Methodology for Sampling Women at High Maternal Risk in Administrative Data

Background: In population level studies, the conventional practice of categorizing women into low and high maternal risk samples relies upon ascertaining the presence of various comorbid conditions in administrative data. Two problems with the conventional method include variability in the recommended comorbidities to consider and inability to distinguish between maternal and fetal risks. High maternal risk sample selection may be improved by using the Obstetric Comorbidity Index (OCI), a system of risk scoring based on weighting comorbidities associated with maternal end organ damage. The purpose of this study was to compare the net benefit of using OCI risk scoring vs the conventional risk identification method to identify a sample of women at high maternal risk in administrative data. Methods: This was a net benefit analysis using linked delivery hospitalization discharge and vital records data for women experiencing singleton births in Georgia from 2008 to 2012. We compared the value identifying a sample of women at high maternal risk using the OCI score to the conventional method of dichotomous identification of any comorbidities. Value was measured by the ability to select a sample of women designated as high maternal risk who experienced severe maternal morbidity or mortality. Results: The high maternal risk sample created with the OCI had a small but positive net benefit (+ 0.6), while the conventionally derived sample had a negative net benefit indicating the sample selection performed worse than identifying no woman as high maternal risk. Conclusions: The OCI can be used to select women at high maternal risk in administrative data. The OCI provides a consistent method of identification for women at risk of maternal morbidity and mortality and avoids confounding all obstetric risk factors with specific maternal risk factors. Using the OCI may help reduce misclassification as high maternal risk and improve the consistency in identifying women at high maternal risk in administrative data

Outcome after steroid withdrawal in pediatric renal transplant patients receiving tacrolimus-based immunosuppression

Background. Corticosteroids have always been an integral part of immunosuppressive regimens in renal transplantation. The primary goal of this analysis was to assess the safety of steroid withdrawal in our pediatric renal transplant recipients receiving tacrolimus-based immunosuppression. Methods. Between December 1989 and December 1996, 82 renal transplantations were performed in pediatric patients receiving tacrolimus-based immunosuppression. Two of these patients lost their grafts within 3 weeks of transplantation (and were still on steroids at the time of graft loss), and were excluded from further analysis. Seventy-four patients (92.5%) were taken off prednisone a median of 5.7 months after transplantation. Of these 74, 56 (70%) remained off prednisone (OFF), and 18 (22.5%) were restarted on prednisone a median of 14.8 months after discontinuing steroids (OFF → ON). 6(7.5%) were never taken off prednisone (ON). The mean follow-up was 59±23 months. Results. The 1-, 3-, and 5-year actuarial patient survival rates in the OFF group were 100%, 98%, and 96%, respectively; in the OFF → ON group, they were 100%, 100%, and 100%, and in the ON group, they were 100%, 83%, and 83%. The 1-, 3-, and 5- year actuarial graft survival rates in the OFF group were 100%, 95%, and 82%, respectively; in the OFF → ON group, they were 100%, 89%, and 83%; and in the ON group, they were 100%, 50%, and 33%. Two of the six graft losses in the OFF group, three out of four in the OFF → ON Group, and two out of five in the ON group, were to chronic rejection. A time-dependent Cox regression analysis showed that the hazard for graft failure for those who came and stayed off prednisone was 0.178 relative to those who were never withdrawn from prednisone (P=0.005). Patients who were 10 years of age or younger were withdrawn from prednisone earlier (median: 5 months) than those older than 10 years (median: 7.3 months, P=0.02). In addition, patients who never had acute rejection were withdrawn from steroids earlier (median: 5 months) than those who had one or more episodes of acute rejection (median: 7.6 months, P=0.001). There was no effect of donor age, race, sex, recipient race, sex, cadaveric versus living donor, 48-hr graft function, panel reactive antibody, and total HLA mismatches or matches on the likelihood of being weaned off steroids. Serum creatinine at most recent follow-up in the OFF group was 1.2±0.5 mg/dl; in the OFF → ON group, it was 1.8±0.9 mg/dl, and in the ON group it was 2.0 mg/dl (P<0.003). The incidence of rejection in the OFF, OFF → ON, and ON groups was 39%, 77%, and 100%, respectively (P<0.05). Conclusion. These data suggest that steroid withdrawal in pediatric renal transplant patients receiving tacrolimus-based immunosuppression is associated with reasonable short- and medium-term patient and graft survival, and acceptable renal function. Patients who discontinue and then resume steroids had patient and graft survival rates comparable with those in patients who discontinue and stay off steroids, but had a higher serum creatinine and a higher incidence of rejection

Pediatric renal transplantation under tacrolimus-based immunosuppression

Background. Tacrolimus has been used as a primary immunosuppressive agent in adult and pediatric renal transplant recipients, with reasonable outcomes. Methods. Between December 14, 1989 and December 31, 1996, 82 pediatric renal transplantations alone were performed under tacrolimus-based immunosuppression without induction anti-lymphocyte antibody therapy. Patients undergoing concomitant or prior liver and/or intestinal transplantation were not included in the analysis. The mean recipient age was 10.6±5.2 years (range: 0.7-17.9). Eighteen (22%) cases were repeat transplantations, and 6 (7%) were in patients with panel-reactive antibody levels over 40%. Thirty-four (41%) cases were with living donors, and 48 (59%) were with cadaveric donors. The mean donor age was 27.3±14.6 years (range: 0.7-50), and the mean cold ischemia time in the cadaveric cases was 26.5±8.8 hr. The mean number of HLA matches and mismatches was 2.8±1.2 and 2.9±1.3; there were five (6%) O-Ag mismatches. The mean follow-up was 4.0±0.2 years. Results. The 1- and 4-year actuarial patient survival was 99% and 94%. The 1- and 4-year actuarial graft survival was 98% and 84%. The mean serum creatinine was 1.1±0.5 mg/all, and the corresponding calculated creatinine clearance was 88±25 ml/min/1.73 m2. A total of 66% of successfully transplanted patients were withdrawn from prednisone. In children who were withdrawn from steroids, the mean standard deviation height scores (Z-score) at the time of transplantation and at 1 and 4 years were - 2.3±2.0, -1.7±1.0, and +0.36±1.5. Eighty-six percent of successfully transplanted patients were not taking anti-hypertensive medications. The incidence of acute rejection was 44%; between December 1989 and December 1993, it was 63%, and between January 1994 and December 1996, it was 23% (P=0.0003). The incidence of steroid-resistant rejection was 5%. The incidence of delayed graft function was 5%, and 2% of patients required dialysis within 1 week of transplantation. The incidence of cytomegalovirus was 13%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 12%. The incidence of early Epstein- Barr virus-related posttransplant lymphoproliferative disorder (PTLD) was 9%; between December 1989 and December 1992, it was 17%, and between January 1993 and December 1996, it was 4%. All of the early PTLD cases were treated successfully with temporary cessation of immunosuppression and institution of antiviral therapy, without patient or graft loss. Conclusions. These data demonstrate the short- and medium-term efficacy of tacrolimus-based immunosuppression in pediatric renal transplant recipients, with reasonable patient and graft survival, routine achievement of steroid and anti- hypertensive medication withdrawal, gratifying increases in growth, and, with further experience, a decreasing incidence of both rejection and PTLD

Variability in Pediatric Infectious Disease Consultants' Recommendations for Management of Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is a common childhood infection. CAP complications, such as parapneumonic empyema (PPE), are increasing and are frequently caused by antibiotic-resistant organisms. No clinical guidelines currently exist for management of pediatric CAP and no published data exist about variations in antibiotic prescribing patterns. Our objectives were to describe variation in CAP clinical management for hospitalized children by pediatric infectious disease consultants and to examine associations between recommended antibiotic regimens and local antibiotic resistance levels. (MRSA) in their community.e or clindamycin use and clindamycin resistance, however, respondents were more likely to recommend an anti-MRSA agent when MRSA prevalence increased.Substantial variability exists in recommendations for CAP management. Development of clinical guidelines via antimicrobial stewardship programs and dissemination of data about local antibiotic resistance patterns represent opportunities to improve care

Interstitial mycosis fungoides, a variant of mycosis fungoides resembling granuloma annulare and inflammatory morphea *

Interstitial mycosis fungoides (IMF) is a rare variant of mycosis fungoides that resembles the interstitial form of granuloma annulare and inflammatory morphea. IMF has received little attention in the literature. Methods:   Clinical, histological, immunophenotypical, and genotypical findings of five cases of IMF were reviewed. The histological and immunophenotypical findings were compared with those of eight cases of interstitial granuloma annulare and six cases of inflammatory morphea. Results:   Five patients with IMF presented with non-indurated, erythematous macules; ill-defined erythematous plaques with slight scale; and nodules on the trunk and proximal limbs. Two of five patients had a prior diagnosis of mycosis fungoides. Skin biopsies revealed a striking dermal interstitial infiltrate of lymphocytes with rare histiocytes that resembled the interstitial form of granuloma annulare or inflammatory morphea. Epidermotropic lymphocytes were present at least focally in all cases. A band-like lymphocytic infiltrate was observed in two of five cases. In contrast, many plasma cells and histiocytes were observed in cases of inflammatory morphea and interstitial granuloma annulare, respectively. With Movat-pentachrome stains, increased dermal mucin deposition was observed in two of five IMF cases, in all cases of interstitial granuloma annulare, and in one of six cases of inflammatory morphea. There was focal loss of elastic fibers in all cases of inflammatory morphea. Immunohistochemical studies of IMF highlighted a dominant population of T cells (CD3+) in the dermis and epidermis. In contrast, moderate numbers of B cells (CD20+) were admixed with T cells and plasma cells in inflammatory morphea. Almost equal numbers of histiocytes (CD68+) and T cells comprised the infiltrate of interstitial granuloma annulare. In two of five IMF cases, a clonal T-cell population was detected by PCR T-cell gamma gene rearrangement analysis. Conclusion:   Mycosis fungoides occasionally presents as an interstitial lymphocytic infiltrate that mimics granuloma annulare and inflammatory morphea. Hematoxylin & eosin (H&E) findings alone can sometimes distinguish the three disorders. Immunophenotyping and genotyping may be helpful in difficult cases. Su LD, Kim YH, LeBoit PE, Swetter SM, Kohler S. Interstitial mycosis fungoides, a variant of mycosis fungoides resembling granuloma annulare and inflammatory morphea. J Cutan Pathol 2002; 29: 135–141. © Blackwell Munksgaard 2002.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72026/1/j.1600-0560.2002.290302.x.pd

Combined liver-kidney transplantation and the effect of preformed lymphocytotoxic antibodies

Thirty-eight sequentially placed liver and kidney allografts were evaluated with respect to patient and graft survival, and the influence of preformed lymphocytotoxic antibodies was analysed. The results suggest that the survival rate of combined liver and kidney transplantation is similar to the survival rate of liver transplantation alone. Sequentially placed kidney allografts may be protected from hyperacute rejection in the presence of donor specific lymphocytotoxic antibodies, but not in all instances. Both patient and kidney allograft survival was lower in positive crossmatch patients (33% and 17% respectively) than in negative crossmatch patients (78% and 75%). High levels of panel reactive antibodies (>10%) also appeared to have a deleterious effect on survival, although the majority of the patients who failed also had a positive crossmatch. Although preformed lymphocytotoxic antibodies are not an absolute contraindication to combined liver-kidney transplantation, they do appear to have a deleterious effect on long-term graft survival. However, more correlation with clinical parameters is needed. © 1994

Design and baseline data from the vanguard of the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS) randomized controlled trial

This paper describes the rationale and design of the vanguard for the Comparison of Depression Interventions after Acute Coronary Syndrome (CODIACS), a multicenter, randomized, controlled trial of a patient preference‐based, stepped care protocol for persistent depressive symptoms after acute coronary syndrome (ACS). The overall aim of the vanguard phase was to determine whether the patient-preference, stepped care protocol, which is based on the intervention used in the recent Coronary Psychosocial Evaluation Studies (COPES) trial, was feasible in patients with recent ACS who were recruited from 5 geographically diverse sites. Innovative design features of this trial include randomization to either initial patient-preference of treatment or to a referred care arm in which the primary care provider decided upon care. Additionally, delivery of psychotherapy was accomplished by telephone, or webcam, depending upon patient preference. The vanguard phase provides estimates of eligibility and screening/enrollment ratios, patient acceptance of screening, and retention. In this report, we describe the innovative features and the baseline results of the vanguard phase of CODIACS. The data from this vanguard study will be used to finalize planning for a large, phase III clinical trial designed to evaluate the effect of treatment on depressive symptoms, coronary events, and death

Hsp90 orchestrates transcriptional regulation by Hsf1 and cell wall remodelling by MAPK signalling during thermal adaptation in a pathogenic yeast

Acknowledgments We thank Rebecca Shapiro for creating CaLC1819, CaLC1855 and CaLC1875, Gillian Milne for help with EM, Aaron Mitchell for generously providing the transposon insertion mutant library, Jesus Pla for generously providing the hog1 hst7 mutant, and Cathy Collins for technical assistance.Peer reviewedPublisher PD

Centralized, Stepped, Patient Preference–Based Treatment for Patients With Post–Acute Coronary Syndrome Depression

IMPORTANCE: Controversy remains about whether depression can be successfully managed after acute coronary syndrome (ACS) and the costs and benefits of doing so. OBJECTIVE: To determine the effects of providing post-ACS depression care on depressive symptoms and health care costs. DESIGN: Multicenter randomized controlled trial. SETTING: Patients were recruited from 2 private and 5 academic ambulatory centers across the United States. PARTICIPANTS: A total of 150 patients with elevated depressive symptoms (Beck Depression Inventory [BDI] score ≥10) 2 to 6 months after an ACS, recruited between March 18, 2010, and January 9, 2012. INTERVENTIONS: Patients were randomized to 6 months of centralized depression care (patient preference for problem-solving treatment given via telephone or the Internet, pharmacotherapy, both, or neither), stepped every 6 to 8 weeks (active treatment group; n = 73), or to locally determined depression care after physician notification about the patient's depressive symptoms (usual care group; n = 77). MAIN OUTCOME MEASURES: Change in depressive symptoms during 6 months and total health care costs. RESULTS: Depressive symptoms decreased significantly more in the active treatment group than in the usual care group (differential change between groups, -3.5 BDI points; 95% CI, -6.1 to -0.7; P = .01). Although mental health care estimated costs were higher for active treatment than for usual care, overall health care estimated costs were not significantly different (difference adjusting for confounding, -$325; 95$2639 to $1989; P = .78). CONCLUSIONS: For patients with post-ACS depression, active treatment had a substantial beneficial effect on depressive symptoms. This kind of depression care is feasible, effective, and may be cost-neutral within 6 months; therefore, it should be tested in a large phase 3 pragmatic trial. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01032018