Anxiety, depression, and suicidal ideation among early adolescents during the COVID-19 pandemic.

BACKGROUND: Anxiety and depression are among the most common and debilitating psychiatric disorders affecting youth, with both related to increased suicide risk. While rates of youth anxiety and depression were increasing before the COVID-19 pandemic, the pandemic further negatively impacted adolescent mental health. Unfortunately, few studies have examined prevalence of these concerns among early adolescents (ages 10-13) longitudinally during the pandemic. METHOD: The current study examined self-reported anxiety and depression symptoms, and suicidal ideation amongst a general pediatrics population of 11- to 13-year-olds (n = 623) from March through September 2020 (early-pandemic) and approximately 7 months later (September 2020 through May 2021; mid-pandemic). Paired samples proportions were used to examine changes in prevalence of moderate to severe anxiety, depression, and suicidal ideation from early- to mid-pandemic. RESULTS: Results highlight high initial rates and stability in anxiety and suicidal ideation, as well as a significant increase in depression (42.9% increase; p < .05) among the full sample during the COVID-19 pandemic. Prevalance of concerns were greatest for females and Hispanic youth during the early-pandemic, and generally highest for females and Medicaid insured youth at mid-pandemic. DISCUSSION: Results extend recent research and underscore the need for continued monitoring of mental health concerns across development for youth who grew up during the COVID-19 pandemic; highlighting the need for sustainable, effective, and accessible early detection, prevention, and intervention strategies. Improving these services is critical to support youth who experienced pandemic-related stressors, and to prepare for supporting youth during future disruptive and isolating events.

No requirement of perioperative glucocorticoid replacement in patients with endogenous Cushing's syndrome - a pilot study.

PURPOSE: Surgical therapy represents the first-line treatment for endogenous Cushing's syndrome (CS). While postoperative glucocorticoid replacement is mandatory after surgical remission, the role of perioperative glucocorticoid therapy is unclear. METHODS: We recruited patients with central or adrenal CS in whom curative surgery was planned and patients who underwent pituitary surgery for other reasons than CS as a control group. Patients did not receive any perioperative glucocorticoids until the morning of the first postoperative day. We performed blood samplings in the morning of surgery, immediately after surgery, in the evening of the day of surgery, and in the morning of the first and third postoperative day before any morning glucocorticoid intake. We continued clinical and biochemical monitoring during the following outpatient care. RESULTS: We recruited 12 patients with CS (seven with central CS, five with adrenal CS) and six patients without CS. In patients with CS, serum cortisol concentrations <5.0 µg/dL (<138 nmol/L) were detected in the morning of the first and third postoperative day in four (33%) and six (50%) patients, respectively. Morning serum cortisol concentrations on the third postoperative day were significantly lower when compared to preoperative measurements (8.5 ± 7.6 µg/dL vs. 19.9 ± 8.9 µg/dL [235 ± 210 nmol/L vs. 549 ± 246 nmol/L], p = 0.023). No patient developed clinical or biochemical signs associated with hypocortisolism. During follow-up, we first observed serum cortisol concentrations >5.0 µg/dL (>138 nmol/L) after 129 ± 97 days and glucocorticoids were discontinued after 402 ± 243 days. Patients without CS did not require glucocorticoid replacement at any time. CONCLUSION: Perioperative glucocorticoid replacement may be unnecessary in patients with central or adrenal CS undergoing curative surgery as first-line treatment.

Adolescent utilization of eating disorder higher level of care: roles of family-based treatment adherence and demographic factors.

BACKGROUND: Outpatient family-based treatment (FBT) is effective in treating restrictive eating disorders among adolescents. However, little is known about whether FBT reduces higher level of care (HLOC) utilization or if utilization of HLOC is associated with patient characteristics. This study examined associations between utilization of eating disorder related care (HLOC and outpatient treatment) and reported adherence to FBT and patient characteristics in a large integrated health system. METHODS: This retrospective cohort study examined 4101 adolescents who received care for restrictive eating disorders at Kaiser Permanente Northern California. A survey was sent to each medical center to identify treatment teams as high FBT adherence (hFBT) and low FBT adherence (lFBT). Outpatient medical and psychiatry encounters and HLOC, including medical hospitalizations and higher-level psychiatric care as well as patient characteristics were extracted from the EHR and examined over 12 months post-index. RESULTS: 2111 and 1990 adolescents were treated in the hFBT and lFBT, respectively. After adjusting for age, sex, race/ethnicity, initial percent median BMI, and comorbid mental health diagnoses, there were no differences in HLOC or outpatient utilization between hFBT and lFBT. Females had higher odds of any utilization compared with males. Compared to White adolescents, Latinos/Hispanics had lower odds of HLOC utilization. Asian, Black, and Latino/Hispanic adolescents had lower odds of psychiatric outpatient care than Whites. CONCLUSIONS: Reported FBT adherence was not associated with HLOC utilization in this sample. However, significant disparities across patient characteristics were found in the utilization of psychiatric care for eating disorders. More efforts are needed to understand treatment pathways that are accessible and effective for all populations with eating disorders.

Adolescents with restrictive eating treated by Family-Based Treatment (FBT) teams had better early weight gain but no differences in the use of intensive outpatient, residential, partial hospital programs or inpatient psychiatry care when compared to those treated by teams with a low adherence to the FBT approach. Factors such as sex, race, ethnicity, mood disorders, and suicidality were associated with the use of psychiatric services. These findings are consistent with previously documented systematic disparities in accessing psychiatric services across patient demographics and should be used to inform the development of proposed care models that are more inclusive and accessible to all patients.

Use of chitin:DNA ratio to assess growth form in fungal cells.

BACKGROUND: Dimorphism, the ability to switch between a 'yeast-like' and a hyphal growth form, is an important feature of certain fungi, including important plant and human pathogens. The switch to hyphal growth is often associated with virulence, pathogenicity, biofilm formation and stress resistance. Thus, the ability to accurately and efficiently measure fungal growth form is key to research into these fungi, especially for discovery of potential drug targets. To date, fungal growth form has been assessed microscopically, a process that is both labour intensive and costly. RESULTS: Here, we unite quantification of the chitin in fungal cell walls and the DNA in nuclei to produce a methodology that allows fungal cell shape to be estimated by calculation of the ratio between cell wall quantity and number of nuclei present in a sample of fungus or infected host tissue. Using the wheat pathogen Zymoseptoria tritici as a test case, with confirmation in the distantly related Fusarium oxysporum, we demonstrate a close, linear relationship between the chitin:DNA ratio and the average polarity index (length/width) of fungal cells. We show the utility of the method for estimating growth form in infected wheat leaves, differentiating between the timing of germination in two different Z. tritici isolates using this ratio. We also show that the method is robust to the occurrence of thick-walled chlamydospores, which show a chitin:DNA ratio that is distinct from either 'yeast-like' blastospores or hyphae. CONCLUSIONS: The chitin:DNA ratio provides a simple methodology for determining fungal growth form in bulk tissue samples, reducing the need for labour-intensive microscopic studies requiring specific staining or GFP-tags to visualise the fungus within host tissues. It is applicable to a range of dimorphic fungi under various experimental conditions.

A patient activation intervention in primary care for patients with chronic pain on long term opioid therapy: results from a randomized control trial.

BACKGROUND: Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. METHODS: The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015-August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. RESULTS: At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18-0.87); higher overall health (OR = 3.14, 95%CI 1.64-6.01); greater use of the patient portal's health/wellness resources (OR = 2.50, 95%CI 1.42-4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29-5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61-4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29-3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27-2.98). CONCLUSION: This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. TRIAL REGISTRATION: The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).

Risk profiles of adults with heavy alcohol use: Drinking patterns, behavioral and metabolic factors, health problems, and racial and ethnic disparities.

BACKGROUND: Heavy alcohol use is a growing risk factor for chronic disease, yet little is known about its co-occurrence with other risk factors and health problems. This study aimed to identify risk profiles of adults with heavy alcohol use and examined potential disparities by race and ethnicity. METHODS: This cross-sectional study included 211,333 adults with heavy alcohol use (in excess of daily or weekly limits recommended by National Institute on Alcohol Abuse and Alcoholism) between June 1, 2013 and December 31, 2014 in Kaiser Permanente Northern California. Latent class analysis was used to examine how heavy drinking patterns clustered with other behavioral and metabolic risk factors and health problems to form risk profiles. Multinomial logistic regression models were fit to examine associations between race, ethnicity, and risk profiles. RESULTS: A 5-class model was selected as best fitting the data and representing clinically meaningful risk profiles: (1) "heavy daily drinking and lower health risks" (DAILY, 44.3%); (2) "substance use disorder and mental health disorder" (SUD/MH, 2.3%); (3) "heavy weekly drinking and lower health risks" (WEEKLY, 19.6%); (4) "heavy daily drinking and more health risks" (DAILY-R, 18.5%); (5) "heavy weekly drinking and more health risks" (WEEKLY-R, 15.3%). American Indian or Alaska Native (AIAN) and Black patients had higher odds than White patients of being in the SUD/MH, DAILY-R, and WEEKLY-R profiles than the DAILY profile. AIAN, Black, and Latino/Hispanic patients had higher odds than White patients of being in the SUD/MH, DAILY-R, and WEEKLY-R profiles rather than the WEEKLY profile. CONCLUSIONS: AIAN, Black, and Latino/Hispanic patients with self-reported heavy drinking were more likely to be in risk profiles with greater alcohol consumption, more health risks, and higher morbidity. Targeted, culturally appropriate interventions for heavy alcohol use that may address other modifiable risk factors are needed to work towards health equity.

Penile melanoma: a pathological report of two cases.

BACKGROUND: Penile melanoma (PM) is a rare tumor, accounting for less than 2% of all penile cancers. PM can occur on the surface of the glans, foreskin, and opening of the urethra. Furthermore, PM primarily affects older individuals and is not associated with sun exposure. Currently, there is no specific staging system for genitourinary tract melanomas, so these tumors are typically staged using the criteria for cutaneous melanoma. Limited data in the literature suggests that PM generally has a poor clinical prognosis. CASE PRESENTATION: Here, we describe two cases of PM. The first case affected a 62-year-old male who presented with hematuria and a painful tumor in the distal urethra, leading to a suspicion of penile cancer. The second case involved a 68-year-old male who noticed a rapidly evolving dark spot on his foreskin. Histological analysis confirmed the presence of melanoma in both patients. The tumors showed a diffuse and strong PRAME-positivity and lacked BRAF mutation in both cases. Additionally, the second tumor harbored an activating CKIT mutation. An enhanced PD-L1 expression was observed in both tumors. CONCLUSIONS: We presented two rare forms of mucosal melanoma and highlighted the entities in the differential diagnosis. Based on our experience PRAME is a helpful marker for making the diagnosis of PM, and PD-L1 can predict the success of the immunotherapy. We also emphasize the need for an organ-specific staging system for PMs.

Disparities in the receipt of alcohol brief intervention: The intersectionality of sex, age, and race/ethnicity.

BACKGROUND AND AIMS: The increasing trend in alcohol consumption among women, exacerbated by the COVID-19 pandemic, is of growing concern. Screening, brief intervention, and referral to treatment in primary care is an efficacious and cost-effective treatment approach for unhealthy alcohol use. However, disparities exist in delivery of brief interventions by sex, age and race/ethnicity. This study measures brief intervention rates among eligible patients by sex, age and race/ethnicity and their intersectionality, in the context of a program of systematic alcohol screening and brief intervention program in adult primary care in a large, integrated health-care delivery system. DESIGN, SETTING AND PARTICIPANTS: This was a population-based observational study among primary care clinics in an integrated health-care delivery system in Northern California, USA. The participants comprised adult (18+) patients (n = 287 551) screening positive for unhealthy alcohol use between January 2014 and December 2017. MEASUREMENTS: Receipt of brief intervention, patient and provider characteristics from electronic health records. FINDINGS: Multi-level logistic regression showed that women had lower odds of receiving brief intervention than men among all age, racial/ethnic groups and drinking levels. Sex differences were greater among those aged 35-49 years [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.64, 0.69]) and 50-65 years (OR = 0.69, 95% CI =0.66, 0.72) than among other age groups. Sex differences in odds of receiving brief intervention were greater for the Latino/Hispanic group for women versus men (OR = 0.69, 95% CI = 0.66, 0.72) and smaller for the Asian/Pacific Islander group (OR = 0.76, 95% CI = 0.72, 0.81). CONCLUSION: In the United States, compared with men, women appear to have lower odds of receiving brief intervention for unhealthy alcohol use across all age groups, particularly during middle age. Black women and Latina/Hispanic women appear to be less likely to receive brief intervention than women in other race/ethnicity groups. Receipt of brief intervention does not appear to differ by drinking levels between men and women.

Development of a Novel LC-MS/MS Multi-Method for the Determination of Regulated and Emerging Food Contaminants Including Tenuazonic Acid, a Chromatographically Challenging Alternaria Toxin.

The regulation of food contaminants in the European Union (EU) is comprehensive, and there are several compounds in the register or being added to the recommendation list. Recently, European standard methods for analysis have also been issued. The quick analysis of different groups of analytes in one sample requires a number of methods and the simultaneous use of various instruments. The aim of the present study was to develop a method that could analyze several groups of food contaminants: in this case, 266 pesticides, 12 mycotoxins, 14 alkaloid toxins, and 3 Alternaria toxins. The main advantage of the herein described approach over other methods is the simultaneous analysis of tenuazonic acid (TEA) and other relevant food contaminants. The developed method unites the newly published standard methods such as EN 15662:2018, EN 17194:2019, EN 17256:2019, EN 17425:2021, EN 17521:2021, which describes the analysis of both regulated and emerging contaminants. The developed method is based on a QuEChERS sample preparation, followed by LC-MS/MS analysis under alkaline mobile phase conditions. The pH of the aqueous eluent was set to 8.3, which resulted in baseline separation among ergot alkaloids and their corresponding epimers, a symmetric chromatographic peak shape for analyzing TEA and fit-for-purpose sensitivity for MS/MS detection in both positive and negative ionization modes. Those compounds, which possess the corresponding isotopically labeled internal standards (ISTD), allowed for direct quantification by the developed method and no further confirmation was necessary. This was proven by satisfactory analyses of a number of quality control (QC), proficiency test (PT), and validation samples.

Associations between alcohol brief intervention in primary care and drinking and health outcomes in adults with hypertension and type 2 diabetes: a population-based observational study.

OBJECTIVES: To evaluate associations between alcohol brief intervention (BI) in primary care and 12-month drinking outcomes and 18-month health outcomes among adults with hypertension and type 2 diabetes (T2D). DESIGN: A population-based observational study using electronic health records data. SETTING: An integrated healthcare system that implemented system-wide alcohol screening, BI and referral to treatment in adult primary care. PARTICIPANTS: Adult primary care patients with hypertension (N=72 979) or T2D (N=19 642) who screened positive for unhealthy alcohol use between 2014 and 2017. MAIN OUTCOME MEASURES: We examined four drinking outcomes: changes in heavy drinking days/past 3 months, drinking days/week, drinks/drinking day and drinks/week from baseline to 12-month follow-up, based on results of alcohol screens conducted in routine care. Health outcome measures were changes in measured systolic and diastolic blood pressure (BP) and BP reduction ≥3 mm Hg at 18-month follow-up. For patients with T2D, we also examined change in glycohaemoglobin (HbA1c) level and 'controlled HbA1c' (HbA1c<8%) at 18-month follow-up. RESULTS: For patients with hypertension, those who received BI had a modest but significant additional -0.06 reduction in drinks/drinking day (95% CI -0.11 to -0.01) and additional -0.30 reduction in drinks/week (95% CI -0.59 to -0.01) at 12 months, compared with those who did not. Patients with hypertension who received BI also had higher odds for having clinically meaningful reduction of diastolic BP at 18 months (OR 1.05, 95% CI 1.00 to 1.09). Among patients with T2D, no significant associations were found between BI and drinking or health outcomes examined. CONCLUSIONS: Alcohol BI holds promise for reducing drinking and helping to improve health outcomes among patients with hypertension who screened positive for unhealthy drinking. However, similar associations were not observed among patients with T2D. More research is needed to understand the heterogeneity across diverse subpopulations and to study BI's long-term public health impact.

Utilization of a Best Practice Alert (BPA) at Point-of-Care for Recruitment into a US-Based Autism Research Study.

Provider referral is one of the most influential factors in research recruitment. To ease referral burden on providers, we adapted the Best Practice Alert (BPA) in the EPIC Electronic Health Record and assessed its utility in recruiting pediatric patients with autism spectrum disorder for the national SPARK study. During a year-long surveillance, 1203 (64.0%) patients were Interested in SPARK and 223 enrolled. Another 754 participants not recruited via the BPA also enrolled; 35.5% of these participants completed their participation compared to 58.3% of BPA-referred participants. Results suggest that (a) a BPA can successfully engage providers in the study-referral process and (b) families who learn about research through their providers may be more engaged and effectively retained.

Use of a Best Practice Alert (BPA) to Increase Diversity Within a US-Based Autism Research Cohort.

We evaluated the success of a best practice alert (BPA) in recruiting underrepresented families into an autism spectrum disorder research cohort by comparing BPA-response outcomes (Interested, Declined, Enrolled, Dismissed) in pediatric primary care practices (TCPs) serving diverse communities with those of subspecialty clinics. Compared to subspecialty clinics, TCPs had higher proportions of Interested responses for patients with private insurance (60.9% vs. 46.2%), Dismissed responses for patients with public insurance (30.1% vs. 20.0%), and Interested responses for non-white patients (47.7% vs. 33.3%). A targeted BPA can help researchers access more diverse groups and improve equitable representation. However, select groups more often had their alert dismissed, suggesting possible selection bias among some pediatricians regarding who should receive information about study opportunities.

Young Adult Substance Use and Healthcare Use Associated With Screening, Brief Intervention and Referral to Treatment in Pediatric Primary Care.

PURPOSE: Screening, brief intervention, and referral to treatment (SBIRT) may impact future comorbidity and healthcare utilization among adolescents screening positive for substance use or mood problems. METHODS: In a randomized trial sample, we compared an SBIRT group to usual care for substance use, mental health, medical diagnoses, and healthcare utilization over 7 years postscreening. RESULTS: In logistic regression models adjusting for patient characteristics, the SBIRT group had lower odds of any substance (Odds Ratio[OR] = 0.80, 95% Confidence Interval [CI] = 0.66-.98), alcohol (OR = 0.69, 95% CI = 0.51-0.94), any drug (OR = 0.73, 95% CI = 0.54-0.98), marijuana (OR = 0.70, 95% CI = 0.50-0.98), and tobacco (OR = 0.83, 95% CI = 0.69-1.00) diagnoses, and lower odds of any inpatient hospitalizations (OR = 0.59, 95% CI = 0.41-0.85) compared with usual care. Negative binomial models examining number of visits among adolescents with at least one visit of that type found that those in the SBIRT group had fewer primary care (incidence rate ratio[iRR] = 0.90, p < .05) and psychiatry (iRR = 0.64, p < .01) and more addiction medicine (iRR = 1.52, p < .01) visits over 7 years compared with usual care. In posthoc analyses, we found that among Hispanic patients, those in the SBIRT group had lower odds of any substance, any drug and marijuana use disorder diagnoses compared with usual care, and among Black/African American patients, those in the SBIRT group had lower odds of alcohol use disorder diagnoses compared with usual care. DISCUSSION: Beneficial effects of adolescent SBIRT on substance use and healthcare utilization may persist into young adulthood.

Predicting severe alcohol use disorders in primary care using number of heavy drinking days.

BACKGROUND AND AIMS: Although screening for unhealthy alcohol use is becoming more common, severe alcohol use disorders (AUDs) associated with the most severe medical and socio-economic sequelae still often go unidentified in primary care. To improve identification of severe AUDs and aid clinical decision-making, we aimed to identify a threshold of heavy drinking days (HDDs) associated with severe AUDs. DESIGN, SETTING AND CASES: This cohort study analyzed electronic health record data of 138 765 adults who reported ≥ 1 HDD (4+ drinks/occasion for women and men aged ≥ 65 years, 5+ for men aged 18-64 years) during a 3-month period at a routine alcohol screening in primary care in a large Northern California, USA health-care system from 2014 to 2017. Our sample was 66.5% male, 59.7% white, 11.0% Asian/Pacific Islander, 5.0% black, 17.4% Latino/Hispanic and 7.0% other/unknown race/ethnicity; the mean age was 40.6 years (standard deviation = 15.2). MEASUREMENTS: We compared sensitivity and specificity of different thresholds of the reported number of HDDs during a 3-month period for predicting severe AUD diagnoses in the following year, in the full sample and by sex and age. FINDINGS: The prevalence of severe AUD diagnoses in the year after the screening was 0.6%. The optimal threshold predicting future severe AUD diagnoses in the full sample was ≥ 5 HDDs during a 3-month period [sensitivity = 68.9%, 95% confidence interval (CI) = 65.9, 72.0; specificity = 63.2%, 95% CI = 62.9, 63.4], but varied by sex and age. Women had a lower threshold than men (4 versus 6 HDDs), which decreased as women aged (from 5 HDDs among 18-24 years to 4 HDDs ≥ 25 years), but increased as men aged (from 5 HDDs among 18-24 years to 6 HDDs among 25-64 years, to 7 HDDs ≥ 65 years). CONCLUSIONS: Five or more heavy drinking days in a 3-month period may indicate heightened risk of future severe alcohol use disorder in an adult primary care population. The optimal thresholds are lower for women than for men, and thresholds decrease as women age but increase as men age.

Alcohol brief intervention, specialty treatment and drinking outcomes at 12 months: Results from a systematic alcohol screening and brief intervention initiative in adult primary care.

BACKGROUND: Alcohol screening, brief intervention and referral to treatment (SBIRT) in adult primary care is an evidence-based, public health strategy to address unhealthy alcohol use, but evidence of effectiveness of alcohol brief intervention (ABI) in real-world implementation is lacking. METHODS: We fit marginal structural models with inverse probability weighting to estimate the causal effects of ABI on 12-month drinking outcomes using longitudinal electronic health records data for 312,056 adults with a positive screening result for unhealthy drinking between 2014 and 2017 in a large healthcare system that implemented systematic primary care-based SBIRT. We examined effects of ABI with and without adjusting for receipt of specialty alcohol use disorder (AUD) treatment, and whether effects varied by patient demographic characteristics and alcohol use patterns. RESULTS: Receiving ABI resulted in significantly greater reductions in heavy drinking days (mean difference [95% CI] = -0.26 [-0.45, -0.08]), drinking days per week (-0.04 [-0.07, -0.01]), drinks per drinking day (-0.05 [-0.08, -0.02]) and drinks per week (-0.16 [-0.27, -0.04]). Effects of ABI on 12-month drinking outcomes varied by baseline consumption level, age group and whether patients already had an AUD, with better improvement in those who were drinking at levels exceeding only daily limits, younger, and without an AUD. CONCLUSIONS: Systematic ABI in adult primary care has the potential to reduce drinking among people with unhealthy drinking considerably on both an individual and population level. More research is needed to help optimize ABI, in particular tailoring it to diverse sub-populations, and studying its long-term public health impact.

An Alternative Strategy for Screening and Confirmation of 330 Pesticides in Ground- and Surface Water Using Liquid Chromatography Tandem Mass Spectrometry.

The presence of pesticide residues in water is a huge worldwide concern. In this paper we described the development and validation of a new liquid chromatography tandem mass spectrometric (LC-MS/MS) method for both screening and quantification of pesticides in water samples. In the sample preparation stage, the samples were buffered to pH 7.0 and pre-concentrated on polymeric-based cartridges via solid-phase extraction (SPE). Highly sensitive detection was carried out with mobile phases containing only 5 mM ammonium formate (pH of 6.8) as an eluent additive and using only positive ionization mode in MS/MS instrument. Hence, only 200-fold sample enrichment was required to set a screening detection limit (SDL) and reporting limit (RL) of 10 ng/L. The confirmatory method was validated at 10 and 100 ng/L spiking levels. The apparent recoveries obtained from the matrix-matched calibration (5-500 ng/L) were within the acceptable range (60-120%), also the precision (relative standard deviation, RSD) was not higher than 20%. During the development, 480 pesticides were tested and 330 compounds fulfilled the requirements of validation. The method was successfully applied to proficiency test samples to evaluate its accuracy. Moreover, the method robustness test was carried out using higher sample volume (500 mL) followed by automated SPE enrichment. Finally, the method was used to analyze 20 real samples, in which some compounds were detected around 10 ng/L, but never exceeded the assay maximum level.

Predictors of early and sustained cessation of heavy drinking over 5 years among adult primary care patients.

AIMS: To identify factors asociated with early and sustained cessation of heavy drinking. DESIGN: Retrospective cohort study over 5 years. SETTING: Kaiser Permanente Northern California, United States. PARTICIPANTS: Adults reporting heavy drinking during primary care-based alcohol screening between 1 June 2013 and 31 May 2014. The sample (n = 85 434) was 40.7% female and 33.8% non-white; mean age was 50.3 years (standard deviation = 18.1). MEASUREMENTS: Following US guidelines, early and sustained cessation of heavy drinking was defined as reporting lower-risk drinking or abstinence at 1 year and to 5 years after achieving early cessation, respectively. Associations between patient characteristics and service use and cessation outcomes were examined using logistic regression with inverse probability weights addressing attrition. FINDINGS: Nearly two-thirds of participants achieved early cessation of heavy drinking. Women [odds ratio (OR) = 1.39, 95% confidence interval (CI) = 1.35, 1.44], middle-age (35-64 years: ORs = 1.16-1.19), non-white race/ethnicity (ORs = 1.03-1.57), medical conditions (OR = 1.05, 95% CI = 1.04, 1.06), psychiatric (OR = 1.10, 95% CI = 1.06, 1.15) and drug use disorders (OR = 1.35, 95% CI = 1.17, 1.56) and addiction treatment (OR = 1.19, 95% CI = 1.09, 1.30) were associated with higher odds of early cessation, while older age (≥ 65 years: OR = 0.91, 95% CI = 0.86, 0.96), smoking (OR = 0.81, 95% CI = 0.77, 0.84), higher index drinking levels (exceeding both daily and weekly limits: OR = 0.30, 95% CI = 0.29, 0.32) and psychiatric treatment (OR = 0.91, 95% CI = 0.84, 0.99) were associated with lower odds. Among those who achieved early cessation (n = 19 200), 60.0% sustained cessation. Associations between patient factors and sustained cessation paralleled those observed in analyses of early cessation. Additionally, routine primary care (OR = 1.57, 95% CI = 1.44, 1.71) and addiction treatment post-1 year (OR = 1.41, 95% CI = 1.19, 1.66) were associated with higher odds of sustained cessation. Lower-risk drinking versus abstinence at 1 year was associated with lower odds of sustained cessation (OR = 0.62, 95% CI = 0.57, 0.66). CONCLUSIONS: Nearly two-thirds of a large, diverse sample of patients who reported heavy drinking in a Californian health-care system achieved early and sustained cessation of heavy drinking. Vulnerable subgroups (i.e. non-white patients and those with psychiatric disorders), patients who received routine primary care and those who received addiction treatment were more likely to sustain cessation of heavy drinking than other participants.

Parent-focused prevention of adolescent health risk behavior: Study protocol for a multisite cluster-randomized trial implemented in pediatric primary care.

Evidence-based parenting interventions play a crucial role in the sustained reduction of adolescent behavioral health concerns. Guiding Good Choices (GGC) is a 5-session universal anticipatory guidance curriculum for parents of early adolescents that has been shown to reduce substance use, depression symptoms, and delinquent behavior. Although prior research has demonstrated the effectiveness of evidence-based parenting interventions at achieving sustained reductions in adolescent behavioral health concerns, public health impact has been limited by low rates of uptake in community and agency settings. Pediatric primary care is an ideal setting for implementing and scaling parent-focused prevention programs as these settings have a broad reach, and prevention programs implemented within them have the potential to achieve population-level impact. The current investigation, Guiding Good Choices for Health (GGC4H), tests the feasibility and effectiveness of implementing GGC in 3 geographically and socioeconomically diverse large integrated healthcare systems. This pragmatic, cluster randomized clinical trial will compare GGC parenting intervention to usual pediatric primary care practice, and will include approximately 3750 adolescents; n = 1875 GGC intervention and n = 1875 usual care. The study team hypothesizes that adolescents whose parents are randomized into the GGC intervention arm will show reductions in substance use initiation, the study's primary outcomes, and other secondary (e.g., depression symptoms, substance use prevalence) and exploratory outcomes (e.g., health services utilization, anxiety symptoms). The investigative team anticipates that the implementation of GGC within pediatric primary care clinics will successfully fill an unmet need for effective preventive parenting interventions. Trial registration: Clinicaltrials.govNCT04040153.

Substance use disorders among primary care patients screening positive for unhealthy alcohol use.

BACKGROUND: Despite high prevalence of polysubstance use, recent data on concurrent alcohol use in patients with specific substance use disorders (SUDs) are lacking. OBJECTIVE: To examine associations between specific SUDs and alcohol consumption levels. METHODS: Using electronic health record data, we conducted a cross-sectional study of 2,720,231 primary care adults screened for alcohol use between 2014 and 2017 at Kaiser Permanente Northern California. Alcohol consumption levels were categorized as no reported use, low-risk use, and unhealthy use (exceeding daily, weekly, or both recommended drinking limits). Using multinomial logistic regression, and adjusting for sociodemographic and health characteristics, we examined the odds of reporting each alcohol consumption level in patients with a prior-year SUD diagnosis (alcohol, cannabis, cocaine, inhalant, opioid, sedative/anxiolytic, stimulant, other drug, nicotine, any SUD except nicotine) compared to those without. RESULTS: The sample was 52.9% female, 48.1% White; the mean age was 46 years (SD = 18). Patients with SUDs were less likely to report low-risk alcohol use relative to no use compared with patients without SUDs. Patients with alcohol or nicotine use disorder had higher odds of reporting unhealthy alcohol use relative to no use; however, patients with all other SUDs (except cocaine) had lower odds. Among patients who reported any alcohol use (n = 861,427), patients with SUDs (except opioid) had higher odds of exceeding recommended limits than those without. CONCLUSION: The associations of unhealthy alcohol use and SUDs suggest that screening for both alcohol and drug use in primary care presents a crucial opportunity to prevent and treat SUDs early.

Normal aging, motor neurone disease, and Alzheimer's disease are characterized by cortical changes in inflammatory cytokines.

The role of increased brain inflammation in the development of neurodegenerative diseases is unclear. Here, we have compared cytokine changes in normal aging, motor neurone disease (MND), and Alzheimer's disease (AD). After an initial analysis, six candidate cytokines, interleukin (IL)- 4, 5, 6, 10, macrophage inhibitory protein (MIP)-1α, and fibroblast growth factor (FGF)-2, showing greatest changes were assayed in postmortem frozen human superior frontal gyri (n = 12) of AD patients, aging and young adult controls along with the precentral gyrus (n = 12) of MND patients. Healthy aging was associated with decreased anti-inflammatory IL-10 and FGF-2 levels. AD prefrontal cortex was associated with increased levels of IL-4, IL-5, and FGF-2, with the largest increase seen for FGF-2. Notwithstanding differences in the specific frontal lobe gyrus sampled, MND patients' primary motor cortex (precentral gyrus) was associated with increased levels of IL-5, IL-6, IL-10, and FGF-2 compared to the aging prefrontal cortex (superior frontal gyrus). Immunocytochemistry showed that FGF-2 is expressed in neurons, astrocytes, and microglia in normal aging prefrontal cortex, AD prefrontal cortex, and MND motor cortex. We report that healthy aging and age-related neurodegenerative diseases have different cortical inflammatory signatures that are characterized by increased levels of anti-inflammatory cytokines and call into question the view that increased inflammation underlies the development of age-related neurodegenerative diseases.