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PURPOSE: Efforts to provide medication assistance to the rural poor in central Louisiana are described. SUMMARY: The Central Louisiana Medication Access Program (CMAP) began functioning in 2001 with the objective of providing medication assistance and medication education to the rural poor in the community. The program serves individuals who use the outpatient clinic at the state-run public hospital in central Louisiana. Patients receive prescription drugs for a variety of chronic conditions, paying only a processing fee of dollar 3 per prescription, with a maximum outlay of dollar 15 per visit. A pharmacist counsels the patients about their medications. The medications are funded both through the program and through assistance programs run by pharmaceutical companies. A total of 5307 patients were enrolled in the CMAP between May 2001 and March 2003, and they received over 140,000 prescriptions at a cost saving to them in excess of dollar 2.5 million. CONCLUSION: The CMAP has been able to provide prescription medications and medication counseling to needy patients in a rural environment at little cost to them. [ABSTRACT FROM AUTHOR]

This article presents several formulas to approximate the required sample size to estimate the arithmetic mean of a lognormal distribution with desired accuracy and confidence under and without the presence of type I censoring to the left. We present tables of exact sample sizes which are based on Land's exact confidence interval of the lognormal mean. Monte Cario estimates of coverage probabilities show the appropriateness of these exact proposed sample sizes at 95% confidence level.

Rationale: Effective interventions to prevent burnout among intensive care unit (ICU) clinicians are urgently needed. Death cafés, group discussions about death, build a sense of community and create a space for reflection on distressing events. Objective: To assess whether participation in regular death cafés can prevent burnout in ICU clinicians (physicians, nurses, pharmacists, therapists). Methods: A randomized clinical trial was conducted from July 2020 to December 2022 in 10 ICUs in Louisiana. Subjects were randomized to attend four psychotherapist-facilitated virtual death cafés or to a control arm. The primary outcome was burnout defined by the Maslach Burnout Inventory-Human Services Survey at 6 months. Depression and anxiety scores were measured, as were qualitative data on stressors, coping, and death café experience. Results: Among 340 clinicians who were screened and gave consent (171 physicians, 169 nonphysicians), 251 participated (mean age, 31.0 ± 6.8 years; 63% female; 72% White; 37% nurses, 27% residents, 25% interns, 11% other). Burnout prevalence was 19% at baseline. Of 136 participants who completed the 6-month follow-up, no significant differences were found between intervention and control for the primary outcome (18% vs. 25%; unadjusted odds ratio, 0.64; 95% confidence interval, 0.26-1.57; P  = 0.33). There were no differences in anxiety or depression. Notably, the study was limited by an inability to achieve target enrollment and a high attrition rate (46%). Conclusions: Virtual death cafés were unable to reduce burnout, although the study was underpowered to detect differences between groups. Clinical trial registered with clinicaltrials.gov (NCT04347811).

Background: High prevalence of depression or anxiety with opioid use for chronic pain complicates co-management and may influence prescribing behaviors., Objective: Compare clinical effectiveness of electronic medical record clinical decision support (EMR-CDS) versus additional behavioral health (BH) care management for reducing rates of high-dose opioid prescriptions., Design: Type 2 effectiveness-implementation hybrid stepped-wedge cluster randomized trial in 35 primary care clinics within a health system in LA, USA., Participants: Patients aged 18+ receiving chronic opioid therapy for non-cancer pain with depression or anxiety and matched controls., Intervention: EMR-CDS included opioid risk mitigation procedures. BH care included cognitive behavioral therapy; depression or anxiety medication adjustments; and case management., Main Measures: Outcomes of interest included difference-in-difference (DID) estimate of changes in probability for prescribing high-dose morphine equivalent daily dose (MEDD ≥50 mg/day and MEDD ≥90), average MEDD, and rates of hospitalization, emergency department use, and opioid risk mitigation., Key Results: Most participants were female with 3+ pain syndromes. Data analysis included 632 patients. Absolute risk differences for MEDD≥50 and ≥90 decreased post-index compared to pre-index (DID of absolute risk difference [95%CI]: -0.036 [-0.089, 0.016] and -0.029 [-0.060, 0.002], respectively). However, these differences were not statistically significant. The average MEDD decreased at a higher rate for the BH group compared to EMR-CDS only (DID rate ratio [95%CI]: 0.85 [0.77, 0.93]). There were no changes in hospitalization and emergency department utilization. The BH group had higher probabilities of new specialty referrals and prescriptions for naloxone and antidepressants., Conclusions: Incorporation of a multidisciplinary behavioral health care team into primary care did not decrease high-dose prescribing; however, it improved adherence to clinical guideline recommendations for managing chronic opioid therapy for non-cancer pain., Trial Registration: ClinicalTrials.gov ID NCT03889418., Competing Interests: Declarations: Conflict of Interest: Dr. Price-Haywood is a member of the Board of Governors for the Patient-Centered Outcomes Research Institute and has received research funding from Pfizer Inc. for non-related studies. The co-authors do not have any COI to report., (© 2024. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Conventionally, mantle cell lymphoma (MCL) is an aggressive CD5-positive B-cell malignancy with poor prognosis and limited survival. However, a small subset of patients presents with indolent disease and can be managed on a 'watch and wait' approach. CD5-negative MCL has recently been recognized as a more favorable variant of MCL, but its clinical and biological implications remain ill-defined. We performed the most extensive review to-date of all reported cases of CD5-negative MCL and included unpublished cases diagnosed at our institutions to further characterize this disease subset. Based on our analysis of 356 cases of CD5-negative MCL, we conclude that median overall survival exceeds 14 years and is independent of favorable prognostic markers such as leukemic non-nodal disease, absence of SOX11, and low Ki-67.

Importance: Obesity, diabetes, and hypertension are common comorbidities in patients with severe COVID-19, yet little is known about the risk of acute respiratory distress syndrome (ARDS) or death in patients with COVID-19 and metabolic syndrome., Objective: To determine whether metabolic syndrome is associated with an increased risk of ARDS and death from COVID-19., Design, Setting, and Participants: This multicenter cohort study used data from the Society of Critical Care Medicine Discovery Viral Respiratory Illness Universal Study collected from 181 hospitals across 26 countries from February 15, 2020, to February 18, 2021. Outcomes were compared between patients with metabolic syndrome (defined as ≥3 of the following criteria: obesity, prediabetes or diabetes, hypertension, and dyslipidemia) and a control population without metabolic syndrome. Participants included adult patients hospitalized for COVID-19 during the study period who had a completed discharge status. Data were analyzed from February 22 to October 5, 2021., Exposures: Exposures were SARS-CoV-2 infection, metabolic syndrome, obesity, prediabetes or diabetes, hypertension, and/or dyslipidemia., Main Outcomes and Measures: The primary outcome was in-hospital mortality. Secondary outcomes included ARDS, intensive care unit (ICU) admission, need for invasive mechanical ventilation, and length of stay (LOS)., Results: Among 46 441 patients hospitalized with COVID-19, 29 040 patients (mean [SD] age, 61.2 [17.8] years; 13 059 [45.0%] women and 15713 [54.1%] men; 6797 Black patients [23.4%], 5325 Hispanic patients [18.3%], and 16 507 White patients [57.8%]) met inclusion criteria. A total of 5069 patients (17.5%) with metabolic syndrome were compared with 23 971 control patients (82.5%) without metabolic syndrome. In adjusted analyses, metabolic syndrome was associated with increased risk of ICU admission (adjusted odds ratio [aOR], 1.32 [95% CI, 1.14-1.53]), invasive mechanical ventilation (aOR, 1.45 [95% CI, 1.28-1.65]), ARDS (aOR, 1.36 [95% CI, 1.12-1.66]), and mortality (aOR, 1.19 [95% CI, 1.08-1.31]) and prolonged hospital LOS (median [IQR], 8.0 [4.2-15.8] days vs 6.8 [3.4-13.0] days; P < .001) and ICU LOS (median [IQR], 7.0 [2.8-15.0] days vs 6.4 [2.7-13.0] days; P < .001). Each additional metabolic syndrome criterion was associated with increased risk of ARDS in an additive fashion (1 criterion: 1147 patients with ARDS [10.4%]; P = .83; 2 criteria: 1191 patients with ARDS [15.3%]; P < .001; 3 criteria: 817 patients with ARDS [19.3%]; P < .001; 4 criteria: 203 patients with ARDS [24.3%]; P < .001)., Conclusions and Relevance: These findings suggest that metabolic syndrome was associated with increased risks of ARDS and death in patients hospitalized with COVID-19. The association with ARDS was cumulative for each metabolic syndrome criteria present.

Introduction: As of November 2021, COVID-19 has killed more than 5 million people globally, including over 750 000 in the USA. Apart from corticosteroids, most available therapeutic options are at best marginally efficient in reducing disease severity and are extremely expensive. The systematic investigation of clinically approved drugs is a priority to determine what does mitigate disease severity. Oestradiol (E2) and progesterone (P4) produce a state of anti-inflammatory immune responses and immune tolerance, and enhanced antibody production. The goal of this trial is to evaluate the efficacy of a short E2 and P4 therapy, in addition to standard of care (SOC), in mitigating disease severity in COVID-19 hospitalised patients., Methods and Analysis: Phase 2, randomised, double blind, placebo-controlled, single-centre trial. Patients hospitalised for confirmed COVID-19, with scores 3-5 on the 9-point WHO ordinal scale are randomised between two arms: (1) Oestradiol cypionate intramuscular (IM) and micronised progesterone oral (PO), in addition to SOC, and (2) placebo, in addition to SOC. The primary outcome is the proportion of patients improving to scores 1 or 2 on the WHO scale through day 28. Secondary outcomes include length of hospital stay, duration of mechanical ventilation, cause of death, readmission rates, change in inflammatory biomarkers between admission and occurrence of primary endpoint, and adverse events. Study sample size will be up to 120 participants. The trial is currently recruiting subjects., Ethics and Dissemination: The sponsor of this study is the Center of Excellence in Sex-Based Biology & Medicine at Tulane University, New Orleans, Louisiana, USA. Ethical approval was obtained from the Tulane institutional review board on 14 May 2021. The study was reviewed by the US Food and Drug Administration and granted Investigational New Drug #152 499. Results of the study will be submitted for publication in a peer-reviewed journal., Trial Registration Number: NCT04865029; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: End-of-life care for patients with cancer is often overly burdensome, and palliative and hospice care are underutilized. The objective of this study was to evaluate whether the mental health diagnoses of anxiety and depression were associated with variation in end-of-life care in metastatic cancer., Methods: This study used electronic health data from 1,333 adults with metastatic cancer who received care at two academic health centers in Louisiana, USA, and died between 1/1/2011-12/31/2017. The study used descriptive statistics to characterize the sample and logistic regression to examine whether anxiety and depression diagnoses in the six months before death were associated with utilization outcomes (chemotherapy, intensive care unit [ICU] visits, emergency department visits, mechanical ventilation, inpatient hospitalization, palliative care encounters, and hospice utilization), while controlling for key demographic and health covariates., Results: Patients (56.1% male; 65.6% White, 31.1% Black) commonly experienced depression (23.9%) and anxiety (27.2%) disorders within six months of death. Anxiety was associated with an increased likelihood of chemotherapy (odds ratio [OR] = 1.42, p = 0.016), ICU visits (OR = 1.40, p = 0.013), and inpatient hospitalizations (OR = 1.85, p < 0.001) in the 30 days before death. Anxiety (OR = 1.95, p < 0.001) and depression (OR = 1.34, p = 0.038) were associated with a greater likelihood of a palliative encounter., Conclusions: Patients with metastatic cancer who had an anxiety disorder were more likely to have burdensome end-of-life care, including chemotherapy, ICU visits, and inpatient hospitalizations in the 30 days before death. Depression and anxiety both increased the odds of palliative encounters. These results emphasize the importance of mental health considerations in end-of-life care., (© 2021 John Wiley & Sons Ltd.)

Even though current prescribing trends reveal that high-dose opioid prescribing and opioid prescribing in general has decreased, sustained efforts are needed to help providers adopt and maintain safe prescribing behaviors. The purpose of this four-year type 2 effectiveness-implementation hybrid stepped wedge cluster randomized trial is to: (1) compare the clinical and cost effectiveness of electronic medical record-based clinical decision support [EMR-CDS] versus additional integrated, collaborative behavioral health [EMR-CDS + BHI-CCM] for opioid management of patients with co-morbid chronic non-cancer pain with depression or anxiety; and (2) examine facilitators and barriers to implementing these interventions within 35 primary care clinics in a integrated delivery health system. The EMR-CDS alerts providers to employ opioid risk mitigation and safe prescribing practices at the point of care. The BHI-CCM consists of primary care embedded community health workers for case management; licensed clinical social workers for cognitive behavioral therapy, and a clinical pharmacist for medication management who provide care management via telemedicine (virtual video or audio only visits) under the guidance of a consulting psychiatrist. The primary outcome is reduction in the percentage of patients with average daily opioid dose ≥50 mg morphine equivalent. Secondary outcomes include changes in service utilization, patient reported outcomes and processes of care. The investigators anticipate that study results will elucidate the role of technology versus care team optimization in changing opioid prescribing behaviors. The investigators further anticipate that integrated mental/behavioral health care will increase value-based care and the efficiency with which guideline concordant care is delivered., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Context: The comfort of patients with cancer near the end of life (EOL) is often undermined by unnecessary and burdensome treatments. There is a need for more research examining racial disparities in EOL care, especially in regions with a history of racial discrimination., Objectives: To examine whether black adults received more burdensome EOL care than white adults in a population-based data set of cancer decedents in Louisiana, a state with a history of slavery and long-standing racial disparities., Methods: This was a retrospective analysis of EOL care from the Research Action for Health Network (REACHnet), a regional Patient-Centered Outcomes Research Institute-funded database. The sample consisted of 875 white and 415 black patients with metastatic cancer who died in Louisiana from 2011 to 2017. We used logistic regression to examine whether race was associated with five indicators of burdensome care in the last 30 days of life: chemotherapy use, inpatient hospitalization, intensive care unit admission, emergency department (ED) admission, and mechanical ventilation., Results: Most patients (85.0%) received at least one indicator of burdensome care: hospitalization (76.5%), intensive care unit admission (44.1%), chemotherapy (29.1%), mechanical ventilation (23.0%), and ED admission (18.3%). Odds ratios (ORs) indicated that black individuals were more likely than white individuals to be hospitalized (OR = 1.66; 95% CI = 1.21-2.28; P = 0.002) or admitted to the ED (OR = 1.57; 95% CI = 1.16-2.13; P = 0.004) during their last month of life., Conclusion: Findings have implications for informing health care decision making near the EOL for patients, families, and clinicians, especially in regions with a history of racial discrimination and disparities., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify characteristics associated with obtaining HIV and syphilis screenings of pregnant women attending a first antenatal visit in Lusaka, Zambia., Results: Among 18,231 participants from April 2015 to January 2016, 95% obtained HIV screening, 29% obtained syphilis screening, and 4% did not obtain antenatal HIV or syphilis screenings. Divorced/separated women were associated with a moderate decrease in prevalence of obtaining HIV (adjusted prevalence ratio (aPR) 0.88, 95% confidence interval (95% CI) 0.82, 0.95) and syphilis (aPR 0.51, 95% CI 0.27, 0.96) screenings compared to married women. Women with previous pregnancies were associated with a slight decrease in prevalence of obtaining HIV screening (aPR 0.97, 95% CI 0.95, 0.99) compared to women without previous pregnancy. Older women ≥ 35 years were associated with a slight decrease in prevalence of obtaining HIV screening (aPR 0.96, 95% CI 0.92, 0.99) compared to younger women. The statistically significant differences were not of clinical relevance as defined by a proportional difference of 10 percent. Findings of this study show that a vast majority of pregnant women are obtaining HIV screenings but not syphilis screenings during first antenatal visit. Provision of antenatal HIV and syphilis screening at first visit is only weakly related to patient level factors.

Objectives: This prospective cohort study examines the clinical effectiveness of electronic medical record clinical decision support (EMR CDS) for opioid prescribing., Methods: Data analysis included primary care patients with chronic opioid therapy for noncancer pain seen within an integrated health delivery system in Louisiana between January 2017 and October 2018. EMR CDS incorporated an opioid health maintenance tool to display the status of risk mitigation, and the medication order embedded the morphine equivalent daily dose (MEDD) calculator and a hyperlink to the Louisiana pharmacy drug monitoring program. Outcome measures included change in the average MEDD and rates of opioid risk mitigation, hospitalization, and emergency department use., Results: Among 14 221 patients, 9% had prescriptions with an average MEDD ≥90 mg. There were no significant changes in MEDD after EMR CDS implementation. Increasing age, Charlson Comorbidity Index score, female sex, black non-Hispanic race, non-opioid pain medication co-prescriptions, and specialty referrals were associated with a lower odds of MEDD ≥90 (high-dose threshold). Medicare or self-pay, substance abuse history, and pain agreements were associated with increased odds of prescribing above this high-dose threshold. After incorporation of EMR CDS, patients had higher rates of urine drug screens (17% vs 7%) and naloxone prescriptions (3% vs 1%, all P < .001). In addition, specialty referrals to physical or occupational therapy, orthopedics, neurology, and psychiatry or psychology increased in the postintervention period. Although emergency department use decreased (rate ratio 0.92; 95% confidence interval 0.89-0.95), hospitalization rates did not change., Conclusions: EMR CDS improved adherence to opioid risk mitigation strategies. Further research examining which practice redesign interventions effectively reduce high-dose opioid prescribing is needed., (Copyright © 2019 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Probiotics are increasingly used for diarrhea, but studies under the Food and Drug Administration and Investigational New Drug program are few. We conducted a phase-one placebo-controlled study of Lactobacillus reuteri DSM 17938 under Investigational New Drug program in 60 children 2-5 years of age (41 L. reuteri, 19 placebos) in a resource-constrained community in Peru. No differences in objective data on adverse events were noted, although some differences based on subjective parental reports for fever and diarrhea were seen.

Objective: The endogenous estrogen 17β-estradiol (E2) promotes metabolic homeostasis in premenopausal women. In a mouse model of post-menopausal metabolic syndrome, we reported that estrogens increased energy expenditure, thus preventing estrogen deficiency-induced adiposity. Estrogens' prevention of fat accumulation was associated with increased serum concentrations of fibroblast growth factor 21 (FGF21), suggesting that FGF21 participates in estrogens' promotion of energy expenditure., Methods: We studied the effect of E2 on FGF21 production and the role of FGF21 in E2 stimulation of energy expenditure and prevention of adiposity, using female estrogen receptor (ER)- and FGF21-deficient mice fed a normal chow and a cohort of ovariectomized women from the French E3N prospective cohort study., Results: E2 acting on the hepatocyte ERα increases hepatic expression and production of FGF21 in female mice. In vivo activation of ERα increases the transcription of Fgf21 via an estrogen response element outside the promoter of Fgf21. Treatment with E2 increases oxygen consumption and energy expenditure and prevents whole body fat accumulation in ovariectomized female WT mice. The effect of E2 on energy expenditure is not observed in FGF21-deficient mice. While E2 treatment still prevents fat accumulation in FGF21-deficient mice, this effect is decreased compared to WT mice. In an observational cohort of ovariectomized women, E2 treatment was associated with lower serum FGF21 concentrations, which may reflect a healthier metabolic profile., Conclusions: In female mice, E2 action on the hepatocyte ERα increases Fgf21 transcription and FGF21 production, thus promoting energy expenditure and partially decreasing fat accumulation., (Copyright © 2019. Published by Elsevier GmbH.)

Background: The effects of atopic and nonatopic asthma phenotypes on asthma morbidity are unclear. Moreover, asthma morbidity in patients without atopy might be mediated by immunoglobulin E (IgE)., Objective: To determine differences in morbidity in patients with asthma with and without atopy in a population of inner-city adolescents with asthma and to assess the impact of total IgE (tIgE) in this population., Methods: Data were obtained from 546 inner-city adolescents in the Asthma Control Evaluation study. A positive skin prick test reaction to 14 aeroallergens and specific IgE to 5 aeroallergens determined atopic status. High (≥75th percentile) and low (≤25th percentile) tIgE levels were categorized. Asthma control (Asthma Control Test) and asthma severity (Composite Asthma Severity Index [CASI]) were measured at multiple time points over 1 year. Fractional exhaled nitric oxide (FeNO) and measurements of morbidity also were collected. Multivariable and repeated measures analyses modeled the relation between atopic status and morbidity., Results: Baseline CASI scores increased 0.90 point (P < .05) and FeNO increased 0.85 natural logarithmic unit (P < .001) in participants with vs without atopy. Repeated measures analyses showed consistent results. Participants without atopy and increased tIgE had FeNO 0.73 natural log unit higher (P < .01) than low tIgE and a nonsignificant increase in CASI. The CASI score and FeNO levels were higher for high than for low tIgE in participants with atopy., Conclusion: In this population, participants with atopic asthma had worse asthma severity and higher FeNO compared with those with nonatopic asthma, but no difference in control. In all participants, higher tIgE indicated worse severity and higher FeNO. In this population, asthma severity and FeNO might be mediated by IgE in the 2 asthma phenotypes., (Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Quadratic inference functions (QIFs) and estimating equations using the conjugate gradient method (CGM) for fitting marginal models to longitudinal data show appealing features in improving the efficiency without making assumptions on the correlation structure. However, our simulation study shows that both methods produce biased and inefficient estimates of regression parameters when time-dependent covariates are present. In this paper, we extend both the QIF and CGM methods for fitting marginal models to longitudinal data with time-dependent covariates. The idea is to restrict the moment conditions to the ones that are only valid to certain types of time-dependent covariates. Our simulations show that efficiency on estimating regression parameters is achieved using modified approaches. Furthermore, we apply the modified approach to anthropometric screening data to evaluate the association between body mass index and morbidity in children in the Philippines., (Copyright © 2014 John Wiley & Sons, Ltd.)

In 2000, the Agency for Toxic Substances and Disease Registry (ATSDR; Atlanta, GA, USA) investigated lung disease in those exposed to the tremolite-contaminated vermiculite mine in Libby, MT, USA. Previously unreported spirometric results are presented here in relation to exposure and radiographic findings. 4,524 study participants were assigned to one of seven mutually exclusive exposure categories. Associations among radiographic findings, spirometric results and exposure were investigated, along with the effect of a reduction in exposure potential when production was moved to a wet process mill in the mid 1970s. Spirometry data for the total population by smoking status and age were within the normal range. Prevalence of pleural plaque increased with age, but was lowest in the environmentally exposed group (0.42-12.74%) and greatest in the W.R. Grace & Co. mineworkers (20-45.68%). For males, there was a significant (4.5%) effect of pleural plaques on forced vital capacity. For W.R. Grace & Co. workers and household contacts, a reduction in plaque (0.11 versus 1.64%) and in diffuse pleural thickening or costophrenic angle obliteration (1.94 and 0.13%) was noted for those exposed after 1976. These analyses do not support a clinically important reduction in spirometry of this cohort. The 1976 reductions in exposure have led to decrease in radiographic changes.

The potential of chronic or acute irritant gas exposures to cause asthma or a variant condition, reactive airways dysfunction syndrome (RADS) was investigated by observing asthma incidence in a large working population, using person-years at risk (P-YR) to compute relative rates (RR). Health data came from employee examinations at 62 pulp and paper plants. The 39122 workers who denied asthma beginning before the observation period included: 19326 denying irritant exposures, with no gassing exposures; 19349 with self-reported irritant exposures, and no gassing; and 447 with documented gassings. Asthma was defined as self-reported asthma beginning after the start of observation. P-YR accrued from September 29, 1986, for the nonexposed and exposed workers, and from date of first gassing for gassed workers, and ended with disease onset in any who developed asthma. RR of asthma with 95% confidence intervals (CI95) were calculated for the exposed and gassed groups, relative to the nonexposed. Exposed (nongassed) workers had an elevated asthma rate, RR=1.48, CI95=1.17-1.86, after adjustment for effects of gender and number of examinations. The rate in gassed workers was not significantly elevated: RR=1.95, CI95=0.75-5.08. Of the five asthma cases occurring after gassings, none conformed to diagnostic criteria for RADS. Chronic exposures were associated with increased rate of asthma onset, which must be interpreted with caution because self-reported data defined both exposure category and disease. Documented gassings were not associated with significantly increased rate, and none of 447 gassed persons developed RADS.

Objective: To derive a method of taking into account the effects of obstruction on the FVC, allowing more accurate assessment of other negative ("restrictive") influences., Design: In 656 subjects with airways obstruction, defined as FEV1/FVC of 0.70 or less, regression of FVC was expressed as percentage of predicted value (FVC %PRED) on potential explanatory variables, including FEV1/FVC. The resulting equation was used to adjust FVC %PRED in 530 other obstructed men, to test whether the adjustment resulted in a different relationship of FVC %PRED to body weight., Setting: A large occupational respiratory surveillance program utilizing rigorously quality-assured and standardized spirometry., Subjects: The study included 5,188 men aged 45 to 65 years who denied fibrogenic dust exposures, including 656 with airways obstruction., Results: There was a significant (p < 0.0001) linear relationship between more severe obstruction (lower FEV1/FVC) and lower FVC %PRED. Depending on which of several predictive equations is used, obstruction explains 15 to 17% of variability in FVC %PRED over the entire range of severity of obstruction. Adjusting for obstruction in the separate group of 530 subjects showed a significantly larger effect of body weight on FVC %PRED., Conclusion: A simple equation can be used to discount the negative effects of obstruction on FVC. This allows more accurate clinical interpretation and can be useful in the analysis of epidemiologic data.

High-pass resolution perimetry, or the "ring test," is a recently developed type of acuity perimetry. To determine its test-retest variability, we studied 10 normals and 10 patients with idiopathic intracranial hypertension (IIH) by testing both eyes four separate times. There was no increase in variability from the center out to 21 degrees of visual field eccentricity. However, there was a significant increase from 22 degrees to 29 degrees in both normals and IIH patients. Unlike light sensitivity threshold automated perimetry, with an increase in threshold level there was no significant increase in variability in either normals or patients. This may be because of the test's method, which thresholds by target size rather than intensity. As expected, there was a large intersubject variability in the patients, with the visual fields being significantly disturbed by analysis of total field, quadrants, concentric rings, and anatomic nerve fiber bundle regions. Surprisingly, there was no significant difference in the total within subject variability of normals and patients. Because with the ring test there is no increase in variability with an increase in threshold, this method of perimetry may have great utility for following patients with disturbed visual fields. The ring test appears to have advantages that promote low test-retest variability.

To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS)

Eight-five patients receiving cytosine arabinoside and daunorubicin as induction therapy of acute myelogenous leukemia were randomly assigned to receive lithium carbonate 300 mg t.i.d. or no lithium. Treatment groups were similar with respect to age, gender, baseline granulocyte counts, and patients who were febrile at presentation. Granulocyte nadirs below 100/cu mm were observed in nearly all patients. The duration of neutropenia was not significantly shorter for patients receiving lithium (23.3 days) than for controls (24.1 days), p = 0.18. The incidence of fever and infection were similar in the two groups. The incidence of complete remission was significantly lower in patients receiving lithium, 75% vs, 49%, p = 0.012, although no physiologic explanation attributable to lithium could be established. Toxicity was minimal, although lithium was discontinued in 44% of patients over the age of 50. The administration of lithium does not have apparent clinical efficacy as an adjuvant to therapy in acute myelogenous leukemia.

During the past 10 years, the Southeastern Cancer Study Group (SECSG) has been engaged in one major adjuvant study and three major advanced disease studies for patients with adenocarcinoma of the breast. The adjuvant study is demonstrating that six months of adjuvant CMF is the therapeutic equivalent of 12 months and that post-operative irradiation is of no added therapeutic benefit. In patients with advanced disease, a low dose 5 drug combination of CMFVP induces more objective responses than single agent 5FU, but improves survival only for those patients with liver metastases when compared to the sequential use of the same 5 single agents. The three drug combination, CAF, utilizing doxorubicin, induces more objective responses than low dose CMFVP, but it does not improve overall survival. The subsets of patients with bone-only metastases, with local chest wall recurrence and with nodular lung metastases benefit from CAF in terms of a longer duration of disease control and longer duration of unmaintained remission, but have only a marginal improvement in survival. The addition of a phase active combination, CAMELEON, (i.e., sequentially alternating therapy) to CAF has not improved the duration of disease control and survival for patients with liver metastases, lymphangitic and nodular lung metastases compared to CAF. Aggressive combination chemotherapeutic approaches to patients with advanced disease provide better and longer disease and tumor control but only marginal improvements in overall survival. Adding additional agents to a maximally tolerable regimen has not improved the therapeutic outcome.

The Southeastern Cancer Study Group, in a prospectively randomized study involving patients with advanced breast cancer, has compared a low dose intermittently administered five-drug regimen including cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone (CMFVP) with an aggressively administered three-drug regimen including cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF). CAF induced more responses and more complete responses and a longer duration of disease control. However, only a marginal difference was demonstrated in overall survival between the two regimens (p = less than 0.10). Patients with a good risk pattern of metastases, i.e. those with nodular local chest wall recurrence, nodular pulmonary metastases, or bone-only metastases were more likely to achieve a response and survive longer than those with a poor risk pattern, i.e. lymphangitic pulmonary metastases, pleural effusion with chest wall ulceration, or widespread metastases, including hepatic. All of the differences between the two regimens were noted in the good risk pattern groups. CAF provided no additional benefit to patients presenting with poor risk patterns of metastases. Adriamycin-containing combinations may achieve a greater degree of tumor cell kill in certain subsets of patients with advanced breast cancer, but this provides only a marginal increase in survival.

We postulate that fibrocystic changes in the female breast are the end result of a series of biochemical events initiated by the mast cell degranulation products histamine and heparin. Two mechanisms are proposed which could lead to mast cell degranulation in breast tissue. First, low progesterone levels lead to decreased intracellular cAMP levels in mast cells which enhance mast cell degranulation. Second, low progesterone levels lead to increased solubilization of breast collagen during tissue turnover. Susceptible individuals may undergo an allergic reaction to soluble collagen resulting in further mast cell degranulation. The degranulation products histamine and heparin may stimulate increased stromal proliferation and vascularization respectively. We provide evidence for the occurrence of histamine release by demonstrating an increased incidence of allergic symptoms in white women with fibrocystic breast changes.