Changes in Surgical Pathology Case Volume and Amendment Rates During the COVID-19 Pandemic.

OBJECTIVES: Surgical pathology volume decreased during the peak of the coronavirus disease 2019 (COVID-19) pandemic. We looked at the 4 months with the greatest reduction in surgical pathology volume during the COVID-19 pandemic and compared them with those same months in 2019 to determine changes in specimen volume. We compared the amendment rates during those periods and types of amendments issued (identification [ID], report defect [RD], diagnostic information [DI]). METHODS: All pathology reports between March to June 2019 and March to June 2020 were extracted from the pathology information system. All amendments issued were extracted over the same period and then subclassified by two pathologists. RESULTS: There was a 52.1% reduction in surgical pathology volume between the 4-month periods in 2019 and 2020 (P = .04). The amendment rate was 0.9% in 2019 compared with 1.4% in 2020, representing a 65.5% increase in amendments overall. There was a 53.3% reduction in amendments issued for ID, a 3.8% reduction in RD, and a 23.2% increase in amendments issued for DI. The change in amendments was not statistically significant. CONCLUSIONS: These findings suggest that a reduction in workload would not improve error rates. The circumstances of the pandemic highlight the many factors contributing to error rates in surgical pathology.

Kidney tubule health scores and their associations with incident CKD in women living with HIV.

OBJECTIVES: Individual kidney tubule biomarkers are associated with chronic kidney disease (CKD) risk in people living with HIV (PLWH). Whether a combination of kidney biomarkers can be integrated into informative summary scores for PLWH is unknown. METHODS: We measured eight urine biomarkers of kidney tubule health at two visits over a 3-year period in 647 women living with HIV in the Women's Interagency Health Study. We integrated biomarkers into factor scores using exploratory factor analysis. We evaluated associations between CKD risk factors and factor scores, and used generalized estimating equations to determine associations between factor scores and risk of incident CKD. RESULTS: Factor analysis identified two unique factor scores: a tubule reabsorption score comprising alpha-1-microglobulin, beta-2-microglobulin and trefoil factor-3; and a tubule injury score comprising interleukin-18 and kidney injury molecule-1. We modelled the two factor scores in combination with urine epidermal growth factor (EGF) and urine albumin. Predominantly HIV-related CKD risk factors were independently associated with worsening tubule reabsorption scores and tubule injury scores. During a median follow-up of 7 years, 9.7% (63/647) developed CKD. In multivariable time-updated models that adjusted for other factor scores and biomarkers simultaneously, higher tubule reabsorption scores [risk ratio (RR) = 1.27, 95% confidence interval (CI): 1.01-1.59 per 1 SD higher time-updated score], higher tubule injury scores (RR = 1.36, 95% CI: 1.05-1.76), lower urine EGF (RR = 0.75, 95% CI: 0.64-0.87), and higher urine albumin (RR = 1.20, 95% CI: 1.02-1.40) were jointly associated with risk of incident CKD. CONCLUSIONS: We identified two novel and distinct dimensions of kidney tubule health that appear to quantify informative metrics of CKD risk in PLWH.

Feasibility and Acceptability of a Program to Promote Positive Affect, Well-Being and Gender Empowerment in Black Women Living with HIV.

While programs and interventions intended to increase positive affect among people living with HIV (PLWH) and other chronic diseases have been associated with improved health outcomes, including decreased depression, programs have not been tailored specifically for Black women. We tailored a program designed to increase positive affect and to decrease depressive symptoms in PLWH to a group format for Black WLWH. We also added skills to increase gender empowerment. We then tested the acceptability and feasibility of this program with 8 Black WLWH. The program was acceptable and relatively feasible, as assessed by women's participation and feedback about program clarity and helpfulness, which women rated above 9 on a 10-point scale. A few women suggested that optimal delivery point for some skills taught would be shortly after HIV diagnosis. A proof-of-concept program intended to bolster positive emotions and gender empowerment and decrease depression can be tailored for Black WLWH and is relatively feasible and acceptable. A randomized controlled trial is needed to assess the preliminary efficacy of this program on positive affect, depression, and other health outcomes for WLWH.

Pharmacogenetic Associations with ADME Variants and Virologic Response to an Initial HAART Regimen in HIV-Infected Women.

BACKGROUND: Clinical response to highly active antiretroviral therapy (HAART) varies among different populations. A portion of this variability may be due to variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of HAART. DESIGN: To identify genetic factors involved in virologic responses to HAART, 13 genes in ADME pathways were analyzed in a cohort of HIV-infected women on HAART. A total of 569 HIV-positive participants from the Women's Interagency HIV Study who initiated HAART from 1994-2012 and had genotype data were included in these analyses. METHODS: Admixture maximum likelihood burden testing was used to evaluate gene-level associations between common genetic variation and virologic response (achieving <80 viral copies/mL) to HAART overall and with specific drug classes. Results: Six statistically significant (P<0.05) gene-level burden tests were observed with response to specific regimen types. CYP2B6, CYP2C19 and CYP2C9 were significantly associated with response to protease inhibitor (PI)-based regimens. CYP2C9, ADH1A and UGT1A1 were significantly associated with response to triple nucleoside reverse transcriptase inhibitor (NRTI) treatment. CONCLUSIONS: Although no genome-wide associations with virologic response to HAART overall were detected in this cohort of HIV-infected women, more statistically significant gene-level burden tests were observed than would be expected by chance (two and a half expected, six observed). It is likely that variation in one of the significant genes is associated with virologic response to certain HAART regimens. Further characterization of the genes associated with response to PI-based treatment is warranted.

Relation of HLA class I and II supertypes with spontaneous clearance of hepatitis C virus.

Human leukocyte antigen (HLA) genotype has been associated with the probability of spontaneous clearance of hepatitis C virus (HCV). However, no prior studies have examined whether this relationship may be further characterized by grouping HLA alleles according to their supertypes, defined by their binding capacities. There is debate regarding the most appropriate method to define supertypes. Therefore, previously reported HLA supertypes (46 class I and 25 class II) were assessed for their relation with HCV clearance in a population of 758 HCV-seropositive women. Two HLA class II supertypes were significant in multivariable models that included: (i) supertypes with significant or borderline associations with HCV clearance after adjustment for multiple tests, and (ii) individual HLA alleles not part of these supertypes, but associated with HCV clearance in our prior study in this population. Specifically, supertype DRB3 (prevalence ratio (PR)=0.4; P=0.004) was associated with HCV persistence, whereas DR8 (PR=1.8; P=0.01) was associated with HCV clearance. Two individual alleles (B*57:01 and C*01:02) associated with HCV clearance in our prior study became nonsignificant in analysis that included supertypes, whereas B*57:03 (PR=1.9; P=0.008) and DRB1*07:01 (PR=1.7; P=0.005) retained their significance. These data provide epidemiologic support for the significance of HLA supertypes in relation to HCV clearance.

Exercise performance comparison of bicaval and biatrial orthotopic heart transplant recipients.

BACKGROUND: The standard biatrial technique for orthotopic heart transplantation uses a large atrial anastomosis to connect the donor and recipient atria. A modified technique involves bicaval and pulmonary venous anastomoses and is believed to preserve the anatomic configuration and physiological function of the atria. Bicaval heart transplantation reduces postoperative valvular regurgitation and is associated with a lower incidence of pacemaker insertion. OBJECTIVE: The aim of this study was to compare postoperative functional capacity and exercise performance in patients with bicaval and biatrial orthotopic heart transplantation. METHODS: Patients were selected for the study if they did not have any of the following: obstructive coronary artery disease (>50% stenosis), severe mitral or tricuspid regurgitation, signs of rejection (grade≥1B-1R) on endomyocardial biopsy during the prior year, respiratory impairment, a permanent pacemaker, orthopedic or muscular impediments, or lived more than 150 miles from the medical center. A total of 27 patients qualified. In 15 patients who received a biatrial heart transplant and 12 patients with a bicaval heart transplant, a stationary bicycle exercise test was performed. Ventilatory gas exchange and maximum oxygen consumption measurements were measured. RESULTS: Recipient and donor characteristics, including body surface area, donor/recipient weight mismatch, immunosuppressive regimen, and self-reported weekly exercise activity, did not differ between the biatrial and bicaval groups (P=not significant [NS]). At peak exercise, similar heart rate, workload, oxygen consumption, carbon dioxide production, ventilation, functional capacity, and exercise duration were found between the 2 groups (P=NS). Patients in the biatrial group were studied later than patients in the bicaval group (6.54±0.71 vs 4.68±0.28 years; P<.001). CONCLUSION: There were no significant differences in the exercise capacity between patients with biatrial versus bicaval techniques for orthotopic heart transplantation. Factors other than the atrial connection (such as cardiac denervation, immunosuppressive drug effect, or physical deconditioning) may be more important determinants of subnormal exercise capacity after heart transplantation. Nevertheless, the reduction in morbidity and postoperative complications and the simplicity in the bicaval technique suggest that bicaval heart transplantation offers advantages when compared with the standard biatrial technique.

Quantitative and qualitative correlates of cervicovaginal herpes simplex virus type 2 shedding among HIV-infected women in the Women's Interagency HIV Study.

We identified demographic, clinical and biological determinants of herpes simplex virus type 2 (HSV-2) shedding among HIV-infected participants in the Women's HIV Interagency Study (WIHS). Cervicovaginal lavage (CVL) specimens from 369 HIV-infected HSV seropositive women were tested with TaqMan polymerase chain reaction (PRC) for detection HSV-2 DNA. Seven percent of women tested positive for HSV-2 DNA in CVL. Significant correlates of the presence of HSV-2 DNA in CVL were being younger, African American or Hispanic race/ethnicity and injecting drugs in the past six months (P < 0.05). A borderline significant trend for reduced viral shedding with higher CD4+ T cell counts was observed (P = 0.08). All women who were never observed with any genital lesions and had consistently negative self-reported history of genital sores throughout the follow-up (n = 29, 8%) were negative for CVL HSV-2 DNA. HSV-2 DNA quantity was significantly associated with having frequent subsequent lesion recurrences (Spearman rho = 0.48, P = 0.016; adjusted prevalence ratio [APR] = 2.5, P = 0.012). Increasing the age of the host was inversely correlated with decreased viral shedding over time. However, a subset of older women continued to shed significant amounts of virus despite passage of time. This study provides genital HSV-2 DNA titre as a quantitative and symptom- and sign-based measures as qualitative predictors of HSV-2 shedding from the lower genital tract among HIV-infected women.

Impairments in memory and hippocampal function in HIV-positive vs HIV-negative women: a preliminary study.

OBJECTIVE: Neurocognitive studies of HIV typically target executive functions dependent on frontostriatal circuitry. The integrity of medial temporal systems has received considerably less attention despite high hippocampal viral load. Studies also predominately involve HIV+ men, though HIV+ women may be at increased risk for cognitive dysfunction due to the high prevalence of psychosocial/mental health problems and lower educational attainment. Our aim was to conduct a preliminary investigation of episodic memory and its neural correlates in HIV-infected and at-risk uninfected women. METHODS: Participants included 54 HIV+ and 12 HIV- women (mean age = 43 years; 86% African American) recruited from the Chicago site of the Women's Interagency HIV Study. Participants completed standardized tests of verbal and visual episodic memory, working memory, and executive function. A subset of 11 women also underwent functional MRI during a delayed verbal episodic memory task. RESULTS: HIV serostatus predicted significantly lower immediate and delayed verbal episodic memory, working memory, and visual memory. Preliminary neuroimaging findings revealed group differences in bilateral hippocampal function, with HIV+ women showing decreased activation during encoding and increased activation during delayed recognition. These alterations correlated with worse episodic verbal memory. CONCLUSIONS: Verbal episodic memory deficits are evident in HIV+ women and may be associated with hippocampal dysfunction at both encoding and retrieval.

Effects of treated and untreated depressive symptoms on highly active antiretroviral therapy use in a US multi-site cohort of HIV-positive women.

This study examines the effects of treated and untreated depressive symptoms on the likelihood of utilization of highly active antiretroviral therapy (HAART) among a multi-site cohort of HIV-infected women who screened positive for probable depression. Data were collected biannually from 1996 through 2001 in a prospective cohort study. Random-effects regression analysis was used to estimate the longitudinal effects of mental health treatment on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load), demographic features (race/ethnicity, income), and behavioural factors (recent crack, cocaine, or heroin use). Use of antidepressants plus mental health therapy, or use of mental health therapy alone significantly increased the probability of HAART utilization, compared to receiving no depression treatment. Use of antidepressants alone did not differ significantly from receiving no depression treatment. African American women and those who used crack, cocaine, or heroin also were less likely to use HAART. These findings suggest that efforts to enhance depressed women's access to psychopharmacologic treatment and therapy may increase their use of the most effective HIV therapies.

Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.

Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.

Ethical problems arising in evidence based complementary and alternative medicine.

Complementary and alternative medicine has become an important section of healthcare. Its high level of acceptance among the general population represents a challenge to healthcare professionals of all disciplines and raises a host of ethical issues. This article is an attempt to explore some of the more obvious or practical ethical aspects of complementary and alternative medicine.

Dissatisfaction with medical care among women with HIV: dimensions and associated factors.

Studies have shown that women with HIV/AIDS in the USA are less likely than men to have access to appropriate health care and to utilize services, including the latest antiretroviral drug therapies. One explanation for this underutilization is patient dissatisfaction with medical care. Dissatisfaction with care has been shown to be associated not only with treatment underutilization, but also with discontinuity of care and poor clinical outcomes. Using Patient Satisfaction Questionnaire data from a national cohort of women with HIV, this study examines levels of dissatisfaction across seven established dimensions of care, and uses multivariate analysis to identify patient characteristics associated with these dimensions (N = 1,303). Women were most dissatisfied with access to care and the technical quality of care, and least dissatisfied with financial aspects of care and their providers' interpersonal manner. Women who reported poor health, who had depressive symptomatology, who were not receiving antiretroviral therapy (ART), who had no consistent care providers or who were Hispanic/Latina were more likely to be dissatisfied across most dimensions of care. Implications for enhancing clinical care for women with HIV/AIDS and overcoming barriers to utilization of care and treatment are discussed.

Pressure amorphization through displacive disorder.

After classifying amorphous materials according to their topology, we review a recently proposed theory of pressure amorphization (PA) that arises from some degree of displacive disorder while retaining a crystalline topology. That theory is based on the notion that one or more branches of the phonon spectrum become soft and flat with increasing pressure and is illustrated by a simple model that possesses the range of features displayed by many of the materials which undergo PA with displacive disorder. We report the results of Langevin simulations of the simple model which show how the probability of amorphization increases with the number of unit cells in the system and support our theory. We comment on how to generalize the model for the study of real systems.

Variation of human immunodeficiency virus type 1 viral RNA levels in the female genital tract: implications for applying measurements to individual women.

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.

A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding.

OBJECTIVES: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. METHODS: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/microl during phases of the menstrual cycle. Samples were assayed for IL-1beta, IL-6, IL-4, IL-8, IL-10, TGFbeta, TNFalpha, INFgamma, MIP1alpha, MIP1beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. RESULTS: Vaginal IL-1beta, IL-4, IL-6, IL-8, IL-10, MIP1beta, RANTES, TGFbeta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. CONCLUSION: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV.

Women and HIV: creating an ambiance of caring.

In their study of women living with or at risk of human immunodeficiency virus (HIV) infection, Schuman et al found that one-third of women reported needing mental health care, but that only two-thirds of those in need had that need met. This article describes an approach to providing mental health services to women with HIV used in our Chicago clinic. What we call the "ambiance of caring" creates an atmosphere in which mental health support can be provided and received. A continuing respectful primary care relationship and a supportive non-judgmental environment are the keys to success. Good communication, sensitive history taking, appropriate assessment tools, and direct questioning in a safe setting will let the patient know that you really care about what she is experiencing. Real-time referrals with a team of social workers, psychologists, and psychiatrists allow the best beginning to the therapeutic relationship. The next decade will provide an opportunity to address the mental health concerns of women with HIV--some of our society's most complex patients.

Drug approval summaries: arsenic trioxide, tamoxifen citrate, anastrazole, paclitaxel, bexarotene.

This report summarizes information on drugs recently approved by the Food and Drug Administration, Office of Drug Evaluation I, Division of Oncology Drug Products. Five applications supporting new claims will be discussed: Trisenox (arsenic trioxide) for induction of remission and consolidation in patients with acute promyelocytic leukemia who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose disease is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression; Nolvadex (tamoxifen citrate) in women with ductal carcinoma in situ, following breast surgery and radiation, to reduce the risk of invasive breast cancer; Arimidex (anastrazole) for first-line treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer; Taxol (paclitaxel), 175 mg/m(2) by 3 h infusion in combination with cisplatin for first-line treatment of advanced ovarian cancer; and Targretin gel (bexarotene) for the topical treatment of cutaneous lesions in patients with stage IA and IB cutaneous T-cell lymphoma who have not tolerated other therapies or who have refractory or persistent disease. Information provided includes rationale for drug development, study design, efficacy and safety results, and pertinent literature references.

Congenital heart block: development of late-onset cardiomyopathy, a previously underappreciated sequela.

OBJECTIVE: We report 16 infants with complete congenital heart block (CHB) who developed late-onset dilated cardiomyopathy despite early institution of cardiac pacing. BACKGROUND: Isolated CHB has an excellent prognosis following pacemaker implantation. Most early deaths result from delayed initiation of pacing therapy or hemodynamic abnormalities associated with congenital heart defects. METHODS: A multi-institutional study was performed to identify common clinical features and possible risk factors associated with late-onset dilated cardiomyopathy in patients born with congenital CHB. RESULTS: Congenital heart block was diagnosed in utero in 12 patients and at birth in four patients. Ten of 16 patients had serologic findings consistent with neonatal lupus syndrome (NLS). A pericardial effusion was evident on fetal ultrasound in six patients. In utero determination of left ventricular (LV) function was normal in all. Following birth, one infant exhibited a rash consistent with NLS and two had elevated hepatic transaminases and transient thrombocytopenia. In the early postnatal period, LV function was normal in 15 patients (shortening fraction [SF] = 34 +/- 7%) and was decreased in one (SF = 20%). A cardiac pacemaker was implanted during the first two weeks of life in 15 patients and at seven months in one patient. Left ventricular function significantly decreased during follow-up (14 days to 9.3 years, SF = 9% +/- 5%). Twelve of 16 patients developed congestive heart failure before age 24 months. Myocardial biopsy revealed hypertrophy in 11 patients, interstitial fibrosis in 11 patients, and myocyte degeneration in two patients. Clinical status during follow-up was guarded: four patients died from congestive heart failure; seven required cardiac transplantation; one was awaiting cardiac transplantation; and four exhibited recovery of SF (31 +/- 2%). CONCLUSIONS: Despite early institution of cardiac pacing, some infants with CHB develop LV cardiomyopathy. Patients with CHB require close follow-up not only of their cardiac rate and rhythm, but also ventricular function.