: These findings of low absolute colorectal cancer risk, and comparatively higher risk of death from other causes, can inform decision-making regarding whether and when to continue colorectal cancer screening beyond age 75 among screen-eligible adults.

A combinatorial droplet microfluidic device integrated with mass spectrometry for enzyme screening.

Mass spectrometry (MS) enables detection of different chemical species with a very high specificity; however, it can be limited by its throughput. Integrating MS with microfluidics has a tremendous potential to improve throughput and accelerate biochemical research. In this work, we introduce Drop-NIMS, a combination of a passive droplet loading microfluidic device and a matrix-free MS laser desorption ionization technique called nanostructure-initiator mass spectrometry (NIMS). This platform combines different droplets at random to generate a combinatorial library of enzymatic reactions that are deposited directly on the NIMS surface without requiring additional sample handling. The enzyme reaction products are then detected with MS. Drop-NIMS was used to rapidly screen enzymatic reactions containing low (on the order of nL) volumes of glycoside reactants and glycoside hydrolase enzymes per reaction. MS "barcodes" (small compounds with unique masses) were added to the droplets to identify different combinations of substrates and enzymes created by the device. We assigned xylanase activities to several putative glycoside hydrolases, making them relevant to food and biofuel industrial applications. Overall, Drop-NIMS is simple to fabricate, assemble, and operate and it has potential to be used with many other small molecule metabolites.

Disentangling the impact of Atlantic Niño on sea-air CO2 flux.

Atlantic Niño is a major tropical interannual climate variability mode of the sea surface temperature (SST) that occurs during boreal summer and shares many similarities with the tropical Pacific El Niño. Although the tropical Atlantic is an important source of CO2 to the atmosphere, the impact of Atlantic Niño on the sea-air CO2 exchange is not well understood. Here we show that the Atlantic Niño enhances (weakens) CO2 outgassing in the central (western) tropical Atlantic. In the western basin, freshwater-induced changes in surface salinity, which considerably modulate the surface ocean CO2 partial pressure (pCO2), are the primary driver for the observed CO2 flux variations. In contrast, pCO2 anomalies in the central basin are dominated by the SST-driven solubility change. This multi-variable mechanism for pCO2 anomaly differs remarkably from the Pacific where the response is predominantly controlled by upwelling-induced dissolved inorganic carbon anomalies. The contrasting behavior is characterized by the high CO2 buffering capacity in the Atlantic, where the subsurface water mass contains higher alkalinity than in the Pacific.

Short-term Endpoints for Cancer Screening Trials: Does Tumor Subtype Matter?

Multicancer early detection tests are precipitating a reexamination of potential short-term endpoints for cancer screening trials. A reduction in advanced stage incidence is a prime candidate, and stage-shift models that substitute early-stage for late-stage survival have been used to predict mortality reduction due to screening. However, standard stage-shift models often ignore prognostic subtypes, effectively implying that cancers detected early also have an associated subtype shift. To illustrate the differences between mortality predictions from stage-shift models that ignore versus preserve prognostic subtype, we use ovarian cancer partitioned by histologic subtype and prostate cancer partitioned by grade. We infer general conditions under which stage-shift models that preserve prognostic subtype are likely to predict mortality reductions that differ from those that ignore subtype and examine the implications for short-term endpoints based on stage in cancer screening trials.

Methane emission, nutrient digestibility, and rumen microbiota in Holstein heifers fed 14 different grass or clover silages as the sole feed.

This experiment investigated the variation in enteric methane production and associated gas exchange parameters, nutrient digestibility, rumen fermentation, and rumen microbiome when a range of silages based on different forage types (grass or clover), and different species within the 2 types, were fed as the sole feed to heifers. Three grass species (perennial ryegrass, festulolium, and tall fescue) and 2 clover species (red clover and white clover) were included. Perennial ryegrass was harvested at 2 maturity stages in the primary growth, white clover was harvested once in the primary growth, and 4 cuts of festulolium and tall fescue and 3 cuts of red clover were harvested during the growing season, giving 14 different silage batches in total. Sixteen Holstein heifers 16 to 21 mo old and 2 to 5 mo in pregnancy were fed the silages ad libitum as the sole feed in an incomplete crossover design. Each silage was fed to 4 heifers, except for the 2 perennial ryegrass silages, which were fed to 8 heifers; in total 64 observations. The CH4 production was measured for 3 d in respiration chambers. Heifers fed clover silages had higher dry matter intake (DMI) compared with heifers fed grass silages, and heifers fed tall fescue silages had the numerically the lowest DMI. Compared with grass silages, feeding clover silages led to higher crude protein digestibility but lower neutral detergent fiber (NDF) digestibility. Rumen pH was higher in heifers fed clover silages compared with those fed grass silages. Based on composition analysis, the rumen microbiota of the heifers clustered clearly according to forage type and species. More specifically, 7 of the 34 dominating rumen bacterial genus-level groups showed higher relative abundances for the clover silages, whereas 7 genus-level groups showed higher abundances for the grass silages. Methane yield was higher for heifers fed grass silages than for those fed clover silages when methane production was related to dry matter and digestible organic matter intake, whereas the opposite was seen when related to NDF digestion. The gross energy lost as methane (CH4 conversion factor, %) reduced from 7.5% to 6.7%, equivalent to an 11% reduction. The present study gives the outlines for choosing the optimal forage type and forage species with respect to nutrient digestibility and enteric methane emission in ruminants.

Association between sociodemographic factors and cholesterol-lowering medication use in U.S. adults post-myocardial infarction.

INTRODUCTION: Cholesterol-lowering medications offer effective secondary prevention after myocardial infarction (MI). Our objective was to evaluate the association between sociodemographic factors and cholesterol-lowering medication use in high-risk adults. METHODS: We conducted an analysis using weighted data from 31,408 participants in the 2017 and 2019 Behavioral Risk Factor Surveillance Systems cross-sectional surveys, who had a self-reported history of MI and high blood cholesterol. The sociodemographic factors evaluated were sex, age, race and ethnicity, annual household income, education level, relationship status, and reported healthcare coverage. We estimated the weighted prevalence of medication use, and weighted prevalence differences (with 95% confidence intervals) across categories, adjusting for sex, age group, healthcare coverage, smoking status, hypertension, and diabetes. RESULTS AND DISCUSSION: Overall, 83% of survey participants with a self-reported history of both MI and high blood cholesterol reported currently using a cholesterol-lowering medication. The prevalence of use was only 61% in those without self-reported healthcare coverage, compared to 85% of those with healthcare coverage (adjusted prevalence difference of -20%; 95% CI: -25% to -14%). Use of cholesterol-lowering medication was relatively low in younger adults and higher in older adults, leveling off after age 65 years. The proportion of Native Hawaiian or Pacific Islanders who were using a cholesterol-lowering medication was relatively low, but otherwise there was little variation by race and ethnicity. Household income, education level, and relationship status were weakly or not associated with medication use. CONCLUSIONS: Knowledge of characteristics of persons who are relatively less likely to be adherent with cholesterol-lowering medications for secondary prevention may be useful to policymakers and healthcare providers involved in the long-term treatment of MI patients. Policy makers might consider a reduced cost prescription coverage for persons without current healthcare coverage who have sustained an MI to reduce future cardiovascular morbidity and mortality.