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1.
J Gen Intern Med ; 34(6): 952-959, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30887431

RESUMEN

BACKGROUND: The patient-centered medical home (PCMH) is a widely adopted primary care model. However, it is unclear whether changes in provider and staff perceptions of clinic PCMH capability are associated with changes in provider and staff morale, job satisfaction, and burnout in safety net clinics. OBJECTIVE: To determine how provider and staff PCMH ratings changed under a multi-year PCMH transformation initiative and assess whether changes in provider and staff PCMH ratings were associated with changes in morale, job satisfaction, and burnout. DESIGN: Comparison of baseline (2010) and post-intervention (2013-2014) surveys. SETTING: Sixty clinics in five states. PARTICIPANTS: Five hundred thirty-six (78.2%) providers and staff at baseline and 589 (78.3%) post-intervention. INTERVENTION: Collaborative learning sessions and on-site coaching to implement PCMH over 4 years. MEASUREMENTS: Provider and staff PCMH ratings on 0 (worst) to 100 (best) scales; percent of providers and staff reporting good or better morale, job satisfaction, and freedom from burnout. RESULTS: Almost half of safety net clinics improved PCMH capabilities from the perspective of providers (28 out of 59, 47%) and staff (25 out of 59, 42%). Over the same period, clinics saw a decrease in the percentage of providers reporting high job satisfaction (- 12.3% points, p = .009) and freedom from burnout (- 10.4% points, p = .006). Worsened satisfaction was concentrated among clinics that had decreased PCMH rating, with those clinics seeing far fewer providers report high job satisfaction (- 38.1% points, p < 0.001). LIMITATIONS: Control clinics were not used. Individual-level longitudinal survey administration was not feasible. CONCLUSION: If clinics pursue PCMH transformation and providers do not perceive improvement, they may risk significantly worsened job satisfaction. Clinics should be aware of this potential risk of PCMH transformation and ensure that providers are aware of PCMH improvements.

2.
Pharmacogenomics J ; 2019 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-30713337

RESUMEN

Effective doctor-patient communication is critical for disease management, especially when considering genetic information. We studied patient-provider communications after implementing a point-of-care pharmacogenomic results delivery system to understand whether pharmacogenomic results are discussed and whether medication recall is impacted. Outpatients undergoing preemptive pharmacogenomic testing (cases), non-genotyped controls, and study providers were surveyed from October 2012-May 2017. Patient responses were compared between visits where pharmacogenomic results guided prescribing versus visits where pharmacogenomics did not guide prescribing. Provider knowledge of pharmacogenomics, before and during study participation, was also analyzed. Both providers and case patients frequently reported discussions of genetic results after visits where pharmacogenomic information guided prescribing. Importantly, medication changes from visits where pharmacogenomics influenced prescribing were more often recalled than non-pharmacogenomic guided medication changes (OR = 3.3 [1.6-6.7], p = 0.001). Case patients who had separate visits where pharmacogenomics did and did not, respectively, influence prescribing more often remembered medication changes from visits where genomic-based guidance was used (OR = 3.4 [1.2-9.3], p = 0.02). Providers also displayed dramatic increases in personal genomic understanding through program participation (94% felt at least somewhat informed about pharmacogenomics post-participation, compared to 61% at baseline, p = 0.04). Using genomic information during prescribing increases patient-provider communications, patient medication recall, and provider understanding of genomics, important ancillary benefits to clinical use of pharmacogenomics.

3.
Pharmacogenet Genomics ; 29(2): 31-38, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30531377

RESUMEN

OBJECTIVE: The objective of this study was to study provider attitudes of and perceived barriers to the clinical use of pharmacogenomics before and during participation in an implementation program. PARTICIPANTS AND METHODS: From 2012 to 2017, providers were recruited. After completing semistructured interviews (SSIs) about pharmacogenomics, providers received training on and access to a clinical decision support tool housing patient-specific pharmacogenomic results. Thematic analysis of SSI was conducted (inter-rater reliability κ≥0.75). Providers also completed surveys before and during study participation, and provider-perceived barriers to pharmacogenomic implementation were analyzed. RESULTS: Seven themes emerged from the SSI (listed from most frequent to least): decision-making, concerns with pharmacogenomic adoption, outcome expectancy, provider knowledge of pharmacogenomics, patient attitudes, individualized treatment, and provider interest in pharmacogenomics. Although there was prestudy enthusiasm among all providers, concerns with clinical utility, time, results accession, and knowledge of pharmacogenomics were frequently stated at baseline. Despite this, adoption of pharmacogenomics was robust, as patient-specific results were accessed at 64% of visits, and medication changes were influenced by provided pharmacogenomic information 42% of the time. Providers reported they had enough time to evaluate the information and the results were easily understood on 74 and 98% of surveys, respectively. Nevertheless, providers consistently felt there was insufficient pharmacogenomic information for most drugs they prescribed and clear guidelines for using pharmacogenomic information were lacking. CONCLUSION: Despite initial concerns about adequate time and knowledge for adoption, providers frequently utilized pharmacogenomic results. Provider-perceived barriers to wider use included lack of clear guidelines and evidence for most drugs, highlighting important considerations for the field of pharmacogenomics.

4.
Clin Gastroenterol Hepatol ; 16(12): 1911-1918.e2, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30130624

RESUMEN

BACKGROUND & AIMS: Guidelines recommend that all colorectal tumors be assessed for mismatch repair deficiency, which could increase identification of patients with Lynch syndrome. This is of particular importance for minority populations, in whom hereditary syndromes are under diagnosed. We compared rates and outcomes of testing all tumor samples (universal testing) collected from a racially and ethnically diverse population for features of Lynch syndrome. METHODS: We performed a retrospective analysis of colorectal tumors tested from 2012 through 2016 at 4 academic centers. Tumor samples were collected from 767 patients with colorectal cancer (52% non-Hispanic white [NHW], 26% African American, and 17% Hispanic patients). We assessed rates of tumor testing, recommendations for genetic evaluation, rates of attending a genetic evaluation, and performance of germline testing overall and by race/ethnicity. We performed univariate and multivariate regression analyses. RESULTS: Overall, 92% of colorectal tumors were analyzed for mismatch repair deficiency without significant differences among races/ethnicities. However, minority patients were significantly less likely to be referred for genetic evaluation (21.2% for NHW patients vs 16.9% for African American patients and 10.9% for Hispanic patients; P = .02). Rates of genetic testing were also lower among minority patients (10.7% for NHW patients vs 6.0% for AA patients and 3.1% for Hispanic patients; P < .01). On multivariate analysis, African American race, older age, and medical center were independently associated with lack of referral for genetic evaluation and genetic testing. CONCLUSION: In a retrospective analysis, we found that despite similar rates of colorectal tumor analysis, minority patients are less likely to be recommended for genetic evaluation or to undergo germline testing for Lynch syndrome. Improvements in institutional practices in follow up after tumor testing could reduce barriers to diagnosis of Lynch diagnosis in minorities.

5.
Clin Transl Sci ; 11(4): 420-427, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29691991

RESUMEN

Acute kidney injury (AKI) limits cisplatin use. We tested whether urine cystatin C (uCyC) and neutrophil gelatinase-associated lipocalin (uNGAL) can preidentify patients at risk for AKI. Patients initiating cisplatin-based chemotherapy were prospectively enrolled. uNGAL/uCyC were measured pre/post-cisplatin administration and compared with serum creatinine (sCr). AKI was defined as sCr increase ≥50% or ≥0.3 mg/dL above baseline. In all, 102 patients were enrolled; 95 provided evaluable data. Twenty-five patients developed AKI. Median baseline and pre-cisplatin uNGAL levels were significantly higher in AKI patients. Although immediate changes in uNGAL/uCyC 2 h after cisplatin were not detectable, post-cisplatin peak values over the course of therapy were markedly and significantly elevated in AKI patients. In multivariate modeling with age, baseline glomerular filtration rate, and histology, maximum uCyC was a significant independent AKI predictor. These findings suggest pre-cisplatin uNGAL and peak uCyC levels can identify patients with increased AKI risk, potentially allowing for tailored modification of cisplatin-based treatment regimens.

6.
Health Serv Res ; 53(1): 469-488, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28560769

RESUMEN

OBJECTIVE: To examine the relationship between medical home transformation and patient experience of chronic illness care. STUDY SETTING: Thirteen safety net clinics located in five states enrolled in the Safety Net Medical Home Initiative. STUDY DESIGN: Repeated cross-sectional surveys of randomly selected adult patients were completed at baseline (n = 303) and postintervention (n = 271). DATA COLLECTION METHODS: Questions from the Patient Assessment of Chronic Illness Care (PACIC) (100-point scale) were used to capture patient experience of chronic illness care. Generalized estimating equation methods were used to (i) estimate how differential improvement in patient-centered medical home (PCMH) capability affected differences in modified PACIC scores between baseline and postintervention, and (ii) to examine cross-sectional associations between PCMH capability and modified PACIC scores for patients at completion of the intervention. PRINCIPAL FINDINGS: In adjusted analyses, high PCMH improvement (above median) was only marginally associated with a larger increase in total modified PACIC score (adjusted ß = 7.7, 95 percent confidence interval [CI]: -1.1 to 16.5). At completion of the intervention, a 10-point higher PCMH capability score was associated with an 8.9-point higher total modified PACIC score (95 percent CI: 3.1-14.7) and higher scores in four of five subdomains (patient activation, delivery system design, contextual care, and follow-up/coordination). CONCLUSIONS: We report that sustained, 5-year medical home transformation may be associated with modest improvement in patient experience of chronic illness care for vulnerable populations in safety net clinics.

7.
Health Serv Res ; 53 Suppl 1: 3207-3226, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29194594

RESUMEN

OBJECTIVE: To develop a short-form Safety Net Medical Home Scale (SNMHS) for assessing patient-centered medical home (PCMH) capability in safety net clinics. DATA SOURCES/STUDY SETTING: National surveys of federally qualified health centers (FQHCs). Interviews with FQHC directors. STUDY DESIGN: We constructed three short-form SNMHS versions and examined correlations with full SNMHS and related primary care assessments. We tested usability with FQHC directors and reviewed scale development with an advisory group. DATA COLLECTION: Federally qualified health center surveys were administered in 2009 and 2013, by mail and online. Usability testing was conducted through telephone interviews with FQHC directors in 2013. PRINCIPAL FINDINGS: Six-, 12-, and 18-question short-form SNMHS versions had Pearson correlations with full scale of 0.84, 0.92, and 0.96, respectively. All versions showed a level of convergent validity with other primary care assessment scales comparable to the full SNMHS. User testers found short forms to be low-burden, though missing some PCMH concepts. Advisory group members expressed caution over missing concepts and appropriate use of short-form self-assessments. CONCLUSIONS: Short-form versions of SNMHS showed strong correlations with full scale and may be useful for brief assessment of safety net PCMH capability. Each short-form SNMHS version may be appropriate for different research, quality improvement, and assessment purposes.

8.
PLoS One ; 12(9): e0185074, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28922398

RESUMEN

Alpha 1-antitrypsin (A1AT) is a serine protease inhibitor that mainly inhibits neutrophil elastase in the lungs. A variant of A1AT at the P1 position with methionine 358 to arginine (A1AT-Pittsburgh) is a rapid inhibitor of thrombin with greatly diminished anti-elastase activity. The P2 residue (position 357) of A1AT-Pittsburgh has been shown to play an important role in interactions with thrombin and kallikrein, but the role of P2 residue in wild-type A1AT has largely been unraveled. Here, we investigated the effects of P2 proline substitutions in wild-type A1AT on interactions with porcine pancreatic elastase (PPE) and human neutrophil elastase (HNE). The mutant A1AT proteins (P357A, P357D, P357K, P357L, P357N, P357S, and P357W) were less efficient than the wild-type A1AT at inhibiting PPE and HNE. Among the mutants, P357D did not form a complex with PPE, whereas P357L, P357N, and P357W showed significantly reduced complex formation with PPE. Surprisingly, mass spectrometry analysis revealed that P357D had two cleavage sites after the P9 alanine and the P3 isoleucine residues. Our results indicate that the size and negative charge of the R group of the P2 residue influence the interaction with elastases. Specifically, the negative charge at the P2 residue is disfavored and the resulting conformational changes in the reactive center loop upon interaction with PPE lead to cleavage at new sites. Overall, the results of this study demonstrate a previously unknown role for P2 residue in determining inhibitory specificity of A1AT.


Asunto(s)
Elastasa de Leucocito/química , alfa 1-Antitripsina/química , Sustitución de Aminoácidos , Animales , Humanos , Elastasa de Leucocito/metabolismo , Mutación Missense , Porcinos , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo
9.
Eur J Cancer ; 72: 177-185, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28033528

RESUMEN

BACKGROUND: The incidence of second malignant neoplasm (SMN) within the first ten years of diagnosis in high-risk neuroblastoma patients treated with modern, intensive therapy is unknown. Further, the underlying germline genetics that contribute to SMN in these survivors are not known. METHODS: The International Neuroblastoma Risk Group (INRG) database of patients diagnosed from 1990 to 2010 was analysed. SMN risk was accessed by cumulative incidence, standardised incidence ratios (SIRs) and absolute excess risk. A candidate gene-based association study evaluated genetic susceptibility to SMN in neuroblastoma survivors. RESULTS: Of the 5987 patients in the INRG database with SMN data enrolled in a clinical trial, 43 (0.72%) developed a SMN. The 10-year cumulative incidence of SMN for high-risk patients was 1.8% (95% confidence interval [CI] 1.0-2.6%) compared with 0.38% (95% CI: 0.22-0.94%) for low-risk patients (P = 0.01). High-risk patients had an almost 18-fold higher incidence of SMN compared to age- and sex-matched controls (SIR = 17.5 (95% CI: 11.4-25.3), absolute excess risk = 27.6). For patients treated on high- and intermediate-risk clinical trials, the SIR of acute myelogenous leukaemia was 106.8 (95% CI: 28.7-273.4) and 127.7 (95%CI: 25.7-373.3), respectively. Variants implicating DNA repair genes XRCC3 (rs861539: P = 0.006; odds ratio: 2.04, 95%CI: 1.19-3.46) and MSH2 (rs17036651: P = 0.009; odds ratio: 0.26, 95% CI: 0.08-0.81) were associated with SMN. CONCLUSION: The intensive multi-modality treatment strategy currently used to treat high-risk neuroblastoma is associated with a significantly increased risk of secondary acute myelogenous leukaemia. Defining the interactions of treatment exposures and genetic factors that promote the development of SMN is critical for optimising survivorship care.


Asunto(s)
Leucemia Mieloide Aguda/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Neuroblastoma/terapia , Sobrevivientes , Adolescente , Adulto , Niño , Preescolar , Terapia Combinada/efectos adversos , Reparación del ADN/genética , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Lactante , Masculino , Medición de Riesgo , Factores de Riesgo , Adulto Joven
10.
MDM Policy Pract ; 2(1): 2381468317713718, 2017 Jan-Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30288423

RESUMEN

Background: Multiple medical organizations recommend using life expectancy (LE) to individualize diabetes care goals. We compare the performance of patient LE predictions made by physicians to LE predictions from a simulation model (the Chicago model) in a cohort of older diabetic patients. DESIGN: Retrospective cohort study of a convenience sample (n = 447) of diabetes patients over 65 years and their physicians. Measurements: Physicians provided LE estimates for individual patients during a baseline survey (2000-2003). The prognostic model included a comprehensive geriatric type 2 diabetes simulation model (the Chicago model) and combinations of the physician estimate and the Chicago model ("And," "Or," and "Average" models). Observed survival was determined based on the National Death Index through 31 December 2010. The predictive accuracy of LE predictions was assessed using c-statistic for 5-year mortality; Harrell's c-statistic, and Integrated Brier score for overall survival. Results: The patient cohort had a mean (SD) age of 73.4 (5.9) years. The majority were female (62.6%) and black (79.4%). At 5 years, 108 (24.2%) patients had died. The c-statistic for 5-year mortality was similar for physicians (0.69) and the Chicago model (0.68), while the average of estimates by physicians and Chicago model yielded the highest c-statistic of any method tested (0.73). The estimates of overall survival yielded a similar pattern of results. Limitations: Generalizability of patient cohort and lack of updated model parameters. Conclusions: Compared with individual methods, the average of LE estimates by physicians and the Chicago model had the best predictive performance. Prognostic models, such as the Chicago model, may complement and support physicians' intuitions as they consider treatment decisions and goals for older patients with chronic conditions like diabetes.

11.
Med Decis Making ; 37(5): 611-617, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-27311651

RESUMEN

BACKGROUND: Diabetes guidelines recommend individualizing glycemic goals (A1C) for older patients. The aim of this study was to assess a personalized Web-based decision support tool. METHODS: We randomized physicians and their patients with type 2 diabetes (≥65 years of age) to a support tool or educational pamphlet (75:25 patients). Prior to a visit, intervention patients interacted with the tool, which provided personalized risk predictions and elicited treatment preferences. Main outcomes included 1) patient-doctor communication, 2) decisional conflict, 3) changes in goals, and 4) intervention acceptability. RESULTS: We did not find significant differences in proportions of patients who had an A1C discussion (91% intervention v. 76% control; P = 0.19). Intervention patients had larger declines in the informed subscale of decisional conflict (-20 v. 0, respectively; P = 0.04). There were no significant differences in proportions of patients with changes in goals (49% v. 28%, respectively; P = 0.08). Most intervention patients reported that the tool was easy to use (91%) and helped them to communicate (84%). A limitation was that this was a pilot trial at one academic institution. CONCLUSIONS: Web-based decision support tools may be a practical approach to facilitating the personalization of goals for chronic conditions. TRIAL REGISTRATION: NCT02169999 ( https://clinicaltrials.gov/show/NCT02169999 ).


Asunto(s)
Diabetes Mellitus Tipo 2/psicología , Medicina de Precisión , Anciano , Anciano de 80 o más Años , Glucemia/metabolismo , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Educación del Paciente como Asunto , Proyectos Piloto
12.
Am J Public Health ; 106(11): 1981-1989, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27631748

RESUMEN

OBJECTIVES: To compare health care use and spending of Medicaid enrollees seen at federally qualified health centers versus non-health center settings in a context of significant growth. METHODS: Using fee-for-service Medicaid claims from 13 states in 2009, we compared patients receiving the majority of their primary care in federally qualified health centers with propensity score-matched comparison groups receiving primary care in other settings. RESULTS: We found that health center patients had lower use and spending than did non-health center patients across all services, with 22% fewer visits and 33% lower spending on specialty care and 25% fewer admissions and 27% lower spending on inpatient care. Total spending was 24% lower for health center patients. CONCLUSIONS: Our analysis of 2009 Medicaid claims, which includes the largest sample of states and more recent data than do previous multistate claims studies, demonstrates that the health center program has provided a cost-efficient setting for primary care for Medicaid enrollees.


Asunto(s)
Financiación Personal/economía , Medicaid/estadística & datos numéricos , Proveedores de Redes de Seguridad/economía , Proveedores de Redes de Seguridad/estadística & datos numéricos , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/economía , Atención Primaria de Salud/estadística & datos numéricos , Estados Unidos
13.
Glycoconj J ; 33(2): 201-8, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26947874

RESUMEN

Glycosylation affects the circulatory half-lives of therapeutic proteins. However, the effects of an additional N-glycosylation in the unstructured region or the loop region of alpha-1 antitrypsin (A1AT) on the circulatory half-life of the protein are largely unknown. In this study, we investigated the role of an additional N-glycosylation site (Q4N/D6T, Q9N, D12N/S14T, A70N, G148T, R178N, or V212N) to the three naturally occurring N-glycosylation sites in human A1AT. A single-dose (445 µg/kg) pharmacokinetic study using male Sprague-Dawley rats showed that, among the seven recombinant A1AT (rA1AT) mutants, Q9N and D12N/S14T showed the highest serum concentration and area under the curve values, as well as similar circulatory half-lives that were 2.2-fold higher than plasma-derived A1AT and 1.7-fold higher than wild-type rA1AT. We further characterized the Q9N mutant regarding the N-glycan profile, sialic acid content, protease inhibitory activity, and protein stability. The results indicate that an additional N-glycosylation in the flexible N-terminal region increases the circulatory half-life of rA1AT without altering its protease inhibitory activity. Our study provides novel insight into the use of rA1AT for the treatment of emphysema with an increased injection interval relative to the clinically used plasma-derived A1AT.


Asunto(s)
alfa 1-Antitripsina/farmacología , alfa 1-Antitripsina/farmacocinética , Animales , Enfisema/tratamiento farmacológico , Enfisema/metabolismo , Glicosilación , Semivida , Humanos , Masculino , Mutación Missense , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacología , alfa 1-Antitripsina/genética
14.
Gastric Cancer ; 19(4): 1066-79, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26581548

RESUMEN

BACKGROUND: Trastuzumab has shown a survival benefit in cases of Her2-positive gastroesophageal cancer (GEC). Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) currently determine eligibility for trastuzumab-based therapy. However, these low-throughput assays often produce discordant or equivocal results. METHODS: We developed a targeted proteomic assay based on selected reaction monitoring mass spectrometry (SRM-MS) and quantified levels (amol/µg) of Her2-SRM protein in cell lines (n = 27) and GEC tissues (n = 139). We compared Her2-SRM protein expression with IHC/FISH, seeking to determine optimal SRM protein expression cutoffs in order to identify HER2 gene amplification. RESULTS: After demonstrating assay development, precision, and stability, Her2-SRM protein measurement was observed to be highly concordant with the HER2/CEP17 ratio, particularly in a multivariate regression model adjusted for SRM expression of the covariates Met, Egfr, Her3, and HER2 heterogeneity, as well as their interactions (cell lines r (2) = 0.9842; FFPE r (2) = 0.7643). In GEC tissues, Her2-SRM protein was detected at any level in 71.2 % of cases. ROC curves demonstrated that Her2-SRM protein levels have a high specificity (100 %) at an upper-level cutoff of >750 amol/µg and sensitivity of 75 % at a lower-level cutoff of <450 amol/µg for identifying HER2 FISH-amplified tumors. An "equivocal zone" of 450-750 amol/µg of Her2-SRM protein was analogous to IHC2+ but represented fewer cases (9-16 % of cases versus 36-41 %). CONCLUSIONS: Compared to IHC, targeted SRM-Her2 proteomics provided more objective and quantitative Her2 expression with excellent HER2/CEP17 FISH correlation and fewer equivocal cases. Along with its multiplex capability for other relevant oncoproteins, these results demonstrate a refined HER2 protein expression assay for clinical application.


Asunto(s)
Hibridación Fluorescente in Situ/métodos , Proteómica/métodos , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Amplificación de Genes , Humanos , Técnicas para Inmunoenzimas , Neoplasias Gástricas/patología
15.
Hum Reprod ; 30(11): 2686-92, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26345686

RESUMEN

STUDY QUESTION: Does an association exist between high normal numbers of CGG trinucleotide repeats on the fragile X mental retardation 1 (FMR1) gene and diminished ovarian reserve (DOR)? SUMMARY ANSWER: This large data set demonstrated that a high normal number of CGG repeats (35-54 repeats) on the FMR1 gene was not significantly correlated with DOR. WHAT IS KNOWN ALREADY: The FMR1 premutation (55-200 repeats) is a known cause of primary ovarian insufficiency. However, the relationship between high normal CGG repeat numbers (35-54 repeats) and ovarian reserve has yet to be conclusively demonstrated. STUDY DESIGN, SIZE, DURATION: This is a retrospective data analysis conducted between January 2012 and February 2014 that included 1287 women. Over 1140 women had complete data. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women, excluding oocyte donors, who presented to a large private practice specializing in reproductive endocrinology and infertility for treatment and who underwent both fragile X and ovarian reserve testing were included. All fragile X testing was performed using triplet repeat PCR, with confirmation of positives by Southern blot. CGG repeat numbers from both alleles were recorded, and the allele with the higher number of repeats was used for statistical calculations. We did not differentiate between patients with one or two high normal alleles. Women with >54 CGG repeats were excluded from the analysis. For our analysis, we considered both a 'high normal' number of CGG repeats (35-44) and an intermediate number of GCC repeats (45-54) as 'high normal'. Ovarian reserve testing was carried out on Cycle Day 2 or 3 and included measurements of FSH, anti-Müllerian hormone (AMH) and antral follicle count (AFC). A generalized linear regression model assuming gamma distribution and log link function that controlled for age was used to assess correlation between CGG repeat number and FSH, AMH and AFC. MAIN RESULTS AND THE ROLE OF CHANCE: As expected, there was a significant correlation between increasing age and increasing FSH and decreasing AFC and AMH for the patients in this study. For every 1-year increase in age, FSH increased by a factor of 1.04, AFC decreased by a factor of 0.93 and AMH decreased by a factor of 0.89. After controlling for age, there was no significant correlation between FMR1 CGG trinucleotide repeat number and FSH (P = 0.23), AFC (P = 0.14) or AMH (P = 0.53). Three subgroup analyses were also performed. We found a significant relationship between increasing CGG repeat number and decreasing AMH levels (P = 0.01) in women >44 years old. The second subgroup analysis included only Caucasian patients and found no significant correlation between CGG repeat number and DOR. In a subgroup analysis comparing women with at least one allele <26 repeats, at least one allele >35 and women with both alleles between 29 and 32, there were no significant associations regarding ovarian reserve in any of these groups. LIMITATIONS, REASONS FOR CAUTION: One limitation of this study is that it involved a heterogeneous population of infertile women with mixed diagnoses. Factors that could affect ovarian reserve, such as medical comorbidities, prior surgeries, family history and endometriosis, were not accounted for. Finally, there was a lack of racial diversity, with Caucasians representing 67.8% of the total population. WIDER IMPLICATIONS OF THE FINDINGS: The findings of this study are generalizable to an infertility population and are in line with several previously published studies. Women who are found to have high normal CGG repeat numbers can be counseled that this is not causative for DOR. Further studies are needed to investigate whether increasing CGG repeat numbers are associated with ovarian responsiveness to gonadotrophin stimulation or IVF outcome.


Asunto(s)
Hormona Antimülleriana/sangre , Proteína del Retraso Mental del Síndrome del Cromosoma X Frágil/genética , Infertilidad Femenina/genética , Reserva Ovárica/genética , Repeticiones de Trinucleótidos/genética , Adulto , Factores de Edad , Femenino , Humanos , Infertilidad Femenina/sangre , Persona de Mediana Edad , Estudios Retrospectivos
16.
Fertil Steril ; 104(2): 398-402.e1, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26049056

RESUMEN

OBJECTIVE: To evaluate the impact of race on in vitro fertilization (IVF) outcomes. DESIGN: Retrospective analysis. SETTING: Private practice. PATIENT(S): All women who underwent a first autologous IVF cycle at Fertility Centers of Illinois from January 2010 to December 2012. INTERVENTION(S): Information was collected on baseline characteristics, cycle parameters, and outcomes. Race was self-reported. MAIN OUTCOME MEASURE(S): Clinical intrauterine pregnancy and live birth rates. RESULT(S): A total of 4,045 women were included: 3,003 white (74.2%), 213 black (5.3%), 541 Asian (13.4%), and 288 Hispanic women (7.1%). A multivariable logistic regression was performed to control for confounders. Compared with white women, the adjusted odds ratio for clinical intrauterine pregnancy was 0.63 (95% confidence interval [CI] 0.44-0.88) in black women, 0.73 (95% CI 0.60-0.90) in Asian women, and 0.82 (95% CI 0.62-1.07) in Hispanic women. The adjusted odds ratio for live birth was 0.50 (95% CI 0.33-0.72) in black women, 0.64 (95% CI 0.51-0.80) in Asian women, and 0.80 (95% CI 0.60-1.06) in Hispanic women compared with white women. The spontaneous abortion rate was 14.6% in white women versus 28.9% in black women, 20.6% in Asian women, and 15.3% in Hispanic women. CONCLUSION(S): Black and Asian women had lower odds of clinical intrauterine pregnancy and live birth and higher rates of spontaneous abortion compared with white women. Further research is needed to better characterize the mechanisms associated with this racial disparity and to improve treatment options for black and Asian women.


Asunto(s)
Afroamericanos/etnología , Grupo de Ascendencia Continental Asiática/etnología , Grupo de Ascendencia Continental Europea/etnología , Fertilización In Vitro/tendencias , Disparidades en Atención de Salud/etnología , Hispanoamericanos/etnología , Adulto , Femenino , Humanos , Nacimiento Vivo/etnología , Embarazo , Estudios Retrospectivos
17.
J Gen Intern Med ; 30(10): 1481-90, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25920468

RESUMEN

BACKGROUND: Churches may provide a familiar and accessible setting for chronic disease self-management education and social support for Latinos with diabetes. OBJECTIVE: We assessed the impact of a multi-faceted church-based diabetes self-management intervention on diabetes outcomes among Latino adults. DESIGN: This was a community-based, randomized controlled, pilot study. SUBJECTS: One-hundred adults with self-reported diabetes from a Midwestern, urban, low-income Mexican-American neighborhood were included in the study. INTERVENTIONS: Intervention participants were enrolled in a church-based diabetes self-management program that included eight weekly group classes led by trained lay leaders. Enhanced usual care participants attended one 90-minute lecture on diabetes self-management at a local church. OUTCOME MEASURES: The primary outcome was change in glycosylated hemoglobin (A1C). Secondary outcomes included changes in low-density lipoproteins (LDL), blood pressure, weight, and diabetes self-care practices. KEY RESULTS: Participants' mean age was 54 ± 12 years, 81 % were female, 98 % were Latino, and 51 % were uninsured. At 3 months, study participants in both arms decreased their A1C from baseline (-0.32 %, 95 % confidence interval [CI]: -0.62, -0.02 %). The difference in change in A1C, LDL, blood pressure and weight from baseline to 3-month and 6-month follow-up was not statistically significant between the intervention and enhanced usual care groups. Intervention participants reported fewer days of consuming high fat foods in the previous week (-1.34, 95 % CI: -2.22, -0.46) and more days of participating in exercise (1.58, 95 % CI: 0.24, 2.92) compared to enhanced usual care from baseline to 6 months. CONCLUSIONS: A pilot church-based diabetes self-management intervention did not reduce A1C, but resulted in decreased high fat food consumption and increased participation in exercise among low-income Latino adults with diabetes. Future church-based interventions may need to strengthen linkages to the healthcare system and provide continued support to participants to impact clinical outcomes.


Asunto(s)
Catolicismo , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/terapia , Intervención Médica Temprana/métodos , Conductas Relacionadas con la Salud/etnología , Hispanoamericanos/etnología , Autocuidado/métodos , Adulto , Anciano , Presión Sanguínea/fisiología , Ejercicio/fisiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
18.
Ann Thorac Surg ; 99(5): 1761-7, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25818569

RESUMEN

BACKGROUND: Although postoperative predicted forced expiratory volume in the first second and diffusing capacity of lung (ppoFEV1% and ppoDLCO%, respectively) have been identified as independent predictors of postoperative pulmonary complications after open lobectomy, it has been suggested that their predictive abilities may not extend to patients undergoing minimally invasive lobectomy. METHODS: We evaluated outcomes in 805 patients undergoing isolated lobectomy through open (n = 585) or minimally invasive approaches (n = 220) using a prospective database. Demographic and physiologic data were extracted and compared with complications classified as pulmonary, cardiac, other, mortality, and any. RESULTS: Patients included 428 women and 377 men; mean age was 65.0 years. Minimally invasive patients were older (66.6 versus 64.3 years, p = 0.006), had better ppoFEV1% (71.5% versus 65.6%, p < 0.001) and performance status (0,1 94.1% versus 88.4%, p = 0.017), and less often underwent induction therapy (0.5% versus 4.8%, p = 0.003). Pulmonary and other complications were less common after minimally invasive lobectomy (3.6% versus 10.4%, p = 0.0034; 8.6% versus 15.8%, p = 0.008). Operative mortality occurred in 1.4% of minimally invasive patients and 3.9% of open patients (p = 0.075). Pulmonary complication incidence was related to predicted postoperative lung function for both minimally invasive and open approaches. On multivariate analysis with stratification for stage, ppoFEV1% and ppoDLCO% were predictive of pulmonary complications for both minimally invasive and open approaches. CONCLUSIONS: Our results suggest that the predictive abilities of ppoFEV1% and ppoDLCO% are retained for minimally invasive lobectomy and can be used to estimate the risk of pulmonary complications.


Asunto(s)
Enfermedades Pulmonares/fisiopatología , Enfermedades Pulmonares/cirugía , Neumonectomía/efectos adversos , Cirugía Torácica Asistida por Video/efectos adversos , Toracotomía/efectos adversos , Anciano , Femenino , Volumen Espiratorio Forzado/fisiología , Humanos , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Neumonectomía/métodos , Valor Predictivo de las Pruebas , Capacidad de Difusión Pulmonar/fisiología , Estudios Retrospectivos , Toracotomía/métodos , Resultado del Tratamiento
19.
Pediatr Blood Cancer ; 62(1): 128-33, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25251613

RESUMEN

BACKGROUND: To investigate the incidence of second malignant neoplasms (SMN) for patients with neuroblastoma, we analyzed patients from the SEER database according to three treatment eras (Era 1: 1973-1989, Era 2: 1990-1996, and Era 3: 1997-2006) corresponding to the introduction of multi-agent chemotherapy, risk-based treatment, and stem cell transplant. PROCEDURES: The SEER database was mined for all patients with neuroblastoma or ganglioneuroblastoma. Cumulative incidence of SMN was calculated with death as a competing risk. A poisson regression model was used to estimate incidence rate ratios and 95% confidence intervals to compare the rates of SMN between patients in different Eras. RESULTS: The analytic cohort included 2,801 patients. Thirty-four patients developed a SMN, accounting for 1.2% of all patients. Of the patients who developed a SMN, 47.1% received radiation for their primary neuroblastoma. Fourteen of the SMN were carcinomas, and 10 were hematologic malignancies, with six cases of acute myelogenous leukemia. There was no difference in the incidence of SMN in Era 1 compared to Era 3 (P = 0.48). The cumulative incidence of SMN at 30 years for high-risk patients was 10.44% (95% CI 3.98-20.52%) compared to 3.57% (95% CI 1.87-6.12%) for non-high-risk patients (P < 0.001). CONCLUSIONS: This study showed no increase in the incidence of SMNs for children treated in the most recent treatment era as compared to earlier Eras. However, as the risk for developing SMN does not plateau, the number of SMNs will likely continue to rise in the cohort of patients treated after 1996. Comprehensive follow-up care for these survivors will be important.


Asunto(s)
Neoplasias Primarias Secundarias/epidemiología , Neuroblastoma/complicaciones , Traumatismos por Radiación/epidemiología , Radioterapia/efectos adversos , Adolescente , Adulto , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Masculino , Estadificación de Neoplasias , Neoplasias Primarias Secundarias/etiología , Neoplasias Primarias Secundarias/mortalidad , Neuroblastoma/mortalidad , Neuroblastoma/radioterapia , Pronóstico , Traumatismos por Radiación/etiología , Traumatismos por Radiación/mortalidad , Factores de Riesgo , Programa de VERF , Tasa de Supervivencia , Adulto Joven
20.
Med Care ; 52(11 Suppl 4): S48-55, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25310638

RESUMEN

BACKGROUND: Few studies have evaluated whether the patient-centered medical home (PCMH) supports patient activation and none have evaluated whether support for patient activation differs among racial and ethnic groups or by health status. This is critical because activation is lower on average among minority patients and those in poorer health. OBJECTIVE: To assess the association between clinic PCMH characteristics and patient perception of clinic support for patient activation, and whether that association varies by patients' self-reported race/ethnicity or health status. PARTICIPANTS: A total of 214 providers/staff and 735 patients in 24 safety net clinics across 5 states. MEASURES: Provider/staff surveys produced a 0-100 score for PCMH characteristics. Patient surveys used the patient activation subscale of the Patient Assessment of Chronic Illness Care to produce a 0-100 score for patient perception of clinic support for patient activation. RESULTS: Across all patients, we did not find a statistically significant association between PCMH score and clinic support for patient activation. However, among the subgroup of minority patients in fair or poor health, a 10-point higher PCMH score was associated with a 14.5-point (CI, 4.4, 24.5) higher activation score. CONCLUSIONS: In a population of safety net patients, higher-rated PCMH characteristics were not associated with patients' perception of clinic support for activation among the full study population; however, we found a strong association between PCMH characteristics and clinic support for activation among minority patients in poor/fair health status. The PCMH may be promising for reducing disparities in patient activation for ill minority patients.


Asunto(s)
Enfermedad Crónica/etnología , Grupos Étnicos , Atención Dirigida al Paciente/organización & administración , Relaciones Profesional-Paciente , Evaluación de Programas y Proyectos de Salud/métodos , Proveedores de Redes de Seguridad/organización & administración , Colorado , Investigación sobre Servicios de Salud , Estado de Salud , Humanos , Idaho , Massachusetts , Oregon , Pennsylvania
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