Rationale, study design and methodology of the LANDMARC trial: a 3-year, pan-India, prospective, longitudinal study to assess management and real-world outcomes of diabetes mellitus.

AIM: India contributes towards a large part of the worldwide epidemic of diabetes and its associated complications. However, there are limited longitudinal studies available in India to understand the occurrence of diabetes complications over time. This pan-India longitudinal study was initiated to assess the real-world outcomes of diabetes across the country. METHODS: The LANDMARC study is the first prospective, multicentre, longitudinal, observational study investigating a large cohort of people with type 2 diabetes mellitus across India over a period of 3 years. The primary objective of this ongoing study is to determine the proportion of people developing macrovascular diabetes complications over the duration of the study (36 months ± 45 days) distributed over seven visits; the secondary objective is to evaluate microvascular diabetes complications, glycaemic control and time-to-treatment adaptation or intensification. Overall, 6300 participants (aged 25-60 years) diagnosed with type 2 diabetes for at least 2 years will be included from 450 centres across India. Data will be recorded for baseline demographics, comorbidities, glycaemic measurements, use of anti-hyperglycaemic medications and any cardiovascular or other diabetes-related events occurring during the observational study period. CONCLUSIONS: The LANDMARC study is expected to reveal the trends in complications associated with diabetes, treatment strategies used by physicians, and correlation among treatment, control and complications of diabetes within the Indian context. The findings of this study will help to identify the disease burden, emergence of early-onset complications and dose titration patterns, and eventually develop person-centred care and facilitate public health agencies to invest appropriate resources in the management of diabetes. (Trial Registration No: CTRI/2017/05/008452).

Safety of herpes zoster vaccination among inflammatory bowel disease patients being treated with anti-TNF medications.

BACKGROUND: The risk of herpes zoster (HZ) is elevated in inflammatory bowel disease (IBD) patients treated with anti-TNF medications. While it is optimal to give herpes zoster vaccine prior to initiation of therapy clinical circumstances may not always allow this. AIM: To determine the safety of giving herpes zoster vaccine while patients are on anti-TNF therapy. METHODS: We conducted a retrospective cohort study involving IBD patients who were followed in the Veterans Affairs (VA) healthcare system between 2001 and 2016. Patients who received herpes zoster vaccine while on anti-TNF medication were identified through vaccination codes and confirmed through individual chart review. Our outcome of interest was development of HZ between 0 and 42 days after herpes zoster vaccine administration. RESULTS: Fifty-six thousand four hundred and seventeen patients with IBD were followed in the VA healthcare system. A total of 59 individuals were on anti-TNF medication when they were given herpes zoster vaccine, and amongst them, 12 (20%) were also taking a thiopurine. Median age at the time of herpes zoster vaccine was 64.9 years and 95% of patients had a Charlson Comorbidity Index of ≥2. Median number of encounters within 42 days after receiving herpes zoster vaccine was two. No case of HZ was found within 0-42 days of HZV administration. CONCLUSION: Our data suggest that co-administering the herpes zoster vaccine to patients who are taking anti-TNF medications is relatively safe. This study significantly expands the evidence supporting the use of herpes zoster vaccine in this population, having included an elderly group of patients with a high Charlson Comorbidity Index who are likely at a much higher risk of developing HZ.

Analysis of Fluorescence Lifetime Imaging Microscopy (FLIM) data. Based on a fully automated Laguerre deconvolution method.

OBJECTIVES: A novel Fluorescence Lifetime Imaging Microscopy (FLIM) deconvolution method based on the linear expansion of fluorescence decays on a set of orthonormal Laguerre functions was recently proposed. The Laguerre deconvolution method applies linear least-square estimation to estimate the expansion coefficients of all pixel decays simultaneously, performing at least two orders of magnitude faster than the other algorithms. In the original Laguerre FLIM deconvolution implementation, however, the Laguerre parameter α is selected using a heuristic approach, making it unsuitable for online applications. METHODS: In this study, we present a fully automated implementation of the Laguerre FLIM deconvolution, whereby the Laguerre parameter α is treated as a free parameter within a nonlinear least-squares optimization scheme. RESULTS: The performance of this method has been successfully validated on simulated data, and experimental FLIM images of standard fluorescent dyes and endogenous tissue fluorescence. CONCLUSIONS: The main advantage of the proposed method is that it does not require any user intervention for tuning up the deconvolution process. Thus, we believe this method will facilitate the translation of FLIM to online applications, including real-time clinical diagnosis.

Economic burden of epilepsy in India.

PURPOSE: The economic burden due to epilepsy is not adequately examined in developing countries. Cost estimates are very important in health care planning and delivery of services. We have estimated the direct and some of the indirect costs of epilepsy in India. METHODS: Epilepsy centers attached to University hospitals in six states of India participated in this study. Data on clinical characteristics, utilization of medical services, and costs were collected in a standardized format. RESULTS: There were 285 patients (mean age, 22.6 + 12.5 years) drawn from six centers in this study. The annual cost of epilepsy per patient was INR 13,755 (USD, 344). The direct cost was INR 3,725 (USD, 93), and the indirect cost was INR 10,031 (USD, 251). Direct cost included medical consultations (INR 329), laboratory services (INR 271), hospitalization charges (INR 316), and cost of travel to clinics (INR 659). The indirect cost included the cost of lost productivity due to seizures, its complications, or attendance to clinics. There are approximately 5 million people with epilepsy in India. The economic burden due to epilepsy to the nation is to the tune of INR 68.75 billion (USD, 1.7 billion). CONCLUSIONS: The annual economic burden of epilepsy in India is 88.2% of GNP per capita and 0.5% of the GNP.

Epilepsy care in six Indian cities: a multicenter study on management and service.

BACKGROUND: Epilepsy care in developing countries is lagging behind than in the developed countries. Precise data on delivery of neurological services for epilepsy is essential to optimize the medical services for epilepsy care with limited resources. OBJECTIVE: This study was carried out in order to examine the management practices and utilization of various medical services for epilepsy in different parts of India. METHODOLOGY: University centers with epilepsy clinics, one each from six states of India, had participated in this study. Demographic data, clinical details, and data on epilepsy care were collected simultaneously on standard proforma. RESULTS: Data on 285 patients with epilepsy (generalized epilepsy: 49.1%, localization-related epilepsy: 49.9%, others: 1%) were included. Mean age of onset of epilepsy was 14.8+11.1 years. Mean delay in diagnosis was 1.5+/-4 years. Mean distance from place of residence to the consulting neurologist was 70+/-82 km. Medical consultations before referral to epilepsy center included general practitioners (54.1%) and specialists (43.3%). Very few patients received services from clinical psychologist or social worker. Investigations included, EEG (63.2%), CT Scan (36.2%). MRI brain (8.5%) and video EEG (2.1%) were limited to a few. Nearly 75.5% were on monotherapy. Newer Anti-Epileptic Drugs (AEDs) were used only in less than 5% patients. CONCLUSION: The services for epilepsy are urban-based and there is underutilization of services, general practitioners and specialists. Newer AEDs (although expensive) are gradually emerging in Indian market. Facilities for epilepsy surgery, therapeutic drug monitoring and services of clinical psychologist or medical social workers are limited.

Landau Kleffner syndrome.

An eight-year-old male child presenting with history of generalized convulsions, gradual loss of speech and generalized EEG (electroencephalography) abnormalities was diagnosed as Landau Kleffner Syndrome. He initially developed generalized convulsions which later changed to partial seizures during the course of illness. He was started on sodium valproate and continued with the drug (30 mg/kg/day) on which, he showed improvement in speech, behavior, hyperkinesis and frequency of convulsions during the follow-up.

Weekly 1-hour infusion of paclitaxel. Clinical feasibility and efficacy in patients with hormone-refractory prostate carcinoma.

BACKGROUND: Preclinically, paclitaxel given according to an intense bolus schedule has significant antitumor activity against human prostate carcinoma cell lines in SCID mice. The authors evaluated the feasibility and efficacy of weekly 1-hour infusion of paclitaxel in patients with metastatic hormone-refractory prostate carcinoma (HRPC). METHODS: A total of 18 patients with progressive metastatic HRPC were enrolled. Patients had to have no prior chemotherapy. Paclitaxel was infused weekly at a dose of 150 mg/m(2) over 1 hour for 6 weeks every 8 weeks. RESULTS: Eighteen patients with a median age of 68.5 years and a median prostate specific antigen (PSA) level of 82 ng/mL (range, 2.17-3196 ng/mL) were enrolled. The median number of prior hormone treatments was 2, and 12 patients on antiandrogens completed antiandrogen withdrawal. Ten of eighteen patients had bone-only metastasis and eight had metastasis to bone with lymph node and/or visceral metastasis. Seventeen patients received a total of 31 cycles (157 courses) and 1 patient refused chemotherapy. All patients were included in response evaluation. Of the 8 [corrected] patients with measurable disease, 4 achieved a major response, with 1 complete response (in the lung) and 3 partial responses (1 in the liver and 2 in the lymph nodes). Seven of eighteen patients (39%) had a PSA decline of >/=50%. The major high grade toxicity was peripheral neuropathy, with 6 patients (35%) developing Grade 3 toxicity. CONCLUSIONS: Weekly 1-hour paclitaxel has activity in patients with HRPC. The major toxicity is peripheral neuropathy. The minimal myelosuppressive effects make a modified schedule (lower doses on the same schedule or a shorter schedule of the same dose) attractive for future combination chemotherapy trials.

Risk factors for small for gestational age births in Ahmedabad, India.

Intra-uterine growth retardation is an important public health problem in many developing countries. The authors conducted a case-control study of low birth weight (LBW) in three teaching hospitals and a population survey in Ahmedabad city, India during 1987-1988. To identify and quantify risk factors for small for gestational age births, we divided the low birth weight and control infants into small for gestational age (SGA, n = 617) and appropriate for gestational age (AGA, n = 1851) using an Indian birth weight by gestational age standard. Logistic regression was used to estimate adjusted odds ratios for important risk factors. Prevalence of risk factors was estimated from a community sample survey of mothers (n = 1102) who had delivered in the past year. Attributable risks were calculated from odds ratios and prevalence data. The most important risk factors for SGA was poor maternal nutritional status (weight < 51 kg) with an attributable risk of 42 per cent. Other significant risk factors were anaemia, primiparity, poor obstetric history, lack of antenatal care and hypertension during pregnancy, and birth defects, each of which contributed only moderately to the attributable risk. The analysis indicates that improvement of maternal nutrition and antenatal care might prevent a substantial portion of SGA births in this and similar populations.

Maternal weight, height and risk of poor pregnancy outcome in Ahmedabad, India.

This paper explores the relationships between maternal weight, height and poor pregnancy outcome using a data set from a case-control study of low birth weight (LBW) and perinatal mortality in Ahmedabad, India. Maternal height and weights were compared between mothers of 611 perinatal deaths, 644 preterm-LBW, and 1465 normal birth weight controls as well as 617 small-for-gestational age (SGA) and 1851 appropriate-for-gestational-age (AGA) births. Weight and height were much lower in this population compared to western standards. Low weight and height were associated with increased risk of perinatal death, prematurity and SGA. After adjusting for confounders, maternal weight remained significantly associated with poor pregnancy outcomes, whereas height was only weakly associated. Attributable risk estimates show that low weight is a much more important contributor to poor outcome than low height. Improvement in maternal nutritional status could lead to substantial improvement in birth outcome in this population.

PIP: In India, researchers analyzed three sets of case control comparisons (611 perinatal deaths vs. 1465 controls, 644 preterm low birth weight [LBW] cases vs. 1465 controls, and 617 small-for-gestational-age [SGA] cases vs. 1851 controls) to investigate the association between maternal weight, height, and weight-height indices and pregnancy outcome. They hoped to identify which maternal anthropometric measure could best predict poor perinatal health. All cases and controls were born at three teaching hospitals in Ahmedabad during 1987-1988. More than 66% of control mothers and around 75% of case mothers weighed less than 50 kg, indicating considerable maternal undernutrition. Low maternal weight was associated with all three poor perinatal outcomes (p 0.01) (adjusted odds ratio [AOR] for perinatal death = 1.6 for 46-50 kg, 1.7 for 41-45 kg, and 2.9 for 40 kg or less; AOR for preterm/LBW = 1.7, 2.5, and 4.9, respectively; AOR for SGA = 1.7, 1.7, and 2.4, respectively). The association between shortness (155 cm) and all three perinatal outcomes was only significant at 150-154 cm for perinatal death (AOR = 1.4), at 150-154 cm and 145-149 cm for preterm/LBW (AOR = 1.3 and 1.5, respectively), and at less than 145 cm and 150-154 cm (AOR = 1.5 and 1.3, respectively) (p 0.01). This association was less than that between maternal weight and perinatal outcomes. The weight-height ratio index and weight-height product index were significantly associated with all three perinatal outcomes (AOR = 1.6-4.9 and 1.4-5.2, respectively; p 0.01). Maternal weight had higher attributable risks than maternal height for perinatal death (37.1% vs. 18.1%), for preterm/LBW (55.6% vs. 18.4%), and for SGA (39.8% vs. 16.4%). Low height was probably mediated through low weight and other factors. These findings show that low weight contributes much more than low height to poor perinatal outcome. Improvement of maternal nutrition, through the Integrated Child Development Services, for example, would likely improve perinatal outcomes.

Postabortal sepsis.

A review of postabortal sepsis following a 2-year study undertaken at the Department of Obstetrics and Gynaecology, SSG Hospital, Baroda is presented here with a view to know the incidence of postabortal sepsis and septic induced abortions and to re-evaluate the effectiveness of the MTP services in reducing its impact on maternal morbidity and mortality, since the implementation of the MTP Act in 1972. It has been observed that postabortal sepsis is a major cause of maternal mortality even now and MCH service is to be improved to reduce the same.

Plasma prolactin in patients with colorectal cancer. Value in follow-up and as a prognosticator.

BACKGROUND: Preoperative plasma prolactin and carcinoembryonic antigen (CEA) levels were assessed to monitor disease recurrence and to identify low-risk and high-risk patients with Dukes B or C colorectal cancer. METHODS: Prolactin and CEA were estimated by radioimmunoassay method. Blood samples were collected preoperatively and sequentially thereafter from patients with colorectal cancer (N = 114); the samples were compared with samples from age-matched healthy control subjects (smokers and nonsmokers, N = 45). For rest of the analysis, patients with Dukes A disease (N = 7) were not included because of the small number. In monitoring recurrences, the criteria for positive test for the two markers was a continual increase in the marker level after an initial decrease or persistent high level of the marker. These were the indicators of relapse or no response to treatment. To determine the efficacy of the preoperative markers, the patients were grouped according to disease status at the end of 3 years, i.e., patients who had response to the treatment modalities (N = 52) and patients who later had progressive disease (N = 55). To determine the prognostic significance of preoperative marker levels, the patients were divided according to the cutoff levels (upper normal limits); for prolactin the cutoff level was 20.0 ng/ml plasma, and for CEA it was 5.0 ng/ml plasma. RESULTS: Both of the markers were significantly high in patients with colorectal cancer compared with the markers of their respective control subjects (P < 0.0001). In monitoring disease course, the predictive power of prolactin was 100%, whereas that of CEA was 66%. Prolactin showed a lead time of 2-3 months. Preoperative prolactin levels were significantly higher in patients who later had progressive disease (P < 0.001) than in patients who had response to the treatments. However, such an intergroup variation was not observed for CEA. Patients with preoperative levels of prolactin greater than 20.0 ng/ml had shorter overall survival times than did those with prolactin levels less than 20.0 ng/ml plasma; such a trend was not observed for patients with CEA levels less than 5.0 ng/ml and those with CEA levels greater than 5.0 ng/ml plasma. CONCLUSION: Prolactin is a better overall marker than is CEA in patients with Dukes B or C colorectal cancer. The authors recommend the use of plasma prolactin levels to help identify low-risk and high-risk patient subgroups so that high-risk patients may be followed up more intensely and treated accordingly. Hyperprolactinemic patients with Dukes B or C disease have shortened survival time.

Hormones in male-patients with advanced esophageal-carcinoma.

Hormones are believed to play a dominant role as promoters in the growth and development of hormone-dependent cancers. Much less is known about the circulating hormones in male patients with oesophageal cancer. This lack of attention led us to evaluate the role of peptide and steroid hormones (by RIA) in male patients with oesophageal cancer (n=49). Blood samples of patients were collected pretherapeutically and data was compared with age matched controls (n=25). In this retrospective study, significantly high levels of FSH (P<0.02), LH (P<0.001) and prolactin (P<0.001) were observed with concomitant low levels of estradiol (P<0.001), DHEA-S (P<0.02) and testosterone (P<0.001) in patients when compared with respective controls. The patients when grouped according to anatomical site and histological type of the tumor, intergroup variation was not observed in these hormones. From our, study, it seems that hormonal imbalance or altered ratio of peptide and steroid hormones might be playing a significant role in the development and/or progression of oesophageal carcinoma in men.

Paraganglioma of the cauda equina.

A case of paraganglioma of the cauda equina is presented. Usually reported to be benign with good prognosis, the present patient had a somewhat different course. The behaviour of the tumour was unusual, with rapid recurrence seen within first month of surgery. The need for total surgical excision and role of adjuvant radiotherapy is highlighted.

Risk factors for preterm and term low birthweight in Ahmedabad, India.

To identify and quantify risk factors for preterm and term low birthweight (LBW) we conducted a hospital-based case-control study, linked with a population survey in Ahmedabad, India. The case-control study of 673 term LBW, 644 preterm LBW cases and 1465 controls showed that low maternal weight, poor obstetric history, lack of antenatal care, clinical anaemia and hypertension were significant independent risk factors for both term and preterm LBW. Short interpregnancy interval was associated with an increased risk of preterm LBW birth while primiparous women had increased risk of term LBW. Muslim women were at a reduced risk of term LBW, but other socioeconomic factors did not remain significant after adjusting for these more proximate factors. Estimates of the prevalence of risk factors from the population survey was used to calculate attributable risk. This analysis suggested that a substantial proportion of term and preterm LBW births may be averted by improving maternal nutritional status, anaemia and antenatal care.

PIP: In 1987-1988, researchers compared data on 1317 low birth weight (LBW) infants and 1465 control infants born in 3 teaching hospitals in Ahmedabad, India to calculate attributable risk (AR) for factors contributing to low birth weight. 673 of the infants were full term yet LBW due to intrauterine growth retardation. 644 of LBW infants were preterm births. They also conducted a population survey in Ahmedabad to estimate the prevalence of risk factors. LBW prevalence stood at 30%. Low maternal weight, poor pregnancy history, lack of prenatal care, clinical anemia, and hypertension were all significant independent risk factors for term and preterm LBW infants (p.05). Primiparous women were more likely to have a term LBW infant than other women (p.05). Interpregnancy intervals =or 6 months was more likely to result in delivery of a preterm LBW infant than longer interpregnancy intervals (p.05). Muslim women were at a much lower risk of delivering a term LBW infant than were Hindu women (p.05). Other than primiparity for term LBW infants (AR=21.9%), maternal weight between 41-45 kg was the single greatest risk factor for LBW (AR=21.5% for term and 19.8% for preterm). Yet low maternal weight had greater adjusted odds ratios (OR) than did maternal weight between 41-45 kg (OR=6.9 and 6.2 vs. OR=3.1 and 2.9). Maternal weight was used to measure nutritional status. Clinical anemia also carried a high Ar, especially for term LBW infants (3.7-8.2% vs. 2.8-7.3% for preterm infants). Another risk factor with considerable AR was no prenatal care (5.8% for term and 14.4% for preterm). These results emphasized the need for health and nutrition interventions to reduce the incidence of both preterm and term LBW infants in urban India.

Levels and risk factors for perinatal mortality in Ahmedabad, India.

To estimate levels and determinants of perinatal mortality, we conducted a hospital-based surveillance and case-control study, linked with a population survey, in Ahmedabad, India. The perinatal mortality rate was 79.0 per 1000, and was highest for preterm low-birth-weight babies. The case-control study of 451 stillbirths, 160 early neonatal deaths and 1465 controls showed that poor maternal nutritional status, absence of antenatal care, and complications during labour were independently associated with substantially increased risks of perinatal death. Multivariate analyses indicate that socioeconomic factors largely operate through these proximate factors and do not have an independent effect. Estimates of attributable risk derived from the prevalence of exposures in the population survey suggest that improvements in maternal nutrition and antenatal and intrapartum care could result in marked reductions of perinatal mortality.

PIP: Levels and risk factors for perinatal mortality in Ahmedabad, India, were investigated through an approach that combined institutional surveillance, a case-control survey, and a linked population-based survey. In the three government teaching hospitals in Ahmedabad, there were 15,893 births in July 1987-June 1988, of which 739 were stillbirths and 517 were early (within the first week of life) neonatal deaths. The case-control study collected detailed data on 451 of these stillbirths and 160 of the early neonatal deaths while the population-based survey covered 1102 women who delivered in the study period. The perinatal mortality rate in the study hospitals was 79/1000 births (46.4/1000 for stillbirths and 34.1/1000 for early neonatal deaths). The relative risk of perinatal mortality was 21.1 (95% confidence interval, 17.8-25.2) for preterm low-birthweight infants compared to full-term normal-birthweight babies, but only 2.6 (2.1-3.2) for full-term low-birthweight infants. Multivariate analysis indicated that the risks of both stillbirth and early neonatal mortality were significantly increased by a history of previous stillbirth, prematurity in the last pregnancy, low maternal weight, clinical anemia, no prenatal care, vaginal bleeding during pregnancy, elevated diastolic blood pressure, convulsions, antepartum hemorrhage, breech delivery, Cesarean section delivery, and congenital malformations. Socioeconomic factors such as low maternal education, agricultural occupation, and lack of a toilet lost all significance after adjustment for confounding factors. Overall, these findings suggest that improved maternal nutrition and antenatal/intrapartum care could have a substantial impact on reducing perinatal mortality in India.