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On the Hawaiian Island of O'ahu, nearly 1,500 on-site sewage disposal systems (OSDS) exist within the Kane'ohe Bay drainage basin, releasing an estimated 3,800 cubic meters (one million gallons) of untreated wastewater into the groundwater each day, threatening stream and coastal water quality. The study area–Kahalu'u, Hawai'i–is characterized by the highest density (units per area) of OSDS in the Kane'ohe Bay drainage basin. This study evaluates hydrologic flow paths from wastewater point sources to groundwater and surface waters by utilizing a combination of unmanned aerial vehicle thermal infrared (UAV-TIR) imaging, stream gauging and seepage runs, and numerical groundwater models (MODFLOW and MT3DMS). Eight coastal groundwater seep locations were identified with UAV-TIR, with all seeps occurring through coastal valley fill sediments. Geochemical analysis of seeps revealed significantly elevated concentrations of all major nutrients compared to surrounding ocean waters. Groundwater nitrogen transport was modeled with MT3DMS and compared to measured concentrations. Most OSDS are located within the valley fill, and MODFLOW results suggest that the valley fill is more hydraulically conductive than the surrounding dike-intruded basalt, thus controlling groundwater and contaminant dispersion to streams and the ocean. Modeling also reveals that groundwater flow from leeward of the Ko'olau ridgeline and from adjacent watersheds to the southeast may be significant hydrologic inputs to the study area.

BackgroundHypoglycemia is a common and serious adverse effect of diabetes treatment, especially for patients using insulin or insulin secretagogues. Guidelines recommend that these patients be assessed for interval hypoglycemic events at each clinical encounter and be provided anticipatory guidance for hypoglycemia prevention.ObjectiveTo determine the frequency and content of hypoglycemia communication in primary care visits.DesignQualitative studyParticipantsWe examined 83 primary care visits from one urban health practice representing 8 clinicians and 33 patients using insulin or insulin secretagogues.ApproachUsing a directed content analysis approach, we analyzed audio-recorded primary care visits collected as part of the Achieving Blood Pressure Control Together study, a randomized trial of behavioral interventions for hypertension. The coding framework included communication about interval hypoglycemia, defined as discussion of hypoglycemic events or symptoms; the components of hypoglycemia anticipatory guidance in diabetes guidelines; and hypoglycemia unawareness. Hypoglycemia documentation in visit notes was compared to visit transcripts.Key ResultsCommunication about interval hypoglycemia occurred in 24% of visits, and hypoglycemic events were reported in 16%. Despite patients voicing fear of hypoglycemia, clinicians rarely assessed hypoglycemia frequency, severity, or its impact on quality of life. Hypoglycemia anticipatory guidance was provided in 21% of visits which focused on diet and behavior change; clinicians rarely counseled on hypoglycemia treatment or avoidance of driving. Limited discussions of hypoglycemia unawareness occurred in 8% of visits. Documentation in visit notes had low sensitivity but high specificity for ascertaining interval hypoglycemia communication or hypoglycemic events, compared to visit transcripts.ConclusionsIn this high hypoglycemia risk population, communication about interval hypoglycemia and counseling for hypoglycemia prevention occurred in a minority of visits. There is a need to support clinicians to more regularly assess their patients’ hypoglycemia burden and enhance counseling practices in order to optimize hypoglycemia prevention in primary care.

IntroductionInhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response.Methods and analysisThis meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses.The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD.Ethics and disseminationThe Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities.PROSPERO registration numberCRD42024508286.

Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users. The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses. A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with   during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of  as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results. Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring  , but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk.

Several studies have documented periodic and quasi-periodic signals from the time series of dMe flare stars and other stellar sources. Such periodic signals, observed within quiescent phases (i.e., devoid of larger-scale microflare or flare activity), range in period from \\(1-1000\\) seconds and hence have been tentatively linked to ubiquitous \\(p\\)-mode oscillations generated in the convective layers of the star. As such, most interpretations for the observed periodicities have been framed in terms of magneto-hydrodynamic wave behavior. However, we propose that a series of continuous nanoflares, based upon a power-law distribution, can provide a similar periodic signal in the associated time series. Adapting previous statistical analyses of solar nanoflare signals, we find the first statistical evidence for stellar nanoflare signals embedded within the noise envelope of M-type stellar lightcurves. Employing data collected by the Next Generation Transit Survey (NGTS), we find evidence for stellar nanoflare activity demonstrating a flaring power-law index of \\(3.25 \\pm 0.20 \\), alongside a decay timescale of \\(200 \\pm 100\\) s. We also find that synthetic time series, consistent with the observations of dMe flare star lightcurves, are capable of producing quasi-periodic signals in the same frequency range as \\(p\\)-mode signals, despite being purely comprised of impulsive signatures. Phenomena traditionally considered a consequence of wave behaviour may be described by a number of high frequency but discrete nanoflare energy events. This new physical interpretation presents a novel diagnostic capability, by linking observed periodic signals to given nanoflare model conditions.