Clinical impact of a novel ambulatory rhythm monitor in children.

Traditional ambulatory rhythm monitoring in children can have limitations, including cumbersome leads and limited monitoring duration. The ZioTM patch ambulatory monitor is a small, adhesive, single-channel rhythm monitor that can be worn up to 2 weeks. In this study, we present a retrospective cross-sectional analysis of the ZioTM monitor's impact in clinical practice. Patients aged 0-18 years were included in the study. A total of 373 studies were reviewed in 332 patients. In all, 28.4% had structural heart disease, and 16.9% had a prior surgical, catheterisation, or electrophysiology procedure. The most common indication for monitoring was tachypalpitations (41%); 93.5% of these patients had their symptoms captured during the study window. The median duration of monitoring was 5 days. Overall, 5.1% of ZioTM monitoring identified arrhythmias requiring new intervention or increased medical management; 4.0% identified arrhythmias requiring increased clinical surveillance. The remainder had either normal-variant rhythm or minor rhythm findings requiring no change in management. For patients with tachypalpitations and no structural heart disease, 13.2% had pathological arrhythmias, but 72.9% had normal-variant rhythm during symptoms, allowing discharge from cardiology care. Notably, for patients with findings requiring intervention or increased surveillance, 56% had findings first identified beyond 24 hours, and only 62% were patient-triggered findings. Seven studies (1.9%) were associated with complications or patient intolerance. The ZioTM is a well-tolerated device that may improve what traditional Holter and event monitoring would detect in paediatric cardiology patients. This study shows a positive clinical impact on the management of patients within a paediatric cardiology practice.

Safety and immunogenicity of an indigenously developed tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap) in adults, adolescents, and children in India.

BACKGROUND: This study assessed safety and immunogenicity of Serum Institute of India Pvt Ltd (SIIPL)'s tetanus toxoid (TT), diphtheria toxoid (DT), and acellular pertussis booster vaccine (Tdap). RESEARCH DESIGN AND METHODS: In this Phase II/III, multicenter, randomized, active-controlled, open-label study, 1500 healthy individuals, aged 4-65 years, were randomized to receive a single dose of SIIPL Tdap or comparator Tdap vaccine (Boostrix®; GlaxoSmithKlines, India). Adverse events (AEs) during initial 30 minutes, 7-day, 30-day post-vaccination were assessed. Blood samples were taken before and 30 days post-vaccination for immunogenicity assessment. RESULTS: No significant differences in incidence of local and systemic solicited AEs were observed between the two groups; no vaccine-related serious AEs were reported. SIIPL Tdap was non-inferior to comparator Tdap in achieving booster responses to TT and DT in 75.2% and 70.8% of the participants, respectively, and to pertussis toxoid (PT), pertactin (PRN), and filamentous hemagglutinin (FHA) in 94.3%, 92.6%, and 95.0% of the participants, respectively. Anti-PT, anti-PRN, and anti-FHA antibody geometric mean titers in both the groups, were significantly higher post-vaccination compared to pre-vaccination. CONCLUSIONS: Booster vaccination with SIIPL Tdap was non-inferior to comparator Tdap with respect to immunogenicity against tetanus, diphtheria, and pertussis and was well tolerated.

Immunogenicity and safety of an indigenously manufactured reconstituted pentavalent (DTwP-HBV+Hib) vaccine in comparison with a foreign competitor following primary and booster immunization in Indian children.

OBJECTIVE: An open label, controlled clinical study was conducted in Indian infants aged 6-14 weeks to compare the immunogenicity and safety of a reconstituted pentavalent vaccine (DTwP-HBV+Hib) of Serum Institute of India Ltd (SIIL) with TritanrixHB+Hiberix vaccine of Glaxo Smithkline (GSK). METHODS: Eligible infants were randomized to receive three doses of the study / comparator vaccine. The vaccines were reconstituted prior to administration, by mixing DTwP-HBV (liquid) with the Hib (lyophilized) vaccine. IgG antibody titres were assessed by ELISA at baseline and after one month following the 3-dose primary immunization schedule. Safety was evaluated after each dose. Further, safety and immunogenicity was also evaluated following a booster dose in the same cohort of children (aged between 15-24 months). SETTING: Tertiary-care hospitals in India Important outcome measures: Immunogenicity and safety following a 3-dose primary vaccination series and a booster vaccination. RESULTS: Post-primary immunization, 100% seroprotection was noted for Diphtheria, Tetanus, Hepatitis B and PRP-Hib components in both the vaccine groups. For pertussis, response was 96.1% in SIIL and 95.4% in GSK group. The overall safety profile as well as persistence of antibodies against all vaccine components up to the time of booster immunization was comparable between the SIIL and GSK groups. A marked rise of all antibody concentrations indicated effective priming. The booster dose was safe, well tolerated with a significant increase in antibody concentrations of all the vaccine antigens in both the groups. CONCLUSION: DTwP-HBV+Hib vaccine of SIIL was found to be safe and immunogenic. This Indian vaccine compared well with the licensed vaccine and is a cost-effective alternative for incorporating into the immunization schedule of various countries so as to control worldwide Hepatitis B and Hib infections.

Safety and immunogenicity of diphtheria-tetanus-pertussis vaccine and hepatitis B vaccine as a new tetravalent combination (DTwP/HB) administered alone and at separate sites (DTwP and HB) including comparison with standard commercially available combination vaccine in Indian infants 6-14 weeks of age.

An open, comparative study was conducted at two tertiary care hospitals in India to assess immunogenicity and reactogenicity following administration of the DTwP/HB combination vaccine (Q-Vac) alone and DTwP and HB (Genevac B) vaccines at separate sites. These vaccines manufactured by Serum Institute of India, Ltd. (SIIL), Pune were compared with DTwP/HB vaccine (Tritanrix HB) manufactured by GlaxoSmithKline (GSK) in infants aged 6-14 weeks. The sample size comprised 447 infants who received DTwP/HB vaccine (Group A-150, SIIL) or DTwP and HB (Group B-147, SIIL) vaccines at separate sites or DTPw/HB vaccine (Group C-150, GSK), in a dose of 0.5 ml intra-muscularly. Pre and postvaccination IgG antibodies were determined by ELISA. Postvaccination, in Group A seroprotection was 99.3%, 100%, 96% and 100% to Diphtheria, Tetanus, Pertussis and HBs components respectively. In Group B (n = 147) it was 98.6%, 100%, 95.9% and 99.3% and in Group C (n = 150), it was 96%, 99.3%, 93.3% and 98.6% to D, T, P and HBs component of the vaccine. Postvaccination, geometric mean titres for each component were comparable across three groups by analysis of variance (ANOVA). Adverse events observed were within the range quoted in literature and no Serious Adverse Event (SAE) was observed. Reactogenicity profile in all three groups was comparable. Q-Vac vaccine manufactured by SIIL was found to be safe and immunogenic. Hepatitis B (HB) component did not interfere with the immune response to DTwP components of the vaccine.

Safety and immunogenicity of an indigenously developed Haemophilus influenzae type b conjugate vaccine through various phases of clinical trials.

In view of the need for a cost effective Haemophilus influenzae type b (Hib) conjugate vaccine, a lyophilized vaccine as capsular polysaccharide (PRP) conjugated to tetanus toxoid (Sii HibPRO) was indigenously developed by Serum Institute of India Ltd., Pune (SIIL). From 2004-07, this new vaccine underwent a series of clinical studies before its licensure by National Regulatory Authority (NRA). This paper discusses the results obtained during the clinical development of this vaccine. On finding the vaccine to be safe in animal toxicity studies, a Phase I single dose study was carried out to assess the safety profile of Sii HibPRO in healthy adult male volunteers. Subsequently, in Phase III pre-licensure study, immunogenicity and safety of Sii HibPRO was assessed and compared with Hib tetanus conjugate vaccine (Act-HIB) of Aventis, France. Immunogenicity was evaluated based upon serum anti-PRP IgG antibody concentrations by ELISA at prevaccination and one month each after the second and third dose. Safety was evaluated by recording details of adverse events after each dose of the vaccine. Postvaccination after the third dose, there was 100% seroprotection (anti PRP IgG titre >or= 0.15 microg/ml) in both the groups. Long term protection (>or=1 microg/ml) was achieved in 95.2% and 98.06% infants in Sii HibPRO and Act-HIB groups, respectively. At 15 months, prior to booster dose, 30 children in each group were evaluated and all were found to be seroprotected. Post booster, all of them responded with a strong boost response. Safety of Sii HibPRO was re-established in the post marketing surveillance in which 2,739 doses were administered to 1,029 infants, in 23 cities across India.

Impact of quality of life on patient expectations regarding phase I clinical trials.

PURPOSE: Quality of life (QOL) is increasingly recognized as a critical cancer-treatment outcome measure, but little is known about the impact of QOL on the patient decision-making process. A pilot study was conducted in an effort to (1) measure the expectations of patients, physicians, and research nurses regarding the potential benefits and toxicities from experimental and standard therapies, and (2) determine the relationship of QOL to patient perceptions regarding treatment options. METHODS: Thirty cancer patients enrolling in phase I clinical trials, their physicians, and their research nurses were administered questionnaires that assessed demographics, QOL, and treatment expectations. RESULTS: Compared with their physicians, patients overestimated potential benefits and toxicities from experimental therapy (mean expected benefit, 59.8% v 23.8%, P <.01; mean expected toxicity, 29.8% v 16.0%, P <.01). Patients estimated a greater potential for benefit (59.8% v 36.8%, P <.01) and less potential for toxicity (29.8% v 45.6%, P =.01) for experimental therapy, compared with standard therapy. Short Form-36 general health perception correlated with patient perception of potential benefit from experimental therapy (r =.48, P =.01). CONCLUSION: Participants in phase I clinical trial have high expectations regarding the success of experimental therapy and discount potential toxicity. Patient QOL may affect the expectation of benefit from experimental therapy and, ultimately, treatment choice. Understanding the interactions between QOL and patient expectations may guide the development of improved strategies to present appropriate information to patients considering early-phase clinical trials.

Limulus vision in the marine environment.

Horseshoe crabs use vision to find mates. They can reliably detect objects resembling potential mates under a variety of lighting conditions. To understand how they achieve this remarkable performance, we constructed a cell based realistic model of the lateral eye to compute the ensembles of optic nerve activity ("neural images") it transmits to the brain. The neural images reveal a robust encocding of mate-like objects that move underwater during the day. The neural images are much less clear at night, even though the eyes undergo large circadian increases of sensitivity that nearly compensate for the millionfold decreasein underwater lighting after sundown. At night the neurral images are noisy, dominated by bursts of nerve impulses from random photon events that occur at low nighttime levels of illumination. Deciphering the eye's input to the brain begins at the first synaptic level with lowpass temporal and spatial filtering. Both neural filtering mechanisms improve the signal-to-noise properties of the eye's input, yielding clearer neural images of potential mates, especiallyat night. Insights about visual processing by the relatively simple visual system of Limulus may aid in the designof robotic sensors for the marine environment.

Prehospital care telemetry--how essential?

The telemeterized ECG, once a necessary and important part of prehospital care, may now be an unnecessary, expensive luxury. Paramedic training now produces a professional capable of diagnosing ECG rhythms as accurately as emergency physicians. ECG telemetry may, however, have utility for esprit de corps, training, evaluation, and supervision of new or less trained paramedics. Recommendations for establishing or renewing community telemetry systems are made.

Retaining sealant on salivary contaminated enamel.

A two-year clinical study comparing sealants done with intentional salivary contamination shows that sealant retention is possible on wet enamel if a bonding agent is used between enamel and sealant. Dental material research implications and clinical possibilities are discussed.

Impact of parental separation and divorce on adopted and nonadopted children.

The impact of parental separation and divorce on adopted and nonadopted children was examined. Although children from nonintact homes showed poorer adjustment than did children from intact homes, the results were comparable for adoptees and nonadoptees. In addition, life stress associated with marital disruption was found to account for the majority of children's adjustment problems.

Use of a bonding agent to reduce sealant sensitivity to moisture contamination: an in vitro study.

Moisture contamination of etched enamel during application of sealant is the most frequently cited reason for sealant failure. In preliminary studies, a dentin bonding agent (Scotchbond Dual Cure, 3M, St. Paul, MN) has been shown to bond adequately to etched enamel after salivary contamination. This study investigated bond strength in vitro, when a bonding agent was used beneath sealants under varied conditions of contamination. Five hundred bovine incisor crowns were separated randomly into eight groups. The enamel samples, etched for 60 sec with a 37% phosphoric acid gel, were contaminated with: 1) fresh whole saliva, air dried, 2) fresh whole saliva, left wet, or 3) moisture from a humidity chamber. All contamination conditions were tested for sealant bond strength with and without the bonding agent as an intermediate layer under the sealant. As controls, both sealant and bonding agent under sealant also were applied to clean etched enamel. Bond strength was measured using a universal testing machine. Data were analyzed using a two-way ANOVA. Under conditions of humidity or intact saliva, sealant alone showed significant reduction in bond strength (P less than 0.001). Bonding agent under sealant on wet contamination yielded bond strengths equivalent to the bond strength obtained when sealant was bonded directly to clean, etched enamel. Bonding agent used without contamination yielded bond strengths significantly greater than the bond strength obtained when using sealant alone without contamination (P less than 0.001). When the saliva was air dried onto the surface, there was no significant difference in bond strengths whether or not a bonding agent was used under the sealant.

Sero-surveillance to assess rubella susceptibility and assessment of immunogenicity and reactogenicity of rubella vaccine in Indian girls aged 18-24 years.

Rubella infection though a mild infection, may cause foetal death or a variety of congenital anomalies. Multiple sero-surveys confirmed that 5-10% women are unexposed to natural or vaccinated rubella virus and remain susceptible to rubella infection. The current study was conducted in 600 girls, aged 18-24 y from Symbiosis International University (SIU), Pune, India to assess their sero-status against rubella infection and to estimate the immunogenicity of rubella vaccine in achieving sero-protective antibody titres. Prior to administration of a single i.m. dose of rubella vaccine (R-vac®) to eligible participants, blood sample (pre-vaccination) was collected. During the 4-6 weeks observation period, adverse events were noted. Then, a second blood sample (post-vaccination) was collected. Significant increase was noted in sero-protection response, viz., 98.6% (post-vaccination) vis-à-vis 66.5% (pre-vaccination); Geometric mean titer (GMT) was significantly higher post-vaccination. Effective measures to introduce rubella vaccination on a larger scale need to be undertaken. An immunization policy with mandatory rubella vaccination for all girls in the reproductive age group and its inclusion in national immunization schedule is highly desirable.

Assessment of safety and immunogenicity of two different lots of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae type b vaccine manufactured using small and large scale manufacturing process.

BACKGROUND: Hib vaccine can be easily incorporated in EPI vaccination schedule as the immunization schedule of Hib is similar to that of DTP vaccine. To meet the global demand of Hib vaccine, SIIL scaled up the Hib conjugate manufacturing process. This study was conducted in Indian infants to assess and compare the immunogenicity and safety of DTwP-HB+Hib (Pentavac(®)) vaccine of SIIL manufactured at large scale with the 'same vaccine' manufactured at a smaller scale. METHODS: 720 infants aged 6-8 weeks were randomized (2:1 ratio) to receive 0.5 ml of Pentavac(®) vaccine from two different lots one produced at scaled up process and the other at a small scale process. Serum samples obtained before and at one month after the 3rd dose of vaccine from both the groups were tested for IgG antibody response by ELISA and compared to assess non-inferiority. RESULTS: Neither immunological interference nor increased reactogenicity was observed in either of the vaccine groups. All infants developed protective antibody titres to diphtheria, tetanus and Hib disease. For hepatitis B antigen, one child from each group remained sero-negative. The response to pertussis was 88% in large scale group vis-à-vis 87% in small scale group. Non-inferiority was concluded for all five components of the vaccine. No serious adverse event was reported in the study. CONCLUSIONS: The scale up vaccine achieved comparable response in terms of the safety and immunogenicity to small scale vaccine and therefore can be easily incorporated in the routine childhood vaccination programme.

Seroprevalence of rubella and immunogenicity following rubella vaccination in adolescent girls in India.

INTRODUCTION: Serologic surveys conducted in different countries indicate that rubella is a worldwide infection. Several such sero surveys conducted in India have also confirmed that 6-47% of women are susceptible to rubella infection. The current study was conducted on 1,329 female adolescents in 12 districts of Maharashtra, India, to assess their serological status in terms of rubella exposure. METHODOLOGY: After enrollment, a pre-vaccination blood sample was collected from the participants followed by rubella vaccination (R-vac). Adverse events were monitored for the next 6-8 weeks, at which time a post-vaccination sample was collected. RESULTS: Pre-vaccination rubella immunity was higher in the urban (80.2%) population compared to the rural (73.1%) population. Following R-vac vaccination, out of 1,159 participants who completed the study, all (100%) in the urban and 99.5% of participants in the rural area developed antibodies against rubella. CONCLUSION: Substantial numbers of women reach childbearing age without immunity against rubella and thus are at a risk of passing the infection to their fetuses, who can then develop subsequent congenital defects leading to congenital rubella syndrome (CRS). An immunization policy recommending vaccination with rubella or rubella containing vaccine is highly desirable to prevent rubella and CRS. 

Safety and immunogenicity of single dose of tetanus-diphtheria (Td) vaccine among non/partially immune children against diphtheria and/or tetanus, Hyderabad, India, 2007.

In Hyderabad, India, diphtheria is common among children aged 5-19 years. On account of low coverage of diphtheria vaccine boosters recommended under the universal immunization programme, a large proportion of children were susceptible/partially immune against diphtheria and/or tetanus. We evaluated immunogenicity and safety of single dose of indigenously developed tetanus-diphtheria (Td) vaccine (diphtheria-toxoid < or =5 Lf) among 483 school children from Hyderabad aged 7-17 years and susceptible/partially immune against diphtheria and/or tetanus. Serological testing 6 weeks after vaccination indicated that vaccine was highly immunogenic with >96% sero-protected against both antigens. The immune response observed indicated a booster response to previously acquired immunity. Administration of additional dose of Td vaccine to the older school children and replacing the tetanus toxoid vaccine with Td in the school health programme would considerably reduce diphtheria burden in Hyderabad.