Mihir Gandhi

Pregnancy outcomes associated with viral hepatitis

Summary.  The aim of this study was to examine the contribution of hepatitis B virus (HBV) and hepatitis C virus (HCV) to pregnancy‐related complications including gestational diabetes mellitus (GDM), preterm birth (PTB), intrauterine growth restriction (IUGR), pre‐eclampsia, antepartum haemorrhage and cholestasis. The Nationwide Inpatient Sample was queried for all pregnancy‐related discharges, pregnancy complications and viral hepatitis from 1995 to 2005. Logistic regression was used to examine the association between HBV, HCV, HBV + HCV and pregnancy‐related complications including GDM, PTB, IUGR, pre‐eclampsia, antepartum haemorrhage, cholestasis and caesarean delivery. Model covariates included maternal age, race, insurance status, substance use and medical complications including liver complication, hypertension, HIV, anaemia, thrombocytopenia and sexually transmitted infections. Of 297 664 pregnant women data available for analysis, 1446 had a coded diagnosis of HBV, HCV or both. High‐risk behaviours, such as smoking, alcohol and substance use were higher in women with either HBV or HCV. Women with HBV had an increased risk for PTB (aOR 1.65, CI [1.3, 2.0]) but a decreased risk for caesarean delivery (aOR 0.686, CI [0.53, 0.88]). Individuals with HCV had an increased risk for GDM (aOR 1.6, CI [1.0, 2.6]). Individuals with both HBV and HCV co‐infection had an increased risk for antepartum haemorrhage (aOR 2.82, CI [1.1, 7.2]). There was no association of viral hepatitis with IUGR or pre‐eclampsia. Women with hepatitis have an increased risk for complications during pregnancy. Research to determine the efficacy and cost‐effectiveness of counselling patients about potential risks for adverse outcomes is warranted.

Induction Chemoradiation Is Not Superior to Induction Chemotherapy Alone in Stage IIIA Lung Cancer

BACKGROUND The optimal treatment strategy for patients with operable stage IIIA (N2) non-small cell lung cancer is uncertain. We performed a systematic review and meta-analysis to test the hypothesis that the addition of radiotherapy to induction chemotherapy prior to surgical resection does not improve survival compared with induction chemotherapy alone. METHODS A comprehensive search of PubMed for relevant studies comparing patients with stage IIIA (N2) non-small cell lung cancer undergoing resection after treatment with induction chemotherapy alone or induction chemoradiotherapy was conducted using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards. Hazard ratios were extracted from these studies to give pooled estimates of the effect of induction therapy on overall survival. RESULTS There were 7 studies that met criteria for analysis, including 1 randomized control trial, 1 phase II study, 3 retrospective reviews, and 2 published abstracts of randomized controlled trials. None of the studies demonstrated a survival benefit to adding induction radiation to induction chemotherapy versus induction chemotherapy alone. The meta-analysis performed on randomized studies (n=156 patients) demonstrated no benefit in survival from adding radiation (hazard ratio 0.93, 95% confidence interval 0.54 to 1.62, p=0.81), nor did the meta-analysis performed on retrospective studies (n=183 patients, hazard ratio 0.77, 95% confidence interval 0.50 to 1.19, p=0.24). CONCLUSIONS Published evidence is sparse but does not support the use of radiation therapy in induction regimens for stage IIIA (N2). Given the potential disadvantages of adding radiation preoperatively, clinicians should consider using this treatment strategy only in the context of a clinical trial to allow better assessment of its effectiveness.

Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790.

Height gain during early childhood is an important predictor of schooling and mathematics ability outcomes.

Aim:  To examine the association between height gain at different stages of early childhood and schooling and cognitive outcomes in 12‐year‐old Malawian children.

External Validation of the CRASH and IMPACT Prognostic Models in Severe Traumatic Brain Injury

An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS] ≤8) consecutively admitted to the National Neuroscience Institute (NNI), Singapore, between February 2006 and December 2009. The CRASH models (base and CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models (core, extended, and laboratory) estimate 6 month mortality and unfavorable outcome. Validation was based on measures of discrimination and calibration. Discrimination was assessed using the area under the receiving operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In the NNI database, the overall observed 14 day mortality was 47.7%, and the observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome. Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI.

Randomised double-blind trial of megestrol acetate vs placebo in treatment-naive advanced hepatocellular carcinoma

Background:Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC.Methods:From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day−1). End points were overall survival (OS) and quality of life.Results:An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92–1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting.Conclusion:Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

Shifts in national rates of inpatient prolapse surgery emphasize current coding inadequacies.

Objective: This study aimed to assess national rates, types, and routes of inpatient surgery for pelvic organ prolapse in the United States in 1998 compared to those in 2007. Methods: We used the 1998 and 2007 Nationwide Inpatient Sample, which represents a stratified, random sample of discharge data from US hospitals. We included women 20 years and older who underwent surgery for prolapse based on diagnosis and procedure codes of the International Classification of Disease, 9th Revision, Clinical Modification. We calculated the number of women undergoing surgery each year and incidence rates. Results: The total number of women undergoing prolapse surgeries was 92,503 in 1998 versus 113,646 in 2007. The incidence rate of surgery increased slightly, from 90.8 to 100.9 per 100,000 women, respectively. The most common procedure was hysterectomy, representing approximately half of prolapse surgeries in 1998 and 2007. Suspension procedures accounted for 18.8% of procedures in 2007, an increase from 6.1% in 1998. Surgeries performed via a minimally invasive route increased from 4.8% in 1998 to 9.4% in 2007. However, it was difficult to determine the route for many procedures based on current ICD-9 codes. There were also no codes that specifically designated mesh kit procedures or minimally invasive sacrocolpopexies. Conclusions: During the last decade, the rate of inpatient prolapse surgery has slightly increased. The proportion of suspension procedures has increased; however, it is difficult to determine the route of these procedures based on current ICD-9 codes. These findings emphasize that ICD-9 procedure codes have not kept up with changes in clinical practice.

Use of endovascular therapy for peripheral arterial lesions: an analysis of the National Trauma Data Bank from 2007 to 2009.

BACKGROUND An endovascular approach is increasingly used for the treatment of peripheral arterial trauma (PAT), but evidence supporting this approach is lacking. The objective of our study was to assess outcomes for endovascular repair (ER) versus operative repair (OR) in PAT. METHODS We used the National Trauma Data Bank from 2007 to 2009 for our analysis, comparing in-hospital morbidity and mortality for all adult patients undergoing ER versus OR for PAT of the upper and lower extremities. Unadjusted and risk-adjusted generalized linear models were performed, with multiple imputation techniques being used to replace missing values. RESULTS Of 8,977 patients, 531 (5.9%) underwent ER. Most patients were male (77.1%) and Caucasian (42.6%), with a mean age of 34.7 years (standard deviation: 14.8). ER was performed more commonly for lower- (n = 370, 10.4%) than upper-extremity lesions (n = 161, 3.0%, P < 0.001). Risk-adjusted analysis showed that ER patients had significantly greater injury severity scores (P < 0.001), were more likely to suffer a blunt (vs. penetrating) mechanism of injury (P < 0.001), and were more likely to have multiple comorbid illnesses (P < 0.001) than OR patients. Overall, risk-adjusted complications were less frequent after ER than OR (risk-adjusted OR: 0.79, P = 0.05), whereas in-hospital mortality between the two groups did not differ (risk-adjusted OR: 1.10, P = 0.59). Length of hospital stay was shorter among ER patients (adjusted mean difference: 0.78 days, P < 0.001), whereas length of intensive care unit stay did not differ between the two groups (P = 0.44). CONCLUSIONS ER appears to be a viable option for patients with PAT. Further research is needed to identify potential subgroups of PAT patients in whom ER may be superior to OR.

Validation of the Simple Shoulder Test in a Portuguese-Brazilian population. Is the latent variable structure and validation of the Simple Shoulder Test Stable across cultures?

Background The validation of widely used scales facilitates the comparison across international patient samples. The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Objective The objective of this study was to translate, culturally adapt and validate the Simple Shoulder Test into Brazilian Portuguese. Also we test the stability of factor analysis across different cultures. Methods The Simple Shoulder Test was translated from English into Brazilian Portuguese, translated back into English, and evaluated for accuracy by an expert committee. It was then administered to 100 patients with shoulder conditions. Psychometric properties were analyzed including factor analysis, internal reliability, test-retest reliability at seven days, and construct validity in relation to the Short Form 36 health survey (SF-36). Results Factor analysis demonstrated a three factor solution. Cronbach’s alpha was 0.82. Test-retest reliability index as measured by intra-class correlation coefficient (ICC) was 0.84. Associations were observed in the hypothesized direction with all subscales of SF-36 questionnaire. Conclusion The Simple Shoulder Test translation and cultural adaptation to Brazilian-Portuguese demonstrated adequate factor structure, internal reliability, and validity, ultimately allowing for its use in the comparison with international patient samples.

Multicenter study of comparative outcomes of hematopoietic stem cell transplant for peripheral T cell lymphoma and natural killer/T-cell lymphoma

Department of Haematology, Singapore General Hospital, Singapore, Duke-NUS Graduate Medical School, Singapore, Department of Haematology-Oncology, National University Cancer Institute, National University Health System, Singapore, National Cancer Centre, Singapore, Department of Haematology, St George’s Hospital and Medical School, London, UK, Department of Clinical Research, Singapore General Hospital, Singapore, and Singapore Clinical Research Institute, Singapore