Wearing Off Effect of OnabotulinumtoxinA Near the End of Treatment Cycle for Chronic Migraine: A 4-Year Clinical Experience.

INTRODUCTION: The injection interval for onabotulinumtoxinA (BoNTA) in the management of chronic migraine (CM) is 12 weeks (78-84 days). The aim of this study was to review patient-reported wearing off effect (WOE) of the therapeutic benefit of BoNTA near the end of the treatment cycle. We intended to describe the demographics of patients at baseline and compare groups of patients with multiple episodes of WOE. METHODS: We conducted a retrospective review of patients with CM who received uninterrupted BoNTA therapy from January 2014 to March 2018. The data from patient-reported WOE (worsening headache variables and neck pain) that occurred during the 4 weeks (28 days) prior to the scheduled re-injection of BoNTA for treatment cycles with injection interval ≤13 weeks and without obvious confounding factors were reviewed. RESULTS: We identified 98 eligible patients and analyzed 471 treatment cycles. Forty-three unique patients reported at least 1 occurrence of WOE. About 24/43 patients reported 1 WOE event and 19/43 patients reported ≥2 WOE events. Between the 2 groups, anxiety disorder and opioid use for headache were statistically significantly different. In the former group, the median interquartile range (IQR) dose of BoNTA was 165 (155, 175) units and the median IQR duration of the antinociceptive effect of BoNTA was 66.5 (63, 71.5) days. In the latter group, the median IQR dose of BoNTA was 167 (155, 173.3) units and the median IQR duration of the antinociceptive effect of BoNTA was 65.3 (62.5, 68.8) days. Up to 32% of these patients reported an increase in the use of abortive therapies to manage the symptoms of WOE. DISCUSSION: The primary goal of BoNTA in the treatment of CM is to mitigate the development of central sensitization. Since the 12-week injection paradigm may not provide sustained antinociceptive effect in all patients, it may account for the failure of response to BoNTA. Repeated occurrences of the WOE can potentially lead to medication overuse and impact quality of life.

Secondary hypothermia in patients with super-refractory status epilepticus managed with propofol and ketamine.

BACKGROUND: Therapeutic hypothermia as a potent nonpharmacologic antiseizure therapy has been investigated experimentally in animal models and humans. Although induced hypothermia has been shown to be neuroprotective in acute convulsive status epilepticus, whether its use will translate into improved outcomes for patients with super-refractory nonconvulsive status epilepticus (SRNCSE) has been debated. No clinical data are available on the occurrence and prognostic impact of secondary hypothermia (s-HT) in patients with SRNCSE. With the possibility of core to periphery redistribution of heat with propofol and a centrally mediated dose-dependent fall in body temperature with ketamine, we aimed to investigate the incidence of s-HT events in patients with SRNCSE managed with propofol and ketamine and their impact on clinical outcomes. METHODS: We performed a retrospective observational analysis of consecutive patients with SRNCSE managed with propofol and/or ketamine in a single-center neurological intensive care unit between December 1, 2012 and December 31, 2015. Patients were divided according to the occurrence of hypothermia (temperature < 35.0 °C) into an s-HT group and a nonhypothermia (n-HT) group. Patients who received targeted temperature management therapy were excluded. We compared the demographics, comorbidities, treatment characteristics, and outcomes between groups. RESULTS: Ninety-nine consecutive patients with SRNCSE managed with propofol and/or ketamine were identified during the study period. Twenty patients who received targeted temperature management were excluded, leaving a total of 79 patients for analysis. Hypothermia was observed in 52% (41/79) of the study population. Ketamine was used in 63/79 patients (80%). Ketamine infusion rates were higher and of longer duration among patients who developed s-HT compared with those who did not (mean dosage: 57.35 ±â€¯26.6 mcg/kg/min vs 37.17 ±â€¯15 mcg/kg/min, P = 0.001; duration: 116.36 ±â€¯81.9 h vs 88 ±â€¯89.7 h, P = 0.048). Propofol was used in 78/79 patients (99%), with no significant differences in characteristics between groups (mean dosage: 46.44 ±â€¯20.2 mcg/kg/min vs 36.9 ±â€¯12.9 mcg/kg/min, P = 0.058; duration: 125.43 ±â€¯96.4 h vs 102.3 ±â€¯87.1 h, P = 0.215). No significant differences in demographics, comorbidities, status epilepticus duration and resolution rates, and outcomes were observed between groups. CONCLUSION: In this single-center retrospective analysis of patients whose SRNCSE is being treated, higher doses and longer durations of ketamine were associated with the occurrence of s-HT. Further investigation is warranted to clarify the thermogenic effects of ketamine and its effect on status epilepticus outcomes.

Serum Aminotransferase Flares in Pregnant and Postpartum Women With Current or Prior Treatment for Chronic Hepatitis B.

BACKGROUND AND AIMS: Antiviral therapy is recommended for pregnant women with chronic hepatitis B (CHB) and hepatitis B virus (HBV) DNA>200,000 IU/mL, but there is less consensus on management of women who discontinue therapy in anticipation of pregnancy or who become pregnant while on therapy. The goal of this study was to describe flares in alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women with current and/or prior treatment. METHODS: This was a multicenter, retrospective study of 67 pregnancies in 56 CHB women treated before and/or during pregnancy. Main outcomes were frequency, severity, and resolution of ALT flare (≥5× upper limit of normal or ≥3× baseline, whichever was higher). RESULTS: During pregnancy, ALT flares (95 to 1064 U/L) were observed in 16% (7/43) of women who stopped treatment before pregnancy and 31% (4/13) of women who discontinued treatment during first trimester, many of whom had high HBV DNA levels (4.9 to 8.0 log IU/mL). No flares (0/11) were observed in women who continued treatment. Postpartum ALT flares (104 to 1584 U/L) were observed in 0% (0/15) of women who were completely untreated during pregnancy, 29% (2/7) of women who discontinued treatment in first trimester, 33% (3/9) of women who stopped treatment at delivery, and 22% (4/18) of women who continued treatment postpartum. CONCLUSIONS: In previously treated women with CHB, ALT flares were common during pregnancy and postpartum, especially if antiviral therapy was discontinued shortly before pregnancy, during first trimester, or at delivery. Thus, these pregnant women should be monitored closely throughout pregnancy and the early postpartum period; larger studies are needed to further characterize the natural history of HBV infection during pregnancy and postpartum.

Serum Alanine Aminotransferase and Hepatitis B DNA Flares in Pregnant and Postpartum Women with Chronic Hepatitis B.

OBJECTIVES: Alterations in the immune system during pregnancy have been associated with reactivation of hepatitis B virus (HBV) in chronic hepatitis B (CHB) women. However, the effects of pregnancy on CHB remain not well understood. The goal of this study was to examine flares in HBV DNA and serum alanine aminotransferase (ALT) during pregnancy and postpartum in CHB women untreated prior to pregnancy. METHODS: This was a multicenter retrospective study of 113 pregnancies in 101 CHB women who presented during pregnancy at two community gastroenterology clinics and two tertiary medical centers in the United States during 1997-2015. Outcomes analyzed included onset, severity, and resolution of flares in HBV and ALT that occurred prior to starting antiviral therapy, if antiviral therapy was subsequently initiated. Women who initiated antiviral therapy during pregnancy were not included in the analysis of postpartum flares. RESULTS: HBV DNA flares were observed in 9% (8/90) of women during pregnancy and 4% (2/48) of women during postpartum. Flares in ALT (99-2522 U/l) were observed in 6% (7/112) of women during pregnancy and 10% (5/51) of women within the first 3 months of delivery. Age, HBeAg positivity, baseline HBV DNA, baseline ALT, gravida, and parity were not found to be significant predictors of flare. CONCLUSIONS: Flares in HBV DNA and ALT can occur during late pregnancy and early postpartum in CHB women, and can be severe. Women with CHB should therefore be closely monitored during pregnancy and early postpartum.

Coronary Revascularization in Chronic and End-Stage Renal Disease: A Systematic Review and Meta-analysis.

Patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) on dialysis have an increased risk for cardiovascular mortality and morbidity secondary to occlusive coronary artery disease. Optimal revascularization strategy is unclear in this high-risk population. We have performed a meta-analysis to compare coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in patients with ESRD and CKD. We searched PubMed, Ovid, MEDLINE, CINAHL, and EMBASE (1980-2013) and found 17 trials (N = 33,584) in the ESRD arm and 6 studies (n = 15,493) in the CKD arm. Two investigators independently collected the data. All the studies were retrospective trials. In the ESRD and CKD groups, we found significantly reduced early mortality with the PCI group with the odds ratio of 2.08 (1.90-2.26; P < 0.00001) and 2.55 (1.45-4.51; P = 0.001), respectively. Contrary to the early mortality results, we found decreased late mortality with the CABG group when compared with the PCI group [odds ratio: 0.86 (0.83-0.89; P < 0.000001) and 0.82 (0.76-0.88; P < 0.00001)] in the ESRD and CKD arm, respectively. When compared with PCI, there was decreased cardiovascular mortality with an odds ratio of 0.61 (0.40-0.92; P = 0.02) in patients who underwent CABG in ESRD population. Similar trends were observed in the incidence of myocardial infarction and repeat revascularization. There is a strong trend for decreased risk of stroke with PCI when compared with CABG in ESRD and CKD populations.

Cardiovascular adverse effects of targeted antiangiogenic drugs: mechanisms and management.

Anticancer treatment has evolved enormously over the last decade. Drugs targeting receptor tyrosine kinases, VEGFR and EGFR have changed the treatment landscape of certain cancers and have shifted the theme of anticancer therapy toward personalized care. However, these newer agents also come with unique side-effect profiles not seen with conventional chemotherapy including serious cardiovascular adverse effects. Hence, meticulous understanding of the adverse effects is crucial in maximizing clinical benefits and minimizing detrimental effects of these newer drugs. We have reviewed the cardiovascular adverse effects of anti-VEGF therapy in this article.

Diagnostic accuracy of telestroke consultation: a Louisiana based tele-network experience.

Background and purpose: Telestroke has grown significantly since its implementation. Despite growing utilization, there is a paucity of data regarding the diagnostic accuracy of telestroke to distinguish between stroke and its mimics. We aimed to evaluate diagnostic accuracy of telestroke consultations and explore the characteristics of misdiagnosed patients with a focus on stroke mimics. Methods: We conducted a retrospective study of all the consultations in our Ochsner Health's TeleStroke program seen between April 2015 and April 2016. Consultations were classified into one of three diagnostic categories: stroke/transient ischemic attack, mimic, and uncertain. Initial telestroke diagnosis was compared with the final diagnosis post review of all emergency department and hospital data. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) for diagnosis of stroke/TIA versus mimic were calculated. Area under receiver-operating characteristic curve (AUC) analysis to predict true stroke was performed. Bivariate analysis based on the diagnostic categories examined association with sex, age, NIHSS, stroke risk factors, tPA given, bleeding after tPA, symptom onset to last known normal, symptom onset to consult, timing in the day, and consult duration. Logistic regression was performed as indicated by bivariate analysis. Results: Eight hundred and seventy-four telestroke evaluations were included in our analysis. Accurate diagnosis through teleneurological consultation was seen in 85% of which 532 were strokes (true positives) and 170 were mimics (true negatives). Sensitivity, specificity, PPV, NPV were 97.8, 82.5, 93.7 and 93.4%, respectively. LR+ and LR- were 5.6 and 0.03. AUC (95% CI) was 0.9016 (0.8749-0.9283). Stroke mimics were more common with younger age and female gender and in those with less vascular risk factors. LR revealed OR (95% CI) of misdiagnosis for female gender of 1.9 (1.3-2.9). Lower age and lower NIHSS score were other predictors of misdiagnosis. Conclusion: We report high diagnostic accuracy of the Ochsner Telestroke Program in discriminating stroke/TIA and stroke mimics, with slight tendency towards over diagnosis of stroke. Female gender, younger age and lower NIHSS score were associated with misdiagnosis.

Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

BACKGROUND: We previously developed a logistic regression algorithm that uses AFP, age, gender, ALK and ALT levels to improve the detection of hepatocellular carcinoma (HCC). In 3,158 patients from 5 independent sites, this algorithm, referred to as the "Doylestown" algorithm, increased the AUROC of AFP 4% to 12% and had equal benefit regardless of tumor size or the etiology of liver disease. AIMS: Analysis of the Doylestown algorithm using samples from individuals taken before their diagnosis of HCC. METHODS: Here, the algorithm was tested using samples at multiple time points from (a) patients with established chronic liver disease, without HCC (120 patients) and (b) 116 patients with HCC diagnosis (85 patients with early stage HCC and 31 patients with recurrent HCC), taken at the time of, and up to 12 months prior to cancer diagnosis. RESULTS: Among patients who developed HCC, comparing the Doylestown algorithm at a fixed cut-off to AFP at 20 ng/mL, the Doylestown algorithm increased the True Positive Rate (TPR) in identification of HCC from 36 to 50%, at a time point of 12 months prior to the conventional HCC detection. Similar results were obtained in those patients with recurrent HCC, where the Doylestown algorithm increased TPR in detection of HCC from 18% to 59%, at 12 months prior to detection of recurrence. CONCLUSIONS: This algorithm significantly improves the prediction of HCC by AFP alone and may have value in the early detection of HCC.

Correction: Application of the Doylestown algorithm for the early detection of hepatocellular carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0203149.].

Subtle presentation of active primary biliary cirrhosis in chronic hepatitis B: a case report.

We are describing an interesting case of two chronic liver diseases in a 48-year-old Chinese woman. While chronic hepatitis B is a common entity in Asia, the patient was later found to have active, asymptomatic primary biliary cirrhosis due to a persistently elevated alkaline phosphatase level after optimal hepatitis B virus DNA suppression on antiviral therapy. This report emphasizes the importance of keeping a high index of suspicion for another potential liver disease process even after a patient has been successfully treated for a primary liver condition. Clinical vigilance, especially in atypical clinical presentations, can result in early accurate diagnosis and prompt treatment.

Intrahepatic distribution of hepatitis B virus antigens in patients with and without hepatocellular carcinoma.

AIM: To study the intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) in chronic hepatitis B patients with and without hepatocellular carcinoma. METHODS: A total of 33 chronic hepatitis B patients (mean age of 40.3 ± 2.5 years), comprising of 14 HBeAg positive and 19 HBeAg negative patients; and 13 patients with hepatitis B virus related hepatocellular carcinoma (mean age of 49.6 ± 4.7 years), were included in our study. Immunohistochemical staining for HBcAg and HBsAg was done using standard streptavidin-biotin-immunoperoxidase technique on paraffin-embedded liver biopsies. The HBcAg and HBsAg staining distributions and patterns were described according to a modified classification system. RESULTS: Compared to the HBeAg negative patients, the HBeAg positive patients were younger, had higher mean HBV DNA and alanine transaminases levels. All the HBeAg positive patients had intrahepatic HBcAg staining; predominantly with "diffuse" distribution (79%) and "mixed cytoplasmic/nuclear" pattern (79%). In comparison, only 5% of the HBeAg-negative patients had intrahepatic HBcAg staining. However, the intrahepatic HBsAg staining has wider distribution among the HBeAg negative patients, namely; majority of the HBeAg negative cases had "patchy" HBsAg distribution compared to "rare" distribution among the HBeAg positive cases. All but one patient with HCC were HBeAg negative with either undetectable HBV DNA or very low level of viremia. Intrahepatic HBcAg and HBsAg were seen in 13 (100%) and 10 (77%) of the HCC patients respectively. Interestingly, among the 9 HCC patients on anti-viral therapy with suppressed HBV DNA, HBcAg and HBsAg were detected in tumor tissues but not the adjacent liver in 4 (44%) and 1 (11%) patient respectively. CONCLUSION: Isolated intrahepatic HBcAg and HBsAg can be present in tumors of patients with suppressed HBV DNA on antiviral therapy; that may predispose them to cancer development.