Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Thyrotropin receptor antibody immunoassays may not be reliable in confirming diagnosis of Painless Thyroiditis.

BACKGROUND: Scintigraphy using 99mTc-pertechnetate (TS) is the diagnostic test to differentiate thyroiditis following Graves' disease (GD) from painless thyroiditis (PT). However, TS may be contraindicated or unavailable. OBJECTIVE: We compared the diagnostic effectiveness of two TSH receptor antibody (TRAb) immunoassays in untreated PT, already confirmed by qualitative and quantitative(99m) Tc-pertechnetate thyroid uptake (TCTU). METHOD: TRAb assay and TS were performed in suspected PT patients. All 67 subjects (27 males) with confirmed diagnosis of PT based on qualitative (subjective) low uptake and quantitative uptake below 0.4% (Normal TcTU: 0.4-4%). During the period of study, we used two 2nd generation TRAb assays. RESULT: Mean age, TSH, free T4 and TcTU were 40.5± 12.7 years, 0.066±0.089 mIU/L, 2.46±2.18 ng/mL and 0.188±0.0503% respectively. Fifteen (22.39%) of our PT patients were TRAb positive. Sensitivity, specificity, accuracy, PPV and NPV of TRAb in predicting thyroiditis were 81%, 75%, 78.2%, 83.6% and 74.4% in Assay 1. The same parameters were 74%, 64%, 71.2%, 76.8% and 62.7% respectively in TRAb Assay 2. However, ROC curve did not reveal any difference between the two assays. CONCLUSION: Negative TRAb value does not reliably distinguish PT from mild GD, in situations where TS is contraindicated or unavailable.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Depth resolved defect characterization of energetic ion irradiated ZnO by positron annihilation techniques and photoluminescence.

Depth resolved positron annihilation spectroscopy (PAS) has been employed to characterize the 1.2 MeV Ar and 800 keV O ion beam induced defects in ZnO. The first extraordinary result was the observation of defects in ion beam irradiated ZnO beyond the maximum penetration depth of the respective ions. The positron annihilation results revealed the formation of vacancy clusters consisting of both VZn and VO in ZnO which are saturated at a threshold radiation dose (defined as nuclear energy loss, Sn × fluence). From the photoluminescence (PL) spectra it has been observed that the PL intensity at the band edge degraded with the increase of open volume defects in ZnO. The evolution of the 2.4 eV PL, which is linked with the oxygen vacancies, is more significant due to Ar irradiation than the oxygen irradiation.

Treatment preferences and outcome in male hypogonadotropic hypogonadism: an Indian perspective.

This retrospective study assessed treatment preferences and outcome with testosterone or HCG / HCG-FSH combination in Indian male idiopathic hypogonadotropic hypogonadism (IHH) subjects (n = 31) above 18 years of age. 38.7% of IHH study subjects had no fertility plans and chose 3 monthly intramuscular testosterone undecanoate. 73.7% of subjects with fertility plans chose human chorionic gonadotropin (HCG) alone due to cost considerations. Spermatogenesis occurred in 21.4% on HCG alone and 60% of subjects on HCG with follicle-stimulating hormone (FSH) combination. Treatment failure is higher than published Western rates. FSH and HCG combination regimen is costly but superior to HCG alone. However, treatment failure still persists, suggesting unknown testicular defect in IHH.

Treatment of Type 2 Diabetes with a Breakable Extended Release Gliclazide Formulation in Primary Care: The Xrise Study.

OBJECTIVE: This study examines whether a new, scored and breakable once daily gliclazide tablet formulation, gliclazide XR 60 mg, that enables a simple 2-steps titration, can improve glycemic control rates in the community. METHODS: In a prospective multicenter study of 4 months duration, organised in the primary care setting of urban India, type 2 diabetes patients, uncontrolled with diet alone or metformin monotherapy, received 1 (60 mg), 1½ (90 mg), or 2 (120 mg) tablets of gliclazide XR 60 mg to achieve a target fasting plasma glucose of 126 mg/dl, or HbA1c of 7%. The primary outcome was the frequency of patients achieving glycemic control. RESULTS: Two hundred eleven investigators recruited 679 patients distributed throughout India. On intention to treat analysis, the number (%, 95% confidence interval, CI) of patients achieving glycemic control was, 526 (81.9, 78.8 to 84.6); with gliclazide XR 60 mg 1 tablet, 285 (42.0, 38.3 to 45.7); 1½ tablets, 143 (21.1, 18.2 to 24.3); and 2 tablets, 98 (14.4, 12.0 to 17.3). Hypoglycaemic episodes were reported by 27 (4.0, 2.8 to 5.7) patients. Mean (95% CI) FPG decreased by 78.3 (73.9 to 82.7, P < 0.01) mg/dl; with 1 tablet gliclazide XR 60 mg, by 66.0 (61.1 to 70.9, P < 0.01) mg/dl; 1-½ tablets, by 80.1 (71.2 to 88.5, P < 0.01) mg/dl; and 2 tablets, by 106.5 (93.4 to 119.5, P< 0.01) mg/dl. HbA1c decreased by 1.5 (1.3 to 1.5, P < 0.01). CONCLUSIONS: In primary care, once daily, breakable extended release gliclazide XR 60 mg, with a simple two step titration to administer maximum recommended dosage is effective in achieving short term glycemic control with a low frequency of hypoglycaemia, in monotherapy or in combination with metformin.

Defects in 6 MeV H+ irradiated hydrothermal ZnO single crystal.

The effect of 6 MeV H(+) irradiation on hydrothermally grown ZnO single crystal has been investigated using high resolution x-ray diffraction (HRXRD) and optical absorption (ultraviolet-visible) spectroscopy. The increase of the diffuse scattering in the reciprocal space maps measured using HRXRD indicates an increase of the point defect density upon irradiation. Within the penetration depth of x-rays of several micrometres, the defect density increased with increasing distance from the sample surface. On the other hand, the near band gap optical absorption became sharper for the irradiated crystal. This reflects enhanced band to band absorption and reduced sub-band gap absorption due to defects. Temperature dependent photoluminescence spectra of the pristine sample show negative thermal quenching (NTQ) of the luminescence which is due to the presence of two or more donor related defects. Upon irradiation, a single dominant donor bound transition can be found without any temperature induced NTQ. Enhancement of the band edge luminescence and reduction of the defect related luminescence is observed at 10 K. Such changes have been discussed in the light of the hydrogen present in the as-grown state of hydrothermal ZnO.

GA-optimized feedforward-PID tracking control for a rugged electrohydraulic system design.

Rugged electrohydraulic systems are preferred for remote and harsh applications. Despite the low bandwidth, large deadband and flow nonlinearities in proportional valves valve and highly nonlinear friction in industry-grade cylinders that comprise rugged systems, their maintenance are much easier than very sophisticated and delicate servocontrol and servocylinder systems. With the target of making the easily maintainable system to perform comparably to a servosystem, a feedforward control has been designed here for compensating the nonlinearities. A PID feedback of the piston displacement has been employed in tandem for absorbing the unmodeled effects. All the controller parameters have been optimized by a real-coded genetic algorithm. The agreement between the achieved real-time responses for step and sinusoidal demands with those achieved by modern servosystems clearly establishes the acceptability of the controller design.

A gas-jet transport and catcher technique for on-line production of radioactive ion beams using an electron cyclotron resonance ion-source.

Radioactive ion beams (RIB) have been produced on-line, using a gas-jet recoil transport coupled Electron Cyclotron Resonance (ECR) ion-source at the VECC-RIB facility. Radioactive atoms∕molecules carried through the gas-jet were stopped in a catcher placed inside the ECR plasma chamber. A skimmer has been used to remove bulk of the carrier gas at the ECR entrance. The diffusion of atoms∕molecules through the catcher has been verified off-line using stable isotopes and on-line through transmission of radioactive reaction products. Beams of (14)O (71 s), (42)K (12.4 h), (43)K (22.2 h), and (41)Ar (1.8 h) have been produced by bombarding nitrogen and argon gas targets with proton and alpha particle beams from the K130 cyclotron at VECC. Typical measured intensity of RIB at the separator focal plane is found to be a few times 10(3) particles per second (pps). About 3.2 × 10(3) pps of 1.4 MeV (14)O RIB has been measured after acceleration through a radiofrequency quadrupole linac. The details of the gas-jet coupled ECR ion-source and RIB production experiments are presented along with the plans for the future.

Photoluminescence and positron annihilation spectroscopic investigation on a H(+) irradiated ZnO single crystal.

Low temperature photoluminescence and room temperature positron annihilation spectroscopy have been employed to investigate the defects incorporated by 6 MeV H(+) ions in a hydrothermally grown ZnO single crystal. Prior to irradiation, the emission from donor bound excitons is at 3.378 eV (10 K). The irradiation creates an intense and narrow emission at 3.368 eV (10 K). The intensity of this peak is nearly four times that of the dominant near band edge peak of the pristine crystal. The characteristic features of the 3.368 eV emission indicate its origin as a 'hydrogen at oxygen vacancy' type defect. The positron annihilation lifetime measurement reveals a single component lifetime spectrum for both the unirradiated (164 ± 1 ps) and irradiated crystal (175 ± 1 ps). It reflects the fact that the positron lifetime and intensity of the new irradiation driven defect species are a little higher compared to those in the unirradiated crystal. However, the estimated defect concentration, even considering the high dynamic defect annihilation rate in ZnO, comes out to be ∼4 × 10(17) cm(-3) (using SRIM software). This is a very high defect concentration compared to the defect sensitivity of positron annihilation spectroscopy. A probable reason is the partial filling of the incorporated vacancies (positron traps), which in ZnO are zinc vacancies. The positron lifetime of ∼175 ps (in irradiated ZnO) is consistent with recent theoretical calculations for partially hydrogen-filled zinc vacancies in ZnO. Passivation of oxygen vacancies by hydrogen is also reflected in the photoluminescence results. A possible reason for such vacancy filling (at both Zn and O sites) due to irradiation has also been discussed.

A unique case of pica of adult onset with interesting psychosexual aspects.

Pica has been considered as the ingestion of inedible substances or atypical food combinations. Pica has been reported widely in pediatric age group and often found to be co existing with obsessive compulsive or major depressive disorder. Reports of pica in elderly age group are relatively uncommon and rarely does it have an adult onset. In this article we present a case of adult onset pica. A young lady with unusual sensation in her abdomen was found to consume iron nails over years and there was history of dyspareunia since her marriage three months back. On query it was known that the lady is having same sex relationship over years. There unique conglomeration of cultural, psychodynamic and physiological determinants which together is responsible for this unusual habit of this lady. Moreover the onset of the disease at a late age and different psychodynamic issues make the case all the more interesting. Whether the pica is an eating disorder or obsessive compulsive disorder is still controversial. Pica has been mentioned in Diagnostic and Statistical Manual IV TR. The present case report warrants the need to look into this entity more closely with regards to its occurrence and etiology.

Positron annihilation lifetime and photoluminescence studies on single crystalline ZnO.

The room temperature positron annihilation lifetime for single crystalline ZnO has been measured as 164 ± 1 ps. The single component lifetime value is very close to but higher than the theoretically predicted value of ~154 ps. Photoluminescence study (at 10 K) indicates the presence of hydrogen and other defects, mainly acceptor related, in the crystal. Defects related to a lower open volume than zinc vacancies, presumably a complex with two hydrogen atoms, are the major trapping sites in the sample. The bulk positron lifetime in ZnO is expected to be a little less than 164 ps.

A process report on physical and psychological determiners of social functioning in leprosy patients.

Management and rehabilitation of leprosy patients needs information aoout the social acceptance and its association with physical and psychological problems of the affected person. Ninety three leprosy patients (72 male and 21 female) were selected from outpatient department of the hospitals/clinics and their demographic and clinical informations were recorded. The patients were screened for common menta diseases using GHQ-60 (Bengali version). The social functioning was assessed using SSFI. Mean age was 35.19 +/- 12.5 years, 69.9% of the subjects were from urban areas. Multibacillary cases accounted for 60.2% of the cases, 21.5% of the patients had deformity, 53.8% of the patients screened positive for common psychiatric diseases. Social functioning impairment of mild, moderate and severe level was 9.7%, 82.8, and 7.5% respectively. On Univariate analysis, presence of deformity was the only variable showing significant association with moderate to severe degree of social impairment. Using decision tree (Exhaustive CHAID) analysis, presence of deformity along with urban residence was strongly predicted severe social functioning impairment. The results of the study show the need to formulate suitable psychosocial intervention strategy especially in the context of high psychiatric morbidity.

A prospective study of suicidal behaviour in Sundarban Delta, West Bengal, India.

BACKGROUND: Deliberate self-harm is a challenging public health issue but there is a paucity of data on non-fatal deliberate self-harm in the literature. We aimed to understand the behaviour of deliberate self-harm, both fatal and nonfatal, in a primary care setting. METHODS: A year-long prospective study of all admitted patients of deliberate self-harm at 13 block primary health centres of the Sundarban region was done to examine the sociodemographic profile and clinical outcome of suicidal behaviour. Data were collected by using an especially devised deliberate self-harm register. Each subject was administered a 20-item case history sheet by trained medical officers and nursing staff. RESULTS: A total of 1614 deliberate self-harm subjects (619 men, 995 women) were admitted during the year, of whom 143 (62 men, 81 women) died. Although women, especially in the younger age groups, constituted the majority of subjects (61.6%), the fatality trend was higher among men than among women (10% v. 8.1%). Poisoning was the commonest (98.4%) method of self-harm, particularly using pesticide. Easy availability of pesticides was a risk factor. Psychosocial stressors, such as conflict with spouse, guardian or in-laws, failed love affairs and economic distress, were the common underlying reasons. The majority of acts of deliberate self-harm (92.6%) were committed inside the home, especially by women. Only a small proportion of subjects had a past or family history of attempt at deliberate self-harm. The overall incidence of fatal and non-fatal deliberate self-harm was 5.98 and 61.51 per 100 000 population, respectively. CONCLUSION: Both fatal and non-fatal pesticide-related deliberate self-harm is a major public health issue in the Sundarban region. An intersectoral approach involving primary health, administration and agriculture may help in developing an effective preventive programme to reduce the morbidity and mortality from deliberate self-harm.

Low-energy positron scattering from dihydropyran.

We report on total cross section measurements for positron scattering from dihydropyran (C(5)H(8)O), with the energy range of the present study being 0.15-48 eV. To the best of our knowledge, there are currently no other corresponding experimental data or theoretical computations against which we can compare our results. The effect of this species' important dipole moment and significant dipole polarizability on the scattering dynamics is considered, as is the opening of the positronium formation channel.

Identifying defects in multiferroic nanocrystalline BaTiO(3) by positron annihilation techniques.

Room temperature ferromagnetism in nanoparticles of otherwise nonmagnetic materials has been attributed to point defects at the surface of the nanoparticles. Here, we have employed positron annihilation spectroscopy to identify the nature of defects in multiferroic BaTiO(3) nanocrystalline materials with varying average particle sizes. Ratio curve analysis of the Doppler broadening profile to a reference profile suggests that the defect is an oxygen vacancy. The decrease of intensity of the intermediate lifetime component with increasing particle size indicates a decrease of surface defect concentration. The large defect concentration in nanocrystalline BaTiO(3) can explain the observed room temperature ferromagnetism.

Persistence of a neonicotinoid insecticide, acetamiprid on chili (Capsicum annum L.).

An experiment was conducted to find out the persistence of two different formulations of Acetamiprid, namely 20% SP (soluble powder) and 20% SL (soluble liquid) in chili. Following three applications @ 20 g a.i./ha and 40 g a.i./ha, the initial deposits were found to be 0.0207, 0.0405, 0.0244 and 0.1039 microg/g. The half-life values of acetamiprid in chili were in the range of 2.24-4.84 days. A waiting period of 1 day is suggested.

Study of parental handling patterns in a primary school of Kolkata.

The intricate pattern of parenting in our socio-cultural context needs evaluation hence this study was done with the objective to reveal the parenting styles of school going children. 141 school children belonging to the age group 6-10 years were included in the study. The Parental Handling Questionnaire a 14-item scale consisting of 10 items of care and 4-items of control was administered to the mothers accompanying the children. Rating was done on a 3-point. The scale showed moderate internal consistency. 5 independent factors with overlapping items of care and control were deduced on factor analysis indicating multidimensional aspects of parenting in our society.

Community Psychiatry Clinics at Sundarban: a clinical and cultural experience.

A series of Community Psychiatric Clinics were conducted in different blocks of Sundarban region of West Bengal. One of the primary objectives of this was to collect clinical epidemiological data on psychiatric morbidity in the region. A total of 26 clinics were conducted in Sagar, Kakdwip, Canning and Gosaba block of the Sundarban region during the period from end 1998 to end 2000. A total of 451 psychiatric cases with diagnostic categories (male 239, female 212) and 215 non-psychiatric cases (male 107 and female 108) were seen in these clinics. Diagnostic Interview Schedules (SCID) and Clinical rating scales like Hamilton Depression Rating Scale and Brief Psychiatric Rating Scales were used to ascertain clinical diagnosis quantitatively. Special emphasis was given on common psychiatric disorders.

Grain size dependence of optical properties and positron annihilation parameters in Bi2O3powder.

Nanocrystalline Bi2O3has been prepared by a ball milling process. The particle size of the ball-milled Bi2O3powder has been determined by the x-ray powder diffraction method and transmission electron microscopy. The absorption spectra, in the spectral range 300-1300 nm, indicate an increase of the optical bandgap for both the direct and indirect transitions due to the reduction of grain size. The defects introduced in Bi2O3during grinding have been investigated by the positron annihilation technique. Positron annihilation results indicate an increase of defects due to ball milling.