Genome-wide association analyses of symptom severity among clozapine-treated patients with schizophrenia spectrum disorders.

Clozapine is the most effective antipsychotic for patients with treatment-resistant schizophrenia. However, response is highly variable and possible genetic underpinnings of this variability remain unknown. Here, we performed polygenic risk score (PRS) analyses to estimate the amount of variance in symptom severity among clozapine-treated patients explained by PRSs (R2) and examined the association between symptom severity and genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activity. Genome-wide association (GWA) analyses were performed to explore loci associated with symptom severity. A multicenter cohort of 804 patients (after quality control N = 684) with schizophrenia spectrum disorder treated with clozapine were cross-sectionally assessed using the Positive and Negative Syndrome Scale and/or the Clinical Global Impression-Severity (CGI-S) scale. GWA and PRS regression analyses were conducted. Genotype-predicted CYP1A2, CYP2D6, and CYP2C19 enzyme activities were calculated. Schizophrenia-PRS was most significantly and positively associated with low symptom severity (p = 1.03 × 10-3; R2 = 1.85). Cross-disorder-PRS was also positively associated with lower CGI-S score (p = 0.01; R2 = 0.81). Compared to the lowest tertile, patients in the highest schizophrenia-PRS tertile had 1.94 times (p = 6.84×10-4) increased probability of low symptom severity. Higher genotype-predicted CYP2C19 enzyme activity was independently associated with lower symptom severity (p = 8.44×10-3). While no locus surpassed the genome-wide significance threshold, rs1923778 within NFIB showed a suggestive association (p = 3.78×10-7) with symptom severity. We show that high schizophrenia-PRS and genotype-predicted CYP2C19 enzyme activity are independently associated with lower symptom severity among individuals treated with clozapine. Our findings open avenues for future pharmacogenomic projects investigating the potential of PRS and genotype-predicted CYP-activity in schizophrenia.

Efficacy and Safety of Reirradiation with Stereotactic Body Radiation Therapy for Locally Recurrent Pancreatic Adenocarcinoma.

AIMS: The purpose of this study was to report on outcomes of a cohort of patients who were treated with reirradiation with stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma. MATERIALS AND METHODS: Patients treated with SBRT reirradiation for locally recurrent pancreatic adenocarcinoma from December 2009 to April 2020 were included in the study. Descriptive statistics were used to record patient demographics, tumour and treatment characteristics. Kaplan-Meier analysis was used to evaluate overall survival, local progression-free survival (LPFS), distant metastasis-free survival and progression-free survival (PFS). RESULTS: In total, 27 patients were included in the study. The median follow-up time from local recurrence was 19.7 months (range 4.2-43.1 months). Most patients received five-fraction SBRT (26/27, 96%). The median overall survival after local recurrence treatment was 18.3 months (range 3.0-42.6 months), with 6-month, 1-year and 2-year overall survival rates of 88.5%, 73.1% and 33.6%. The median LPFS after local recurrence treatment was 16.2 months (range 2.3-33.6 months), with 6-month, 1-year and 2-year LPFS rates of 95.8%, 62.9% and 27.2%. Peri-SBRT chemotherapy improved LPFS (median 17.5 versus 8.5 months; P = 0.010) and overall survival (median 19.3 versus 5.5 months; P = 0.049). Tumours ≤ 3 cm in the greatest dimension showed better local control (median LPFS 19.2 versus 10.2 months; P = 0.130). There was one case (4%) of acute grade 3 pain and one case (4%) of late grade 3 gastrointestinal toxicity. CONCLUSIONS: Reirradiation with five-fraction SBRT is safe, but local control remains suboptimal. Patients with smaller tumours experienced improved outcomes, as did patients whose treatment plan included the administration of peri-SBRT chemotherapy.

Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

PURPOSE: Thirty-day mortality of patients with hip fracture is well researched and predictive; validated scoring tools have been developed (Nottingham Hip Fracture Score, NHFS). COVID-19 has significantly greater mortality in the elderly and comorbid patients which includes hip fracture patients. Non-operative treatment is not appropriate due to significantly higher mortality, and therefore, these patients are often exposed to COVID-19 in the peri-operative period. What is unclear is the effect of concomitant COVID-19 infection in these patients. METHODS: A multicentre prospective study across ten sites in the United Kingdom (responsible for 7% of hip fracture patients per annum in the UK). Demographic and background information were collected by independent chart review. Data on surgical factors included American Society of Anesthesiologists (ASA) score, time to theatre, Nottingham Hip fracture score (NHFS) and classification of fracture were also collected between 1st March 2020 and 30th April 2020 with a matched cohort from the same period in 2019. RESULTS: Actual and expected 30-day mortality was found to be significantly higher than expected for 2020 COVID-19 positive patients (RR 3.00 95% CI 1.57-5.75, p < 0.001), with 30 observed deaths compared against the 10 expected from NHFS risk stratification. CONCLUSION: COVID-19 infection appears to be an independent risk factor for increased mortality in hip fracture patients. Whilst non-operative management of these fractures is not suggested due to the documented increased risks and mortality, this study provides evidence to the emerging literature of the severity of COVID-19 infection in surgical patients and the potential impact of COVID-19 on elective surgical patients in the peri-operative period.

Correction to: Thirty-day mortality following surgical management of hip fractures during the COVID-19 pandemic: findings from a prospective multi-centre UK study.

The published online version contains mistake, as the Fig. 1 legend should read "Kaplan-Meier survival curve for 30-day survival for 2020 cohort COVID-19 positive vs COVID-19 negative" whilst the Fig. 2 legend should read "Kaplan-Meier survival curve for 30-day survival 2020 COVID-19 negative group vs 2019 cohort".

Detection of non-tuberculous mycobacterial species using PCR-RFLP analysis in trans-tracheal washes in cattle and buffaloes with respiratory distress.

BACKGROUND: Bovine tuberculosis (bTB) is a chronic disease of cattle with high economic importance in livestock farming caused by Mycobacterium bovis and bears a zoonotic potential. There are some non-tuberculous mycobacteria (NTM) which cause disease similar to bTB and interfere with diagnosis of bTB. Non-tuberculous mycobacteria are saprophytic in nature but some of them may cause pulmonary infections, mastitis, lesions in respiratory tract and lymph nodes of cattle, due to which they are being recognized worldwide and interfere with the diagnosis of bTB. AIMS: The aim of the study was to detect NTM species from cattle and buffaloes with respiratory distress using biochemical test and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis (PRA). METHODS: A total of 50 trans-tracheal washes were collected from cattle (n=41) and buffaloes (n=9) with respiratory distress. The samples were inoculated on Middlebrook 7H10 media after proper decontamination with 4% NaOH. The isolate obtained was identified by biochemical testing. Extracted DNA from samples and isolate was subjected to PRA which involved hsp65 gene amplification (439 bp) and RFLP analysis of amplified product. RESULTS: Out of 50 trans-tracheal washes only one isolate of Mycobacterium kansasii (n=1) (2%) was obtained which was confirmed by biochemical testing and PRA. Mycobacterium kansasii (n=4) (8%), Mycobacterium intracellulare (n=1) (2%), and Mycobacterium vaccae (n=1) (2%) were identified by PRA. CONCLUSION: The study emphasizes the importance of NTM in animals. Polymerase chain reaction-restriction fragment length polymorphism analysis is a more reliable and rapid method for identification of NTM than conventional methods.

Atypical theileriosis with cutaneous involvement in a cow in India: a case report.

Bovine tropical theileriosis caused by Theileria annulata is an overwhelming haemoprotozoan tick-borne disease in taurine and cross-bred cattle in Punjab, India. However, there seems to be no report from India of cutaneous nodules associated with the disease. This report describes a five-year-old cross-bred cow presented to a university clinic with a history of fever, inappetence and malaise for the past six to seven days. Clinical examination revealed normal vital parameters, pale mucous membranes, mild enlargement of the prescapular lymph nodes and multiple subcutaneous nodular masses (2-4 cm) on the neck and abdomen. Haematology revealed mild anaemia and leucopenia with 48% neutrophils, 48% lymphocytes and 4% eosinophils. Romanowsky-stained smears of fineneedle aspiration biopsy samples from swollen lymph nodes and subcutaneous masses showed an increased number of lymphoid cells, suggesting cutaneous lymphomatosis. However, a critical examination of the smears from subcutaneous nodules showed a large number of Koch's blue bodies in macrophages and lymphoblasts, and several piroplasms were also noticed within the red blood cells in lymph node smears. A peripheral blood smear revealed mild to moderate parasitaemia. Extracted DNA from the parasitologically positive blood sample was subjected to nested polymerase chain reaction (nPCR) using T. annulata speciesspecific primers encoding the 30-kiloDalton major sporozoite surface antigen. The desired 572-base pair amplified product of the nPCR was comparable to the positive control. This seems to be a rare case of T. annulata in an adult cross-bred cow, showing cutaneous nodular involvement.

La theilériose bovine tropicale est une maladie causée par le protozoaire Theileria annulata et transmise par les tiques, affectant massivement les populations de bovins et de bovidés métis au Pendjab (Inde). Il semble toutefois que la présence de nodules cutanés associés à la maladie n'y ait jamais été rapportée jusqu'à présent. Les auteurs décrivent le cas soumis à une clinique vétérinaire universitaire d'une vache métisse âgée de cinq ans qui présentait depuis six à sept jours un tableau fébrile accompagné d'une perte d'appétit et d'un affaiblissement général. À l'examen clinique, les paramètres vitaux étaient normaux mais une pâleur des membranes muqueuses a été observée, ainsi qu'un gonflement modéré des ganglions lymphatiques préscapulaires et de nombreuses masses nodulaires sous-cutanées (de 2 à 4 cm d'épaisseur) au niveau du cou et de l'abdomen. L'hématologie a mis en évidence une anémie modérée et une leucopénie, les leucocytes se répartissant en 48 % de neutrophiles, 48 % de lymphocytes et 4 % d'éosinophiles. Les frottis à coloration de Romanowsky d'une biopsie par aspiration à l'aiguille fine des ganglions lymphatiques enflés et des masses sous-cutanées ont fait apparaître une augmentation du nombre de cellules lymphatiques évocatrice d'une lymphomatose cutanée. Néanmoins, un examen critique des prélèvements de nodules sous-cutanés a permis de constater la présence d'un grand nombre de corps bleus de Koch dans les macrophages et les lymphoblastes ; en outre, de nombreux piroplasmes ont été trouvés dans les globules rouges des frottis de ganglions lymphatiques. Un frottis de sang périphérique a permis de quantifier la parasitémie comme étant de niveau faible à modéré. L'ADN extrait de l'échantillon de sang à parasitologie positive a été soumis à une amplification en chaîne par polymérase nichée (nPCR) utilisant des amorces spécifiques de T. annulata codant pour l'antigène majeur de surface (30 kDa) du sporozoïte. Le produit amplifié par nPCR de la séquence souhaitée de 572 paires de bases était similaire à celui de l'échantillon de contrôle positif. Il s'agit probablement d'un cas rare d'infection à T. annulata chez une vache adulte métisse présentant des manifestations nodulaires cutanées.

La teileriosis tropical bovina causada por Theileria annulata es una devastadora enfermedad hemoprotozoaria transmitida por garrapatas que afecta al ganado taurino e híbrido del Punjab (India). Ahora bien, en la India no parece haber ningún caso descrito de esta enfermedad que se acompañe de la presencia de nódulos cutáneos. Los autores describen el caso de una vaca de cinco años híbrida que fue presentado a una clínica universitaria con un cuadro de fiebre, pérdida de apetito y decaimiento en los seis a siete días anteriores. El examen clínico puso de manifiesto parámetros vitales normales, mucosas pálidas, leve hipertrofia de los ganglios linfáticos prescapulares y múltiples bultos subcutáneos de tipo nodular (2 a 4 cm) en cuello y abdomen. El análisis hematológico reveló una leve anemia y leucocitopenia, con un 48% de neutrófilos, un 48% de linfocitos y un 4% de eosinófilos. Tras proceder a una biopsia de ganglios inflamados y bultos subcutáneos por aspiración con aguja fina, el examen de frotis de estas muestras con tinción de Romanowsky reveló un número excesivo de células linfáticas, lo que parece apuntar a una linfomatosis cutánea. No obstante, al examinar más a fondo los frotis de nódulos subcutáneos se observó que macrófagos y linfoblastos albergaban un gran número de cuerpos azules de Koch. También se observaron varios piroplasmas dentro de los eritrocitos presentes en los frotis de ganglios linfáticos. Un frotis de sangre periférica reveló una parasitemia entre leve y moderada. El ADN extraído de esta muestra de sangre positiva fue sometido a una técnica de reacción en cadena de la polimerasa (PCR) anidada en la que se emplearon cebadores específicos de la especie T. annulata que codifican el antígeno de superficie principal de 30 kDa del esporozoíto. La deseada secuencia de 572 pares de bases amplificada por PCR resultó comparable con la correspondiente secuencia de la muestra positiva de control. Parece tratarse pues de un caso raro de infestación por T. annulata de una vaca adulta híbrida que se acompaña de nódulos cutáneos.

Guidelines for training in cardiovascular magnetic resonance (CMR).

These "Guidelines for training in Cardiovascular Magnetic Resonance" were developed by the Certification Committee of the Society for Cardiovascular Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

End-of-radiation PSA as a novel prognostic factor in patients undergoing definitive radiation and androgen deprivation therapy for prostate cancer.

BACKGROUND: In men undergoing definitive radiation for prostate cancer, it is unclear whether early biochemical response can provide additional prognostic value beyond pre-treatment risk stratification. METHODS: Prostate cancer patients consecutively treated with definitive radiation at our institution by a single provider from 1993 to 2006 and who had an end-of-radiation (EOR) PSA (n=688, median follow-up 11.2 years). We analyzed the association of an EOR PSA level, obtained during the last week of radiation, with survival outcomes. Multivariable-adjusted cox proportional hazards models were constructed to assess associations between a detectable EOR PSA (defined as ⩾0.1 ng ml-1) and biochemical failure-free survival (BFFS), metastasis-free survival (MFS), prostate cancer-specific survival (PCSS) and overall survival (OS). Kaplan-Meier survival curves were constructed, with stratification by EOR PSA. RESULTS: At the end of radiation, the PSA level was undetectable in 30% of patients. Men with a detectable EOR PSA experienced inferior 10-year BFFS (49.7% versus 64.4%, P<0.001), 10-year MFS (84.8% versus 92.0%, P=0.003), 10-year PCSS (94.3% versus 98.2%, P=0.007) and 10-year OS (75.8% versus 82.5%, P=0.01), as compared to men with an undetectable EOR PSA. Among National Comprehensive Care Network (NCCN) intermediate- and high-risk men who were treated with definitive radiation and androgen deprivation therapy (ADT), a detectable EOR PSA was more strongly associated with PCSS than initial NCCN risk level (EOR PSA: HR 5.89, 95% CI 2.37-14.65, P<0.001; NCCN risk level: HR 2.01, 95% CI 0.74-5.42, P=0.168). Main study limitations are retrospective study design and associated biases. CONCLUSIONS: EOR PSA was significantly associated with survival endpoints in men who received treatment with definitive radiation and ADT. Whether the EOR PSA can be used to modulate treatment intensity merits further investigation.

Unscreened older men diagnosed with prostate cancer are at increased risk of aggressive disease.

BACKGROUND: To evaluate the relationship between PSA testing history and high-risk disease among older men diagnosed with prostate cancer. METHODS: Records from 1993 to 2014 were reviewed for men who underwent radiotherapy for prostate cancer at age 75 years or older. Patients were classified into one of four groups based on PSA-testing history: (1) no PSA testing; (2) incomplete/ineffective PSA testing; (3) PSA testing; or (4) cannot be determined. Outcomes of interest were National Comprehensive Cancer Network (NCCN) risk group (that is, low, intermediate or high risk) and biopsy grade at diagnosis. Multivariable logistic regression was used to determine the association between PSA testing history and high-risk cancer. RESULTS: PSA-testing history was available in 274 (94.5%) of 290 subjects meeting study criteria. In total, 148 men (54.0%) underwent PSA testing with follow-up biopsy, 72 (26.3%) underwent PSA testing without appropriate follow-up, and 54 men (19.7%) did not undergo PSA testing. Patients who underwent PSA testing were significantly less likely to be diagnosed with NCCN high-risk cancer (23.0% vs 51.6%, P<0.001). On multivariable analysis, men with no/incomplete PSA testing had more than three-fold increased odds of high-risk disease at diagnosis (odds ratio 3.39, 95% confidence interval 1.96-5.87, P<0.001) as compared to the tested population. CONCLUSIONS: Older men who underwent no PSA testing or incomplete testing were significantly more likely to be diagnosed with high-risk prostate cancer than those who were previously screened. It is reasonable to consider screening in healthy older men likely to benefit from early detection and treatment.

Review article: Risk factors for poor outcome following surgical treatment for rotator cuff tear.

The Medline database was searched using key words: 'rotator cuff', 'tear', and 'treatment'. 12 studies that involved (1) surgical treatment for rotator cuff tear, (2) measurement of pre- and post-operative pain score, functional score, and/or patient satisfaction, (3) patients that failed to improve functionally or had poor satisfaction, (4) preoperative examination of risk factors that could lead to poor outcome, and (5) a minimum follow-up of 6 months were reviewed to identify risk factors associated with poor outcome following surgical treatment for rotator cuff tear. The most common risk factor was tear size, followed by open compensation claim, age, and time from injury to surgery.

Diagnostic value of lactate levels in acute abdomen disorders.

The supply of oxygen is limited in certain intra abdominal conditions due to direct vascular invasion or inflammatory process, resulting in high lactate levels. Aim of this study was to find the predictive value of lactate levels in the peritoneal fluid (PF) and blood of patients with acute abdomen. The study comprised of fifty patients with acute abdominal conditions, admitted in emergency ward of tertiary care hospital, thirty patients were with surgical abdomen (group I) and twenty patients with non surgical abdomen (group II). Lactate was estimated in PF and blood on Blood Gas Analyzer (NOVA, M-7). The mean lactate levels in PF were significantly higher in group I as compared to group II (14.65 ± 1.195 vs. 5.92 ± 0.97 mmol/L, p < 0.001). There was no significant difference in blood lactate levels in both the groups. When PF and blood lactate levels were compared within groups, we found that PF levels were significantly higher than blood in group I (14.65 ± 1.195 vs. 3.85 ± 0.54 mmol/L, p < 0.001) but not in group II (5.92 ± 0.97 vs. 4.36 ± 0.95 mmol/L). Diagnostic value was obtained using ROC curve. Cut off values obtained for PF lactate, difference and ratio of PF and blood lactate (≥6.4 mmol/L, ≥3.3 and ≥2.1 respectively) are at very high degree of sensitivity and specificity. So it can be useful marker of surgical emergency in patients with acute intra abdominal pathology, especially in clinically ill patients or in whom physical examination is not yielding because of neurologic disorders or unresponsiveness.

Novel mutations in typical and atypical genetic loci through exome sequencing in autosomal recessive cerebellar ataxia families.

Nearly a thousand mutations mapping to 60 different loci have been identified in cerebellar ataxias. However, almost 50% of the cases remain genetically uncharacterized and there is a difference in prevalence as well as in the phenotypic spectrum of ataxia among various geographical regions. This poses a challenge for setting up a genetic panel for screening ataxia. In our ataxic cohort of 1014 families, 61% are genetically uncharacterized (UC). We investigated the potential of whole exome sequencing in conjunction with homozygosity mapping (HM) to delineate the genetic defects in three uncharacterized families with recessive inheritance each manifesting some unusual phenotype: (i) infantile onset ataxia with hearing loss (IOAH), (ii) Juvenile onset cerebellar ataxia with seizures (JCS) and (iii) Friedreich ataxia-like (FA-like). We identified a novel missense mutation in c10orf2 in the family with IOAH, compound heterozygous mutations in CLN6 in the family with JCS and a homozygous frame-shift mutation in SACS in the FA-like patient. Phenotypes observed in our families were concordant with reported phenotypes of known mutations in the same genes thus obviating the need for functional validation. Our study revealed novel variations in three genes, c10orf2, CLN6, and SACS, that have so far not been reported in India. This study also demonstrates the utility of whole exome screening in clinics for early diagnosis.

Comparing hand hygiene measures in a neonatal ICU: a randomized crossover trial.

OBJECTIVE: To compare plain soap, alcohol hand rub and iodophors as hand hygiene measures in a neonatal intensive care unit (NICU). DESIGN: Randomized, crossover, three-armed, controlled trial with blinded outcome measurement. SETTING: Level III NICU. PARTICIPANTS: 35 NICU nurses. INTERVENTION: Participants were assigned to plain soap hand washing, alcohol hand rub and povidone-iodine hand scrub by a random cross-over design. Interventions were preceded by 14-day neutral periods. Cultures from hands were taken before and after each hand-hygiene use, prior to 5 patient-care activities. MAIN OUTCOME MEASURE: The primary outcome was mean post-hygiene colony forming unit count (CFU-C). RESULTS: There were differences between soap, alcohol and povidone groups vis a vis posthygiene CFUC [median: 60, 8 and 10.5, respectively (P<0.001)], absolute reduction in CFU-C [median: 15, 100 and 40, respectively (P<0.001)], percent reduction in CFUC [median: 33.3, 92 and 87, respectively (P<0.001)] and proportion with low CFU-C [47%, 71% and 72%, respectively (P<0.001)]. Alcohol [Adjusted OR 3.2 (95% CI 1.9, 5.3)], povidone-iodine [AOR 3.1 (95% CI 1.8, 5.3)] and high prehygiene CFU-C (>300) [AOR 0.18 (95% CI 0.1, 0.3)] were independently associated with low CFU-C. CONCLUSION: After a 2 minute hand wash at entry into NICU, alcohol hand rub and povidone-iodine scrub are superior to plain soap hand wash for subsequent decontamination of hands of nurses working in NICU.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

BACKGROUND & OBJECTIVES: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. METHODS: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. RESULTS: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. INTERPRETATION & CONCLUSIONS: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Impact of body mass index on thyroid functions in Indian children.

OBJECTIVE: There is controversy about the relation of thyroid functions and body mass index. The present study was aimed to assess the relationship between thyroid function and body mass index in Indian school children. DESIGN: Population survey. PATIENTS: Data were collected from 25 schools in 19 cities across five different geographical zones of India. Children, who consented, were evaluated for anthropometry and blood tests. Children were categorized as overweight and obese based on standard BMI criteria. MEASUREMENTS: Serum samples were analysed for free T3, free T4, TSH and anti-TPO antibodies. RESULTS: A total of 13,691 children in the age group of 5-18 years formed the study population. The mean age and mean BMI were 11·9 ± 3·0 years and 18·48 ± 3·89 kg/m² respectively. Among these, 2119 (15·5%) children were overweight and 536 (3·9%) were obese. Subclinical hypothyroidism was present in 943 (6·9%) children.FT3 and TSH levels increased and FT4 levels decreased with increasing BMI in euthyroid boys and girls. Prevalence of SCH was significantly higher in obese/overweight children (9·0%, vs 6·5%; P = 0·034) as compared with normal BMI children. CONCLUSIONS: Serum FT3 and TSH were positively while FT4 was negatively associated with BMI in apparently healthy euthyroid children.

Dyslipidemia in subclinical hypothyroidism in an Indian population.

OBJECTIVES: In view of inconsistent reports on the prevalence of dyslipidemia in subclinical hypothyroidism (SCH), we studied lipid abnormalities in Indian subjects with SCH. DESIGN AND METHODS: A cross sectional study of 5343 subjects divided in two groups, Group-1 (age≤18 years) and Group-2 (age>18 years) was undertaken. They were further subdivided on the basis of their thyroid functional status: Normal (Control); SCH with TSH≤10.0mIU/L (SCH-1); and SCH with TSH>10mIU/L (SCH-2). RESULTS: Prevalence of SCH was 14.7%. The only lipid abnormality in children and adolescents was low HDL in subjects with TSH>10mIU/L compared with controls. Serum total cholesterol (TC), and LDL cholesterol (LDL) were significantly higher in adults with TSH>10mIU/L compared to controls. There were no significant changes in lipid parameters in subjects with SCH having TSH≤10.0mIU/L, compared to controls. Serum TSH was positively and FT3 and FT4 were negatively correlated with TC and LDL. CONCLUSIONS: Atherogenic lipid abnormalities were observed in adult subjects with SCH-2 (TSH>10.0mIU/L), and not in subjects with SCH-1 who had TSH≤10.0mIU/L in Indian population.

Reference intervals of serum lipid profile in healthy Indian school children and adolescents.

OBJECTIVE: To develop age and sex specific reference intervals of serum lipid parameters in healthy Indian children in the age group of 6-17 years. PARTICIPANTS: Study subjects were selected from the schools of Delhi. Children with BMI either in overweight or obese category were excluded to generate reference intervals. The final analysis included 3076 children with BMI in normal range for age. RESULTS: The mean±SD, 3rd, 10th, 25th, 50th, 75th, 90th and 97th centile values of lipid parameters are presented. All these parameters were significantly higher in girls than in boys. About 89.2% subjects had total cholesterol in acceptable range while 9.1% had borderline elevated and 1.5% had elevated TC. Optimal serum triglyceride levels were seen in 45.1% subjects while optimal levels of HDL cholesterol were seen in 0.3% subjects only. CONCLUSIONS: Reference intervals of serum lipid parameters for healthy Indian children (6-17 years) are presented.

Bone health in healthy Indian population aged 50 years and above.

UNLABELLED: One thousand six hundred healthy subjects aged more than 50 years, residing in Delhi, were evaluated for bone mineral metabolic parameters. High prevalence of osteoporosis (35.1% subjects) was observed in this population. Bone mineral density (BMD) correlated positively with body mass index (BMI) and negatively with PTH levels. No correlation was observed with serum 25(OH)D levels. INTRODUCTION: To assess the bone health status in elderly Indians and compare peripheral DXA (pDXA) with central DXA in evaluation of osteoporosis. METHODS: The study involved 1,600 healthy subjects more than 50 years of age residing in Delhi, India, who underwent anthropometric, biochemical, and hormonal evaluation. BMD was measured by DXA at lumbar spine, hip, and distal radius; and by pDXA at forearm and calcaneum. RESULTS: Seven hundred ninety-two males and 808 postmenopausal females, with a mean age of 57.67 ± 9.46 years were evaluated. Osteoporosis was present in 35.1% subjects (M-24.6%, F-42.5%) and osteopenia in 49.5% (M-54.3%, F-44.9%). Prevalence of osteoporosis increased with age in females, but not in males. BMD at all sites, except distal radius, was positively correlated with BMI (r=0.037, p=0.14). Total body BMD was negatively correlated with alkaline phosphatase (r= -0.184, p<0.00001) and PTH levels (r= -0.099, p<0.00001), respectively. No significant correlation was observed between serum 25(OH)D levels and BMD at any site. BMD at forearm and calcaneum, measured using pDXA, showed strong positive correlation with BMD measured by central DXA. pDXA had sensitivity of 88%, specificity of 55%, and negative and positive predictive values of 89% and 52%, respectively, at T-score -2.5 at peripheral sites compared to central DXA. CONCLUSIONS: A high prevalence of osteoporosis was observed in elderly Indian subjects. pDXA has high negative predictive value, making it a useful tool in population screening for osteoporosis.