Standardized approach to extract candidate outcomes from literature for a standard outcome set: a case- and simulation study.

AIMS: Standard outcome sets enable the value-based evaluation of health care delivery. Whereas the attainment of expert opinion has been structured using methods such as the modified-Delphi process, standardized guidelines for extraction of candidate outcomes from literature are lacking. As such, we aimed to describe an approach to obtain a comprehensive list of candidate outcomes for potential inclusion in standard outcome sets. METHODS: This study describes an iterative saturation approach, using randomly selected batches from a systematic literature search to develop a long list of candidate outcomes to evaluate healthcare. This approach can be preceded with an optional benchmark review of relevant registries and Clinical Practice Guidelines and data visualization techniques (e.g. as a WordCloud) to potentially decrease the number of iterations. The development of the International Consortium of Health Outcome Measures Heart valve disease set is used to illustrate the approach. Batch cutoff choices of the iterative saturation approach were validated using data of 1000 simulated cases. RESULTS: Simulation showed that on average 98% (range 92-100%) saturation is reached using a 100-article batch initially, with 25 articles in the subsequent batches. On average 4.7 repeating rounds (range 1-9) of 25 new articles were necessary to achieve saturation if no outcomes are first identified from a benchmark review or a data visualization. CONCLUSION: In this paper a standardized approach is proposed to identify relevant candidate outcomes for a standard outcome set. This approach creates a balance between comprehensiveness and feasibility in conducting literature reviews for the identification of candidate outcomes.

Functional role of iNOS-Rac2 interaction in neutrophil extracellular traps (NETs) induced cytotoxicity in sepsis.

BACKGROUND: Recent reports from this lab have demonstrated a higher incidence of NETs, nitrosative, as well as oxidative stress, and have a direct correlation with the severity of sepsis and organ damage. However, the mechanistic perspective of NETs induced organ damage has not been understood at the cellular and molecular level. Interaction of inducible nitric oxide synthase (iNOS) with Rac2 in regulating reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation and its implications in microbial killing has been reported. This study was, therefore, undertaken in neutrophils of sepsis patients to investigate the functional importance of iNOS-Rac2 interaction in ROS/ RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death. METHODS: The study was conducted on 100 patients with sepsis and 50 healthy volunteers. Interaction between iNOS and Rac2 was performed using co-immunoprecipitation and co-immunolabeling assay. Free radicals involving ROS and RNS were evaluated using cytochrome c reduction assay. NETs formation was evaluated by fluorescence microscopy. The cytotoxic effect of NETs was assessed on lung carcinoma cell line (A549) using colorimetric Alamar blue assay. RESULTS: Enhanced interaction between iNOS and Rac2 was found in sepsis neutrophils in comparison with control. This was accompanied by an increased level of superoxide (O2.-), nitric oxide (NO), and peroxynitrite (ONOO-) which were decreased in the presence of NAC, DPI, and 1400 W, signifying the role of iNOS-Rac2 interaction. Enhanced NETs release from activated sepsis neutrophils were abrogated in the presence of DPI. NETs from sepsis neutrophils exert a cytotoxic effect on lung epithelial cells (A549) in a concentration-dependent manner. CONCLUSION: Our findings exhibit the functional role of iNOS-Rac2 interaction in ROS/RNS, peroxynitrite generation, NETs generation, and NETs mediated cell death.

Nitrosative stress and cytokines are linked with the severity of sepsis and organ dysfunction.

OBJECTIVE: An imbalance in oxidant-antioxidant status may impact the severity of sepsis. We hypothesised links between nitrosative stress and pro-inflammatory cytokines and their correlation with the severity of sepsis and associated organ dysfunction. METHODS: The hypothesis was tested in 110 patients with sepsis (in whom a disease severity score (APACHE II) and assessment of organ failure score (SOFA) were determined) and 55 healthy volunteers. Neutrophil inducible nitric oxide synthase (iNOS) expressions at mRNA and protein levels were estimated by real-time PCR and immuno-precipitation followed by Western blotting, respectively. Nitric oxide (NO) content was assessed in neutrophils by confocal microscopy, plasma nitrite by the Griess reaction and inflammatory cytokines (TNF-α, IFN-γ and IL-8) by ELISA (in plasma) and real-time PCR (in neutrophils). Serum bilirubin and creatinine were determined by routine methods and lung function by the PaO2/FiO2 ratio. RESULTS: Increased neutrophil iNOS expression and NO content, plasma total nitrite content and pro-inflammatory cytokines were present in sepsis patients (all P < 0.001). Plasma nitrite correlated with cytokines, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.63-0.85, P < 0.001). Cytokines correlated with nitrite, APACHE II, SOFA, PaO2/FiO2 ratio, serum bilirubin and creatinine clearance (all r2 0.35-0.85, P < 0.001). CONCLUSION: Neutrophils iNOS expression, NO content, plasma nitrite and cytokines have a role in the assessment of the severity of sepsis and organ toxicity.

Calculation of free and bioavailable vitamin D and its association with bone mineral density in Malaysian women.

INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women. MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae. RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD. CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.

Evaluation of oxidative stress and antioxidant status: Correlation with the severity of sepsis.

Sepsis is a condition caused by infection followed by unregulated inflammatory response which may lead to the organ dysfunction. During such condition, over-production of oxidants is one of the factors which contribute cellular toxicity and ultimately organ failure and mortality. Antioxidants having free radicals scavenging activity exert protective role in various diseases. This study has been designed to evaluate the levels of oxidative and antioxidative activity in sepsis patients and their correlation with the severity of the sepsis. A total of 100 sepsis patients and 50 healthy controls subjects were enrolled in this study from the period October 2016 to June 2017. The investigation included measurements of oxidative enzyme, myeloperoxidase (MPO), antioxidant enzymes including superoxide dismutase activity (SOD) and catalase activity (CAT) and cytokines (TNF-α, IL-8 and IFN-γ). Furthermore, the level of these activities was correlated with severity of sepsis. Augmented levels of oxidants were found in sepsis as demonstrated by DMPO nitrone adduct formation and plasma MPO level activity (1.37 ± 0.51 in sepsis vs 0.405 ± 0.16 in control subjects). Cytokines were also found to be increased in sepsis patients. However, plasma SOD and CAT activities were significantly attenuated (P < .001) in the sepsis patients compared with controls subjects. Moreover, inverse relation between antioxidant enzymes (SOD and CAT) and organ failure assessment (SOFA), physiological score (APACHE II), organ toxicity specific markers have been observed as demonstrated by Pearson's correlation coefficient. This study suggests that imbalance between oxidant and antioxidant plays key role in the severity of sepsis.

Performance of medical students in final professional examination: Can in-course continuous assessments predict students at risk?

Background: Assessment drives students' learning. It measures the level of students' understanding. We aimed to determine whether performance in continuous assessment can predict failure in the final professional examination results. Methods: We retrieved the in-course continuous assessment (ICA) and final professional examination results of 3 cohorts of medical students (n = 245) from the examination unit of the International Medical University, Seremban, Malaysia. The ICA was 3 sets of composite marks derived from course works, which includes summative theory paper with short answer questions and 1 of the best answers. The clinical examination includes end-of-posting practical examination. These examinations are conducted every 6 months in semesters 6, 7 and 8; they are graded as pass/fail for each student. The final professional examination including modified essay questions (MEQs), 1 8-question objective structured practical examination (OSPE) and a 16-station objective structured clinical examination (OSCE), were graded as pass/fail. Failure in the continuous assessment that can predict failure in each component of the final professional examination was tested using chi-square test and presented as odds ratio (OR) with 95% confidence interval (CI). Results: Failure in ICA in semesters 6-8 strongly predicts failure in MEQs, OSPE and OSCE of the final professional examination with OR of 3.8-14.3 (all analyses p< 0.001) and OR of 2.4-6.9 (p<0.05). However, the correlation was stronger with MEQs and OSPE compared to OSCE. Conclusion: ICA with theory and clinical examination had a direct relationship with students' performance in the final examination and is a useful assessment tool.

Hepatitis C Virus-associated Membranoproliferative Glomerulonephritis Treated with Directly Acting Antiviral Therapy.

Hepatitis C virus (HCV) infection has been shown to affect kidneys with various histopathological pattern on the kidney biopsy. These commonly include a membranoproliferative glomerulonephritis (MPGN) pattern with mixed cryoglobulinemia (CG), thrombotic microangiopathy, membranous nephropathy, and vasculitis affecting medium and small vessels of the kidneys causing polyarteritis nodosa. It has been rarely associated with MPGN without detectable CG. We present one such patient who presented to us with HCV-associated MPGN without detectable CG, who recovered completely with directly acting antiviral therapy without any immunosuppression.

Development and Testing of a Cognitive Behavioral Therapy Resource for Children's Dental Anxiety.

Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for dental anxiety; however, access to therapy is limited. The current study aimed to develop a self-help CBT resource for reducing dental anxiety in children, and to assess the feasibility of conducting a trial to evaluate the treatment efficacy and cost-effectiveness of such an intervention. A mixed methods design was employed. Within phase 1, a qualitative "person-based" approach informed the development of the self-help CBT resource. This also employed guidelines for the development and evaluation of complex interventions. Within phase 2, children, aged between 9 and 16 y, who had elevated self-reported dental anxiety and were attending a community dental service or dental hospital, were invited to use the CBT resource. Children completed questionnaires, which assessed their dental anxiety and health-related quality of life (HRQoL) prior to and following their use of the resource. Recruitment and completion rates were recorded. Acceptability of the CBT resource was explored using interviews and focus groups with children, parents/carers and dental professionals. For this analysis, the authors adhered to the Mixed Methods Appraisal Tool criteria. There were 24 families and 25 dental professionals participating in the development and qualitative evaluation of the CBT resource for children with dental anxiety. A total of 56 children agreed to trial the CBT resource (66% response rate) and 48 of these children completed the study (86% completion rate). There was a significant reduction in dental anxiety (mean score difference = 7.7, t = 7.9, df = 45, P < 0.001, Cohen's d ES = 1.2) and an increase in HRQoL following the use of the CBT resource (mean score difference = -0.03, t = 2.14, df = 46, P < 0.05, Cohen's d ES = 0.3). The self-help approach had high levels of acceptability to stakeholders. These findings provide preliminary evidence for the effectiveness and acceptability of the resource in reducing dental anxiety in children and support the further evaluation of this approach in a randomized control trial. Knowledge Transfer Statement: This study details the development of a guided self-help Cognitive Behavioral Therapy resource for the management of dental anxiety in children and provides preliminary evidence for the feasibility and acceptability of this approach with children aged between 9 and 16 y. The results of this study will inform the design of a definitive trial to examine the treatment- and cost-effectiveness of the resource for reducing dental anxiety in children.

A scoping review of the uses of the care index in children.

OBJECTIVE: To conduct a scoping review of literature to describe how the care index (CI) and restorative index (RI) are used in child populations and to determine whether they are fit for purpose. BASIC RESEARCH DESIGN: Scoping review conducted using the Arksey and O'Malley (2005) framework. METHOD: Electronic and manual literature searches (1980-2015) were conducted. Titles and abstracts were screened, full-texts of potential studies were reviewed two reviewers extracted data independently, followed by data charting and summarising. RESULTS: Out of 104 articles meeting all criteria, most were cross-sectional (92%), and 56% were conducted in UK and Brazil. Most commonly (63%) studies used CI and RI to obtain epidemiological data on dental care levels. Of the studies that defined CI and RI, most used and specified the standard definition. The CI and RI scores varied either due to patient related factors such as age, gender or dental care related factors including, cost of treatment and method of provider remuneration. CONCLUSION: Overall, it is recommended that future studies should clearly state the definitions and thresholds used to obtain CI and RI, which would enable comparison between communities and allow temporal trends to be studied. Additionally, deriving separate CI and RI scores for groups based on caries extent would help to highlight inequalities in the provision of care. Further research is needed to explore the applicability of CI and RI to changing approaches to caries management with current care recommendations emphasising on minimal treatment and secondary prevention.

Oral Health Inequalities: Relationships between Environmental and Individual Factors.

Recent research has emphasized the relationships between environmental and individual factors that may influence population oral health and lead to health inequalities. However, little is known about the effect of interactions between environmental and individual factors on inequalities in clinical (e.g., decayed teeth) and subjective oral health outcomes (e.g., oral health-related quality of life [OHQoL]). This cohort study aimed to explore the direct and mediated longitudinal interrelationships between key environmental and individual factors on clinical and subjective oral health outcomes in adults. Self-reported measures of OHQoL and individual (sense of coherence [SOC], social support, stress, oral health beliefs, dental behaviors, and subjective socioeconomic status [SES]) and environmental factors (SES and social network) were collected at baseline and 3-mo follow-up, together with a baseline clinical examination of 495 adult employees of an automobile parts manufacturer in India. Lagged structural equation modeling was guided by the adapted Wilson and Cleary/Brunner and Marmot model linking clinical, individual, and environmental variables to quality of life. The study provides tentative evidence that SES may influence levels of resources such as social support and SOC, which mediate stress and in turn may influence subjective oral health outcomes. Accordingly, the present findings and the adapted Wilson and Cleary/Brunner and Marmot model on which they are predicted provide support for the psychosocial pathway being key in the SES-oral health relationship. The pathways through which environmental factors interact with individual factors to impact subjective oral health outcomes identified here may bring opportunities for more targeted oral health promotion strategies.

Correlation between two chemiluminescence based assays for quantification of hepatitis B surface antigen in patients with chronic hepatitis B infection.

PURPOSE: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing hepatitis B virus (HBV) infection. In India many commercial assays are available for detection of HBsAg but very few can measure it quantitatively. The present study presents the comparative evaluation of two methods and their correlation with serum HBsAg in chronic hepatitis B (CHB) patients. MATERIALS AND METHODS: Consecutive patients of CHB were included and there HBsAg levels were measured by two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii) Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by real-time polymerase chain reaction (qPCR). RESULTS: Total of 136 patients were included in the study and there was a significant overall correlation between both the assays (correlation coefficient [r] = 0.83; P < 0.001). Assays correlated well with each other across all subgroups of CHB: treatment naοve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n = 104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti-HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136) as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg QT assay (A1) also correlated well with HBV DNA in the treatment naοve group (r = 0.69; P < 0.001, n = 32). CONCLUSIONS: Our study hence proved that both the assays are comparable and a simple qualitative assay with in-house modification can be used easily for quatitation of HBsAg in clinical samples.

A multicentre UK study of GVHD following DLI: rates of GVHD are high but mortality from GVHD is infrequent.

DLIs are frequently used following haematopoietic SCT (HSCT) in patients with risk of relapse but data on GVHD following DLI are scarce. We report on 68 patients who received DLI following HSCT. Most patients developed GVHD following DLI (71%), which was acute in 22 patients (32%) almost half of whom had grade III-IV acute GVHD (aGVHD). Thirty patients (44%) developed cGVHD which followed aGVHD in four patients and was graded severe in nine patients. Corticosteroids were the most common first-line therapy for both acute and chronic GVHD. A wide range of second/third-line agents included cyclosporin, mycophenolate, tacrolimus, imatinib, infliximab and ECP. Relapse of initial malignancy occurred in 37%. Relapse was significantly less frequent in those receiving pre-emptive DLI. Relapse rates were also lower in those with GVHD (31%) than those without GVHD (50%), but this did not reach statistical significance. At 55 months post DLI, 34% of patients had died most commonly from relapse and 22% had on-going GVHD. Although GVHD was an important cause of morbidity post DLI (71%), only 6% died from GVHD. Although most patients develop GVHD post DLI and may require consecutive therapies, mortality from GVHD is infrequent. DLI remains an important option for relapse post transplant and manipulation of the GVT effect needs to be optimised to induce remission without morbidity from GVHD.

Chronic pelvic ischemia: etiology, pathogenesis, clinical presentation and management.

Overactive bladder (OAB) and bladder pain syndrome (BPS) although common, are vaguely defined and difficult to diagnose and manage etiologies of storage-type lower urinary tract symptoms (LUTS). The lack of optimal management options is a direct consequence of deficient understanding of the pathophysiologic mechanisms underlying these conditions. These conditions are especially prevalent in females, and cumulative contemporary epidemiological, clinical and laboratory evidence implicates ischemia as one of the key players in the pathophysiologic foundation of both these disorders. Taken together they make up "the" diagnostic as well as therapeutic black-hole in urologic practice. Much akin to chronic ischemic heart disease, chronic ischemia-reperfusion has been shown to cause degenerative changes at cellular and subcellular level in the bladder mucosa, smooth muscle fibers, and vesical neural and microvascular structures leading to a hypersensitive, hyperactive bladder initially, which with time invariably progresses into a failed, fibrotic and pressurized bladder. Diagnosis and management of these diseases are currently symptom focused and remains a source of much frustration. Consideration of role of ischemia connotates hope and could lead to a paradigm shift in the management of these patients with a completely new therapeutic armamentarium attacking the pathology itself. The aim of the current review is to provide a clinical thought perspective on the etiology/pathophysiology of chronic pelvic ischemia and its role as a precursor to the aforementioned conditions, and shed some light upon the potential management strategies to consider.

Extracorporeal photopheresis for treatment of adults and children with acute GVHD: UK consensus statement and review of published literature.

Extracorporeal photopheresis (ECP) has been used for over 20 years to treat acute GVHD (aGVHD) and chronic GVHD. Evidence on the efficacy of response in aGVHD has continued to accrue and data suggest that there is a good response and prolonged survival in both children and adults with grade II-IV aGVHD. Unlike chronic GVHD where treatment schedules are typically one or two times monthly for 12-18 months, patients with aGVHD respond rapidly to an intense weekly treatment schedule for 8 weeks, typically allowing steroids to be discontinued without flare-ups of aGVHD. Maintenance ECP therapy is generally not required. Many centres across Europe and United States treat aGVHD with ECP as second-line therapy and responses are excellent in a subset of patients. Unlike other second-line therapies, ECP is not immunosuppressive and has no reported drug interactions. Importantly, ECP does not have a negative impact on the graft-versus-malignancy effect of the transplant. This statement aims to select those patients most likely to respond to treatment and summarises treatment and monitoring schedules for the management of aGVHD in adult and paediatric patients to ensure the correct patients are treated with the optimal protocol for efficacy.

Chronic pelvic ischemia: etiology, pathogenesis, clinical presentation and management.

Overactive Bladder (OAB) and Bladder Pain Syndrome (BPS) although common, are vaguely defined and difficult to diagnose and manage etiologies of storage--type lower urinary tract symptoms (LUTS). The lack of optimal management options is a direct consequence of deficient understanding of the pathophysiologic mechanisms underlying these conditions. These conditions are especially prevalent in females, and cumulative contemporary epidemiological, clinical and laboratory evidence implicates ischemia as one of the key players in the pathophysiologic foundation of both these disorders. Taken together they make up 'the' diagnostic as well as therapeutic black--hole in urologic practice. Much akin to chronic ischemic heart disease, chronic ischemia--reperfusion has been shown to cause degenerative changes at cellular and sub--cellular level in the bladder mucosa, smooth muscle fibers, and vesical neural and microvascular structures leading to a hypersensitive, hyperactive bladder initially, which with time invariably progresses into a failed, fibrotic and pressurized bladder. Diagnosis and management of these diseases are currently symptom focused and remains a source of much frustration. Consideration of role of ischemia connotates hope and could lead to a paradigm shift in the management of these patients with a completely new therapeutic armamentarium attacking the pathology itself.

Relevance of hepatitis B surface antigen levels in patients with chronic hepatitis B during 5 year of tenofovir treatment.

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥ 1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg-positive and HBeAg-negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg-positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV-infected patients treated with tenofovir exhibit a significant (≥ 1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg-positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion.

Hepatitis B vaccination with or without hepatitis B immunoglobulin at birth to babies born of HBsAg-positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babies: a randomized controlled trial.

Vertical transmission of Hepatitis B virus HBV can result in a state of chronic HBV infection and its complications. HBV vaccination with or without hepatitis B immunoglobulin (HBIG) prevents transmission of overt infection to the babies. However, whether it also prevents occult HBV infection in babies is not known. Consecutive pregnant women of any gestation found to be HBsAg positive were followed till delivery, and their babies were included in the study. Immediately after delivery, babies were randomized to receive either HBIG or placebo in addition to recombinant HBV vaccine (at 0, 6, 10 and 14 weeks). The primary end-point of the study, assessed at 18 weeks of age, was remaining free of any HBV infection (either overt or occult) plus the development of adequate immune response to vaccine. The babies were further followed up for a median of 2 years of age to determine their eventual outcome. Risk factors for HBV transmission and for poor immune response in babies were studied. Of the 283 eligible babies, 259 were included in the trial and randomized to receive either HBIG (n=128) or placebo (n=131) in addition to recombinant HBV vaccine. Of the 222 of 259 (86%) babies who completed 18 weeks of follow-up, only 62/222 (28%) reached primary end-point. Of the remaining, 6/222 (3%) developed overt HBV infection, 142/222 (64%) developed occult HBV infection, and 12/222 (5%) had no HBV infection but had poor immune response. All 6 overt infections occurred in the placebo group (P=0.030), while occult HBV infections were more common in the HBIG group (76/106 [72%] vs. 66/116 [57%]; P=0.025). This may be due to the immune pressure of HBIG. There was no significant difference between the two groups in frequency of babies developing poor immune response or those achieving primary end-point. The final outcome of these babies at 24 months of age was as follows: overt HBV infection 4%, occult HBV infection 42%, no HBV infection but poor immune response 8% and no HBV infection with good immune response 28%. Women who were anti-HBe positive were a low-risk group, and their babies were most likely to remain free of HBV infection (occult or overt) and had good immune response to the vaccine. Maternal HBeAg-positive status and negativity for anti-HBe predicted not only overt but also any infection (both overt and occult) in babies. In addition, high maternal HBV DNA and treatment with vaccine alone were significant factors for overt HBV infection in babies. The current practice of administration of vaccine with HBIG at birth to babies born of HBsAg-positive mothers is not effective in preventing occult HBV infection in babies, which may be up to 40%. Because the most important risk factors for mother-to-baby transmission of HBV infection are the replicative status and high HBV DNA level in mothers; it will be worthwhile investigating the role of antivirals and HBIG administration during pregnancy to prevent mother-to-child transmission of HBV infection.