A novel prognostic system based on clinical and laboratory parameters for childhood Guillain-Barre syndrome.

AIM: To develop a score based on clinical and laboratory parameters in acute-phase of GBS to predict outcome at 6 months. METHODS: Clinical and laboratory assessment at admission including blood neutrophil-to-lymphocyte ratio (NLR), pre and post-immunotherapy serum albumin was prospectively performed in pediatric-GBS cases at a tertiary-care hospital over 1 year. Clinical features and laboratory test results were compared between children with complete (Hughes Disability Score; HDS ≤ 1) and incomplete recovery (HDS > 1) at 6 months from onset, using univariate and multivariate analysis. Area-under-receiver-operating-characteristic-curve (AUC) of predictors of prognosis and their optimal cutoffs were assessed. RESULTS: Forty-six patients were enrolled (mean age 69.1 ± 35.2 months; male 57.6%). Factors on admission that independently predicted poor-outcome at 6 months were older age, feeble voice, lower NLR and lower post-immunotherapy serum albumin. AUCs and optimal cutoffs of NLR and post-immunotherapy serum albumin for predicting disability at 6 months were 0.729, 0.781 and ≤ 1.65, ≤ 34.5 g/L, respectively. AUCs of clinical parameters such as older age and feeble voice were 0.749 and 0.713 respectively. King GBS outcomescore including all predictors had maximum AUC of 0.971 (95% CI 0.921-1.02). The score at cutoff ≥ 3 demonstrated excellent sensitivity (92.3%) and specificity (96.7%) to determine poor outcome. CONCLUSIONS: This new prognostic system may be beneficial in recognising children-at-risk of poor prognosis who may benefit from additional treatment.

Role of neuroimaging in children with first unprovoked seizure: A prospective observational study.

OBJECTIVE: To evaluate the incidence and type of neuroimaging abnormalities in first unprovoked seizure (FUS) in children. To investigate the association of neuroimaging abnormalities with clinical variables. METHODS: A prospective observational study enrolled children aged 6 months-14 years with FUS over one year at a tertiary-care teaching hospital, Northern India and subjected them to neuroimaging. Factors associated with abnormal neuroimaging were assessed using Chi square/Fischer Exact test. RESULTS: Out of 115 cases, 40 (34.8%) had abnormal neuroimaging. Frequent findings were inflammatory granuloma (70%) including Neurocysticercosis (NCC) (40%), ill-defined granuloma, calcified nodule and tuberculoma followed by white matter signal alterations. Inflammatory granuloma was significantly associated with age >2 years and focal seizures. Calcified nodule was more common in children >10 years. Other neuro-abnormalities like cerebral atrophy, gliosis, infarcts, and white matter changes were significantly prevalent with generalized seizures, perinatal asphyxia, and developmental delay. CONCLUSION: High prevalence of abnormalities in FUS, especially focal seizures, due to NCC warrants neuroimaging in all children with FUS in India.

Neuroradiologic Features Associated With Severe Restriction of Functional Mobility in Children With Cerebral Palsy in North India.

BACKGROUND: Few studies have focused on magnetic resonance imaging (MRI) brain findings associated with functional mobility in cerebral palsy. OBJECTIVE: To determine association between MRI findings and Gross Motor Functional Classification System (GMFCS) levels in cerebral palsy. METHODS: Prospective-observational study conducted in Pediatric Neurology Clinic at a public teaching hospital, Northern India. First 3 new cases of cerebral palsy were enrolled on particular neuro-clinic day per week for 1 year. Functional mobility was classified according to GMFCS. Association between MRI findings, cerebral palsy type, and GMFCS levels were evaluated using χ2 test. RESULTS: A total of 138 cases (mean age 2.71 [SD = 1.91] years; male [64.5%]) were enrolled. Reported types of cerebral palsy were as follows: spastic quadriplegia (47.8%), spastic diplegia (28.35%), spastic hemiplegia (11.6%), extrapyramidal (6.5%), and ataxic/hypotonic (5.8%). GMFCS were classified into level 1 (13%), level 2 (7.2%), level 3 (4.3%), level 4 (10.9%), and level 5 (64.5%). Spastic quadriplegia and extrapyramidal cerebral palsy were significantly associated with higher (severe) levels (IV and V), whereas spastic diplegia and hemiplegia were significantly associated with lower (mild) levels (I-III) of GMFCS. MRI features of periventricular white matter injury, deep gray matter injury, basal ganglia and thalamic changes, and superficial gray matter injury were significantly associated with severe levels of GMFCS (V and IV). MRI was normal in 8 children (5 = mild category, 3 = severe category). CONCLUSION: Severe cerebral palsy is most often associated with spastic quadriplegia, extrapyramidal cerebral palsy, superficial gray matter lesions, deep gray matter lesions, and periventricular white matter injury. This information is useful for anticipating and addressing the needs of children with cerebral palsy and for prognostication.

Clinical Profile and Predictors of Mechanical Ventilation in Guillain-Barre Syndrome in North Indian Children.

OBJECTIVE: To describe the clinical-laboratory profile of pediatric Guillain-Barre syndrome and delineate features associated with need of mechanical ventilation. METHODS: In a prospective observational study at tertiary care hospital, clinical-laboratory assessment and nerve conduction studies were documented in consecutive children hospitalized with Guillain-Barre syndrome according to Brighton criteria. Clinical-laboratory features were compared between ventilated and nonventilated patients using univariate and multivariate analysis. RESULTS: Forty-six children (27 boys) with a mean age of 69.1±35.2 months were enrolled. History of preceding infection was present in 47.8%, bulbar palsy in 43.5%, feeble voice in 41.3%, sensory involvement in 13%, and autonomic involvement in 39.5%. Tetraparesis was noted in 87% of cases. Hughes disability scale >3 was noted in 44 children at admission and 39 (84.7%) at discharge. The most common electrophysiological type was acute motor axonal neuropathy (46.5%) followed by acute motor sensory axonal neuropathy (39.5%), acute inflammatory demyelinating polyneuropathy (7%), and inexcitable nerves (7%). Nine (19.7%) children were ventilated, 3 (6.5%) died or were lost, and 43 were discharged. Factors associated with need of mechanical ventilation on univariate analysis were older age, hypertension, bulbar palsy, feeble voice, lower Medical Research Council (MRC) sum, raised total leucocyte count, and history of preceding infection. Logistic regression revealed older age, history of predisposing illness, lower MRC sum at presentation, and bulbar palsy as independent predictors of mechanical ventilation. CONCLUSIONS: The most common electrophysiological subtype in northern Indian children is acute motor axonal neuropathy. Older age, preceding infection, low MRC sum, and bulbar palsy are predictors of mechanical ventilation in pediatric Guillain-Barre syndrome.

Shock index is better than conventional vital signs for assessing higher level of care and mortality in severe sepsis or shock.

BACKGROUND: Conventional vital signs alone have limitations in determining the physiological status. Age-adjusted shock-index (SIPA), a comprehensive physiological variable, defined as the ratio of heart rate (HR) and systolic blood pressure (SBP) may be better at predicting hemodynamic stability and outcome than vital signs. OBJECTIVES: To compare discriminatory power of SIPA against vital signs in assessing higher level of care (vasopressor use and mechanical ventilation) and early mortality in severe sepsis/septic shock. METHODS: Prospective cohort study of 116children <14 years with severe sepsis/septic shock admitted at emergency department of a tertiary care hospital. Association between abnormal signs (raised heart-rate; HR, lower systolic blood-pressure; SBP, high SIPA) and higher level of care and early mortality at 0 and completed 6 hours (t0, t6) were assessed using univariate/multivariate analysis. Area-under-receiver-operating-characteristic curves (AUROC) of SIPA and conventional vital signs for outcome variables and their correlation with arterial lactate using Pearson's-coefficient were noted. RESULTS: High SIPA was independently associated with higher level of care i.e. vasopressor use, mechanical ventilation (AUROC t0: 0.698, 0.730; AUROC t6; 0.733, 0.735) as well as early mortality (AUROC t0: 0.638; AUROC t6:0.721) at t0 and t6. At t0, only high SIPA (r2 = 0.313) fairly correlated with arterial lactate (4.5 mmol/L). At t6, HR and SBP showed weak and SIPA (r2 = 0.434) demonstrated moderate correlation with arterial lactate. CONCLUSIONS: SIPA performs better than conventional vital-signs in recognising higher-level-of-care and early mortality.

Lactate Measurements and Their Association With Mortality in Pediatric Severe Sepsis in India: Evidence That 6-Hour Level Performs Best.

PURPOSE: To investigate association of static and dynamic lactate indices with early mortality (within 48 hours of admission), as well as need for vasopressors and mechanical ventilation in pediatric severe sepsis/shock. To explore optimal cutoffs of lactate indices. We hypothesized that dynamic indices are superior to static indices in predicting early mortality. METHODS: This prospective cohort study involved children (aged <14 years) admitted in emergency department, tertiary care teaching hospital in North India with severe sepsis/shock (2015-2016). Arterial lactate was measured at admission (X0) and after 6 hours (X6). Primary outcome of the measurement was early mortality. Association between lactate indices- lactate at 0 hours (Lac0), lactate after 6 hours (Lac6), time-weighted average (LacTW), delta (ΔLac), clearance (LacCl%) and early mortality, need for vasopressors, and mechanical ventilation-was assessed using Student t test/Mann-Whitney test. Area under the receiver operating characteristic curve (AUROC) for early mortality deduced for all lactate indices and compared with reference (Lac0). Optimal cutoffs (maximizing both sensitivity and specificity) and their positive predictive value (PPV) and negative predictive value (NPV) were determined. RESULTS: During the study period, 116 children were assessed. Septic shock was present at admission in 56.9% children; 50% of children died during the next 48 hours. Lac0, Lac6, and LacTW were significantly higher, and LacCl% was lower in nonsurvivors versus survivors (all P < .001). Lac6 (0.837 [0.76-0.91]) had significantly higher AUROC (95% confidence interval) than Lac0 (0.77; P = .03). Abnormal lactate metrics (higher Lac0, Lac6, LacTW, and lower LacCl%) were associated with vasopressors need and mechanical ventilation. On logistic regression, Lac6 emerged as an independent predictor of early mortality as well as vasopressor and mechanical ventilation need. The optimal cutoff of Lac6 for identifying early mortality with good sensitivity, specificity, PPV, and NPV was ≥2.65 (76, 85, 83, 78). CONCLUSIONS: Lactate6 is the best marker associated with early mortality and higher level of care in severe sepsis/septic shock in resource-poor regions.

Combined score based on arterial lactate, aspartate transaminase and prolonged capillary refill time is a useful diagnostic criterion for identifying severe dengue.

BACKGROUND: Taking into consideration, the variable performance of WHO's dengue case definition and the magnitude of epidemics in India, a score based on clinical and laboratory parameters is required for the early identification of severe dengue. METHODS: A retrospective observational study of children (aged ≤12 y) presenting with dengue, defined as per the WHO 2009 classification and NS1 antigen/IgM ELISA positivity, was conducted at a tertiary care hospital from 2013 to 2015. Clinical laboratory parameters were compared between severe/non-severe dengue using univariate and multivariate analysis. Areas under receiver operating characteristic curves (AUROCs), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were obtained for independent and composite markers. RESULTS: Of 135 dengue patients, 46 (34.1%) had non-severe dengue and 89 (65.9%) had severe dengue. Logistic regression determined prolonged capillary refill time (CRT), lactate ≥2.9 mmol/L and serum aspartate transaminase (AST) ≥135 IU/L as predictive for severe dengue. AUROCs of lactate, AST and combined score incorporating AST, lactate and prolonged CRT for identifying severity were 7.55, 7.23 and 8.5, respectively. The combined score cut-off ≥1 had 87.6% sensitivity, 65.2% specificity, 83% PPV and 73.2% NPV. The combined score cut-off ≥3 had 100% specificity and 100% PPV.  However, AST >135 IU/L and lactate >2.9 mmol/L together had 97.8% specificity and 97.1% PPV for identifying severity. CONCLUSIONS: The presence of either 'prolonged capillary refill time with one deranged biochemical parameter' or 'both deranged biochemical parameters' is nearly 100% specific for severity of dengue.

Prediction Rule for Scrub Typhus Meningoencephalitis in Children: Emerging Disease in North India.

OBJECTIVES: To evaluate the proportion of scrub typhus meningoencephalitis among children with acute encephalitis syndrome and to outline its differentiating features. To develop a prediction rule for scrub typhus meningoencephalitis. METHODS: A prospective cohort study was conducted at a tertiary care public hospital in Northern India. Consecutive patients of acute encephalitis syndrome who met our inclusion criteria were enrolled over 2 years. Standardized workup including serum IgM against Orientia tsutsugamushi was performed. Clinical and laboratory features were compared between IgM-positive and IgM-negative patients. The area under the receiver operating characteristic curve of the score derived from "independent predictors" was measured. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated at different cut-offs of the score. RESULTS: Scrub typhus IgM enzyme-linked immunosorbent assay was positive in 66/352 patients (18.8%). Longer duration of fever and prodromal stage along with eschar, hepatomegaly, lymphadenopathy, and pneumonia were significantly more prevalent in scrub typhus meningoencephalitis. However, petechiae were frequent in non-scrub typhus patients. Leucocytosis, lymphocytosis, thrombocytopenia, hypoalbuminemia, and elevated levels of serum bilirubin, serum transaminases, and cerebrospinal fluid protein were associated with scrub typhus meningoencephalitis. Logistic regression revealed fever for >8 days, pneumonia, absence of petechiae, cerebrospinal fluid protein >1000 mg/L, and serum glutamic oxaloacetic transaminase >100 IU/L as independent "predictors" of scrub typhus meningoencephalitis. The area under the receiver operating characteristic curve (95% confidence interval) of the prediction score was 0.832 (0.78-0.89). Score at cutoff ≥1 had 91% sensitivity, 96.1% negative predictive value, and at cutoff ≥4 had 99.7% specificity, 88.9% positive predictive value, 83.1% negative predictive value, 40.3 positive likelihood ratio, 0.88 negative likelihood ratio for identifying scrub typhus meningoencephalitis. CONCLUSION: Prediction score may help physicians in peripheral areas to identify and treat scrub typhus meningoencephalitis, an emerging cause of acute encephalitis syndrome in India.

Shock Index-A Useful Noninvasive Marker Associated With Age-Specific Early Mortality in Children With Severe Sepsis and Septic Shock: Age-Specific Shock Index Cut-Offs.

BACKGROUND: Aim of the study was to analyze the association of shock index (SI) from 0 to 6 hours with early mortality in severe sepsis/septic shock and to explore its age-specific cut-off values. To investigate association of change in SI over first 6 hours with early mortality. METHODS: A prospective cohort study of children (<14 years) admitted in emergency department, tertiary care hospital with severe sepsis or septic shock, divided into 3 groups: group 1: 1 month to <1 year; group 2: 1 to <6 years; group 3: 6 to 12 years. Shock index (SI = heart rate/systolic blood pressure) measured at admission (X0) and hourly till 6 hours (X1-6). Primary outcome was death within 48 hours of admission. Area under receiver operating characteristic curves were constructed for SI (0-6). Optimal cut-offs of SI 0 and SI 6, maximizing both sensitivity and specificity were determined and positive and negative predictive values (PPV, NPV) were calculated. RESULTS: From 2015 to 2016, 120 children were recruited. Septic shock was present at admission in 56.7% children. Early mortality was 50%. All hourly shock indices (SI 0-6) were higher among nonsurvivors in group 2 (P ≤ .03) and group 3 (P < .001). In group 1, SI after 2 hours was higher in nonsurvivors (P 2-6: ≤ .02). Area under receiver operating characteristic curves (95% CI) for SI at 0 hour was 0.72 (0.5-0.9), 0.66 (0.5-0.8), and 0.77 (0.6-0.9) and at 6 hours was 0.8 (0.6-1), 0.75 (0.6-0.9), and 0.8 (0.7-1) in 3 groups. The cut-off values of SI 0 (sensitivity; specificity; PPV; NPV) in 3 groups: 1.98 (77; 75; 67; 83), 1.50 (65; 65; 68; 63), and 1.25 (90; 67; 77; 83) and SI6: 1.66 (85; 80; 73; 89), 1.36 (73; 70; 73; 70), and 1.30 (74; 73; 78; 69). Improvement of SI over 6 hours was associated with better outcome. Children with higher SI at both time points had higher mortality than those with SI score below the cut-offs (P = .001). CONCLUSIONS: Age-specific SI cut-off values may identify children at high risk of early mortality in severe sepsis/septic shock and allow for better targeted management.

Impact of financial support and focussed group counselling on treatment abandonment in children with acute lymphoblastic leukaemia. Experience over 22 years from North India.

OBJECTIVES: Efforts are being made worldwide to prevent abandonment in children with leukaemia. The study aimed to determine changes in treatment refusal, treatment abandonment rates, and its reasons in response to financial support and focussed group counselling. METHODS: A retrospective cohort study conducted at paediatric haematology-oncology unit, King George's Medical University, Lucknow among children <18 years admitted with acute lymphoblastic leukaemia from 1995 to 2017. Study divided into three periods: Phase 1 (1995-March 2003): Basic support, Phase 2 (April 2003-June 2009): Financial support and Phase 3 (July 2009-2017): Financial, social support with group counselling. Phase 3- subdivided into 3a: group counselling and 3b: intensified group counselling. RESULTS: Number of children registered for treatment during phase 1, 2, 3a, 3b: 176, 200, 360, and 305. Treatment refusal decreased significantly over time: 21% vs 14.5% vs 12.5% vs 5.9% (P < 0.001), especially during phase 3b. Although no change was found in treatment abandonment during phase 2, abandonment significantly reduced in phase 3a (20.3%) as compared with phase 1 (30.2%), with the proportion of children abandoning, due to financial constraints, declining. Abandonment further reduced in phase 3b vs phase 3a (11.1% vs 20.3%) (P = 0.001). After adjusting for other variables, abandonment was found to decrease independently in phase3 (a, b) as compared with phase 1 (P1 = 0.017, P2 = 0.007). CONCLUSIONS: Although helpful, financial assistance unaccompanied by counselling may be insufficient to bring a radical change. Hence, parental counselling, emphasising on treatment adherence and the aftermaths of treatment abandonment, is indispensable for preventing abandonment in semi-literate populations.

Prevalence, predictors, causes of treatment refusal and abandonment in children with acute lymphoblastic leukaemia over 18 years in North India. Treatment phase affecting factors: A step towards better focussed counselling.

BACKGROUND: Treatment refusal or abandonment are among the major causes of the survival gap between developed and developing countries. METHODS: This retrospective observational study analyzed records of children aged <18 years with acute lymphoblastic leukemia (ALL) registered for treatment at a tertiary-care teaching hospital, North India, between 1995 and 2012. Children who refused or abandoned therapy were tracked, and reasons for refusal/abandonment were recorded by telephone interviews or by surface mail. Sociodemographic parameters were compared using chi-square/Student t-test to identify predictors of refusal/abandonment. RESULTS: Treatment refusal was noted in 16.8% (96/572) of children with ALL; it was statistically higher for infants (p = 0.004), girls (p = 0.04), children of parents with poor literacy (p < 0.001), and those of lower socioeconomic status (p < 0.001). Main causes of treatment refusal were financial constraints (59.4%) and a misplaced belief about the incurability of cancer (22.9%). Therapy once started, was abandoned by 139/476 children (29.2%), the majority (41%) during induction, followed by maintenance (17.9%). Major reasons for abandonment were financial constraints (34.5%), false perception of cure (20%), poor general condition of the child (15%), no improvement in the child (13%), and blood donation refusal (3%). The reasons cited were different in different treatment phases. Abandonment was statistically higher in children from rural background (p < 0.001) or lower socioeconomic status (p < 0.001), and in those with fathers having a lower literacy status (p < 0.001). Low hemoglobin (p = 0.01) and severe wasting (p = 0.01) was greater in children who abandoned treatment. CONCLUSION: Treatment refusal or abandonment, noted in 40% of children, was due mainly to monetary difficulties, disbeliefs regarding curability, or false perceptions of cure; these factors need to be addressed to improve survival, particularly in children from rural areas and those of parents with a lower literacy status.