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This secondary analysis studied 50 transcripts of women who shared day-to-day experiences of lower urinary tract symptoms (LUTS) and characterized temporal (time-associated) features of living with LUTS. Findings revealed two overarching, time-associated themes: The Complexity of LUTS and The Quest for Empowerment over LUTS. Findings suggest the temporal burden of LUTS is the accumulated impact of symptoms and symptom management on women's daily lives within multiple contexts across the life course. Increasing nurses' knowledge of the temporal context of LUTS may heighten awareness and improve symptom detection and management. Key Words Women's health, lower urinary tract symptoms, qualitative research, chronic illness, bladder, prevention., Research Summary Introduction Research on women's lived experience of LUTS has illuminated the severity of the symptom burden and its impact on quality of life. However, there remains a need [...]

Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV,) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV, values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV, 2.75 L) to create the individualized prediction equations. There was significant between individual variability in the rate of FEV, decline, with the interval for the annual rate of decline that contained 95% of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD. Trial registration: Lung Health Study--ClinicalTrials.gov, no. NCT00000568; Pan-Canadian Early Detection of Lung Cancer Study--ClinicalTrials.gov, no. NCT00751660, Chronic obstructive pulmonary disease (COPD) is a global health burden that affects 300 million people worldwide (1) resulting in more than 3 million deaths annually. (1,2) Although COPD is defined [...]

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Background: Randomized clinical trials have not yet demonstrated the mortality benefit of smoking cessation. Objective: To assess the long-term effect on mortality of a randomly applied smoking cessation program. Design: The Lung Health Study was a randomized clinical trial of smoking cessation. Special intervention participants received the smoking intervention program and were compared with usual care participants. Vital status was followed up to 14.5 years. Setting: 10 clinical centers in the United States and Canada. Patients: 5887 middle-aged volunteers with asymptomatic airway obstruction. Measurements: All-cause mortality and mortality due to cardiovascular disease, lung cancer, and other respiratory disease. Intervention: The intervention was a 10-week smoking cessation program that included a strong physician message and 12 group sessions using behavior modification and nicotine gum, plus either ipratropium or a placebo inhaler. Results: At 5 years, 21.7% of special intervention participants had stopped smoking since study entry compared with 5.4% of usual care participants. After up to 14.5 years of follow-up, 731 patients died: 33% of lung cancer, 22% of cardiovascular disease, 7.8% of respiratory disease other than cancer, and 2.3% of unknown causes. All-cause mortality was significantly lower in the special intervention group than in the usual care group (8.83 per 1000 person-years vs. 10.38 per 1000 person-years; P = 0.03). The hazard ratio for mortality in the usual care group compared with the special intervention group was 1.18 (95% CI, 1.02 to 1.37). Differences in death rates for both lung cancer and cardiovascular disease were greater when death rates were analyzed by smoking habit. Limitations: Results apply only to individuals with airway obstruction. Conclusion: Smoking cessation intervention programs can have a substantial effect on subsequent mortality, even when successful in a minority of participants.

Background: The Lung Health Study (LHS), a 5-year, randomized, prospective clinical trial, studied the effects of smoking intervention and therapy with inhaled antieholinerglc bronchndilators on [FEV.sub.1] in participants who were [...]

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Study objective: To assess cardiovascular conditions and other side effects associated with the use of nicotine polacrilex (NP), 2 mg. Design: A multicentered randomized control trial of early intervention for [...]

The Chronic Obstructive Pulmonary Disease Early Intervention Trial, or Lung Health Study, is a multicenter randomized clinical trial sponsored by the Division of Lung Diseases of the National Heart, Lung, [...]

Chronic obstructive pulmonary disease (COPD) is an increasing and significant health problem in the United States. Standardization of detection methods and the improvement of prevention techniques are principal efforts of the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). Cigarette smoking is recognized as the single most important cause of COPD. The Lung Health Study (LHS) is a clinical trial that was initiated by the NHBLI to determine whether the use of a prescribed inhaled bronchodilator and a smoking intervention program can reduce the annual decline (over 5 years) of lung function in cigarette smokers who have mild to moderate airflow limitation. In this study, the status of lung function was measured as the forced expiratory volume or FEV1. To validate these results the quality control of the method used for testing FEV1, known as spirometry, was evaluated. Current cigarette smokers, aged 35 to 60 years, were solicited from 10 clinical centers. Ten cigarettes on any day in the previous month qualified individuals for participation. After three screening sessions, a cohort of 5,887 subjects were selected. Two-thirds were randomly assigned to a special intervention (SI) group, and the remainder formed a usual care (UC) group. The SI group was further subdivided into groups who used either a bronchodilator or a placebo. Subjects and technicians were instructed in the careful performance of spirometric testing. To be able to detect the smallest change in the results, the subjects' preparation, acceptance of the procedure, and ability to reproduce the same results, technician training and monitoring, equipment maintenance and calibration, and the statistical processing of the results were carefully managed throughout the study. The findings demonstrated that the quality control of the spirometry program was highly successful. (Consumer Summary produced by Reliance Medical Information, Inc.)

Inflammation in areas of fibrosis (i-IFTA) in posttransplant biopsies is part of the diagnostic criteria for chronic active TCMR (CA TCMR -- i-IFTA ≥ 2, ti ≥ 2, t ≥ 2). We evaluated i-IFTA and CA TCMR in the DeKAF indication biopsy cohorts: prospective (n = 585, mean time to biopsy = 1.7 years); cross-sectional (n = 458, mean time to biopsy = 7.8 years). Grouped by i-IFTA scores, the 3-year postbiopsy DC-GS is similar across cohorts. Although a previous acute rejection episode (AR) was more common in those with i-IFTA on biopsy, the majority of those with i-IFTA had not had previous AR. There was no association between type of previous AR (AMR, TCMR) and presence of i-IFTA. In both cohorts, i-IFTA was associated with markers of both cellular (increased Banff i, t, ti) and humoral (increased g, ptc, C4d, DSA) activity. Biopsies with i-IFTA = 1 and i-IFTA ≥ 2 with concurrent t ≥ 2 and ti ≥ 2 had similar DC-GS. These results suggest that (a) i-IFTA≥1 should be considered a threshold for diagnoses incorporating i-IFTA, ti, and t; (b) given that i-IFTA ≥ 2,t ≥ 2, ti ≥ 2 can occur in the absence of preceding TCMR and that the component histologic scores (i-IFTA,t,ti) each indicate an acute change (albeit i-IFTA on the nonspecific background of IFTA), the diagnostic category “CA TCMR” should be reconsidered.

ABSTRACTPurpose: Oculocutaneous albinism type 1A (OCA1A), with lifelong absent melanin in skin, hair, and eyes, is the most severe type of albinism with greatest ametropia and poorest vision. We evaluated the relationship between age when spectacles were begun and visual outcome, in addition to status of refraction, in OCA1A.Methods: After IRB approval, a retrospective review of 70 consecutive charts of patients with OCA1A identified 24 fitting inclusion criterion of BCVA recorded at age 10–12 years. Exclusion criteria were those with other vision-threatening diagnoses and patients seen for a single visit.We recorded sex, age at beginning glasses, and refraction and BCVA at age 10–12 and most recent visit. Data were arbitrarily grouped by those initiating glasses at ≤ age 12 months and > age 12 months.Results: Regression analysis showed a larger degree of astigmatism was weakly associated with worse vision at age 10–12 years. A weakly positive relationship was found between poorer BCVA at last visit and older age at which glasses were initiated. All receiving glasses by age 1 and only half receiving glasses when older had improved visual acuity from age 10–12 years to last follow up.Conclusion: Additional study of a larger sample of this rare disorder is needed to determine if early glasses wear improves later BCVA.

Among patients with out-of-hospital cardiac arrest (OHCA) and ventricular fibrillation, more than half present with refractory ventricular fibrillation unresponsive to initial standard advanced cardiac life support (ACLS) treatment. We did the first randomised clinical trial in the USA of extracorporeal membrane oxygenation (ECMO)-facilitated resuscitation versus standard ACLS treatment in patients with OHCA and refractory ventricular fibrillation.

Hypogammaglobulinemia (serum IgG levels < 7.0 g/L) has been associated with increased risk of COPD exacerbations but has not yet been shown to predict hospitalizations.

Inflammation in areas of fibrosis (i‐IFTA) in posttransplant biopsy specimens has been associated with decreased death‐censored graft survival (DC‐GS). Additionally, an i‐IFTA score ≥ 2 is part of the diagnostic criteria for chronic active TCMR (CA TCMR). We examined the impact of i‐IFTA and t‐IFTA (tubulitis in areas of atrophy) in the first biopsy for cause after 90 days posttransplant (n = 598); mean (SD) 1.7 ± 1.4 years posttransplant. I‐IFTA, present in 196 biopsy specimens, was strongly correlated with t‐IFTA, and Banff i. Of the 196, 37 (18.9%) had a previous acute rejection episode; 96 (49%) had concurrent i score = 0. Unlike previous studies, i‐IFTA = 1 (vs 0) was associated with worse 3‐year DC‐GS: (i‐IFTA = 0, 81.7%, [95% CI 77.7 to 85.9%]); i‐IFTA = 1, 68.1%, [95% CI 59.7 to 77.6%]; i‐IFTA = 2, 56.1%, [95% CI 43.2 to 72.8%], i‐IFTA = 3, 48.5%, [95% CI 31.8 to 74.0%]). The association of i‐IFTA with decreased DC‐GS remained significant when adjusted for serum creatinine at the time of the biopsy, Banff i, ci and ct, C4d and DSA. T‐IFTA was similarly associated with decreased DC‐GS. Of these indication biopsies, those with i‐IFTA ≥ 2, without meeting other criteria for CA TCMR had similar postbiopsy DC‐GS as those with CA TCMR. Those with i‐IFTA = 1 and t ≥ 2, ti ≥ 2 had postbiopsy DC‐GS similar to CA TCMR. Biopsies with i‐IFTA = 1 had similar survival as CA TCMR when biopsy specimens also met Banff criteria for TCMR and/or AMR. Studies of i‐IFTA and t‐IFTA in additional cohorts, integrating analyses of Banff scores meeting criteria for other Banff diagnoses, are needed. This study of indication biopsies examines i‐IFTA scores and their association with subsequent graft outcomes.

Background:Humanitarian medical missions attempt to lessen the burden of limited access to cardiac surgery in low- and middle-income countries. While organizations express difficulties obtaining follow-up information, there is currently little evidence to support the various assumptions for lack of data. This study examines the factors influencing long-term patient follow-ups on repeated short-term cardiac surgery missions across nine countries. Methods:A retrospective analysis of CardioStart International'sdatabase (RedCap) was conducted to investigate demographic, socioeconomic, and surgical factors associated with follow-ups. Results:A total of 550 pediatric (50%) and adult (50%) cardiac surgery patients displayed a follow-up rate of 14.7%, with no significant difference between populations (P= 1). Mean follow-up time was 1.5 years postoperative. Countries were highly variable, with Dominican Republic and Vietnam showing follow-up rates of 30.4% and 43.2%, respectively, while Brazil, Nepal, and Tanzania had no follow-ups (P< 0.0001). The 11 surrogate factors for socioeconomic status, including home amenities and technology access, were predominantly insignificant, with the exception of phone access showing an unexpectedly decreased follow-up rate (11.6%, P= 0.006). Surgical intervention was a significant factor (P= 0.009). No adult cardiac surgery trends were noted; however, congenital cases demonstrated increased follow-ups in patients with higher Risk Adjusted Congenital Heart Surgery scores, with ventricular septal defects (32.5%) exceeding atrial septal defects (7.3%). Conclusions:Follow-ups correlate with mission factors, including location and types of intervention, more so than previously assumed socioeconomic and technological factors. Thus, certain missions may require more allocation of resources and adapted organizational policies to overcome site-specific barriers to follow-up.

Tacrolimus trough and dose requirements vary dramatically between individuals of European and African American ancestry. These differences are less well described in other populations. We conducted an observational, prospective, multicenter study from which 2595 kidney transplant recipients of European, African, Native American, and Asian ancestry were studied for tacrolimus trough, doses, and genetic determinants of metabolism. We studied the well‐known variants and conducted a CYP3A4/5 gene‐wide analysis to identify new variants. Daily doses, and dose‐normalized troughs were significantly different between the four groups (P< .001). CYP3A5*3(rs776746) was associated with higher dose‐normalized tacrolimus troughs in all groups but occurred at different allele frequencies and had differing effect sizes. The CYP3A5*6(rs10264272) and *7(rs413003343) variants were only present in African Americans. CYP3A4*22(rs35599367) was not found in any of the Asian ancestry samples. We identified seven suggestive variants in the CYP3A4/5 genes associated with dose‐normalized troughs in Native Americans (P= 1.1 × 10−5‐8.8 × 10−6) and one suggestive variant in Asian Americans (P= 5.6 × 10−6). Tacrolimus daily doses and dose‐normalized troughs vary significantly among different ancestry groups. We identified potential new variants important in Asians and Native Americans. Studies with larger populations should be conducted to assess the importance of the identified suggestive variants. Tacrolimus doses and troughs vary between kidney transplant recipients of different ancestries, which is possibly related to new variants identified in recipients of Native American and Asian ancestry.

Genetic variation across the human leukocyte antigen loci is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFRat different time‐points, out to 5 years posttransplantation. We conducted GWASmeta‐analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRScalculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFRat 1‐year posttransplant. Thirty‐two percent of the variability in eGFRat 1‐year posttransplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFRposttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRSbeing a significant predictor of eGFRposttransplant, the effect size of common genetic factors is limited compared to clinical variables. Polygenic risk score of nontransplant eGFR is a significant predictor of eGFR at 1 year posttransplant, but the effect size contributed by these common genetic variants is limited compared to that of clinical variables.

The DeKAF study was developed to better understand the causes of late allograft loss. Preliminary findings from the DeKAF cross-sectional cohort (with follow-up < 20 months) have been published. Herein, we present long-term outcomes in those recipients (mean follow-up ± SD, 6.6 ± 0.7 years). Eligibility included being transplanted prior to October 1, 2005; serum creatinine ≤ 2.0 mg/dL on January 1, 2006; and subsequently developing new-onset graft dysfunction leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Histologic findings and DSA were studied in relation to postbiopsy outcomes. Long-term follow-up confirms and expands the preliminary results of each of 3 studies: (1) increasing inflammation in area of atrophy (irrespective of inflammation in nonscarred areas [Banff i]) was associated with increasingly worse postbiopsy death-censored graft survival; (2) hierarchical analysis based on Banff scores defined clusters (entities) that differed in long-term death-censored graft survival; and (3) C4d−/DSA− recipients had significantly better (and C4d+/DSA+ worse) death-censored graft survival than other groups. C4d+/DSA- and C4d−/DSA+ had similar intermediate death-censored graft survival. Clinical and histologic findings at the time of new-onset graft dysfunction define high- vs low-risk groups for long-term death-censored graft survival, even years posttransplant. These findings can help differentiate groups for potential intervention studies.

Perforated peptic ulcers are a surgical emergency that can be repaired using either laparoscopic surgery (LS) or open surgery (OS). No consensus has been reached on the comparative outcomes and safety of each approach. Using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, we conducted a 12-year retrospective review (2005–2016) and identified 6260 adult patients who underwent either LS (n= 616) or OS (n= 5644) to repair perforated peptic ulcers. To mitigate selection bias and adjust for the inherent heterogeneity between groups, we used propensity-score matching with a case (LS):control (OS) ratio of 1:3. We then compared intraoperative outcomes such as operative time, and 30-day postoperative outcomes including infectious and non-infectious complications, and mortality. Propensity-score matching created a total of 2462 matched pairs (616 in the LS group, 1846 in the OS group). Univariate analysis demonstrated successful matching of patient characteristics and baseline clinical variables. We found that OS was associated with a shorter operative time (67.0 ± 28.6 min, OS versus 86.9 ± 57.5 min, LS; P< 0.001) but a longer hospital stay (8.6 ± 6.2 days, OS versus 7.8 ± 5.9 days, LS; P= 0.001). LS was associated with a lower rate of superficial surgical site infections (1.5%, LS versus 4.2%, OS; P= 0.032), wound dehiscence (0.3%, LS versus 1.6%, OS; P= 0.030), and mortality (3.2%, LS versus 5.4%, OS; P= 0.009). Fewer than 10% of patients with perforated peptic ulcers underwent LS, which was associated with reduced length of stay, lower rate of superficial surgical site infections, wound dehiscence, and mortality. Given our results, a greater emphasis should be provided to a minimally invasive approach for the surgical repair of perforated peptic ulcers.

Background: Previous reports have suggested that prophylactic indomethacin decreases cerebral blood flow and may play a role in the development of ischemic brain injury and developmental handicaps. Objective: To assess the neurodevelopmental outcome of subjects at 36 months' corrected age (CA) who, as low-birth-weight infants, received prophylactic low-dose indomethacin within the first 24 hours of life to prevent patent ductus arteriosus. Setting: Newborn intensive care nursery and outpatient follow-up clinic at Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minn. Design: Ninety infants with birth weights of 600 to 1250 g were entered into a prospective, randomized, controlled trial to receive either prophylactic indomethacin, 0.1 mg/kg, or placebo in the first 24 hours and again every 24 hours for 6 doses to prevent patent ductus arteriosus. Nonresponders were treated with standard therapeutic indomethacin or ligation. Neurodevelopmental assessment at approximately 36 months' CA included medical and developmental histories, physical examinations, and developmental testing using the Bayley II Scales of Infant Development on subjects up to 42 months' CA. Subjects were classified as (1) normal, (2) mildly to moderately abnormal, or (3) severely impaired. Results: Forty-two (98%) of 43 subjects who received prophylactic indomethacin survived compared with 46 (98%) of 47 who received placebo. Sixty-six (75%) of 88 survivors were seen for neurodevelopmental assessment at 36 months' CA. This group included 29 (69%) of 42 who received prophylactic indomethacin and 37 (80%) of 46 who received placebo. Twenty-three (79%) of 29 infants in the prophylactic indomethacin group had normal neurodevelopmental assessments at 36 months' CA compared with 26 (70%) of 37 placebo-treated subjects (P=.68). Of 4 significantly impaired subjects treated with prophylactic indomethacin, 1 had spastic diplegia; 1, spastic quadriplegia; 1, cognitive delay; and 1, significant motor delay. Of 8 significantly impaired placebo-treated subjects, 7 had spastic diplegia; 1, microcephaly. Conclusion: The use of prophylactic low-dose indomethacin when initiated in the first 24 hours of life in low-birth-weight infants to prevent patent ductus arteriosus is not associated with adverse neurodevelopmental outcome at 36 months' CA. Arch Pediatr Adolesc Med. 2000;154:598-602

Impact on Gas Exchange, Lung Compliance, and End-Expiratory Lung Volume Study objectives: To determine the effects of different levels of positive end-expiratory pressure (PEEP) during partial liquid ventilation (PLV) on [...]

COPD is an age-related disease. The role of cellular senescence in COPD has not been fully elucidated. This study examined the relationship between telomere length of peripheral blood leukocytes and clinical outcomes, including health status, rate of exacerbations, and risk of mortality in individuals with COPD.

Purpose:To evaluate change in best corrected visual acuity (BCVA) during the second decade of life and the effects of albinism type and extraocular muscle surgery on BCVA in children with albinism.Methods:In this retrospective longitudinal study, 41 patients with albinism with clinic visits recording binocular BCVA at least once between the ages of 10 and 13 years (visit A) and again between the ages of 17 and 20 years (visit B) were included. Type of albinism, age at each visit, and interval eye muscle surgeries were recorded for each patient.Results:Forty (98%) patients showed BCVA improvement or stability between visits A and B. There was no significant effect of interval extraocular muscle surgery on BCVA. Those carrying either a clinically presumed or moleculary confirmed diagnosis of oculocutaneous albinism types 1B and 2 had the best visual outcomes, consistent with previous studies.Conclusions:In the majority of patients with albinism, significant improvement in BCVA occurs during the second decade of life. Extraocular muscle surgery was not a significant factor in BCVA improvement in albinism. Overall, the assessments support the finding of improvement of visual acuity in children with albinism at earlier ages and provide new information beneficial in predicting visual outcomes in the second decade of life.[[J Pediatr Ophthalmol Strabismus. 2018;55(4):254–259.]

Beyond the first posttransplant year, 3% of kidney transplants fail annually. In a prospective, multicenter cohort study, we tested the relative impact of early versus late events on risk of long-term death-censored graft failure (DCGF). In grafts surviving at least 90 days, early events (acute rejection [AR] and delayed graft function [DGF] before day 90) were recorded; serum creatinine (Cr) at day 90 was defined as baseline. Thereafter, a 25% rise in serum Cr or new-onset proteinuria triggered graft biopsy (index biopsy, IBx), allowing comparison of risk of DCGF associated with early events (AR, DGF, baseline serum Cr >2.0 mg/dL) to that associated with later events (IBx). Among 3678 patients followed for 4.7 ± 1.9 years, 753 (20%) had IBx at a median of 15.3 months posttransplant. Early AR (HR = 1.77, P< .001) and elevated Cr at Day 90 (HR = 2.56, P< .0001) were associated with increased risk of DCGF; however, later-onset dysfunction requiring IBx had far greater impact (HR = 13.8, P< .0001). At 90 days, neither clinical characteristics nor early events distinguished those who subsequently did or did not undergo IBx or suffer DCGF. To improve long-term kidney allograft survival, management paradigms should promote prompt diagnosis and treatment of both early and later events.

In deep brain stimulation (DBS) of the subthalamic nucleus for treatment of Parkinson's Disease, a commonly encountered stimulation side effect is involuntary muscle contractions from spread of electrical current to cortico‐spinal and cortico‐bulbar fibers in the internal capsule. During surgery, a variety of techniques, including microelectrode recording (MER), are used to avoid positioning the DBS electrode too close to the internal capsule. At some centers, MER includes stimulating through the microelectrode (microstimulation). To assess if intraoperative microstimulation can help avoid positioning the DBS electrode too close to the internal capsule. From clinical records, we compiled microelectrode and DBS‐electrode locations, microstimulation effect thresholds and DBS side effect thresholds. We found that capsular macrostimulation thresholds were significantly lower in cases where capsular microstimulation effects were observed. In addition, we found that lower‐threshold for microstimulation‐induced involuntary muscle contractions from a given DBS electrode contact predicts a lower threshold for involuntary muscle contractions as a side effect of stimulation with that contact. Specifically, our results suggest that capsular macrostimulation thresholds below 2V are avoided when the product of microstimulation threshold (in µA) and distance (in mm) is greater than 500. intraoperative microstimulation can help avoid positioning the DBS electrode too close to the internal capsule.

Observational data have been conflicted regarding the potential role of HIV antiretroviral therapy (ART) as a causative factor for, or protective factor against, COPD. We therefore aimed to investigate the effect of immediate versus deferred ART on decline in lung function in HIV-positive individuals.

COPD is a chronic inflammatory disorder associated with oxidative stress. Serum bilirubin has potent antioxidant actions, and higher concentrations have been shown to protect against oxidative stress. The relation between serum bilirubin and COPD progression is unknown.

Conventional treatments for patients with type 2 diabetes are often inadequate. We aimed to assess outcomes of diabetes control and treatment risks 2 years after adding Roux-en-Y gastric bypass to intensive lifestyle and medical management.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease of the middle aged and elderly with a prevalence of one million persons worldwide. The fibrosis spreads from affected alveoli into contiguous alveoli, creating a reticular network that leads to death by asphyxiation. Lung fibroblasts from patients with IPF have phenotypic hallmarks, distinguishing them from their normal counterparts: pathologically activated Akt signaling axis, increased collagen and α-smooth muscle actin expression, distinct gene expression profile, and ability to form fibrotic lesions in model organisms. Despite the centrality of these fibroblasts in disease pathogenesis, their origin remains uncertain. Here, we report the identification of cells in the lungs of patients with IPF with the properties of mesenchymal progenitors. In contrast to progenitors isolated from nonfibrotic lungs, IPF mesenchymal progenitor cells produce daughter cells manifesting the full spectrum of IPF hallmarks, including the ability to form fibrotic lesions in zebrafish embryos and mouse lungs, and a transcriptional profile reflecting these properties. Morphological analysis of IPF lung tissue revealed that mesenchymal progenitor cells and cells with the characteristics of their progeny comprised the fibrotic reticulum. These data establish that the lungs of patients with IPF contain pathological mesenchymal progenitor cells that are cells of origin for fibrosis-mediating fibroblasts. These fibrogenic mesenchymal progenitors and their progeny represent an unexplored target for novel therapies to interdict fibrosis.

PURPOSE: To evaluate the effects of randomly assigning smokers who have early chronic obstructive pulmonary disease (COPD) to a smoking-cessation intervention on the symptoms of chronic cough, chronic phlegm production, wheezing and shortness of breath, and to determine the effects of quitting smoking on these symptoms. SUBJECTS AND METHODS: A total of 5,887 male and female smokers 35 to 60 years of age with early COPD [defined as a forced expiratory volume in the first second ([FEV.sub.1]) of 55% to 90% of predicted and [FEV.sub.1]/forced vital capacity (FVC) [is less than] 0.70] were enrolled in a 5-year clinical trial. Two-thirds of participants were randomly assigned to smoking-intervention groups and one-third to a usual-care group. The intervention groups attended 12 intensive smoking-cessation sessions that included behavior modification techniques and the use of nicotine chewing gum. One intervention group was treated with ipratropium bromide by inhaler; the other intervention group received placebo inhalers. The usual-care group was advised to stop smoking. All participants were followed annually. Smoking status was biochemically validated by salivary cotinine measurements or exhaled carbon monoxide values. RESULTS: Validated 5-year sustained smoking cessation occurred in 22% of participants in the intervention compared with only 5% of participants in the usual-care group. At the end of the study, the prevalence of each of the four symptoms in the two intervention groups was significantly less than in the usual-care group (P [is less than] 0.0001). For example, among participants who did not report cough at baseline, 15% of those in the intervention groups had cough at least 3 months during the year, compared with 23% of those in usual care. Sustained quitters had the lowest prevalence of all four symptoms, whereas continuous smokers had the greatest prevalence of these symptoms. Changes in symptoms occurred primarily in the first year after smoking cessation. Respiratory symptoms were associated with greater declines in [FEV.sub.1] during the study (P [is less than] 0.001). Ipratropium bromide had no long-term effects on respiratory symptoms. CONCLUSIONS: In this prospective randomized trial using an intention-to-treat analysis, smokers with early COPD who were assigned to a smoking-cessation intervention had fewer respiratory symptoms after 5 years of follow-up. Am J Med. 1999;106:410-416. [C] 1999 by Excerpta Medica, Inc.

Purpose. To describe the factors associated with interest of homeless former smokers in helping homeless smokers quit.Methods. A cross-sectional survey administered to an optimized convenience sample of homeless persons (n = 4570) at emergency shelters, transitional housing units, and open encampments in 80 cities across Minnesota. The in-person survey response rate was 90%.Analysis. Chi-square tests and t-tests for univariate analysis.Results. Of 4534 participants completing the smoking questions, 546 participants (12%) self-identified as former smokers, of which 59% expressed interest in helping homeless smokers quit. Significant predictors of reported interest in helping included racial/ethnic background (p < .05), number of people known who had quit smoking (p < .01), and receiving social services as an adult (p < .01).Conclusion. Homeless former smokers are a potential resource for peer support programs to promote smoking cessation among homeless current smokers.

COPD is a chronic inflammatory disorder with high risk of cardiovascular morbidity and mortality. Adiponectin is a hormone that has antiinflammatory, antidiabetic, and antiatherogenic activities. We investigated the relationship of serum adiponectin to health outcomes in COPD.

Background:There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1.

Abstract: The feeding and oviposition behavior of postdiapausal Eustenopus villosus (Boheman) on young and late stage buds, respectively of yellow starthistle, Centaurea solstitialis L., was documented in the laboratory and field. Postdiapausal adult feeding on young buds took over an hour to complete in most cases and was conducted by both sexes. Feeding bouts generally occurred in the sequence of explore, feeding, and budwalk. Oviposition included a feeding phase to prepare an oviposition cavity within the bud; thus, oviposition bouts included some of the same behavioral elements as postdiapausal feeding. The standard sequence of behavioral elements involved with oviposition included exploring, feeding, turning, ovipositing, and budwalking. The feeding element during the oviposition bout often lasted 2 h and was similar in the field and in the lab. Postdiapausal adult feeding on young capitula and stems, and larval feeding on developing ovaries and achenes, makes this weevil especially destructive on a per insect basis.

Correlated response data arise often in biomedical studies. The generalized estimation equation (GEE) approach is widely used in regression analysis for such data. However, there are few methods available to check the adequacy of regression models in GEE. In this paper, a graphical method is proposed based on Cook and Weisberg's marginal model plot. A bootstrap method is applied to obtain the reference band to assess statistical uncertainties in comparing two marginal mean functions. We also propose using the generalized additive model (GAM) in a similar fashion. The proposed two methods are easy to implement by taking advantage of existing smoothing and GAM softwares for independent data. The usefulness of the methodology is demonstrated through application to a correlated binary data set drawn from a clinical trial, the Lung Health Study. Copyright © 2001 John Wiley & Sons, Ltd.

Weextend Wei and Tanner's (1991) multiple imputation approach insemi-parametric linear regression for univariate censored datato clustered censored data. The main idea is to iterate the followingtwo steps: 1) using the data augmentation to impute for censoredfailure times; 2) fitting a linear model with imputed completedata, which takes into consideration of clustering among failuretimes. In particular, we propose using the generalized estimatingequations (GEE) or a linear mixed-effects model to implementthe second step. Through simulation studies our proposal comparesfavorably to the independence approach (Lee et al., 1993), whichignores the within-cluster correlation in estimating the regressioncoefficient. Our proposal is easy to implement by using existingsoftwares.

To compare the physiologic and pathologic effects of conventional ventilation (CV) and high-frequency ventilation (HFV) during partial liquid ventilation (PLV) with perflubron after surfactant treatment with the results of HFV plus surfactant in an animal lung-injury model created by saline lavage. We also studied the dose effects of perflubron during HFV.

Background.This study describes baseline and Year 1 predictors of abstinence from smoking for the 3523 intervention participants who had complete annual 5-year follow-up data in the Lung Health Study (LHS).

BackgroundIn laboratory research, nicotine administration is associated with increases in blood pressure. In epidemiologic research, however, the amount of reported cigarette smoking has no consistent relation with blood pressure. The objective of this study was to examine the relation of a nicotine metabolite (salivary cotinine) to systolic and diastolic blood pressure in current smokers being screened for entry to a clinical trial. Methods and ResultsData were obtained from 5164 middle-aged cigarette smokers during screening for the Lung Health Study. Multiple linear regression was used to examine the association of salivary cotinine and number of cigarettes smoked per day to systolic and diastolic blood pressure with age, body mass, years of education, alcohol intake, and recent caffeinated beverage use controlled in all analyses. Although smoking frequency was unrelated to blood pressure, salivary cotinine was related to greater systolic blood pressure in both men and women and greater diastolic blood pressure in men. ConclusionsThe association between salivary cotinine and blood pressure in these analyses suggests that long-term nicotine exposure may be related to modest elevations in blood pressure in cigarette smokers. (Am Heart J 1999;137:928-31.)

Summary: A prospective and randomized clinical trial of an inception cohort of diabetic kidney recipients to test the hypothesis that maximized metabolic control of diabetes prevents or delays diabetic nephropathy in the renal allografts was initiated approximately three years ago. Notwithstanding the fact that all our diabetic patients were on prednisone and therefore metabolically unstable, we achieved and maintained a clear difference between the standard control (group A) and the maximized control patients (group B). At 13 months of study, the mean fasting blood glucose mg% (A: 24222, B: 1309, p<0.001), nonfasting blood glucose (A: 27640, B: 13510, p<0.001), 24 hour urine glucose (A: 8516, B: 51, p<0.001), and glycosylated hemoglobin % (A: 130.9, B: 100.8, p<0.01) were all clearly and statistically significantly higher for the group A patients. These results show the feasibility of such a trial using the tools available today to treat diabetes.

The relationships between stressful life events and subsequent mortality and morbidity were determined prospectively over 6 years for 12,866 men participating in the Multiple Risk Factor Intervention Trial (MRFIT). Also evaluated was the impact of life events on cardiovascular outcomes for persons exhibiting and not exhibiting coronary prone (Type A) behavior. Subjects completed life events checklists at baseline and each of five annual visits. Participants were also administered the Jenkins Activity Survey measure of Type A behavior at baseline and a subsample of 3110 participants was categorized as to behavior type based on the structured interview assessment method. Cox proportional hazard analyses indicated that number of life events experienced during each of 6 years of follow-up was unrelated to risk in the subsequent year of CHD death or fatal plus nonfatal MI and was inversely related to total mortality. The impact of life events on cardiovascular risk did not differ by behavior type category.

The relation of self-selected leisure-time physical activity (LTPA) to first major coronary heart disease (CHD) events and overall mortality was studied in 12 138 middle-aged men participating in the Multiple Risk Factor Intervention Trial. Total LTPA over the preceding year was quantitated in mean minutes per day at baseline by questionnaire, with subjects classified into tertiles (low, moderate, and high) based on LTPA distribution. During seven years of follow-up, moderate LTPA was associated with 63% as many fatal CHD events and sudden deaths, and 70% as many total deaths as low LTPA (P&lt;.01). Mortality rates with high LTPA were similar to those in moderate LTPA; however, combined fatal and nonfatal major CHD events were 20% lower with high as compared with low LTPA (P&lt;.05). These risk differentials persisted after statistical adjustments for possible confounding variables, including other baseline risk factors and Multiple Risk Factor Intervention Trial group assignments. It is concluded that LTPA has a modest inverse relation to CHD and overall mortality in middle-aged men at high risk for CHD.(JAMA 1987;258:2388-2395)

Purpose: To report the 1-year motor and sensory outcomes for patients with acquired comitant esotropia managed with preoperative prism adaptation.

Increased childhood mortality and reduced longevity persist in the resource-limited settings with the highest populations of sickle cell disease (SCD) (Piel et al., New Engl J Med 2017). A high catabolic rate caused by multiple phenomena including compensatory erythropoiesis suggest increased calorie and nutritional requirements for individuals with SCD; however, a vast majority of individuals with SCD live under malnourished conditions. Also, it is unknown if the survival of offspring is influenced by the parents' diet and if the diet of individuals has a gender-specific effect on their survival.

Few studies have examined how developing obesity in early adulthood affects the course of asthma.