Prospective research on infants with mild encephalopathy: the PRIME study.

OBJECTIVE: To determine short-term outcomes of infants with evidence of hypoxia-ischemia at birth and classified as mild neonatal encephalopathy (NE) at <6 h of age. STUDY DESIGN: Prospective multicenter study. Mild NE was defined as ⩾1 abnormal category in modified Sarnat score. Primary outcome was any abnormality on early amplitude integrated electroencephalogram (aEEG) or seizures, abnormal brain magnetic resonance imaging (MRI) or neurological exam at discharge. RESULTS: A total of 54/63 (86%) of enrolled infants had data on components of the primary outcome, which was abnormal in 28/54 (52%): discontinuous aEEG (n=4), MRI (n=9) and discharge exam (n=22). Abnormal tone and/or incomplete Moro were the most common findings. MRI abnormalities were confined to cerebral cortex but two infants had basal ganglia and/or thalamus involvement. The 18 to 24 months follow-up is ongoing. CONCLUSIONS: A larger than expected proportion of mild NE infants with abnormal outcomes was observed. Future research should evaluate safety and efficacy of neuroprotection for mild NE.

Gadolinium DTPA Enhancement Characteristics of the Rat Sciatic Nerve after Crush Injury at 4.7T.

BACKGROUND AND PURPOSE: Traumatic peripheral nerve injury is common and results in loss of function and/or neuropathic pain. MR neurography is a well-established technique for evaluating peripheral nerve anatomy and pathology. However, the Gd-DTPA enhancement characteristics of acutely injured peripheral nerves have not been fully examined. This study was performed to determine whether acutely crushed rat sciatic nerves demonstrate Gd-DTPA enhancement and, if so, to evaluate whether enhancement is affected by crush severity. MATERIALS AND METHODS: In 26 rats, the sciatic nerve was crushed with either surgical forceps (6- to 20-N compressive force) or a microvascular/microaneurysm clip (0.1-0.6 N). Animals were longitudinally imaged at 4.7T for up to 30 days after injury. T1WI, T2WI, and T1WI with Gd-DTPA were performed. RESULTS: Forceps crush injury caused robust enhancement between days 3 and 21, while clip crush injury resulted in minimal-to-no enhancement. Enhancement after forceps injury peaked at 7 days and was seen a few millimeters proximal to, in the region of, and several centimeters distal to the site of crush injury. Enhancement after forceps injury was statistically significant compared with clip injury between days 3 and 7 (P < .04). CONCLUSIONS: Gd-DTPA enhancement of peripheral nerves may only occur above a certain crush-severity threshold. This phenomenon may explain the intermittent observation of Gd-DTPA enhancement of peripheral nerves after traumatic injury. The observation of enhancement may be useful in judging the severity of injury after nerve trauma.

A comparative hospital-based observational study of mono- and co-infections of malaria, dengue virus and scrub typhus causing acute undifferentiated fever.

Positive serology for dengue and/or scrub typhus infection with/without positive malarial smear (designated as mixed or co-infection) is being increasingly observed during epidemics of acute undifferentiated febrile illnesses (AUFIs). We planned to study the clinical and biochemical spectrum of co-infections with Plasmodium sp., dengue virus and scrub typhus and compare these with mono-infection by the same organisms. During the period from December 2012 to December 2013, all cases presenting with AUFIs to a single medical unit of a referral centre in Garhwal region of the north Indian state of Uttarakhand were retrospectively selected and categorised aetiologically as co-infections, malaria, dengue or scrub typhus. The groups thus created were compared in terms of demographic, clinical, biochemical and outcome parameters. The co-infection group (n = 49) was associated with milder clinical manifestations, fewer, milder and non-progressive organ dysfunction, and lesser need for intensive care, mechanical ventilation and dialysis as compared to mono-infections. When co-infections were sub-grouped and compared with the relevant mono-infections, there were differences in certain haematological and biochemical parameters; however, this difference did not translate into differential outcomes. Scrub typhus mono-infection was associated with severe disease in terms of both morbidity and mortality. Malaria, dengue and scrub typhus should be routinely tested in all patients with AUFIs. Co-infections, whether true or due to serological cross-reactivity, appear to be a separate entity so far as presentation and morbidity is concerned. Further insight is needed into the mechanism and identification of the protective infection.

Evaluation for Blunt Cerebrovascular Injury: Review of the Literature and a Cost-Effectiveness Analysis.

BACKGROUND AND PURPOSE: Evaluation for blunt cerebrovascular injury has generated immense controversy with wide variations in recommendations regarding the need for evaluation and the optimal imaging technique. We review the literature and determine the most cost-effective strategy for evaluating blunt cerebrovascular injury in trauma patients. MATERIALS AND METHODS: A comprehensive literature review was performed with data extracted to create a decision-tree analysis for 5 different strategies: anticoagulation for high-risk (based on the Denver screening criteria) patients, selective DSA or CTA (only high-risk patients), and DSA or CTA for all trauma patients. The economic evaluation was based on a health care payer perspective during a 1-year horizon. Statistical analyses were performed. The cost-effectiveness was compared through 2 main indicators: the incremental cost-effectiveness ratio and net monetary benefit. RESULTS: Selective anticoagulation in high-risk patients was shown to be the most cost-effective strategy, with the lowest cost and greatest effectiveness (an average cost of $21.08 and average quality-adjusted life year of 0.7231). Selective CTA has comparable utility and only a slightly higher cost (an average cost of $48.84 and average quality-adjusted life year of 0.7229). DSA, whether performed selectively or for all patients, was not optimal from both the cost and utility perspectives. Sensitivity analyses demonstrated these results to be robust for a wide range of parameter values. CONCLUSIONS: Selective CTA in high-risk patients is the optimal and cost-effective imaging strategy. It remains the dominant strategy over DSA, even assuming a low CTA sensitivity and irrespective of the proportion of patients at high-risk and the incidence of blunt cerebrovascular injury in high-risk patients.

Stylomandibular tunnel widening versus narrowing: a useful tool in evaluating suprahyoid mass lesions.

AIM: To evaluate whether qualitative and quantitative assessments of stylomandibular tunnel asymmetry are useful in lesion localization and differentiation. MATERIALS AND METHODS: The stylomandibular tunnel was measured in 60 control patients at CT to determine normal side-to-side variation. Twenty-one patients in the study group with suprahyoid neck masses were divided into two subgroups, those with widening and those with narrowing of the pathological side. Surgical and pathological findings in these subgroups were compared for site of origin and histology. RESULTS: Stylomandibular tunnel diameters in the control group had a mean variation of 0.9 mm (range: 0-3 mm, SD: 0.83 mm). Two-tailed t-test yielded a p-value of 0.018 for a variation of 3 mm and this was chosen as the threshold for disease. The widened stylomandibular tunnel group all had parotid gland lesions extending into the pre-styloid parapharyngeal space. The narrowed stylomandibular tunnel group had adenopathy, schwannomas, and paragangliomas/glomus vagale tumours arising from the post-styloid parapharyngeal space. CONCLUSION: Qualitative assessment for asymmetry of the stylomandibular tunnel surpass the 3 mm threshold for pathology. Widening of the stylomandibular tunnel is primarily from deep lobe parotid lesions extending into the pre-styloid parapharyngeal space. Narrowing of the stylomandibular tunnel can be from adenopathy, schwannomas, and paragangliomas arising from the post-styloid parapharyngeal space.

Contribution of medical colleges to tuberculosis control in India under the Revised National Tuberculosis Control Programme (RNTCP): lessons learnt & challenges ahead.

Medical college faculty, who are academicians are seldom directly involved in the implementation of national public health programmes. More than a decade ago for the first time in the global history of tuberculosis (TB) control, medical colleges of India were involved in the Revised National TB Control Programme (RNTCP) of Government of India (GOI). This report documents the unique and extraordinary course of events that led to the involvement of medical colleges in the RNTCP of GOI. It also reports the contributions made by the medical colleges to TB control in India. For more than a decade, medical colleges have been providing diagnostic services (Designated Microscopy Centres), treatment [Directly Observed Treatment (DOT) Centres] referral for treatment, recording and reporting data, carrying out advocacy for RNTCP and conducting operational research relevant to RNTCP. Medical colleges are contributing to diagnosis and treatment of human immunodeficiency virus (HIV)-TB co-infection and development of laboratory infrastructure for early diagnosis of multidrug-resistant and/or extensively drug-resistant TB (M/XDR-TB) and DOTS-Plus sites for treatment of MDR-TB cases. Overall, at a national level, medical colleges have contributed to 25 per cent of TB suspects referred for diagnosis; 23 per cent of 'new smear-positives' diagnosed; 7 per cent of DOT provision within medical college; and 86 per cent treatment success rate among new smear-positive patients. As the Programme widens its scope, future challenges include sustenance of this contribution and facilitating universal access to quality TB care; greater involvement in operational research relevant to the Programme needs; and better co-ordination mechanisms between district, state, zonal and national level to encourage their involvement.

Folic acid supplementation prevents phenytoin-induced gingival overgrowth in children.

OBJECTIVE: Gingival overgrowth is an important adverse effect of phenytoin (PHT) therapy, occurring in about half of the patients. This study aimed to evaluate the effect of oral folic acid supplementation (0.5 mg/day) for the prevention of PHT-induced gingival overgrowth (PIGO) in children with epilepsy aged 6-15 years on PHT monotherapy for 6 months. METHODS: This was a randomized, double-blind, placebo-controlled trial conducted at a tertiary level hospital from May 2008 to June 2009. Children aged 6-15 years started on PHT monotherapy within last 1 month were eligible for inclusion. Preexisting gingival overgrowth, use of other folic acid antagonists, and macrocytic anemia were exclusion criteria. Trial subjects were randomized to receive either folic acid or placebo. The primary outcome measure was incidence of any degree of gingival overgrowth after 6 months of PHT monotherapy. The trial was registered with clinicaltrials.gov (NCT00781196). RESULTS: A total of 120 children were recruited, 62 and 58, respectively, in folic acid and placebo arms. The 2 arms were comparable at baseline. Twenty-one percent of patients in the folic acid arm developed PIGO, as compared with 88% receiving placebo (p < 0.001). Absolute risk reduction of PIGO by folic acid was 67% (95% confidence interval 54%-80%), and relative risk reduction was 0.76. CONCLUSIONS: Oral folic acid was found to decrease the incidence of PIGO in children on PHT monotherapy, in a statistically significant and clinically relevant manner. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that folic acid supplementation, 0.5 mg/day, is associated with prevention of gingival overgrowth in children taking PHT monotherapy.

Magnetic resonance spectroscopy in ring enhancing lesions.

We report a 4 year old girl with ring enhancing lesions in brain CT, initially diagnosed as neurocysticercosis but did not respond to cysticidal therapy. A Magnetic resonance spectropscopy (MRS) revealed lipid peaks suggestive of tuberculoma which was successfully treated with antituberculosis therapy. This report highlights the role of MRS in the diagnosis of ring enhancing lesios.

Developing leadership interventions for black and minority ethnic staff: A case study of the National Health Service (NHS) in the U.K.

PURPOSE: The National Health Service (NHS) is the largest employer in the U.K. but, despite decades of equal opportunities legislation, its senior management workforce does not reflect the diversity of either the wider NHS workforce or the U.K. population. The aim of the paper is to consider the range of management interventions available to organisations like the NHS to deliver change in the area of promotion of Black and minority ethnic staff. DESIGN/METHODOLOGY/APPROACH: Intervention programmes in a range of public and private organisations are reviewed and the nature of barriers to promotion and the range of interventions to overcome these are explored. The paper uses the paradigm of institutional racism to examine the ways in which the NHS discriminates against certain sections of its workforce. The methods used include a literature review combined with key stakeholder interviews. A comparative dimension which involved a review of research on leadership initiatives in the U.S.A. was also undertaken. FINDINGS: The literature review found that there were a range of initiatives which could be implemented by public organisations such as the NHS to increase the presence of Black and Minority Ethnic (BME) staff in senior management positions. Most of these interventions were largely focused on the individual. Much more progress on institutional or organisational change needed to be made before the NHS could be perceived as a model employer in this area. The literature review also indicated that there is little published research on such initiatives within other European Union countries. ORIGINALITY/VALUE: The paper is targeted at both policy makers and human resource officers responsible for equality and diversity issues within large organisations, who have a remit to improve the career pathways of staff. The analysis provided offers a set of critical tools and interventions that have not hitherto been well examined in the U.K. context.

Emergence of G12 rotavirus strains in Delhi, India, in 2000 to 2007.

The prospect that rotavirus diarrhea in children may soon be prevented by vaccines has placed a new priority on understanding the diversity of rotavirus strains and the mechanism by which these strains evolve over time. We have characterized a total of 465 rotavirus strains collected in North India from 2000 to 2007 for G and P types by reverse transcription-PCR and sequencing. The novel G12 rotavirus strains recently detected in other countries were first detected in India in 2001 and have emerged as the predominant strains in Delhi, India, during 2005 to 2007. While the VP7 sequence was highly homologous among G12 strains isolated in Delhi, suggesting recent emergence from a common ancestor, the strains had a diverse constellation of other gene segments, demonstrating substantial reassortment. For the entire period, the common rotavirus G types G1 (26%), G2 (25%), and G9 (14%) comprised 65% of the strains, and common P types, P[4] (19%), P[6] (22%), and P[8] (35%), comprised 76% of the total P types. Of note, we detected a high percentage of unusual (17%) strains and fecal specimens with mixed (12% G and 15% P) rotavirus infections having a variety of genomic constellations. For the first time, we identified two novel rotavirus strains with unusual G/P combinations, G2P[11] and G3P[11], in patients with diarrhea. The study highlights the great diversity among rotaviruses isolated from Indian children, the opportunity for genetic reassortment between strains, and the emergence of a novel G12 strain in our country. Due to the demonstrated effect of antigenic diversity on rotavirus vaccines, it will be important to continue careful monitoring of these strains as rotavirus vaccine programs are implemented in India.

Multi-minicore disease: a rare form of myopathy.

BACKGROUND: Multi-minicore disease is a rare form of myopathy characterized by slowly progressive or nonprogressive muscle weakness and characteristic multiple cores within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. MATERIALS AND METHODS: A ll cases of multi-minicore disease diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. RESULT: During a period of two years (January 2004 to December 2005), we received 985 muscle biopsies for various reasons. Of which, 15 were diagnosed as myopathies and four of which were of multi-minicore disease. Thus, multi-minicore disease comprises 0.40% of all muscle diseases and 26.6% of all myopathies. All were male and presented in early childhood (first decade of life) with generalized hypotonia and muscle weakness. All of them had dysmorphic facies and three had high arched palate. CPK levels were normal and EMG was myopathic except in one patient. Microscopic examination revealed minimal changes with Type I fibers' predominance but characteristic multiple cores in the myofibers. Ultrastructural examination showed both structured and unstructured cores. CONCLUSIONS: Multi-minicore disease, although a rare form of myopathies, should be suspected in children who present with generalized hypotonia and slowly progressive muscle weakness along with dysmorphic facies.

Nemaline rod myopathy: a rare form of myopathy.

Nemaline rod myopathy (NM) is a rare form of congenital myopathy characterized by slowly progressive or nonprogressive muscle weakness and pathognomonic rod-like structures within the muscle fibers. To the best of our knowledge, this is first documentation of the clinicopathological features of this rare entity from India. All cases of NM diagnosed in our laboratory were retrieved. Clinical and pathological features were reviewed. During a period of 1.5 years (Jan 2004 to June 2005), we received 750 muscle biopsies for various reasons. Of which, 15 were diagnosed as congenital myopathies and four as nemaline rod myopathies. Thus, NM comprises 0.53% of all muscle diseases and 22.6% of all congenital myopathies. All of them presented in childhood (first five years of life) with generalized hypotonia, feeding problems, repeated respiratory infections and muscle weakness. Both males and females were equally affected. The CPK levels were normal and EMG was myopathic. Microscopic examination revealed minimal changes but characteristic red-colored material was seen on modified Gomori trichrome staining which was immunopositive to alpha actinin. Ultrastructural examination confirmed this material to be nemaline rods. NM, although a rare form of congenital myopathies, should be suspected in children who present with generalized hypotonia, repeated chest infections and slowly progressive muscle weakness. This report highlights the importance of histochemistry and ultrastructural examination in the diagnosis of this entity, in the absence of the availability of methodology for genetic studies.