Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

Identification of Novel PROP1 and POU1F1 Mutations in Patients with Combined Pituitary Hormone Deficiency.

Growth hormone deficiency (GHD) results from variations affecting the production and release of growth hormone (GH) and is of 2 types: isolated growth hormone deficiency (IGHD) and combined pituitary hormone deficiency (CPHD). IGHD results from mutations in GH1 and GHRHR while CPHD is associated with defects in transcription factor genes PROP1, POU1F1, and HESX1. The present study reports on screening of POU1F1, PROP1, and HESX1 in CPHD patients and the novel variations identified. Fifty-one CPHD patients from 49 unrelated families clinically diagnosed on the basis of biochemical and imaging investigations along with 100 controls were enrolled. Detailed family history was noted from all participants and 5 ml blood samples drawn were processed for DNA isolation followed by direct sequencing of POU1F1, PROP1, and HESX1genes. Of the 51 patients, 8 were females and 43 were males. Mean height standard deviation score (SDS) and weight SDS were -5.50 and -2.76, respectively. Thirty-six of the 51 patients underwent MRI of which 9 (25%) had normal pituitary structure and morphology while 27 (75%) showed abnormalities. Molecular analysis revealed 10 (20%) patients to have POU1F1 and PROP1 mutations/variations of which 5 were novel and 2 previously reported. No mutations were identified in HESX1. The novel variations identified were absent in the 100 healthy individuals screened and the control database Exome Aggregation Consortium (ExAC). Reported POU1F1 and PROP1 mutation hotspots were absent in our patients. Instead, novel POU1F1 changes were identified suggesting existence of a distinct mutation spectrum in our population.

An unusual cause of reversible axonal neuropathy and hypertension in a 10-year-old girl.

A 10-year-old girl, who was referred with refractory epilepsy, had 1.5 years of episodic abnormal behavior. On examination, she also had hypertension and peripheral neuropathy. Hypoglycemia with correspondingly high insulin levels was documented during a confusional episode. MRI of the abdomen revealed an islet cell tumor in the body of the pancreas. One year after tumor excision, both the neuropathy and hypertension showed remarkable improvement. A final diagnosis of insulinoma with hypoglycemic axonal neuropathy and hypertension (reversed with tumor excision) was made. Insulinoma is the commonest cause of hyperinsulinemic hypoglycemia in adults, but is rare in childhood. To our knowledge, distal symmetrical motor-sensory axonal neuropathy has been described in only 40 patients, and hypertension has not been reported with insulinoma.

Identification of a novel mutation in an Indian patient with CAII deficiency syndrome.

Carbonic anhydrase II (CAII) deficiency syndrome characterized by osteopetrosis (OP), renal tubular acidosis (RTA), and cerebral calcifications is caused by mutations in the carbonic anhydrase 2 (CA2) gene. Severity of this disorder varies depending on the nature of the mutation and its effect on the protein. We present here, the clinical and radiographic details along with, results of mutational analysis of the CA2 gene in an individual clinically diagnosed with renal tubular acidosis, osteopetrosis and mental retardation and his family members to establish genotype-phenotype correlation. A novel homozygous deletion mutation c.251delT was seen in the patient resulting in a frameshift and a premature stop codon at amino acid position 90 generating a truncated protein leading to a complete loss of function and a consequential deficiency of the enzyme making this a pathogenic mutation. Confirmation of clinical diagnosis by molecular methods is essential as the clinical features of the CAII deficiency syndrome are similar to other forms of OP but the treatment modalities are different. Genetic confirmation of the diagnosis at an early age leads to the timely institution of therapy improving the growth potential, reduces other complications like fractures, and aids in providing prenatal testing and genetic counseling to the parents planning a pregnancy.

Congenital adrenal hyperplasia: Results of medical therapy on appearance of external genitalia.

OBJECTIVE: Girls with congenital adrenal hyperplasia show a variable degree of genital masculinization at birth. Antenatal dexamethazone treatment for the mother is known to reduce the severity of this condition. There are however few data on the effect of postnatal steroid therapy on the cosmetic appearance of the external genitalia. PATIENTS AND METHOD: We report the appearance of the external genitalia of three girls with classical congenital adrenal hyperplasia followed up by steroid therapy alone. RESULTS: Growth of the labia majora and a relative reduction in clitoral size improved the appearance of the external genitalia in these three girls. CONCLUSION: There seems to be improvement in the external appearance of genitalia with postnatal steroid therapy. This could allay parental concerns and help in the planning of corrective surgery peripubertally with the informed consent of the child.

Tuberculosis of the thyroid gland: magnetic resonance imaging appearances.

Tuberculosis involving the thyroid gland is a rare occurrence. We report a case of cytologically-diagnosed thyroid gland tuberculosis in a 21-year-old man who presented with thyroid swelling of short duration, and describe the magnetic resonance (MR) imaging appearances of the lesion, which to our knowledge, has not been previously described. We also report a rare complication of abscess formation in the track of the fine needle aspiration. The intermediate signal intensity of the lesions on both T1- and T2-weighted MR images may provide a clue about tuberculosis, as clinical suspicion is low due to the rarity of the disease.

PET/CT localisation of a scapular haemangiopericytoma with tumour-induced osteomalacia.

Oncogenic osteomalacia, or tumour-induced osteomalacia (TIO), is a rare paraneoplastic syndrome characterised by hypophosphataemia, phosphaturia, inappropriately low serum levels of 1,25-dihydroxyvitamin D for hypophosphataemia. TIO is caused by mesenchymal tumours that secrete phosphaturic substances, leading to increased renal wasting of phosphates. These tumours are very small in size and grow slowly. Localisation of these tumours has always been difficult with the available biochemical and imaging techniques. At times, despite all efforts, the tumour could not be localised. We report our experience with a 42-year-old woman with TIO where whole-body magnetic resonance imaging could not localise the tumour, a scapular haemangiopericytoma. PET/CT was helpful in the localisation of the tumour which, when surgically removed, resulted in the normalisation of biochemical parameters with clinical improvement.

Correlation of cell counts and indices in testicular FNAC with histology in male infertility.

OBJECTIVE: To evaluate the value of percentage cell counts and cell indices in testicular fine needle aspiration cytology (FNAC) in male infertility and their correlation with histologic categories as seen in open testicular biopsies. STUDY DESIGN: Differential cell counts were performed, and cell indices, including spermatic index, Sertoli cell index and sperm-Sertoli cell index, were calculated in testicular fine needle aspiration (FNA) smears in 30 azoospermic males whose open testicular biopsies were classified as normal spermatogenesis in 10 cases, maturation arrest in 5, hypospermatogenesis in 6, Sertoli cell only syndrome in 5 and tubular/peritubular sclerosis in 4. RESULTS: In normal spermatogenesis, FNA smears showed up to 40% Sertoli cells, and spermatozoa were the predominant spermatogenetic cell type. There was a progressive increase in Sertoli cell percentage and Sertoli cell index and reduction in spermatozon percentage, spermatic index and sperm-Sertoli cell index with increasing severity of reduction in spermatogenesis in different histologic categories. The differences between mean counts and indices in normal spermatogenesis and other histologic categories were statistically significant (P < .01). CONCLUSION: The percent cell counts and cell indices in testicular FNAC correlate with histologic categories and are useful in evaluating male infertility.