Siddharth shah | University of Alabama - Tuscaloosa (original) (raw)

Papers by Siddharth shah

Tropical gastroenterology : official journal of the Digestive Diseases Foundation

The diagnosis of ulcerative colitis is based on combination of clinical, endoscopic and pathologi... more The diagnosis of ulcerative colitis is based on combination of clinical, endoscopic and pathological findings. However cases have been reported showing atypical endoscopic and histological features in ulcerative colitis. Hence the objective of this study was to determine the atypical features of new onset ulcerative colitis in adult population. A total 110 newly diagnosed cases of ulcerative colitis were enrolled in the study over a period of five years. The diagnosis of ulcerative colitis was made by correlating clinical, endoscopic and histological features. Biopsies from representative areas were processed routinely. Endoscopic and histological evaluation was carried out for atypical features. Majority of the patients (75.4%) were between 21-50 years of age with male to female ratio of 2.2:1. A significant number of patients showed atypical endoscopic findings in the form of rectal sparing in 12 (10.9%) and skip lesions in 24 (21.8%) patients. Atypical features noted on histology...

British Journal of Neurosurgery, 2012

Spinal cord arterio-venous malformations (AVMs) are rare and the diagnosis is often delayed or mi... more Spinal cord arterio-venous malformations (AVMs) are rare and the diagnosis is often delayed or missed. We describe two cases presenting in different ways, as subarachnoid haemorrhage (SAH) or myelopathy. A catheter angiogram confirmed the diagnosis following which they were treated with coil occlusion or embolisation, or a combination of both, without any complications.

The Journal of the Association of Physicians of India, 2013

According to the ICMR-INDIAB study, there are 62.4 million people living with diabetes in India. ... more According to the ICMR-INDIAB study, there are 62.4 million people living with diabetes in India. Type 2 diabetes (T2DM) is a progressive disease and hampers the quality of life of the patients due to micro and macrovascular complications. There are few studies on the status of glycemic control in the country. Such data would be useful to allocate health resources and plan measures for instituting better control of diabetes. The A1chieve study was an observational study of patients 66,726 with T2DM who were initiated, on or switched to, insulin analogues, alone or in combination with oral glucose lowering drugs at the discretion of their physician in accordance with local, routine clinical practice. This study reports on the participants in India from the A1chieve study. Baseline data of A1chieve study in 20,554 Indian T2DM patients showed that the mean HbA(1c) was 9.2%. Diabetes control was worse in those with longer duration of diabetes (9.9 +/- 5.5 years). Use of insulin was clear...

Diabetes Technology & Therapeutics, 2013

A1chieve(®) (Novo Nordisk A/S, Bagsværd, Denmark) was a prospective, multicenter, nonintervention... more A1chieve(®) (Novo Nordisk A/S, Bagsværd, Denmark) was a prospective, multicenter, noninterventional study in 66,726 people with type 2 diabetes mellitus (T2DM) in 28 countries beginning biphasic insulin aspart 30 (aspart premix), insulin detemir, or insulin aspart in routine clinical care. A subgroup of 27,594 insulin-naive people began therapy with aspart premix with or without oral agents. Safety and effectiveness data were taken from clinic records at baseline and after 24 weeks. Seven regional country groupings were prespecified. Mean final insulin dose ranged from 0.68±0.26 U/kg/day (Middle East/Gulf) to 0.38±0.14 U/kg/day (South Asia). The baseline glycated hemoglobin (HbA1c) level varied from 10.5±2.0% (Latin America) to 9.2±1.3% (South Asia), with reductions from -2.9±2.1% (Latin America) to -1.9±1.3% (South Asia). The proportion of people reaching an HbA1c level of <7.0% was highest in China (56%) and lowest in North Africa (22%). Fasting plasma glucose level reductions were from -6.4±5.3 mmol/L (Latin America) to -3.6±2.6 mmol/L (South Asia). Most people began aspart premix twice daily, varying from 91% (North Africa) to 70% (Latin America). Improvement in HbA1c increased with baseline dose frequency (once daily, -1.5±1.4%; twice daily, -2.2±1.6%; three times daily, -2.9±2.2%). Insulin-naive people with T2DM beginning aspart premix insulin in routine clinical practice in non-western nations had clinically useful improvements in blood glucose control after 24 weeks in all seven regions. Improvements from baseline for glucose control variables were greater than cross-regional differences in those variables at 24 weeks.

Diabetes Therapy, 2013

Introduction: Diabetes therapy should balance glycemic control with risk of adverse events. This ... more Introduction: Diabetes therapy should balance glycemic control with risk of adverse events. This sub-analysis of the A 1 chieve study evaluated clinical safety and effectiveness of insulin detemir in different age-groups (B40 years, [40-65 years, and [65 years) of insulin-experienced and insulin-naïve people with type 2 diabetes. Methods: A 1 chieve was an international, openlabel, non-interventional, 24-week study in 66,726 people with type 2 diabetes starting/ switching to therapy with biphasic insulin aspart 30, insulin detemir or insulin aspart (alone/in combination) in routine clinical practice. This sub-analysis evaluated clinical safety and effectiveness in patients starting/ switching to insulin detemir (±oral glucoselowering drugs). Results: In total, 15,241 patients were included in the sub-analysis. In all age-groups, the proportion of participants experiencing any, major or nocturnal hypoglycemia was significantly (all p\0.05) reduced relative to baseline, except in insulin-naïve patients for any and nocturnal hypoglycemia, where there was a significant increase or no significant change in patients aged [65 years and The A 1 chieve trial was registered with ClinicalTrials.gov (NCT00869908).

TENCON 2007 - 2007 IEEE Region 10 Conference, 2007

The alias-free nature of non uniform sampling schemes can be used to design wideband digitizers. ... more The alias-free nature of non uniform sampling schemes can be used to design wideband digitizers. Existing non uniform digitizer designs have a finite alias-free bandwidth because of time quantization of sampling instants. This paper proposes a new design for a non uniform digitizer in which the sampling instants are no longer time quantized. Hence, there is no upper limit on the alias-free bandwidth and the entire analog bandwidth of the digitizer front end can be used for alias-free sampling of a wideband analog waveform.

Diabetes Therapy, 2014

The aim of the study was to investigate the clinical safety and effectiveness of starting insulin... more The aim of the study was to investigate the clinical safety and effectiveness of starting insulin aspart (aspart) therapy in people with type 2 diabetes mellitus (T2DM) as a sub-analysis of the multinational, non-interventional A1chieve study. Insulin-naïve and insulin-experienced people with T2DM in routine clinical care starting aspart alone at baseline and continuing aspart alone, changing to biphasic insulin aspart 30 (aspart premix) or adding a basal insulin by study end, were included. Safety, tolerability, and efficacy were evaluated over 24 weeks. Overall, 3,898 people started aspart at baseline. Of the 3,313 with 24-week data, 1,545 (46.6%) continued with aspart, 1,379 (41.6%) switched to aspart premix, and 214 (6.5%) added basal insulin, while the remainder switched to other regimens. No serious adverse drug reactions were reported. The proportion of participants reporting hypoglycemia decreased from baseline to week 24 in the aspart alone group (11.2% versus 4.1%, p < 0.001) and in the aspart + basal insulin group (13.1% versus 7.5%, p = 0.040), and was 3.7% at week 24 in the aspart premix group. The mean HbA1c decreased from baseline to week 24 (aspart: -2.1 ± 2.0% [-23 ± 22 mmol/mol], aspart premix: -2.3 ± 1.7% [-25 ± 19 mmol/mol], aspart + basal insulin: -2.0 ± 2.1% [-22 ± 23 mmol/mol]; p < 0.001). Insulin aspart therapy was well tolerated and was associated with improved glucose control over 24 weeks in people with T2DM.

Indian journal of endocrinology and metabolism, 2014

DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to... more DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India. This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The…

International Journal of Clinical Practice, 2008

The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study ass... more The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions. Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen. Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients. The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

International Journal of Clinical Practice, 2009

International Journal of Clinical Practice, 2009

International Journal of Clinical Practice, 2009

European Journal of Paediatric Neurology, 2010

We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 ... more We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 year old boy presented with stroke at the age of 14 years and again 6 months later. His mother had long standing episodic headaches diagnosed as migraine. Grandmother was initially diagnosed with multiple sclerosis and had recurrent strokes at age 18 years and 49 years. MRI scanning showed a diffuse leukoencephalopathy with microhaemorrhages in all three individuals. All of the family members had cataracts but did not have retinal arterial changes. Sequence analysis of COL4A1 revealed the heterozygous missense mutation c.2263G-->A in exon 30, responsible for a glycine-to-arginine substitution (p.Gly755Arg) in both the index case and mother. Grandmother died at the age of 73 years and DNA analysis was not possible. Mutation in COL4A1 should be considered in families with a history of autosomal dominant cerebral vasculopathy, even in the absence of porencephaly.

Diabetes Research and Clinical Practice, 2010

While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets &a... more While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets <7.0% in order to reduce the long-term risk of diabetic complications, many individuals with type 2 diabetes do not achieve these targets. Fear of hypoglycemia provides a major barrier to improving blood glucose control as a result of delayed insulin initiation and failure to appropriately titrate insulin following initiation. Modern insulin analogs were designed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins (or similar blood glucose control with reduced hypoglycemic risk). While this has been demonstrated in randomized controlled trials, there is a need to confirm these findings in an everyday clinical setting. The A(1)chieve study will evaluate adverse events and effectiveness of premix (biphasic insulin aspart 30 [NovoMix 30]), basal (insulin detemir [Levemir]), and meal-time (insulin aspart [NovoRapid]) insulin analogs in people with type 2 diabetes in near-routine clinical practice. A(1)chieve is an international, prospective, multi-center, open-label, non-interventional, 24-week study of people with type 2 diabetes using an insulin analog. The study will recruit 60 000 people from 30 countries across four continents (Asia, Africa, South America, and Europe). The primary aim of the study is to assess the adverse event profile of the study insulins in routine clinical practice, including rates of hypoglycemia. In addition, effectiveness (HbA(1c), fasting plasma glucose, and postprandial plasma glucose) and patient quality of life outcomes will be measured. Comprehensive epidemiological data will be collected at baseline, including recent plasma glucose results and hypoglycemic episodes, prevalence of diabetes-related complications, and measures of current standards of care. Thus, A(1)chieve should provide important information about how insulin analogs perform in daily clinical practice.

Developmental Medicine & Child Neurology, 2012

To describe the clinical and radiological features of four new families with a childhood presenta... more To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were identified. COL4A1 mutation analysis was performed in all index cases and, where possible, in affected family members. The three male and one female index cases presented with recurrent childhood-onset stroke, infantile hemiplegia/spastic quadriplegia, and infantile spasms. Additional features such as congenital cataracts and anterior segment dysgenesis were present. Microcephaly and developmental delay/learning difficulties were present in three cases. Three cases had one or more family member affected in multiple generations, with a total of 11 such individuals identified. The clinical features showed a wide intrafamilial variation. Magnetic resonance imaging (MRI) showed bilateral white matter change in all cases, except in one mutation-positive family member. Unilateral or bilateral porencephaly was present in cases with infantile hemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1 year and 6 years for the children with presentation in infancy and 12 months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene. COL4A1 mutations can present in children with infantile hemiplegia/quadriplegia, stroke or epilepsy, and a motor disorder. The presence of eye features and white matter change on MRI in childhood can help point towards the diagnosis. Once the diagnosis is made, a careful search can identify affected family members.

Current Medical Research and Opinion, 2009

The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of ... more The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs). IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA(1c) < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire. A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%. Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline. This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

American Journal of Therapeutics, 2008

There is increasing emphasis on chronic kidney disease (CKD), owing to its prevalence and its ass... more There is increasing emphasis on chronic kidney disease (CKD), owing to its prevalence and its association with cardiovascular risk. Important issues concerning treatment of CKD are delaying its progression, improving patients' quality of life, and decreasing related mortality. These issues can be addressed with certain therapeutic options, targeting proteinuria, anemia, and secondary hyperparathyroidism. The management options and possible benefits related to treatment of these complications of CKD are reviewed.

Advances in Therapy, 2009

The IMPROVE ™ study is an openlabel, nonrandomized, observational study aimed at determining the ... more The IMPROVE ™ study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 coun-highlight the need for timely and appropriately intensive insulin-based therapy.

We address the problem of selecting a point from a unit simplex, uniformly at random. This proble... more We address the problem of selecting a point from a unit simplex, uniformly at random. This problem is important, for instance, when random multinomial probability distributions are required. We show that a previously proposed algorithm is incorrect, and demonstrate a corrected algorithm.

Tropical gastroenterology : official journal of the Digestive Diseases Foundation

The diagnosis of ulcerative colitis is based on combination of clinical, endoscopic and pathologi... more The diagnosis of ulcerative colitis is based on combination of clinical, endoscopic and pathological findings. However cases have been reported showing atypical endoscopic and histological features in ulcerative colitis. Hence the objective of this study was to determine the atypical features of new onset ulcerative colitis in adult population. A total 110 newly diagnosed cases of ulcerative colitis were enrolled in the study over a period of five years. The diagnosis of ulcerative colitis was made by correlating clinical, endoscopic and histological features. Biopsies from representative areas were processed routinely. Endoscopic and histological evaluation was carried out for atypical features. Majority of the patients (75.4%) were between 21-50 years of age with male to female ratio of 2.2:1. A significant number of patients showed atypical endoscopic findings in the form of rectal sparing in 12 (10.9%) and skip lesions in 24 (21.8%) patients. Atypical features noted on histology...

British Journal of Neurosurgery, 2012

Spinal cord arterio-venous malformations (AVMs) are rare and the diagnosis is often delayed or mi... more Spinal cord arterio-venous malformations (AVMs) are rare and the diagnosis is often delayed or missed. We describe two cases presenting in different ways, as subarachnoid haemorrhage (SAH) or myelopathy. A catheter angiogram confirmed the diagnosis following which they were treated with coil occlusion or embolisation, or a combination of both, without any complications.

The Journal of the Association of Physicians of India, 2013

According to the ICMR-INDIAB study, there are 62.4 million people living with diabetes in India. ... more According to the ICMR-INDIAB study, there are 62.4 million people living with diabetes in India. Type 2 diabetes (T2DM) is a progressive disease and hampers the quality of life of the patients due to micro and macrovascular complications. There are few studies on the status of glycemic control in the country. Such data would be useful to allocate health resources and plan measures for instituting better control of diabetes. The A1chieve study was an observational study of patients 66,726 with T2DM who were initiated, on or switched to, insulin analogues, alone or in combination with oral glucose lowering drugs at the discretion of their physician in accordance with local, routine clinical practice. This study reports on the participants in India from the A1chieve study. Baseline data of A1chieve study in 20,554 Indian T2DM patients showed that the mean HbA(1c) was 9.2%. Diabetes control was worse in those with longer duration of diabetes (9.9 +/- 5.5 years). Use of insulin was clear...

Diabetes Technology & Therapeutics, 2013

A1chieve(®) (Novo Nordisk A/S, Bagsværd, Denmark) was a prospective, multicenter, nonintervention... more A1chieve(®) (Novo Nordisk A/S, Bagsværd, Denmark) was a prospective, multicenter, noninterventional study in 66,726 people with type 2 diabetes mellitus (T2DM) in 28 countries beginning biphasic insulin aspart 30 (aspart premix), insulin detemir, or insulin aspart in routine clinical care. A subgroup of 27,594 insulin-naive people began therapy with aspart premix with or without oral agents. Safety and effectiveness data were taken from clinic records at baseline and after 24 weeks. Seven regional country groupings were prespecified. Mean final insulin dose ranged from 0.68±0.26 U/kg/day (Middle East/Gulf) to 0.38±0.14 U/kg/day (South Asia). The baseline glycated hemoglobin (HbA1c) level varied from 10.5±2.0% (Latin America) to 9.2±1.3% (South Asia), with reductions from -2.9±2.1% (Latin America) to -1.9±1.3% (South Asia). The proportion of people reaching an HbA1c level of <7.0% was highest in China (56%) and lowest in North Africa (22%). Fasting plasma glucose level reductions were from -6.4±5.3 mmol/L (Latin America) to -3.6±2.6 mmol/L (South Asia). Most people began aspart premix twice daily, varying from 91% (North Africa) to 70% (Latin America). Improvement in HbA1c increased with baseline dose frequency (once daily, -1.5±1.4%; twice daily, -2.2±1.6%; three times daily, -2.9±2.2%). Insulin-naive people with T2DM beginning aspart premix insulin in routine clinical practice in non-western nations had clinically useful improvements in blood glucose control after 24 weeks in all seven regions. Improvements from baseline for glucose control variables were greater than cross-regional differences in those variables at 24 weeks.

Diabetes Therapy, 2013

Introduction: Diabetes therapy should balance glycemic control with risk of adverse events. This ... more Introduction: Diabetes therapy should balance glycemic control with risk of adverse events. This sub-analysis of the A 1 chieve study evaluated clinical safety and effectiveness of insulin detemir in different age-groups (B40 years, [40-65 years, and [65 years) of insulin-experienced and insulin-naïve people with type 2 diabetes. Methods: A 1 chieve was an international, openlabel, non-interventional, 24-week study in 66,726 people with type 2 diabetes starting/ switching to therapy with biphasic insulin aspart 30, insulin detemir or insulin aspart (alone/in combination) in routine clinical practice. This sub-analysis evaluated clinical safety and effectiveness in patients starting/ switching to insulin detemir (±oral glucoselowering drugs). Results: In total, 15,241 patients were included in the sub-analysis. In all age-groups, the proportion of participants experiencing any, major or nocturnal hypoglycemia was significantly (all p\0.05) reduced relative to baseline, except in insulin-naïve patients for any and nocturnal hypoglycemia, where there was a significant increase or no significant change in patients aged [65 years and The A 1 chieve trial was registered with ClinicalTrials.gov (NCT00869908).

TENCON 2007 - 2007 IEEE Region 10 Conference, 2007

The alias-free nature of non uniform sampling schemes can be used to design wideband digitizers. ... more The alias-free nature of non uniform sampling schemes can be used to design wideband digitizers. Existing non uniform digitizer designs have a finite alias-free bandwidth because of time quantization of sampling instants. This paper proposes a new design for a non uniform digitizer in which the sampling instants are no longer time quantized. Hence, there is no upper limit on the alias-free bandwidth and the entire analog bandwidth of the digitizer front end can be used for alias-free sampling of a wideband analog waveform.

Diabetes Therapy, 2014

The aim of the study was to investigate the clinical safety and effectiveness of starting insulin... more The aim of the study was to investigate the clinical safety and effectiveness of starting insulin aspart (aspart) therapy in people with type 2 diabetes mellitus (T2DM) as a sub-analysis of the multinational, non-interventional A1chieve study. Insulin-naïve and insulin-experienced people with T2DM in routine clinical care starting aspart alone at baseline and continuing aspart alone, changing to biphasic insulin aspart 30 (aspart premix) or adding a basal insulin by study end, were included. Safety, tolerability, and efficacy were evaluated over 24 weeks. Overall, 3,898 people started aspart at baseline. Of the 3,313 with 24-week data, 1,545 (46.6%) continued with aspart, 1,379 (41.6%) switched to aspart premix, and 214 (6.5%) added basal insulin, while the remainder switched to other regimens. No serious adverse drug reactions were reported. The proportion of participants reporting hypoglycemia decreased from baseline to week 24 in the aspart alone group (11.2% versus 4.1%, p < 0.001) and in the aspart + basal insulin group (13.1% versus 7.5%, p = 0.040), and was 3.7% at week 24 in the aspart premix group. The mean HbA1c decreased from baseline to week 24 (aspart: -2.1 ± 2.0% [-23 ± 22 mmol/mol], aspart premix: -2.3 ± 1.7% [-25 ± 19 mmol/mol], aspart + basal insulin: -2.0 ± 2.1% [-22 ± 23 mmol/mol]; p < 0.001). Insulin aspart therapy was well tolerated and was associated with improved glucose control over 24 weeks in people with T2DM.

Indian journal of endocrinology and metabolism, 2014

DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to... more DiabCare India 2011 was a cross-sectional study in patients with diabetes mellitus, undertaken to investigate the relationship between diabetes control, management and complications in a subset of urban Indian diabetes patients treated at referral diabetes care centres in India. This was a cross-sectional, multicentre (330 centres) survey in 6168 diabetes patients treated at general hospitals, diabetes clinics and referral clinics across India. Patient data, including medical and clinical examination reports during the past year were collected during their routine visit. The…

International Journal of Clinical Practice, 2008

The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study ass... more The IMPROVE study is a multinational, open-label, non-randomised, 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) treatment in type 2 diabetes in routine clinical practice. The principal aims of this report were to characterise the baseline population and physicians' treatment decisions. Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible. At baseline, demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30, the glycaemic targets set and the regimens chosen. Data from 51,286 patients were included in analyses. Baseline glycaemic control was poor in all eight countries in the present analysis and in all prestudy treatment groups [no therapy, oral antidiabetic drugs (OADs) only, insulin with or without OADs], and the rates of vascular complications were high. Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30, target-setting for postprandial glucose levels was variable. A twice-daily regimen was used to start BIAsp 30 therapy for 80% or more of patients. The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy, particularly insulin, is commonly delayed in clinical practice. Although postprandial glucose control was a key driver for physicians' choice of BIAsp 30, this was not consistently reflected in the targets set.

International Journal of Clinical Practice, 2009

International Journal of Clinical Practice, 2009

International Journal of Clinical Practice, 2009

European Journal of Paediatric Neurology, 2010

We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 ... more We describe a three generation family with recurrent strokes and cataracts. The index case, a 14 year old boy presented with stroke at the age of 14 years and again 6 months later. His mother had long standing episodic headaches diagnosed as migraine. Grandmother was initially diagnosed with multiple sclerosis and had recurrent strokes at age 18 years and 49 years. MRI scanning showed a diffuse leukoencephalopathy with microhaemorrhages in all three individuals. All of the family members had cataracts but did not have retinal arterial changes. Sequence analysis of COL4A1 revealed the heterozygous missense mutation c.2263G-->A in exon 30, responsible for a glycine-to-arginine substitution (p.Gly755Arg) in both the index case and mother. Grandmother died at the age of 73 years and DNA analysis was not possible. Mutation in COL4A1 should be considered in families with a history of autosomal dominant cerebral vasculopathy, even in the absence of porencephaly.

Diabetes Research and Clinical Practice, 2010

While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets &a... more While evidenced-based guidelines promote glycated hemoglobin (HbA(1c)) targets <7.0% in order to reduce the long-term risk of diabetic complications, many individuals with type 2 diabetes do not achieve these targets. Fear of hypoglycemia provides a major barrier to improving blood glucose control as a result of delayed insulin initiation and failure to appropriately titrate insulin following initiation. Modern insulin analogs were designed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins (or similar blood glucose control with reduced hypoglycemic risk). While this has been demonstrated in randomized controlled trials, there is a need to confirm these findings in an everyday clinical setting. The A(1)chieve study will evaluate adverse events and effectiveness of premix (biphasic insulin aspart 30 [NovoMix 30]), basal (insulin detemir [Levemir]), and meal-time (insulin aspart [NovoRapid]) insulin analogs in people with type 2 diabetes in near-routine clinical practice. A(1)chieve is an international, prospective, multi-center, open-label, non-interventional, 24-week study of people with type 2 diabetes using an insulin analog. The study will recruit 60 000 people from 30 countries across four continents (Asia, Africa, South America, and Europe). The primary aim of the study is to assess the adverse event profile of the study insulins in routine clinical practice, including rates of hypoglycemia. In addition, effectiveness (HbA(1c), fasting plasma glucose, and postprandial plasma glucose) and patient quality of life outcomes will be measured. Comprehensive epidemiological data will be collected at baseline, including recent plasma glucose results and hypoglycemic episodes, prevalence of diabetes-related complications, and measures of current standards of care. Thus, A(1)chieve should provide important information about how insulin analogs perform in daily clinical practice.

Developmental Medicine & Child Neurology, 2012

To describe the clinical and radiological features of four new families with a childhood presenta... more To describe the clinical and radiological features of four new families with a childhood presentation of COL4A1 mutation. We retrospectively reviewed the clinical presentation. Investigations included radiological findings and COL4A1 mutation analysis of the four cases. Affected family members were identified. COL4A1 mutation analysis was performed in all index cases and, where possible, in affected family members. The three male and one female index cases presented with recurrent childhood-onset stroke, infantile hemiplegia/spastic quadriplegia, and infantile spasms. Additional features such as congenital cataracts and anterior segment dysgenesis were present. Microcephaly and developmental delay/learning difficulties were present in three cases. Three cases had one or more family member affected in multiple generations, with a total of 11 such individuals identified. The clinical features showed a wide intrafamilial variation. Magnetic resonance imaging (MRI) showed bilateral white matter change in all cases, except in one mutation-positive family member. Unilateral or bilateral porencephaly was present in cases with infantile hemiplegia, and a diagnosis of clinical stroke was supported by the presence of intracerebral haemorrhage. The age at diagnosis was between 1 year and 6 years for the children with presentation in infancy and 12 months after stroke in a 14-year-old male. Three new pathogenic mutations were identified in the COL4A1 gene. COL4A1 mutations can present in children with infantile hemiplegia/quadriplegia, stroke or epilepsy, and a motor disorder. The presence of eye features and white matter change on MRI in childhood can help point towards the diagnosis. Once the diagnosis is made, a careful search can identify affected family members.

Current Medical Research and Opinion, 2009

The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of ... more The aim of this subanalysis of the IMPROVE study was to evaluate the safety and effectiveness of initiating biphasic insulin aspart 30/70 (BIAsp 30) in type 2 diabetes patients uncontrolled on oral antidiabetic drugs (OADs). IMPROVE is a 26-week, open-label, non-randomised, international observational study in type 2 diabetes patients prescribed BIAsp 30 in routine clinical practice. The total cohort comprised 52 419 patients from various pre-study therapies. Here results from the subgroup of previously insulin-naïve patients are reported. Changes in glycated haemoglobin (HbA(1c)), fasting blood glucose (FBG), postprandial blood glucose (PPBG), weight, dose, proportion of patients achieving HbA(1c) < 7.0%, and rates of major and minor hypoglycaemic events were recorded. Treatment satisfaction was assessed using a validated questionnaire. A total of 29 160 insulin-naïve patients were included; mean age 55.6 years, diabetes duration 7.3 years, baseline HbA(1c) 9.24%. Significant reductions were seen for HbA(1c) (-2.12%; p < 0.0001), FBG (-4.07 mmol/L; p < 0.0001) and PPBG after all meals (mean: -5.27 mmol/L; p < 0.0001); 39.2% of patients achieved HbA(1c) < 7.0% without hypoglycaemia. Better glycaemic control was seen in patients treated with BIAsp 30 twice-daily (BID) both at baseline and final visit, or BID at baseline and three-times daily at final visit, compared with other regimens. The rate of major hypoglycaemic events decreased significantly, while the rate of minor hypoglycaemic events increased. Better glycaemic control and a lower rate of minor hypoglycaemia were observed in patients using BIAsp 30 without OADs than with OADs. There was no clinically relevant change in weight (-0.07 kg; p < 0.0001). At final visit, 59.7% of patients were extremely/very satisfied with treatment, compared with 10.2% at baseline. This open-label, non-randomised, observational study demonstrated that initiating insulin therapy with BIAsp 30 significantly improved glycaemic control in insulin-naïve patients previously poorly controlled on OADs. The rate of major hypoglycaemia was reduced and treatment satisfaction increased after initiation of BIAsp 30. Furthermore, better glycaemic control was achieved with BIAsp 30 without OAD compared to with OAD.

American Journal of Therapeutics, 2008

There is increasing emphasis on chronic kidney disease (CKD), owing to its prevalence and its ass... more There is increasing emphasis on chronic kidney disease (CKD), owing to its prevalence and its association with cardiovascular risk. Important issues concerning treatment of CKD are delaying its progression, improving patients' quality of life, and decreasing related mortality. These issues can be addressed with certain therapeutic options, targeting proteinuria, anemia, and secondary hyperparathyroidism. The management options and possible benefits related to treatment of these complications of CKD are reviewed.

Advances in Therapy, 2009

The IMPROVE ™ study is an openlabel, nonrandomized, observational study aimed at determining the ... more The IMPROVE ™ study is an openlabel, nonrandomized, observational study aimed at determining the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) treatment in subjects with type 2 diabetes from 11 coun-highlight the need for timely and appropriately intensive insulin-based therapy.

We address the problem of selecting a point from a unit simplex, uniformly at random. This proble... more We address the problem of selecting a point from a unit simplex, uniformly at random. This problem is important, for instance, when random multinomial probability distributions are required. We show that a previously proposed algorithm is incorrect, and demonstrate a corrected algorithm.