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Microsatellite instability (MSI) is a potential indicator of prognosis in patients with colorectal cancer (CRC). To date, there are a limited number of studies which investigated its role in advanced CRC. Our study investigated the value of high degree of MSI (MSI-H) in patients treated with 5-FU/oxaliplatin-based chemotherapy which has been done by only one further study recently. In this study, we investigated tumour tissues from 108 patients with metastatic CRC who were treated in a prospective, randomised trial comparing two oxaliplatin and 5-FU-based therapy regimens (FUFOX vs. CAPOX) involving a total of 474 patients. We determined the incidence and prognostic value of a high degree of microsatellite instability. The specimens were analysed by PCR corresponding to the National Institute of Health reference panel. In addition, immunostaining of the mismatch repair proteins MLH1, MSH2 and MSH6 was performed. The incidence of MSI-H was 4%. MSI-H was correlated with a lower rate of disease control compared to non-MSI-H patients ( p = 0.02). However, there was no correlation between MSI-H and progression-free survival or overall survival. MSI-H incidence in metastatic CRC was low. Our data suggest that MSI-H may be correlated with a poorer response to a 5-FU/oxaliplatin treatment. This finding needs confirmation in a larger cohort. [ABSTRACT FROM AUTHOR]

Discusses the effects of competing seasonal-adjustment procedures on the univariate time-series properties of the adjusted series using the U.S. quarterly macroeconomic data. Properties of seasonal-adjustment procedures; Autocorrelation and partial autocorrelation functions of a set of quarterly time series; Evidence of a mixture of deterministic and stochastic seasonal components.

Objective: To determine the proportion of primary care patients who are experienced by their physicians as "difficult," and to assess the association of difficulty with physical and mental disorders, functional impairment, health care utilization, and satisfaction with medical care.Design: Survey.Setting: Four primary care clinics.Patients: Six-hundred twenty-seven adult patients.Measurements: Physician perception of difficulty (Difficult Doctor-Patient Relationship Questionnaire), mental disorders and symptoms (Primary Care Evaluation of Mental Disorders, [PRIME-MDI]), functional status (Medical Outcomes Study Short-Form Health Survey [SF-20]), utilization of and satisfaction with medical care by patient self-report.Results: Physicians rated 96 (15%) of their 627 patients as difficult (site range 11-20%). Difficult patients were much more likely than not-difficult patients to have a mental disorder (67% vs 35% [corrected], p < .0001). Six psychiatric disorders had particularly strong associations with difficulty: multisomatoform disorder (odds ratio [OR] = 12.3. 95% confidence interval [CI] = 5.9-26.8), panic disorder (OR = 6.9, 95% CI = 2.6-18.1), dysthymia (OR = 4.2, 95% CI = 2.0-8.7), generalized anxiety (OR = 3.4, 95% CI = 1.7-7.1), major depressive disorder (OR = 3.0, 95% CI = 1.8-5.3), and probable alcohol abuse or dependence (OR = 2.6, 95% CI = 1.01-6.7). Compared with not-difficult patients, difficult patients had more functional impairment, higher health care utilization, and lower satisfaction with care, whereas demographic characteristics and physical illnesses were not associated with difficulty. The presence of mental disorders accounted for a substantial proportion of the excess functional impairment and dissatisfaction in difficult patients.Conclusions: Difficult patients are prevalent in primary care settings and have more psychiatric disorders, functional impairment, health care utilization, and dissatisfaction with care. Future studies are needed to determine whether improved diagnosis and management of mental disorders in difficult patients could diminish their excess disability, health care costs, and dissatisfaction with medical care, as well as the physicians experience of difficulty. [ABSTRACT FROM AUTHOR]

Editorial. Comments on the meaning of symptoms and its relation with patient satisfaction. Definitions of symptoms; Association of symptoms with specific disorders; Effect of symptom outcome on patient satisfaction; Comparison between somatization and persistent organic pathology; Importance of doctor-patient communication.

Objectives: Research with lesbian, gay, and bisexual (LGB) older widows rarely focuses on familial relationships. Studies on heterosexual spousal bereavement indicate older widows face issues influencing identity but show resilience by maintaining close relationships with adult children and extended family. Though research with older LGB widows suggests similarities around loss and resilience, grief and family engagement are markedly different., Methods: Guided by Relational Cultural Theory, which illuminates how LGB women cope through connection/disconnection, this qualitative descriptive study employed semistructured, open-ended interviews with 16 LGB women, 60-85 years of age from across the United States who had lost a spouse or partner within the past 5 years. We conducted interviews regarding the perception of self as bereaved LGB women and sustained or altered relationships with biological and chosen families following the loss of their spouses/partners., Results: Findings are illustrated in three themes around acceptance, support, and identity. Participants: (a) experienced differing levels of acceptance, tolerance, and inclusion from biological families; (b) experienced family or friends "disappearing" or providing critical support following a spouse/partner's death; and (c) negotiated challenges by creating or seeking out families of choice, new communities, and a better understanding of themselves., Discussion: While LGB widows share some grief experiences with heterosexual widows, they also experience varying biological family acceptance and support, as well as the need for friends and families of choice as advocates. It is important to recognize the unique consequences of spousal loss for this population and be cognizant of the differences in normative grief., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Genetic counseling careers continue to evolve, yet there remains a lack of information about hiring trends in the genetic counseling profession. In this study, job advertisements in the United States and Canada were analyzed, using the National Society of Genetic Counselors (NSGC) Job Connections and the American Board of Genetic Counseling (ABGC) eBlasts from 2014 to 2016 to appraise job roles, qualifications, settings, specialties, and type. NSGC had 1875 advertised openings from 2014 to 2016, while ABGC had 373 advertised openings. Jobs containing a "counseling" role increased as a percentage from 2014 to 2016 when advertised by NSGC (χ 2  = 25.52, p < 0.000001) but decreased each year from 2014 to 2016 as a percentage when advertised through ABGC (χ 2  = 14.29, p = 0.0008). In the ABGC job postings, it was noted that 36% of job postings were advertised for other specialties (not solely cancer, pediatric, or prenatal) in 2014, and increased to 67% in 2016 (χ 2  = 10.09, p = 0.02). Examining the job specialties posted by ABGC and NSGC, several new or unique roles were found in the job advertisements such as ophthalmology counselor, variant curator, rare diseases information specialist, and clinical policy analyst. Roles for temporary, contract or fellowship positions are possibly becoming more common, along with small upturns in positions that are off-site or remote. In analyzing the changing workforce, there was a statistically significant decrease identified in jobs advertised by NSGC in the laboratory setting from 28% in 2014 to 17% in 2016 (χ 2  = 24.12, p = 0.000024). This information on the evolving career of genetic counseling is valuable for the current workforce and training programs as they adapt with the changing landscape of the profession., (© 2019 National Society of Genetic Counselors.)

Rationale: A molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility., Objectives: This study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults., Methods: The study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts., Measurements and Main Results: In receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity., Conclusions: SeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).

As of May 2017, there were 4242 Certified Genetic Counselors (CGC) (American Board of Genetic Counseling, Inc. 2017) and 41 graduate-level genetic counseling training programs (Accreditation Council for Genetic Counseling 2017) in North America, and the demand for CGCs continues to increase. In the Fall of 2015 the Genetic Counselor Workforce Working Group, comprised of representatives from the American Board of Genetic Counseling (ABGC), the Accreditation Council for Genetic Counseling (ACGC), the Association of Genetic Counseling Program Directors (AGCPD), the American Society of Human Genetics (ASHG), and the National Society of Genetic Counselors (NSGC) commissioned a formal workforce study to project supply of and demand for CGCs through 2026. The data indicate a shortage of genetic counselors engaged in direct patient care. Assuming two scenarios for demand, supply is expected to reach equilibrium between 2024 and 2030. However, given the rate of growth in genetic counseling training programs in the six months since the study was completed, it is reasonable to expect that the number of new programs may be higher than anticipated by 2026. If true, and assuming that growth in programs is matched by equivalent growth in clinical training slots, the supply of CGCs in direct patient care would meet demand earlier than these models predict.

Unlabelled: A patient's transition from the inpatient to the outpatient setting is complex and prone to medical errors. This subsequently increases patient morbidity and cost to the healthcare system., Methods: Our quality improvement initiative used a licensed clinical social worker from within a Family Medicine residency clinic to serve as a Transitions of Care Coordinator (TOCC) with the goal of decreasing patient morbidity and system cost., Results: The number of documented patient contacts by our primary care office in the postdischarge period increased significantly after implementation of the TOCC (3.1% vs 40.2%, P=.01). Pearson correlation during our postimplementation period suggested an inverse relationship between contact by a TOCC and emergency department (ED) and hospital utilization rates (r=-0.68, P=.05 and r=0.062, P=.005, respectively). However, the percentage of ED visits (11.9% vs 20.8%, P=.02) and hospital readmissions (5.6% vs 13.7%, P=.01) significantly increased overall between the pre-and postimplementation periods., Conclusions: The implementation of a TOCC within a military Family Medicine residency clinic significantly increased the frequency of ED visits and readmissions to the inpatient service for patients discharged from the Family Medicine inpatient service.

Purpose: To compare short-term outcomes of repeat penetrating keratoplasty (PK) to those of Boston type 1 keratoprosthesis (KPro). Our hypothesis was that visual outcomes were superior for KPro compared to PK., Methods: This is a retrospective, nonrandomized, intermediate-term case series. Consecutive adults with one or more failed PKs who underwent either PK or KPro between January 2008 and December 2010 were included. Demographics, indication for the initial PK, comorbidities, concomitant procedures, and complications were considered. Only one procedure in each eye was included. All KPro procedures were retained in the analyses., Results: Fifty-three patients underwent PK and 27 received KPro. Mean follow-up was 19.5 months in the PK group and 16.5 months in the KPro group. KPro eyes had worse mean preoperative vision (hand motions vs counting fingers, P=.01) and more comorbidities. In the postoperative period, 35% of PK eyes and 45% of KPro eyes attained best-ever visual acuity of 20/70. Forty-seven percent of PK eyes vs 40% of KPro eyes were able to retain this visual acuity. Two-year rate of failure to retain visual acuity better than the baseline was higher for PK eyes, though not at a statistically significant level (hazard ratio [HR]=1.67; 95% CI, 0.78-3.60; P=.19). Two-year cumulative rate of graft failure (loss of clarity for PK and removal/replacement for KPro) was higher for PK eyes (HR=3.23; 95% CI, 1.12-9.28; P=.03). Retinal detachment, endophthalmitis, and glaucoma rates were similar (P=.6 for all)., Conclusions: These results demonstrate less frequent graft failure, greater visual improvement, and greater likelihood of maintaining the visual improvement in KPro eyes vs PK.

Background: Interest in global health and international electives is growing among Emergency Medicine (EM) residents in the United States (US). The majority of EM residency programs offer opportunities for international electives. The degree of participation among residents and type of support provided by the residency program, however, remains unclear., Study Objectives: To explore the current state of global health education among EM residents who participate in international electives., Methods: A 12-question survey was e-mailed to the program directors of the 192 EM residency programs in the US. The survey included questions about the number of residents participating in international electives and the types of preparation, project requirements, supervision, and feedback participating residents receive., Results: The response rate was 53% with 102 responses. Seventy-five of 102 (74%) programs reported that at least one resident participated in an international elective in the 2010-2011 academic year. Forty-three programs (42%) report no available funding to support any resident on an international elective. Residents receive no preparation for international work in 41 programs (40%). Only 25 programs (26%) required their residents to conduct a project while abroad. Forty-nine programs (48%) reported no formal debriefing session, and no formal feedback was collected from returning residents in 57 of 102 (59%) programs., Conclusion: The majority of EM residencies have residents participating in international electives. However, the programs report variable preparation, requirements, and resident supervision. These results suggest a need for an expanded and more structured approach to international electives undertaken by EM residents., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Unnecessary right ventricular (RV) pacing in patients with implantable cardioverter defibrillators (ICD) may adversely affect heart failure morbidity and total mortality. Inhibition of Unnecessary RV Pacing with AV Search Hysteresis in ICDs (INTRINSIC RV) is a prospective, multicenter, randomized trial evaluating outcomes in ICD recipients programmed to single-chamber pacing (VVI) versus dual-chamber (DDDR) pacing with AV search hysteresis (AVSH)., Methods: Patients underwent ICD implant (for standard indications). The ICD was programmed to DDDR with AVSH regardless of any need for pacing. Rate-adaptive pacing was set at 60-130 ppm with dynamic AV delay from 200 to 90 ms. AVSH was programmed to search every 32 intervals and extend the AV delay by 50%. One week post-implant patients with ICDs were interrogated to assess the percentage of RV pacing with the expectation that most would have <20% RV pacing and would be randomized into INTRINSIC RV. Early analysis showed that targets for randomization were not met. AVSH parameters were modified under a protocol amendment to increase AV delay extension to 100%. We report findings related to this programming change based upon analyses of (nonrandomized) data pre- and post-amendment., Results: Twenty-one percent of patients (n = 314) were enrolled pre-amendment and 79% (n = 1,216) were enrolled post-amendment. The mean percentage of RV pacing at the 1-week visit was 41.4 +/- 29.6% pre-amendment and 14.7 +/- 22.6% post-amendment (P < 0.0001). The proportion of patients eligible for randomization (RV pacing <20% at the 1-week visit) was 31.2% pre-amendment and 76.8% post-amendment (P < 0.0001)., Conclusion: AVSH can dramatically reduce the percentage of RV pacing among ICD recipients.

Genetic disorders are recognized to play an increasing role in pediatrics. Close to 10% of diseases among hospitalized children have been ascribed to Mendelian traits inherited as single gene defects, not a surprising figure considering that approximately 1000 inborn errors of metabolism (IEM) have been identified to date, primarily through the detection of endogenous metabolites abnormally accumulated in biological fluids and tissues. The laboratory discipline that covers the biochemical diagnosis of IEM is known as clinical biochemical genetics, and is defined as one concerned with the evaluation and diagnosis of patients and families with inherited metabolic disease, monitoring of treatment, and distinguishing heterozygous carriers from non-carriers by metabolite and enzymic analysis of physiological fluids and tissues. The biochemical genetics laboratory differs from the clinical chemistry laboratory in the extent of interpretation necessary to make its results meaningful to the clinician. While dramatic advances in molecular genetics have greatly changed the landscape of diagnostic options for many genetic disorders, a biochemical approach remains the dominant force for the diagnosis and monitoring of IEM. Owing to the stereotypical clinical presentation of many of these disorders, a major role of the biochemical genetics laboratory is to analyze ever more complex metabolic profiles to reach a preliminary diagnosis, which then needs to be confirmed by enzymic and/or molecular studies in vitro. Accordingly, the role of biochemical genetics in the pediatric practice of the 21st century is to provide a multicomponent screening process that can be divided into four major components: (i) at-risk screening (prenatal diagnosis); (ii) newborn screening (testing of presymptomatic patients); (iii) high-risk screening (testing of symptomatic patients); and (iv) postmortem screening (metabolic autopsy). The focus of our laboratory is to apply state-of-the-art technology such as tandem mass spectrometry to bring as many as possible IEM within the boundaries of newborn screening programs, and to investigate the role played by individual disorders in maternal complications of pregnancy, pediatric acute/fulminant liver failure, and sudden and unexpected death in early life.

We present data on the costs and impact of chronic renal failure, the primary renal diseases leading to end-stage renal disease in children, and review the adaptive responses and the pathophysiology and complications of uremia in experimental animals and in man. A treatment strategy is summarized.

Background: Recently there has been increased interest in the special mental health needs of women. We used data from the PRIME-MD 1000 study to assess gender differences in the frequency of mental disorders in primary care settings, and to explore the potential impact of these differences on health-related quality of life (HRQL)., Subjects and Methods: One thousand primary care patients (559 women) were interviewed during the PRIME-MD study, which was conducted at four primary care clinics affiliated with university hospitals throughout the eastern United States. Patients completed a one-page questionnaire in the waiting room prior to being seen by the physician; patients and physicians then completed together a clinician evaluation guide that used DSM-III-R algorithms to diagnose mood, anxiety, somatoform, eating, and alcohol related disorders. Health-related quality of life was assessed with the Medical Outcomes Study SF-20 General Health Survey., Results: Women were more likely than men to have at least one mental disorder (43% versus 33%, P < 0.05). Higher rates were particularly prominent for mood disorders (31% of women versus 19% of men, odds ratio [OR] = 1.9, 95% confidence interval [CI] 1.4 to 2.6), anxiety disorders (22% versus 13%, OR = 1.9, CI = 1.3 to 2.8), and somatoform disorders (18% versus 9%, OR = 2.2, CI = 1.5 to 3.4). Psychiatric comorbidity was also more common in women (26% of women had two or more mental disorders versus 15% of men, P < 0.05). Unadjusted HRQL scores, ranging from 0 to 100, with 100 = best health, were all significantly lower in women than in men (eg, physical function = 67 in women versus 76 in men, P < 0.0001; mental health = 69 in women versus 76 in men, P < 0.0001). Many HRQL differences persisted after controlling for age, education, ethnicity, marital status, and number of physical disorders; however, differences in HRQL were eliminated in 5 of 6 domains after controlling for number of mental disorders. When compared with female patients of male physicians, female patients of female physicians demonstrated similar satisfaction with care, health care utilization, HRQL, and recognition rate of mental disorders., Conclusions: In the 1,000 patients of the PRIME-MD study, mood, anxiety, and somatoform disorders and psychiatric comorbidity were all significantly more common in women than men. The HRQL scores were poorer in women than men, although most of this difference was accounted for by the difference in prevalence of mental disorders. These data suggest that one of the most important aspects of a primary care physician's care of female patients is to screen for and treat common mental disorders.

The purpose of this study was to determine the current level of psychiatric training in internal medicine residencies, satisfaction with this training, and perceived need, if any, for more training. Surveys were mailed to all training directors of accredited primary care (N = 178) and categorical (N = 410) internal medicine residencies in the United States; 110 primary care (62%) and 238 categorical (58%) training directors returned the surveys. Seventy-five percent of categorical and 66% of primary care training directors thought their program should spend more time on psychiatric disorders. For all categories of psychiatric disorder, training intensity was greater and satisfaction with training higher in the primary care programs, but less than half of the directors were satisfied with their current level of training, e.g., 33% of categorical and 47% of primary care directors were satisfied with their residents training concerning depression. Training in somatoform disorders, psychotropic drugs, and office psychotherapy were most frequently identified as deficient. The most favored additions to the curriculum were psychiatric consultants in medical clinics and on medical wards. Although most outpatient care for psychiatric disorders is given by primary care physicians, internal medicine training directors perceive current levels of training in their residencies as inadequate. Innovative collaborations between medicine and psychiatry departments will be necessary if treatment of psychiatric disorders in primary care is to be improved.

Oocyte donation has made pregnancy a realistic option for women who want to become pregnant yet are unable to produce viable, healthy eggs. This article reviews oocyte donation technology, discusses ways that donor programs can deal effectively with the legal and ethical issues involved, and describes the role of the in vitro fertilization nurse.