Cervical Cancer Screening Behaviors Among Asian Indians in the United States: A Systematic Review.

While Asian Indians (AIs) are the third fastest-growing Asian minority population in the United States, they fall short of the Healthy People cervical cancer screening target goals, with rates averaging 70% compared to 83% among non-Hispanic Whites. The purpose of this systematic review is to examine factors influencing cervical cancer screening behaviors among AIs in the US. Medline, CINAHL, PubMed, PsychINFO, and ProQuest databases were searched for qualitative and quantitative studies conducted between 1990 and 2017 that focused on cervical cancer screening behaviors among AIs in the US. The seven selected quantitative cross-sectional descriptive studies show that acculturation, length of stay in the US, age, education level, employment, cultural beliefs, and language influence cervical cancer screening behaviors among AIs in the US. Results from this systematic review inform development of culturally sensitive interventions to raise awareness and engagement in cervical cancer screening among AIs.

Treatment Status of Hepatocellular Carcinoma Does Not Influence Rates of Sustained Virologic Response: An HCV-TARGET Analysis.

Recent studies have suggested a negative impact of hepatocellular carcinoma (HCC) on sustained virologic response (SVR) to hepatitis C virus (HCV) direct acting antivirals (DAAs). We compared the effectiveness of DAAs in patients with cirrhosis, with and without HCC, and in those with HCC partially treated or untreated (PT/UT-HCC) versus completely treated (CT-HCC). HCC status was based on imaging 6 months before or 2 months after start of DAA therapy. Absence and presence of enhancing lesions after HCC treatment defined CT-HCC and PT/UT-HCC, respectively. Using minimally adjusted logistic regression, the association between the presence of HCC and SVR rates was estimated. Among the 1,457 patients with cirrhosis from HCV-TARGET with complete virologic data (per-protocol population) who did not undergo liver transplantation during treatment and followup, 1,300 were without HCC, 91 with CT-HCC, and 66 with PT/UT-HCC. Most patients were genotype 1 (81%) and treatment-experienced (56%), 41% had history of prior decompensation, and the median pretreatment Model for End-Stage Liver Disease was 9 (range 6-39). The SVR rates were 91% for patients without HCC, 84% for CT-HCC, and 80% for PT/UT-HCC. The presence of HCC (versus not having HCC) was associated with significantly lower odds of achieving SVR (odds ratio [OR] = 0.51, 95% confidence interval [CI]: 0.33-0.81; P = 0.003). However, among those with HCC, HCC treatment status (PT/UT-HCC versus CT-HCC) did not show association with SVR (OR = 0.79, 95% CI: 0.35-1.79, P = 0.569). Conclusions: The presence of HCC reduces the likelihood of SVR by 50%, but with no evident difference in those with completely treated HCC versus partially treated/untreated HCC.

Using Unsupervised Machine Learning to Identify Subgroups Among Home Health Patients With Heart Failure Using Telehealth.

This study explored the use of unsupervised machine learning to identify subgroups of patients with heart failure who used telehealth services in the home health setting, and examined intercluster differences for patient characteristics related to medical history, symptoms, medications, psychosocial assessments, and healthcare utilization. Using a feature selection algorithm, we selected seven variables from 557 patients for clustering. We tested three clustering techniques: hierarchical, k-means, and partitioning around medoids. Hierarchical clustering was identified as the best technique using internal validation methods. Intercluster differences among patient characteristics and outcomes were assessed with either χ test or one-way analysis of variance. Ranging in size from 153 to 233 patients, three clusters displayed patterns that differed significantly (P < .05) in patient characteristics of age, sex, medical history of comorbid conditions, use of beta blockers, and quality of life assessment. Significant (P < .001) intercluster differences in number of medications, comorbidities, and healthcare utilization were also revealed. The study identified patterns of association between (1) mental health status, pulmonary disorders, and obesity, and (2) healthcare utilization for patients with heart failure who used telehealth in the home health setting. Study results also revealed a lack of prescription guideline-recommended heart failure medications for the subgroup with the highest proportion of older female adults.

Short Course of Postoperative Hepatitis B Immunoglobulin Plus Antivirals Prevents Reinfection of Liver Transplant Recipients.

BACKGROUND: Hepatitis B immune globulin (HBIG) has been an integral component of prophylaxis against hepatitis B virus (HBV) recurrence in liver transplantation (LT) recipients, but HBIG is costly and inconvenient to administer, prompting consideration of alternative regimens. METHODS: In this retrospective cohort, we report on the success of antiviral therapy combined with a short course (in hospital only) HBIG in liver transplant recipients with HBV DNA less than 100 IU/mL pre-LT. RESULTS: A total of 42 hepatitis B surface antigen (HBsAg) positive, human immunodeficiency virus and hepatitis D virus-negative patients with pretransplant HBV DNA undetectable to 100 IU/mL who received HBIG 5000 IU in anhepatic phase and daily for 5 days together with nucleos(t)ide analogues indefinitely yielded 1- and 3-year cumulative incidences of recurrence, defined by positive serum HBsAg, of 2.9% (upper 95% confidence interval, 19%). One patient had HBV viremia 16 months post-LT without detectable HBsAg. Both patients with either HBsAg positivity or viremia had recurrent hepatocellular carcinoma diagnosed within a month of detection. Post-LT survival was 98% and 94% at 1 and 5 years, respectively. CONCLUSIONS: We conclude that a very short course of HBIG combined with long-term antiviral therapy is highly effective in preventing HBV recurrence and should be the preferred strategy for LT recipients with undetectable or low-level viremia at time of LT.

Reduced Toxicity Conditioning and Allogeneic Hematopoietic Progenitor Cell Transplantation for Recessive Dystrophic Epidermolysis Bullosa.

Recessive dystrophic epidermolysis bullosa is a severe, incurable, inherited blistering disease caused by COL7A1 mutations. Emerging evidence suggests hematopoietic progenitor cells (HPCs) can be reprogrammed into skin; HPC-derived cells can restore COL7 expression in COL7-deficient mice. We report two children with recessive dystrophic epidermolysis bullosa treated with reduced-toxicity conditioning and HLA-matched HPC transplantation.

A novel trial of topotecan, ifosfamide, and carboplatin (TIC) in children with recurrent solid tumors.

BACKGROUND: Ifosfamide, carboplatin, and etoposide (ICE) in children with refractory or recurrent solid tumors and lymphomas has resulted in good overall response rates (ORR). Etoposide, a topoisomerase-II inhibitor, however, has been associated with a significant increase in secondary leukemia. The rationale for substituting topotecan, a topoisomerase-I inhibitor, for etoposide in this regimen, a topoisomerase-II inhibitor, includes its limited toxicity profile and decreased leukemogenicity. Furthermore, topotecan in combination with both alkylators and platinating agents are additive and/or synergistic against a variety of solid tumors. PROCEDURE: Patients with relapsed/refractory solid tumors received ifosfamide (9 g/m2 ) and carboplatin (area under the curve: 3 mg/ml/min). Topotecan was also administered at 0.5 mg/m2 /day × 3 days (N = 12) and in a small cohort (N = 3) at 0.75 mg/m2 /day. RESULTS: Fifteen patients were entered onto study. Two patients developed seizures/encephalitis secondary to ifosfamide. One patient had dose-limiting thrombocytopenia secondary to TIC that resolved with supportive care. Patients received a median of three cycles (1-3) of TIC. Of the 14 evaluable patients for response, 4/14 had a complete response (CR), 2/14 had a partial response (PR), and 1/14 patients had stable disease (SD). The ORR (CR + PR) was 43%. CONCLUSION: TIC chemotherapy is feasible and tolerable in children and adolescents with refractory/recurrent solid tumors and lymphomas and results in a 43% excellent ORR in this poor-risk group of patients. A larger cohort of patients, especially in Wilms tumor and central nervous system (CNS) tumors, should be studied in the future to attempt to confirm these preliminary findings. Pediatr Blood Cancer 2015;62:274-278. © 2014 Wiley Periodicals, Inc.

Enhanced survival during experimental Listeria monocytogenes sepsis in neonatal mice prophylactically treated with Th1 and macrophage immunoregulatory cytokines and mediators.

BACKGROUND: Impairments in T-cell and macrophage-mediated host defense lead to increased infection-related morbidity and mortality in neonates, partly because of immaturity in T helper (Th)1 function. Listeria monocytogenes (Lm) is an intracellular pathogen disproportionately causing severe disease among neonates and the immunocompromised. Intact macrophage and Th1-mediated immune responses are critical for Lm clearance. We and others have previously demonstrated downregulation of Th1 and macrophage immunoregulatory cytokines in cord blood versus adult peripheral blood. We sought to determine whether therapeutic or prophylactic single agent or combination recombinant murine interleukin (rmIL)-12, rmIL-18, recombinant murine macrophage-colony stimulating factor (rmM-CSF), recombinant murine granulocyte macrophage-colony stimulating factor (rmGM-CSF) and recombinant murine interferon (rmIFN)-γ would enhance survival during experimental neonatal Lm sepsis. METHODS: A 90% lethal dose (LD90) of Lm was established in C57/BL/6 neonatal mice. rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and rmIFN-γ were administered singly or sequentially, before or after LD90 Lm inoculation; ampicillin was administered 24 hours after inoculation. RESULTS: Therapeutic doses of rmIL-12, rmIL-18, rmM-CSF, rmGM-CSF and rmIFN-γ as single agents and sequential therapy with rmM-CSF + (rmIL-12 and/or rmIL-18) + rmIFN-γ in addition to ampicillin were not associated with increased survival. However, prophylactic single doses of rmIL-12, rmIL-18, rmM-CSF and rmIFN-γ and prophylactic sequential doses of rmM-CSF + (rmIL-12 and/or rmIL-18) + rmIFN-γ in addition to ampicillin were associated with significantly enhanced survival compared with ampicillin alone. CONCLUSIONS: These data suggest prophylactic administration of macrophage and Th1 immunoregulatory cytokines can potentially overcome deficits in neonatal immunity to protect against Lm.

A comparison of bronchoalveolar lavage versus lung biopsy in pediatric recipients after stem cell transplantation.

Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications after hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome after BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonary infiltrates on chest radiograph and/or computed tomography scan. The 1-year probability of undergoing BAL was 43.0% after allogeneic stem cell transplantation (alloSCT) and 8.5% after autologous stem cell transplantation (autoSCT) (P = .001). Sixteen of the 193 patients (8%) patients underwent 19 LBs. The probability of undergoing LB at 1 year after HSCT was 9.3%. No grade III or IV adverse events related to either procedure were observed. Of the 101 BALs performed, 40% (n = 40) were diagnostic, with a majority revealing a bacterial pathogen. Among the 19 LBs performed, 94% identified an etiology. In multivariate analysis, myeloablative conditioning alloSCT conferred the highest risk of requiring a BAL (hazard ratio [HR],8.5; P = .0002). The probability of 2-year overall survival was 20.2% in patients who underwent BAL, 17.5% for patients who underwent biopsy, and 67.4% for patients who had neither procedure. In multivariate analysis, only the requirement of a BAL was independently associated with an increased risk of mortality (HR, 2.96; P < .0001). In summary, in this cohort of pediatric HSCT recipients, BAL and LB were used in approximately 35% and 8% of pediatric HSCTs with diagnostic yields of approximately 40% and 94%, respectively, and were both associated with poor long-term outcomes.

A retrospective study on patient characteristics and telehealth alerts indicative of key medical events for heart failure patients at a home health agency.

OBJECTIVE: To explore association of patient characteristics and telehealth alert data with all-cause key medical events (KMEs) of emergency department (ED) visits and hospitalizations as well as cardiac-related KMEs of ED visits, hospitalizations, and medication changes. MATERIALS AND METHODS: A 6-month retrospective study was conducted of electronic patient records of heart failure (HF) patients using telehealth services at a Massachusetts home health agency. Data collected included patient demographic, psychosocial, disease severity factors and telehealth vital signs alerts. Association between patient characteristics and KMEs was analyzed by Generalized Estimating Equations. RESULTS: The sample comprised 168 patients with a mean age of 83 years, 56% females, and 96% white. Ninety-nine cardiac-related KMEs and 87 all-cause KMEs were recorded for the subjects. Odds of a cardiac-related KME increased by 161% with the presence of valvular co-morbidity (p=0.001) and 106% with increased number of telehealth alerts (adjusted p<0.0001). Odds of an all-cause KME increased by 124% (p=0.02), 127% (p=0.01), and 70% (adjusted p<0.0001) with the presence of cancer co-morbidity, anxiety, and increased number of telehealth alerts, respectively. Overall, only 3% of all telehealth alerts were associated with KMEs. CONCLUSIONS: The very low proportion of telehealth vital sign alerts associated with KMEs indicates that telehealth alerts alone cannot inform the need for intervention within the larger context of HF care delivery in the homecare setting. Patient-relevant data such as psychosocial and symptom status, involvement with HF self-management, and presence of co-morbidities could further inform the need for interventions for HF patients in the homecare setting.

Risk factors associated with liver injury and impact of liver injury on transplantation-related mortality in pediatric recipients of allogeneic hematopoietic stem cell transplantation.

In adults, hepatic complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with significant morbidity and transplantation-related mortality (TRM). However, there is a paucity of parallel data on the incidence of, and risk factors for, liver injury (LI) and the impact of LI on TRM in pediatric allo-HSCT recipients. We compared total bilirubin, direct bilirubin, and alanine aminotransferase values before allo-HSCT and at 1 month, day +100, and 12 months after allo-HSCT in 248 patients who received either a myeloablative conditioning (MAC) regimen (n = 109) or a reduced-toxicity/reduced-intensity conditioning (RTC/RIC) regimen (n = 139). LI was defined as grade ≥ 2 hyperbilirubinemia according to the National Cancer Institute's Common Terminology Criteria for Adverse Events 3.0/4.0 (total bilirubin, >1.95 mg/dL, 1.5 times above the upper limit of normal for our laboratory). Univariate and multivariate logistic regression models were used to identify risk factors for LI and TRM. The incidence of LI at 1 month after allo-HSCT was 14.1%. The median bilirubin level was 3.5 mg/dL (range, 1.97 to 32.2 mg/dL). Only LI as defined by total bilirubin level, but not by direct bilirubin or alanine aminotransferase level, was found to be a significant predictor for TRM. The 1-year TRM was 60.7% (95% confidence interval, 42.6% to 78.7%) in patients with LI at 1 month after allo-HSCT, compared with 14.6% (95% confidence interval, 9.9% to 19.4%) (P < .0001) in patients those who did not have liver injury. Multivariate analysis identified age (P = .03), total body irradiation (P = .007), bacterial bloodstream infection (BBSI) (P = .001), and invasive fungal infection (IFI) (P = .002) as significant risk factors for developing LI at 1 month. On multivariate analysis for risk factors for TRM, only LI at 1 month after allo-HSCT (P < .0001), primary graft failure (P = .001), BBSI (P = .003), and systemic viral infection (P = .04) were identified as significant risk factors for TRM. LI before allo-HSCT conditioning was not associated with higher TRM. Although the incidence of LI in pediatric allo-HSCT recipients is low, LI is associated with very high TRM. BBSI and IFI are the primary risk factors for LI.

Association of comorbidities with home care service utilization of patients with heart failure while receiving telehealth.

BACKGROUND: Comorbidities adversely impact heart failure (HF) outcomes. Telehealth can assist healthcare providers, especially nurses, in guiding their patients to follow the HF regimen. However, factors, including comorbidity patterns, that act in combination with telehealth to reduce home care nursing utilization are still unclear. PURPOSE: The purpose of this article was to examine the association of the comorbidity characteristics of HF patients with nursing utilization along with withdrawal from telehealth service during an episode of tele-home care. METHODOLOGY: A descriptive, correlational study design using retrospective chart review was used. The sample comprised Medicare patients admitted to a New England home care agency who had HF as a diagnosis and had used telehealth from 2008 to 2010. The electronic documentation at the home care agency served as the data source, which included Outcome and Assessment Information Set data of patients with HF. Logistic and multiple regression analyses were used to analyze data. RESULTS: The sample consisted of 403 participants, of whom 70% were older than 75 years, 55% were female, and 94% were white. Comorbidities averaged 5.19 (SD, 1.92), ranging from 1 to 11, and nearly 40% of the participants had 5 or more comorbidities. The mean (SD) nursing contacts in the sample was 9.9 (4.7), ranging from 1 to 26, and 52 (12.7%) patients withdrew from telehealth service. For patients with HF on telehealth, comorbidity characteristics of anemia, anxiety, musculoskeletal, and depression were significantly associated with nursing utilization patterns, and renal failure, cancer, and depression comorbidities were significantly associated with withdrawal from telehealth service. CLINICAL IMPLICATIONS: Knowledge of the association of comorbidity characteristics with the home care service utilization patterns of patients with HF on telehealth can assist the home health nurse to develop a tailored care plan that attains optimal patient outcomes. Knowledge of such associations would also focus home care resources, avoiding redundancy of resource utilization in this era of strained healthcare resources.

The efficacy of tailored interventions for self-management outcomes of type 2 diabetes, hypertension or heart disease: a systematic review.

AIM: To evaluate the evidence on the effectiveness of tailored interventions on self-management behaviours in individuals with heart disease, hypertension or type 2 diabetes. BACKGROUND: Tailored interventions are designed for individuals based on their unique characteristics, related to the outcome of interest, and derived from an individual assessment. Recognizing the differences between individuals and delivering interventions tailored to the individual could increase the likelihood of sustained self-management of long-term conditions. Review methods. A review of randomized controlled trials published between 2001 and 2010 was undertaken using the following databases: Pubmed, WOS, CINAHL, ERIC, ASP, PsychInfo and SSA. The search terms included tailored intervention(s), and self-management of chronic diseases included in the aim. Reference lists from relevant articles were also examined for additional references. RESULTS: Ten studies were included in the review. Tailored interventions had no impact on self-management activities such as medication adherence, self-monitoring, exercise, smoking, or diet control. However, tailored interventions were modestly successful in improving specific self-management behaviours of dietary fat intake, levels of physical activity or screening. Studies included in the review generally suffered from compromised methodological issues of inadequately powered sample size, non-blinding of data collection or intervention delivery and inadequate reporting of the randomization process. CONCLUSION: When cost and resource utilization is taken into consideration, tailored interventions may not be more effective than standard interventions in improving self-management behaviours in individuals with long-term conditions. Future research should explore the effect of robust and resource-optimized tailored interventions on self-management outcomes for long-term conditions with high-quality trials.

Anti-inflammatory pharmacotherapy with ketoprofen ameliorates experimental lymphatic vascular insufficiency in mice.

BACKGROUND: Disruption of the lymphatic vasculature causes edema, inflammation, and end-tissue destruction. To assess the therapeutic efficacy of systemic anti-inflammatory therapy in this disease, we examined the impact of a nonsteroidal anti-inflammatory drug (NSAID), ketoprofen, and of a soluble TNF-alpha receptor (sTNF-R1) upon tumor necrosis factor (TNF)-alpha activity in a mouse model of acquired lymphedema. METHODS AND FINDINGS: Lymphedema was induced by microsurgical ablation of major lymphatic conduits in the murine tail. Untreated control mice with lymphedema developed significant edema and extensive histopathological inflammation compared to sham surgical controls. Short-term ketoprofen treatment reduced tail edema and normalized the histopathology while paradoxically increasing TNF-alpha gene expression and cytokine levels. Conversely, sTNF-R1 treatment increased tail volume, exacerbated the histopathology, and decreased TNF-alpha gene expression. Expression of vascular endothelial growth factor-C (VEGF-C), which stimulates lymphangiogenesis, closely correlated with TNF-alpha expression. CONCLUSIONS: Ketoprofen therapy reduces experimental post-surgical lymphedema, yet direct TNF-alpha inhibition does not. Reducing inflammation while preserving TNF-alpha activity appears to optimize the repair response. It is possible that the observed favorable responses, at least in part, are mediated through enhanced VEGF-C signaling.

The clinical spectrum of lymphatic disease.

Lymphatic disease is quite prevalent, and often not well clinically characterized. Beyond lymphedema, there is a broad array of human disease that directly or indirectly alters lymphatic structure and function. The symptomatic and objective presentation of these patients can be quite diverse. In this review, we have attempted to provide a systematic overview of the subjective and objective spectrum of lymphatic disease, with consideration of all of the categories of disease that primarily or secondarily impair the functional integrity of the lymphatic system. Lymphedema is discussed, along with chromosomal disorders, lymphangioma, infectious diseases, lymphangioleiomyomatosis, lipedema, heritable genetic disorders, complex vascular malformations, protein-losing enteropathy, and intestinal lymphangiectasia.

Gorham's disease: an osseous disease of lymphangiogenesis?

Gorham's disease, also known as massive osteolysis, Gorham-Stout disease, vanishing bone disease, or, phantom bone disease is a rare disorder of the musculoskeletal system. The disease is characterized by osteolysis in bony segments, with localized proliferation of lymphatic channels. The presence of abundant, leaky systemic lymphatic vessels is often accompanied by chylous ascites. There is no standardized treatment available for Gorham's disease, and its molecular mechanisms remain unclear. Future strategies for understanding Gorham's disease should emphasize its apparent identity as a disease of disordered lymphangiogenesis. Breakthroughs in lymphatic research have identified several lymphangiogenic pathways that may play a relevant role in Gorham's disease.