Patterns of emergency room visits, admissions and death following recommended pediatric vaccinations - a population based study of 969,519 vaccination events

Background

The risk of immediate adverse events due to the inflammation created by a vaccine is a potential concern for pediatric vaccine programs.

Methods

We analyzed data on children born between March 2006 and March 2009 in the province of Ontario. Using the self-controlled case series design, we examined the risk of the combined endpoint of emergency room visit and hospital admission in the immediate 3 days post vaccination to a control period 9-18 days after vaccination. We examined the end points of emergency room visits, hospital admissions and death separately as secondary outcomes.

Results

We examined 969,519 separate vaccination events. The relative incidence of our combined end point was 0.85 (0.80-0.90) for vaccination at age 2 months, 0.74 (0.69-0.79) at age 4 months and 0.68 (0.63-0.72) at age 6 months. The relative incidence was reduced for the individual endpoints of emergency room visits, admissions and death. There were 5 or fewer deaths in the risk interval of all 969,519 vaccination events. In a post hoc analysis we observed a large reduction in events in the immediate 3 days prior to vaccination suggesting a large healthy vaccinee effect.

Conclusion

There was no increased incidence of the combined end point of emergency room visits and hospitalizations in the 3-day period immediately following vaccination, nor for individual endpoints or death. The health vaccinee effect could create the perception of worsening health following vaccines in the absence of any vaccine adverse effect and could also mask an effect in the immediate post-vaccination period.     

Focal Choroidal Excavation in Retinal Dystrophies

Aim: To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt’s disease (STGD), and Best disease in the Indian population. Methods: This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. Results: FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. Conclusion: Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.     

Novel HGPRT 293 A>G point mutation presenting as neonatal acute renal failure

We report on a rare case of hypoxanthine guanine phosphoribosyl transferase (HGPRT) deficiency that presented in the newborn period with acute renal failure (ARF). The clinical diagnosis was made on the basis of non-oliguric ARF and evidence of crystal nephropathy on renal biopsy. HGPRT deficiency was eventually confirmed by enzymatic and genetic testing, showing a novel point mutation, 293 A>G. Immediate treatment consisted of peritoneal dialysis with, initially, lactate- then bicarbonate-buffered 1.36% glucose solution together with oral administration of allopurinol. Follow-up after more than 4 years continued to show hyper-echogenic kidneys with almost normal renal glomerular function. There continues to be no neurobehavioural abnormalities.     

Analyzing biological rhythms in clinical trials

BackgroundThe human body exhibits a variety of biological rhythms. There are patterns that correspond, among others, to the daily wake / sleep cycle, a yearly seasonal cycle and, in women, the menstrual cycle. Sine/cosine functions are often used to model biological patterns for continuous data, but this model is not appropriate for analysis of biological rhythms in failure time data.MethodsWe consider a method appropriate for analysis of biological rhythms in clinical trials. We present a method to provide an estimate and confidence interval of the time when the minimum hazard is achieved. A motivating example from a clinical trial of adjuvant of pre-menopausal breast cancer patients provides an important illustration of the methodology in practice.ResultsAdapting the Cosinor method to the Weibull proportional hazards model is proposed as useful way of modeling the biological rhythm data. It presents a method to estimate the time that achieves the minimum hazard along with its associated confidence interval. The application of this technique to the breast cancer data revealed that the optimal day for pre-resection incisional or excisional biopsy of 28-day cycle (i.e. the day associated with the lowest recurrence rate) is day 8 with 95% CI 5–10. We found that older age, fewer positive nodes, smaller tumor size, and experimental treatment are important prognostic factors of longer relapse-free survival.ConclusionsThe analysis of biological/circadian rhythms is usually handled by Cosinor rhythmometry method. However, in FTD this is simply not possible. In this case, we propose to adapt the Cosinor method to the Weibull proportional hazard model. The advantage of the proposed method is its ability to model survival data. This method is not limited to breast cancer data, and may be applied to any biological rhythms linked to right censored data.     

Supraclavicular nodal failure in patients with one to three positive axillary lymph nodes treated with breast conserving surgery and breast irradiation, without supraclavicular node radiation

The purpose of this study was to evaluate the risk factors associated with supraclavicular nodal failure (SCF) in patients with one to three positive axillary nodes treated with breast conserving surgery and axillary dissection without supraclavicular node radiation (S/C RT) to aid in the selection of patients for S/C RT. Two hundred two breast conservation patients with one to three positive axillary nodes on axillary dissection treated with breast irradiation without S/C RT and 20 patients with S/C RT between August 1985 and May 2002 were identified and retrospectively evaluated. The Kaplan-Meier method was used to determine SCF-free and overall survival curves. Risk factors for SCF were examined. The median follow-up from surgery was 72 months (range: 4-195). Nine of 202 patients (4%) failed in the ipsilateral breast, 4 (2%) in the ipsilateral supraclavicular lymph nodes, 4 (2%) in the ipsilateral axillary and/or internal mammary nodes and 30 (15%) distantly. The 5- and 10-year SCF-free survival was 97.92%. The overall survival at 5, 10, and 15 years was 91.35%, 75.58%, and 67.18%, respectively. SCFs were associated with high grade or ER negative cancers, but not with number of positive nodes. Two of the four SCFs were associated with distant metastases, and two with local failures. One patient with a SCF was salvaged and is disease-free at 134 months. The overall low incidence of SCF in patients with one to three positive nodes treated with breast radiation alone after breast conserving surgery and adequate axillary dissection suggests that additional S/C RT is unnecessary in this cohort. When it occurs, supraclavicular nodal failure is often associated with distant metastases.     

Maxillofacial Surgeon as Fact Witness for Medico-Legal Cases: Indian Scenario

An Oral and Maxillofacial surgeon at any time during the practice will encounter medicolegal cases (MLC). There are lacunae in the knowledge and understanding of the correct method of dealing with such cases. Many of the practitioners are apprehensive and anxious as they have to interact with individuals and systems outside the normal realm of practice. In today’s arena, it is of utmost importance to be aware of legal system and law of the land. An OMF surgeon needs to have thorough understanding in recording and maintenance of the details of all MLCs and presenting the same in the court. Professional guidelines for expert witness are often not well recognised as those relating to the clinical practice. Surgeon has an obligation to conduct him/herself to highest ethical standards. This article provides insight into the details of registration of MLC, examination and recording of injuries, collecting medico-legal evidences and writing a medico legal report. Also discusses the court proceedings and possible questions that may be faced by the surgeon in the court.     

Understanding sickle cell carrier status identified through newborn screening: a qualitative study

The expansion of newborn screening (NBS) is increasing the generation of incidental results, notably carrier results. Although carrier status is generally understood to be clinically benign, concerns persist that parents may misunderstand its meaning, with deleterious effects on children and their families. Expansion of the NBS panel in Ontario, Canada in 2006 to include sickle cell disorders drew attention to the policy challenge of incidental carrier results. We conducted a study of consumer and provider attitudes to inform policy on disclosure. In this paper, we report the results of (i) qualitative interviews with health-care providers, advocates and parents of carrier infants and (ii) focus groups with new parents and individuals active with the sickle cell community. Lay and provider participants generally believed that carrier results were clinically insignificant. However, some uncertainty persisted among lay consumers in the form of conjecture or doubt. In addition, consumers and advocates who were most informed about the disease articulated insistent yet dissonant claims of clinical significance. Meanwhile, providers referenced research knowledge to offer an equivocal assessment of the possibility and significance of clinically symptomatic carrier status. We conclude that many interpretations of carrier status are in circulation, failing to fit neatly into the categories of ‘clinically significant'' or ‘benign.'' This creates challenges for communicating clearly with parents – challenges exacerbated by inconsistent messages from screening programs regarding the significance of sickle cell carrier status. Disclosure policy related to incidentally generated infant carrier results needs to account for these complex realities.