Nutrient requirements determined by grain yield and protein content to optimize N, P, and K fertilizer management in China.

Nutrient requirement for crop growth, defined as the amount of nutrient that crops take up from soil to produce a specific grain yield, is a key parameter in determining fertilizer application rate. However, existing studies primarily focus on identifying nitrogen (N), phosphorus (P), and potassium (K) requirements solely in relation to grain yield, neglecting grain protein content, a crucial index for wheat grain quality. Addressing this gap, we conducted multi-site, multi-cultivar, and multi-year field trials across three ecological regions of China from 2016 to 2020 to elucidate variations in nutrient requirements for grain yield and grain protein. The research findings revealed that wheat grain yield ranged from 4.1 to 9.3 Mg ha-1 (average 6.9 Mg ha-1) and grain protein content ranged from 98 to 157 g kg-1 (average 127 g kg-1) across the three regions. Notably, the N requirement exhibited a nonlinear correlation with the wheat grain yield but a linear increase with increasing grain protein, while the P and K requirements positively correlated with grain yield and protein content. Regression models were formulated to determine the nutrient requirements (MENR), enabling the prediction of N, P, and K requirements for leading cultivars with varying grain yields and protein contents. Implementing nutrient requirements based on MENR projections resulted in substantial reductions in fertilizer rates: 22.0 kg ha-1 N (10.7 %), 9.9 kg ha-1 P (20.2 %), and 8.1 kg ha-1 K (16.3 %). This translated to potential savings of 0.4 Mt. N, 0.23 Mt. P, and 0.17 Mt. K, consequently mitigating 5.5 Mt. CO2 greenhouse-gas emission and yielding an economic benefit of 0.8 billion US$ annually in China. These findings underscore the significance of considering grain yield and protein content in estimating nutrient requirements for fertilizer recommendations to realize high-yielding, high-protein wheat production, and minimize overfertilization and associated environmental risks.

The impact of more restrictive hydrocodone rescheduling on unintentional pediatric opioid exposures.

PURPOSE: To evaluate the impact of rescheduling hydrocodone combination products (HCPs) from schedule III of the Controlled Substances Act to the more restrictive schedule II on unintentional pediatric exposures (≤5 years old). METHODS: Using U.S. data on outpatient retail pharmacy dispensing, emergency department (ED) visits, and poison center (PC) exposure cases, we assessed trends in prescriptions dispensed and unintentional pediatric exposure cases involving hydrocodone (rescheduled from III to II) compared to oxycodone (schedule II) and codeine (schedule III for combination products) using descriptive and interrupted time-series (ITS) analyses during the 16 quarters before and after the October 2014 rescheduling of HCPs. RESULTS: Dispensing of hydrocodone products was declining before rescheduling but declined more steeply post-rescheduling. In ITS analyses, both hydrocodone and oxycodone had significant slope decreases in PC case rates in the post versus pre-period that was larger for hydrocodone, while codeine had a small but significant slope increase in PC case rates. An estimated 4202 ED visits for pediatric hydrocodone exposures occurred in the pre-period and 2090 visits occurred in the post-period, a significant decrease of 50.3%. Oxycodone exposures showed no significant decrease. CONCLUSIONS: Pediatric hydrocodone unintentional exposure ED visits and PC cases decreased after HCP rescheduling more than would be expected had the pre-rescheduling trend continued; the acceleration in the decrease in hydrocodone PC cases was partially offset by a slowing in the decrease in codeine-involved cases. The trend changes were likely due to multiple factors, including changes in dispensing that followed the rescheduling. Unintentional pediatric medication exposures and poisonings remain a public health concern requiring ongoing, multifaceted mitigation efforts.

Trends and driving forces of agricultural carbon emissions: A case study of Anhui, China.

To facilitate accurate prediction and empirical research on regional agricultural carbon emissions, this paper uses the LLE-PSO-XGBoost carbon emission model, which combines the Local Linear Embedding (LLE), Particle Swarm Algorithm (PSO) and Extreme Gradient Boosting Algorithm (XGBoost), to forecast regional agricultural carbon emissions in Anhui Province under different scenarios. The results show that the regional agricultural carbon emissions in Anhui Province generally show an upward and then downward trend during 2000-2021, and the regional agricultural carbon emissions in Anhui Province in 2030 are expected to fluctuate between 11,342,100 tones and 14,445,700 tones under five different set scenarios. The projections of regional agricultural carbon emissions can play an important role in supporting the development of local regional agriculture, helping to guide the input and policy guidance of local rural low-carbon agriculture and promoting the development of rural areas towards a resource-saving and environment-friendly society.

Successful Interventional Treatment of Pyopneumothorax Caused by Streptococcus constellatus Associated with Hashimoto's Thyroiditis: A Case Report and Literature Review.

Background: Streptococcus constellatus rarely causes pyopneumothorax, which is a serious state and requires a surgery. However, not every patient can tolerate surgery and individualized solutions are needed. Furthermore, many known situations are risk factors of S. constellatus infection, but S. constellatus pyopneumothorax associated with Hashimoto's thyroiditis has not been reported. Case Presentation: We present the case of a 74-year-old male with multiple encapsulated pyopneumothorax caused by S. constellatus. Given his respiratory failure, we provided two-stage percutaneous right empyema radiography for catheter drainage in the radiology interventional department instead of surgery. Moreover, an occult Hashimoto's thyroiditis was discovered in the patient, which was possibly associated with S. constellatus pyopneumothorax. Levothyroxine was administered to improve his situation. Conclusion: To our knowledge, it is the first case described in this context. We provided an alternative treatment for S. constellatus encapsulated pyopneumothorax in patient who might not tolerate surgery. We also revealed the possible relationship between S. constellatus pyopneumothorax and Hashimoto's thyroiditis.

The impact of hydrocodone rescheduling on utilization, abuse, misuse, and overdose deaths.

PURPOSE: To evaluate the impact of increased federal restrictions on hydrocodone combination product (HCP) utilization, misuse, abuse, and overdose death. METHODS: We assessed utilization, misuse, abuse, and overdose death trends involving hydrocodone versus select opioid analgesics (OAs) and heroin using descriptive and interrupted time-series (ITS) analyses during the nine quarters before and after the October 2014 rescheduling of HCPs from a less restrictive (CIII) to more restrictive (CII) category. RESULTS: Hydrocodone dispensing declined >30% over the study period, and declines accelerated after rescheduling. ITS analyses showed that immediately postrescheduling, quarterly hydrocodone dispensing decreased by 177M dosage units while codeine, oxycodone, and morphine dispensing increased by 49M, 62M, and 4M dosage units, respectively. Postrescheduling, hydrocodone-involved misuse/abuse poison center (PC) case rates had a statistically significant immediate drop but a deceleration of preperiod declines. There were small level increases in codeine-involved PC misuse/abuse and overdose death rates immediately after HCP's rescheduling, but these were smaller than level decreases in rates for hydrocodone. Heroin-involved PC case rates and overdose death rates increased across the study period, with exponential increases in PC case rates beginning 2015. CONCLUSIONS: HCP rescheduling was associated with accelerated declines in hydrocodone dispensing, only partially offset by smaller increases in codeine, oxycodone, and morphine dispensing. The net impact on hydrocodone and other OA-involved misuse/abuse and fatal overdose was unclear. We did not detect an immediate impact on heroin abuse or overdose death rates; however, the dynamic nature of the crisis and data limitations present challenges to causal inference.

Nurse-led care versus usual care on cardiovascular risk factors for patients with type 2 diabetes: a systematic review and meta-analysis.

OBJECTS: This study aims to systematically evaluate the effectiveness of nurse-led cares on cardiovascular risk factors among individuals with type 2 diabetes mellitus. DESIGN: Systematic review and meta-analysis. METHODS: The electronic databases PubMed, EMBASE, CINAHL and Cochrane Library databases were searched for randomised controlled trials of nurse-led care for individuals with type 2 diabetes mellitus (T2DM) published in English from inception to 23 December 2021. Random effects models were used to calculate weighted mean differences (WMD) with 95%CI. RESULTS: 13 articles were included in the meta-analysis, with a total of3757 participants. Considering baseline measurements, pooled analysis showed that nurse-led care significantly decreased the glycosylated haemoglobin (HbA1c) (WMD=-0.68 mmol/L; 95% CI -0.85 to -0.52; p<0.001), body mass index (BMI) (WMD=-0.54 kg/m2; 95% CI: -0.97 to -0.11; p=0.01) and systolic blood pressure (SBP) (WMD=-1.17 mmHg; 95% CI: -2.11 to -0.22; p=0.02) for patients with T2DM. But there was no difference in low-density lipoprotein cholesterol (LDL-c) (WMD=-2.50 mg/dL ; 95% CI: -5.07 to 0.08; p=0.06) between the nurse-led and control groups. CONCLUSION: Nurse-led care is an effective and accessible intervention that could improve HbA1c, SBP, BMI levels among individuals with T2DM. PROSPERO REGISTRATION NUMBER: CRD42021248275.

Identification of potential drug name confusion errors in the Sentinel System.

PURPOSE: In July 2015, the US Food and Drug Administration (FDA) published a drug safety communication regarding errors in prescribing and dispensing of the antidepressant Brintellix (vortioxetine) and the antiplatelet Brilinta (ticagrelor) that arose due to proprietary drug name confusion. Brintellix is indicated for major depressive disorder; Brilinta is indicated to reduce cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome or history of myocardial infarction. Brintellix was renamed to Trintellix in May 2016. Using Brilinta and Brintellix as a proof-of-concept feasibility use case, we assessed whether drug name confusion errors between the pair could be identified in electronic health care data via the combination of a claims-based algorithm and limited manual claims data review. METHODS: Using data from the Sentinel System, we defined potential errors as Brintellix users without an on- or off-label indication for Brintellix, without a dispensing for a drug with the same indications as Brintellix, and with an on- or off-label indication for Brilinta between -365 and +30 days after index Brintellix dispensing; the reverse was done for Brilinta. We manually reviewed claims profiles of potential cases. RESULTS: We identified 27 (0.1%) potential errors among 21 208 Brintellix users; 16 appeared to be likely errors based on claims profile review. Fifty-one (0.3%) of the 16 779 Brilinta users were identified as potential errors, and four appeared to be likely errors. CONCLUSIONS: A claims-based algorithm combined with manual review of claims profiles could identify potential drug name confusion errors, and narrow down likely errors that warrant further investigation.

A new analytic tool developed to assess safe use recommendations.

PURPOSE: Develop a flexible analytic tool for the Food and Drug Administration's (FDA's) Sentinel System to assess adherence to safe use recommendations with two capabilities: characterize adherence to patient monitoring recommendations for a drug, and characterize concomitant medication use before, during, and/or after drug therapy. METHODS: We applied the tool in the Sentinel Distributed Database to assess adherence to the labeled recommendation that patients treated with dronedarone undergo electrocardiogram (ECG) testing no less often than every 3 months. Measures of length of treatment, time to first ECG, number of ECGs, and time between ECGs were assessed. We also assessed concomitant use of contraception among female users of mycophenolate per label recommendations (concomitancy 4 weeks before through 6 weeks after discontinuation of mycophenolate). Unadjusted results were stratified by age, month-year, and sex. RESULTS: We identified 21 457 new episodes of dronedarone use of greater than or equal to 90 days (July 2009 to September 2015); 86% had greater than or equal to one ECG, and 22% met the recommendation of an ECG no less often than every 3 months. We identified 21 942 new episodes of mycophenolate use among females 12 to 55 years (January 2016 to September 2015); 16% had greater than or equal to 1 day of concomitant contraception dispensed, 12% had concomitant contraception use for greater than or equal to 50% of the 4 weeks before initiation through 6 weeks after mycophenolate; younger females had more concomitancy. These results may be underestimates as the analyses are limited to claims data. CONCLUSIONS: We developed a tool for use in databases formatted to the Sentinel Common Data Model that can assess adherence to safe use recommendations involving patient monitoring and concomitant drug use over time.

The Effect of FDA Drug Safety Communications on Patterns of Tiotropium Dispensing: A U.S. Health Plan Claims Database Study.

BACKGROUND: The FDA issued 2 main drug safety communications (DSCs) on the cardiovascular safety of tiotropium in March 2008 (warning of a potential increased stroke risk) and January 2010 (informing of an absence of a significant increased stroke risk or cardiovascular events based on findings from a large trial). OBJECTIVE: To describe the effect of the FDA DSCs on medication dispensing of tiotropium in a large U.S. claims database. METHODS: Initiation of tiotropium products among patients with chronic obstructive pulmonary disease (COPD) aged 40 years and older was determined monthly from 2006-2012 using medication dispensing from the IMS Lifelink Health Plan Claims Database. Similarly, monthly initiation of products containing long-acting beta-agonists (LABAs) was calculated to explore product switching. The effect of the 2008 and 2010 FDA DSCs was measured using interrupted time-series analysis. Subgroups of patients with greater cardiovascular risk were also examined. RESULTS: A decreasing trend in initiation of tiotropium-containing products was present before the initial 2008 DSC. The decline in tiotropium initiation continued until January 2010, accompanied by an increased initiation of LABA-containing products in patients with COPD. In the presence of the existing decreasing trend, the initial DSC was followed by an immediate 2.8% (P = 0.02) further reduction in tiotropium initiation. Tiotropium initiation increased 2.5% (P = 0.03) immediately after the 2010 DSC, reducing the overall decline in rate and stabilizing (flattening) the trend. No significant changes in dispensing level or trend were observed among COPD patients with cardiovascular comorbidity. CONCLUSIONS: Cardiovascular safety concerns may have affected tiotropium initiation as indicated by the decrease in tiotropium dispensing shown immediately following the initial DSC. The effect was alleviated as concerns lessened following the most recent DSC. DISCLOSURES: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors are employed by the FDA and have no conflict of interest relevant to the content of this study. The views expressed herein do not necessarily represent the views of the FDA.

Patterns of Immediate-Release and Extended-Release Opioid Analgesic Use in the Management of Chronic Pain, 2003-2014.

Importance: Many stakeholders are working to improve the safe use of immediate-release (IR) and extended-release/long-acting (ER/LA) opioid analgesics. However, little information exists regarding the relative use of these 2 formulations in chronic pain management. Objectives: To describe the distribution of IR and ER/LA opioid analgesic therapy duration and examine adding and switching patterns among patients receiving long-term IR opioid analgesic therapy, defined as at least 90 consecutive days of IR formulation use. Design, Setting, and Participants: A retrospective cohort study of 169 million individuals receiving opioid analgesics from across 90% of outpatient retail pharmacies in the United States from January 1, 2003, to December 31, 2014, using the IQVIA Health Vector One: Data Extract Tool. Analyses were conducted from March 2015 to June 2017. Exposures: Receipt of dispensed IR or ER/LA opioid analgesic prescription. Main Outcomes and Measures: Distribution of therapy frequency and duration of IR and ER/LA opioid analgesic use, and annual proportions of patients receiving long-term IR opioid analgesic therapy who added an ER/LA formulation while continuing to use an IR formulation, switched to an ER/LA formulation, or continued receiving IR opioid analgesic therapy only. Results: Among the 169 280 456 patients included in this analysis, 168 315 458 patients filled IR formulations and 10 216 570 patients filled ER/LA formulations. A similar percentage of women received ER/LA (55%) and IR (56%) formulations, although those receiving ER/LA formulations (72%) were more likely to be aged 45 years or older compared with those receiving IR formulations (46%). The longest opioid analgesic episode duration was 90 days or longer for 11 563 089 patients (7%) filling IR formulations and 3 103 777 patients (30%) filling ER/LA formulations. The median episode duration was 5 days (interquartile range, 3-10 days) for patients using IR formulations and 30 days (interquartile range, 21-74 days) for patients using ER/LA formulations. From January 1, 2003, to December 31, 2014, a small and decreasing proportion of patients with long-term IR opioid analgesic therapy added (3.8% in 2003 to 1.8% in 2014) or switched to (1.0% in 2003 to 0.5% in 2014) an ER/LA formulation. Conclusions and Relevance: Most patients receiving opioid analgesics, whether for short or extended periods, use IR formulations. Once receiving long-term IR opioid analgesic therapy, patients are unlikely to add or switch to an ER/LA formulation.

Trends in rates of acetaminophen-related adverse events in the United States.

PURPOSE: The goal of this study is to summarize trends in rates of adverse events attributable to acetaminophen use, including hepatotoxicity and mortality. METHODS: A comprehensive analysis of data from three national surveillance systems estimated rates of acetaminophen-related events identified in different settings, including calls to poison centers (2008-2012), emergency department visits (2004-2012), and inpatient hospitalizations (1998-2011). Rates of acetaminophen-related events were calculated per setting, census population, and distributed drug units. RESULTS: Rates of poison center calls with acetaminophen-related exposures decreased from 49.5/1000 calls in 2009 to 43.5/1000 calls in 2012. Rates of emergency department visits for unintentional acetaminophen-related adverse events decreased from 58.0/1000 emergency department visits for adverse drug events in 2009 to 50.2/1000 emergency department visits in 2012. Rates of hospital inpatient discharges with acetaminophen-related poisoning decreased from 119.8/100 000 hospitalizations in 2009 to 108.6/100 000 hospitalizations in 2011. After 2009, population rates of acetaminophen-related events per 1 million census population decreased for poison center calls and hospitalizations, while emergency department visit rates remained stable. However, when accounting for drug sales, the rate of acetaminophen-related events (per 1 million distributed drug units) increased after 2009. Prior to 2009, the rates of acetaminophen-related hospitalizations had been slowly increasing (p-trend = 0.001). CONCLUSIONS: Acetaminophen-related adverse events continue to be a public health burden. Future studies with additional time points are necessary to confirm trends and determine whether recent risk mitigation efforts had a beneficial impact on acetaminophen-related adverse events. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Determining the predictive value of Read codes to identify congenital cardiac malformations in the UK Clinical Practice Research Datalink.

PURPOSES: The purposes of this study were to determine (i) the positive predictive value (PPV) of multiple Read codes used to identify congenital cardiac malformation (CCM) cases in the UK Clinical Practice Research Datalink (CPRD); (ii) the accuracy of the diagnosis date; and (iii) the source of information that the general practitioners (GPs) use for validating the diagnosis suggested by the code. METHODS: Eight hundred eighty-eight records with Read diagnostic and procedures codes for CCM, between January 1996 and November 2010, were identified from CPRD. Questionnaires were sent to GPs to verify the diagnoses and date of the code-identified events. RESULTS: A total of 719 questionnaires were returned (81% response rate). The PPV of the CCM codes was 93% (670/719). Thirty-one percent of cases had a different event date than the one recorded in the electronic medical record (EMR); 10% of these differing dates were within 30 days of the code-identified CCM date. GPs used a variety of data sources to confirm CCM diagnoses. Although the EMR was the most frequently used data source (70%), 66% reported using consultation letters, 9% reported using clinical notes or paper charts, and 35% of GPs reported using the hospital record to confirm the CCM diagnosis. CONCLUSIONS: Clinical Practice Research Datalink Read codes for CCMs have 93% PPV and most likely point to true cases. However, the accuracy of diagnosis dates and the age at diagnosis may not be as reliable. The findings of this study indicate that GPs use information beyond what is available for researchers in the EMR to confirm clinical diagnoses when responding to validation questionnaires. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Antidepressant medication dispensing among montelukast initiators.

OBJECTIVE: This study investigates the potential association between montelukast use and psychiatric adverse events by monitoring changes in antidepressant medication dispensing rates before and after initiating montelukast. METHODS: The primary study group of montelukast initiators was identified using the Wolters Kluwer's SOURCE Lx® pharmacy claims database (WK). This group included 232,159 patients ≤45 years old who had at least two montelukast prescriptions from 2003 to 2007. Comparison groups comprised of 264,704 fluticasone initiators and 89,635 long-acting ß-agonist corticosteroid (LABA/ICS) initiators were also identified. Antidepressant medication dispensing rates in these three groups were determined using WK, and changes in rates before and after the first asthma controller medication prescription date were evaluated using interrupted time-series analysis (ITS). ITS was performed separately for four age categories, with a focus on youth (12-17 years) and young adult (18-24 years). RESULTS: For patients 18-24 years old, antidepressant medication dispensing rates increased significantly after initiating montelukast [1.93% (1.55-2.32%, p < 0.001)] but also after initiating fluticasone and LABA/ICS [1.72% (1.30-2.15%, p < 0.001) and 2.76% (2.35-3.17%, p < 0.001)]. Similar patterns were observed across the three medication groups for other age categories but these differences were not all significant. CONCLUSIONS: Small increases in antidepressant medication dispensing rates occurred after initiating montelukast. However, similar increases were observed in the fluticasone and LABA/ICS comparison groups. The results of this study cannot support a specific association between initiation of montelukast treatment and an increase in psychiatric adverse effects.

Use of selective serotonin reuptake inhibitors in pregnancy and cardiac malformations: a propensity-score matched cohort in CPRD.

PURPOSE: Research on the association of maternal selective serotonin reuptake inhibitor (SSRI) use and cardiac malformations in the offspring has yielded conflicting findings. We therefore sought to further investigate the association using data from a large population-based cohort in the UK. METHODS: The study population consisted of 149 464 pregnancies ending in a live birth between January/1996 and November/2010 from the Clinical Practice Research Datalink's Mother Baby Link. We created propensity-score matched cohorts of first-trimester SSRI users who did not use other antidepressants in the same gestational period ('SSRI users', n=3046) and non-antidepressant users (no use from the 3 months before pregnancy through the second trimester of pregnancy, 'non-users'; n=8991). Weighted logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of cardiac malformations overall and septal defects diagnosed in the first year of life, or in the first 6 years of life. RESULTS: Sixteen infants with cardiac malformations were identified among SSRI users; 10 of them were septal defects. Among non-users, there were 48 infants with cardiac malformations, 26 of whom had septal defects. The OR (95% CI) for cardiac malformations was 1.00 (0.50; 2.00), and for septal defects was 1.15 (0.46; 2.87). Results were similar for cardiac malformations diagnosed in the first 6 years of life, and in several sensitivity analyses that were also implemented. CONCLUSIONS: The results of this study are most compatible with no association between maternal use of SSRIs in early pregnancy and cardiac malformations or septal defects in the offspring. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Retinal thickness in eyes of older normal individuals and its implication for the diagnosis of glaucoma.

PURPOSE: Retinal thickness (RT) is a useful measurement for describing diseases that affect the thickness of the retina, such as glaucoma. Existing normative data are derived from relatively young individuals; however, glaucoma is most prevalent in older individuals. We therefore studied the RT in older normal individuals. PATIENTS AND METHODS: Participants of the Baltimore Eye Study, persons accompanying patients, and staff were recruited and underwent visual field testing and a comprehensive eye examination by a glaucoma specialist. RT was measured with the retinal thickness analyzer (RTA, Talia Technology) and RT values in specific regions were derived using a custom-designed MatLab program. RESULTS: One hundred and three eyes of sixty-two individuals were studied. Mean age was 61 years. Sixty-six percent were female and 82% were of European descent. The average mean deviation on visual field testing was 0.03 dB and the average pattern SD was 1.51 dB. The mean RT of the entire macula was 159+/-16 microm, and was lowest in the foveal pit and highest in the parafoveal annulus. The average distance from the foveal pit to the thickest point in the parafoveal annulus was 1240+/-138 microm. The mean RT of the entire macula was slightly less in older individuals (slope=-5.7 microm/10 y, P=0.02) but the height of the parafoveal annulus relative to the foveal pit, which is determined by the combined thickness of the parafoveal nerve fibers, ganglion cells, inner plexiform layer, and inner nuclear layer, did not vary with age (P=0.62). CONCLUSIONS: Although the average RT of the entire macula was slightly thinner with increasing age, the height of the parafoveal annulus relative to the foveal pit did not change with age and would therefore seem to be a better marker of neuronal tissue health than the average RT of the entire macula.

Agreement among glaucoma specialists in assessing progressive disc changes from photographs in open-angle glaucoma patients.

PURPOSE: To determine the agreement among glaucoma specialists in assessing progressive disc changes from photographs in a cohort of patients with glaucomatous visual field loss. DESIGN: Retrospective cohort study. METHODS: Three glaucoma specialists, masked to chronological sequence, examined pairs of optic disc stereophotographs to determine whether the appearance of the optic disc had changed. Eyes for which the observers disagreed were adjudicated to reach a consensus about which discs had changed over time. RESULTS: Sequential stereophotographs, separated in time by a median of 26 months (range, five to 50), from 164 eyes of 111 patients were analyzed. Among the three observers, the number of interpretable discs judged to have changed was 11 of 155 (7%) for Observer 1, 17 of 155 (11%) for Observer 2, and 44 of 155 (28%) for Observer 3 (kappa = 0.20). Sixty-six eyes (43%) required adjudication. After adjudication, the consensus was that 10 discs had changed, six eyes in which the disc was worse in the later photograph and four eyes in which the disc was judged to appear more glaucomatous in the earlier photograph. CONCLUSION: Interobserver agreement among glaucoma specialists in judging progressive optic disc change from stereophotographs was slight to fair. After masked adjudication, in 40% of the cases in which the optic disc appeared to have progressed in glaucoma severity, the photograph of the "worse" optic disc was in fact taken at the start of the study. Caution must be exercised when using disc change on photographs as the "gold standard" for diagnosing open-angle glaucoma or determining its progression.

Genome wide association for substance dependence: convergent results from epidemiologic and research volunteer samples.

BACKGROUND: Dependences on addictive substances are substantially-heritable complex disorders whose molecular genetic bases have been partially elucidated by studies that have largely focused on research volunteers, including those recruited in Baltimore. Maryland. Subjects recruited from the Baltimore site of the Epidemiological Catchment Area (ECA) study provide a potentially-useful comparison group for possible confounding features that might arise from selecting research volunteer samples of substance dependent and control individuals. We now report novel SNP (single nucleotide polymorphism) genome wide association (GWA) results for vulnerability to substance dependence in ECA participants, who were initially ascertained as members of a probability sample from Baltimore, and compare the results to those from ethnically-matched Baltimore research volunteers. RESULTS: We identify substantial overlap between the home address zip codes reported by members of these two samples. We find overlapping clusters of SNPs whose allele frequencies differ with nominal significance between substance dependent vs control individuals in both samples. These overlapping clusters of nominally-positive SNPs identify 172 genes in ways that are never found by chance in Monte Carlo simulation studies. Comparison with data from human expressed sequence tags suggests that these genes are expressed in brain, especially in hippocampus and amygdala, to extents that are greater than chance. CONCLUSION: The convergent results from these probability sample and research volunteer sample datasets support prior genome wide association results. They fail to support the idea that large portions of the molecular genetic results for vulnerability to substance dependence derive from factors that are limited to research volunteers.

The influence of educational attainment on depression and risk of type 2 diabetes.

OBJECTIVES: We investigated the association between major depressive disorder and type 2 diabetes, whether that association is explained by health behaviors, and whether it is influenced by educational attainment. METHODS: We used discrete-time Cox proportional hazards models to determine the risk of type 2 diabetes associated with depression in a 23-year population-based cohort study. RESULTS: Major depressive disorder was associated with higher risk of type 2 diabetes (hazard ratio [HR]=1.62) after we controlled for age, gender, race, education, smoking status, alcohol use, social network size, and antidepressant use. This association was more pronounced after we controlled for body mass index, family history, and health behaviors (HR=2.04; 95% confidence interval=1.09, 3.81). In stratified analyses, the risk associated with major depressive disorder was elevated among those with 12 or fewer years of education compared with those with at least some education beyond high school. CONCLUSIONS: The risk of type 2 diabetes associated with major depressive disorder persists over the life course and is independent of the effects of health behaviors, body mass index, and family history. Education is an important moderator of this association.

Test-retest variability in structural and functional parameters of glaucoma damage in the glaucoma imaging longitudinal study.

PURPOSE: To determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma. PATIENTS AND METHODS: In this cohort study, the authors analyzed the imaging studies and visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement. RESULTS: In this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MD), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm for rim area, and 32.8 microm and 31.8 microm for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, cup shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0, 2.3, 5.7, 3.1, and 3.4, respectively. CONCLUSIONS: The variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage.

[Preparation and purification of polyclonal antibody against chymopapain].

OBJECTIVE: To prepare and purify polyclonal antibody against chymopapain, and to make a foundation for establishing an immunossay for chymopapain. METHODS: New Zealand rabbit was immunized with chymopapain. Antiserum was purified by Protein A and analyzed by ELISA. RESULTS: The titer of the antiserum obtained in this experiment by ELISA was up to 1:380000 and the purity was proved to be high by SDS-PAGE.