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1.
Am J Perinatol ; 39(8): 878-882, 2022 06.
Article in English | MEDLINE | ID: mdl-33142339

ABSTRACT

OBJECTIVE: The authors aim to compare all code blue events, regardless of the need for chest compressions, in the neonatal intensive care unit (NICU) versus the pediatric intensive care unit (PICU). We hypothesize that code events in the two units differ, reflecting different disease processes. STUDY DESIGN: This is a retrospective analysis of 107 code events using the code narrator, which is an electronic medical record of real-time code documentation, from April 2018 to March 2019. Events were divided into two groups, NICU and PICU. Neonatal resuscitation program algorithm was used for NICU events and a pediatric advanced life-support algorithm was used for PICU events. Events and outcomes were compared using univariate analysis. The Mann-Whitney test and linear regressions were done to compare the total code duration, time from the start of code to airway insertion, and time from airway insertion to end of code event. RESULTS: In the PICU, there were almost four times more code blue events per month and more likely to involve patients with seizures and no chronic condition. NICU events more often involved ventilated patients and those under 2 months of age. The median code duration for NICU events was 2.5 times shorter than for PICU events (11.5 vs. 29 minutes), even when adjusted for patient characteristics. Survival to discharge was not different in the two groups. CONCLUSION: Our study suggests that NICU code events as compared with PICU code events are more likely to be driven by airway problems, involve patients <2 months of age, and resolve quickly once airway is taken care of. This supports the use of a ventilation-focused neonatal resuscitation program for patients in the NICU. KEY POINTS: · Code blue events are four times more common in PICU.. · NICU code events are 2.5 times shorter in duration compared with PICU events.. · NICU code events are more likely to be attributed to a problem with an airway..


Subject(s)
Cardiopulmonary Resuscitation , Intensive Care Units, Pediatric , Child , Hospitals , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Retrospective Studies , Tertiary Healthcare
2.
Am J Perinatol ; 2022 Jun 23.
Article in English | MEDLINE | ID: mdl-35617959

ABSTRACT

OBJECTIVE: This study aimed to describe resuscitation practices in level-IV neonatal intensive care units (NICUs) and identify possible areas of improvement. STUDY DESIGN: This study was a cross-sectional cohort survey and conducted at the Level-IV NICUs of Children's Hospital Neonatal Consortium (CHNC). The survey was developed with consensus from resuscitation and education experts in the CHNC and pilot tested. An electronic survey was sent to individual site sponsors to determine unit demographics, resuscitation team composition, and resuscitation-related clinical practices. RESULTS: Of the sites surveyed, 33 of 34 sites responded. Unit average daily census ranged from less than 30 to greater than 100, with the majority (72%) of the sites between 30 and 75 patients. A designated code response team was utilized in 18% of NICUs, only 30% assigned roles before or during codes. The Neonatal Resuscitation Program (NRP) was the exclusive algorithm used during codes in 61% of NICUs, and 34% used a combination of NRP and the Pediatric Advanced Life Support (PALS). Most (81%) of the sites required neonatal attendings to maintain NRP training. A third of sites (36%) lacked protocols for high-acuity events. A code review process existed in 76% of participating NICUs, but only 9% of centers enter code data into a national database. CONCLUSION: There is variability among units regarding designated code team presence and composition, resuscitation algorithm, protocols for high-acuity events, and event review. These inconsistencies in resuscitation teams and practices provide an opportunity for standardization and, ultimately, improved resuscitation performance. Resources, education, and efforts could be directed to these areas to potentially impact future neonatal outcomes of the complex patients cared for in level-IV NICUs. KEY POINTS: · Resuscitation practice is variable in level-IV NICUs.. · Resuscitation algorithm training is not uniform. · Standardized protocols for high-acuity low-occurrence (HALO) events are lacking.

3.
J Pediatr ; 238: 174-180.e3, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34242670

ABSTRACT

OBJECTIVE: To evaluate the trends, proportions, risk factors, resource utilization, and outcomes of neonatal birth trauma in the US. STUDY DESIGN: This cross-sectional study of in-hospital births used the Nationwide Inpatient Sample for 2006-2014. We divided the cases by type of birth trauma: scalp injuries and major birth trauma. Linear regression for yearly trends and logistic regression were used for risk factors and outcomes. A generalized linear model was used, with a Poisson distribution for the length of stay and a gamma distribution for total spending charges. RESULTS: A total of 982 033 weighted records with neonatal birth trauma were found. The prevalence rate increased by 23% from (from 25.3 to 31.1 per 1000 hospital births). Scalp injuries composed 80% of all birth traumas and increased yearly from 19.87 to 26.46 per 1000 hospital births. Major birth trauma decreased from 5.44 to 4.67 per 1000 hospital births due to decreased clavicular fractures, brachial plexus injuries, and intracranial hemorrhage. There were significant differences in demographics and risk factors between the 2 groups. Compared with scalp injuries, major birth trauma was associated with higher odds of hypoxic-ischemic encephalopathy, seizures, need for mechanical ventilation, meconium aspiration, and sepsis. Length of stay was increased by 56%, and total charges were almost doubled for major birth trauma. CONCLUSIONS: Neonatal birth trauma increased over the study period secondary to scalp injuries. Major birth trauma constitutes a significant health burden. Scalp injuries are also associated with increased morbidity and might be markers of brain injury in some cases.


Subject(s)
Birth Injuries/epidemiology , Craniocerebral Trauma/epidemiology , Birth Injuries/mortality , Cross-Sectional Studies , Databases, Factual , Delivery, Obstetric/adverse effects , Delivery, Obstetric/statistics & numerical data , Female , Humans , Infant, Newborn , Male , Pregnancy , Retrospective Studies , Risk Factors , United States/epidemiology
4.
Ann Hematol ; 100(2): 309-320, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33415422

ABSTRACT

Coronavirus disease 2019 is caused by severe acute respiratory syndrome coronavirus 2. Primarily an infection of the lower respiratory tract, it is now well known to cause multisystem abnormalities. Hematologic manifestations constitute a significant area of concern. Severe acute respiratory syndrome coronavirus 2 infects monocytes and endothelial cells leading to a complex downstream cascade, cytokine storm, and eventual intravascular thrombosis. Coronavirus disease 2019 causes lymphopenia, neutrophilia, and thrombocytopenia. Prophylactic anticoagulation is vital in patients with coronavirus disease 2019, as its effect on the coagulation system is associated with significant morbidity and mortality. The disease can cause both arterial and venous thromboses, especially pulmonary embolism and pulmonary microthrombi. A high index of suspicion is indispensable in recognizing these complications, and timely institution of therapeutic anticoagulation is vital in treating them. Virus-induced disseminated intravascular coagulation is uncommon but shares some similarities to sepsis-induced disseminated intravascular coagulation. Marked elevations in hematologic biomarkers such as lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein are associated with worse outcomes. Understanding the pathophysiology and recognizing factors associated with poor prognosis are crucial in improving patient outcomes with coronavirus disease 2019.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , SARS-CoV-2/isolation & purification , Biomarkers/blood , COVID-19/prevention & control , COVID-19/virology , Ferritins/blood , Fibrin Fibrinogen Degradation Products/analysis , Hematologic Diseases/blood , Hematologic Diseases/complications , Hematologic Diseases/drug therapy , Humans , Lymphopenia/blood , Lymphopenia/complications , Lymphopenia/drug therapy , SARS-CoV-2/physiology , Thrombocytopenia/blood , Thrombocytopenia/complications , Thrombocytopenia/drug therapy
5.
Int J Clin Pract ; 75(11): e14533, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34129744

ABSTRACT

BACKGROUND: Lung cancer is one of the leading causes of cancer mortality in the United States. The use of precision medicine in the past 10 years has significantly changed the therapeutic landscape of lung cancer. Management of advanced nonsmall cell lung cancer (NSCLC) has transitioned from a chemotherapeutic approach to targeted treatments and immunotherapeutic agents. Several tyrosine kinase inhibitors (TKIs) have been approved for patients with targeted mutations and patients who do not have driver mutations; immunotherapy has been recently approved as frontline therapy, which has resulted in marked improvement in overall survival and added a new tool in our armamentarium. AIMS: The purpose of this review is to highlight recent advancements in diagnostic approach and management strategies in patients with metastatic NSCLC. MATERIALS AND METHODS: A literature search was conducted on Medline (via PubMed) and National Comprehensive Cancer Network Guidelines using the keywords "precision diagnosis," "advanced non-small cell lung cancer," "target therapies," and "immunotherapy." CONCLUSION: The use of next-generation sequencing has significantly changed our understanding of molecular oncogenic mechanisms of lung cancer. These advancements have created a paradigm shift in the treatment strategies of metastatic lung cancer from primarily chemotherapeutic approach to increasing use of targeted therapies and immune checkpoint inhibitors (ICI) leading to better survival rates and lesser toxicity.


Subject(s)
Antineoplastic Agents , Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Mutation
6.
PLoS Med ; 17(7): e1003183, 2020 07.
Article in English | MEDLINE | ID: mdl-32692751

ABSTRACT

BACKGROUND: Undernutrition during intrauterine life and early childhood is hypothesised to increase the risk of cardiovascular disease (Developmental Origins of Health and Disease Hypothesis), but experimental evidence from humans is limited. This hypothesis has major implications for control of the cardiovascular disease epidemic in South Asia (home to a quarter of world's population), where a quarter of newborns have low birth weight. We investigated whether, in an area with prevalent undernutrition, supplemental nutrition offered to pregnant women and their offspring below the age of 6 years was associated with a lower risk of cardiovascular disease in the offspring when they were young adults. METHODS AND FINDINGS: The Hyderabad Nutrition Trial was a community-based nonrandomised controlled intervention trial conducted in 29 villages near Hyderabad, India (1987-1990). Protein-calorie food supplement was offered daily to pregnant and lactating women (2.09 MJ energy and 20-25 g protein) and their offspring (1.25 MJ energy and 8-10 g protein) until the age of six years in the 15 intervention villages, but not in the 14 control villages. A total of 1,826 participants (949 from the intervention villages and 877 from the control villages, representing 70% of the cohort) at a mean age of 21.6 years (62% males) were examined between 2009 and 2012. The mean body mass index (BMI) of the participants was 20 kg/m2 and the mean systolic blood pressure was 115 mm Hg. The age, sex, socioeconomic position, and urbanisation-adjusted effects of intervention (beta coefficients and 95% confidence intervals) on outcomes were as follows: carotid intima-media thickness, 0.01 mm (-0.01 to 0.03), p = 0.36; arterial stiffness (augmentation index), -1.1% (-2.5 to 0.3), p = 0.097; systolic blood pressure, 0.5 mm Hg (-0.6 to 1.6), p = 0.36; BMI, -0.13 kg/m2 (-0.75 to 0.09), p = 0.093; low-density lipoprotein (LDL) cholesterol, 0.06 mmol/L (-0.07 to 0.2), p = 0.37; and fasting insulin (log), -0.06 mU/L (-0.19 to 0.07), p = 0.43. The limitations of this study include nonrandomised allocation of intervention and lack of data on compliance, and potential for selection bias due to incomplete follow-up. CONCLUSIONS: Our results showed that in an area with prevalent undernutrition, protein-calorie food supplements offered to pregnant women and their offspring below the age of 6 years were not associated with lower levels of cardiovascular risk factors among offspring when they were young adults. Our findings, coupled with evidence from other intervention studies to date, suggest that policy makers should attach limited value to cardiovascular health benefits of maternal and child protein-calorie food supplementation programmes.


Subject(s)
Cardiovascular Diseases/prevention & control , Dietary Supplements , Adolescent , Body Mass Index , Cardiovascular Diseases/blood , Cardiovascular Diseases/etiology , Carotid Intima-Media Thickness , Female , Follow-Up Studies , Humans , India , Male , Malnutrition/diet therapy , Maternal Nutritional Physiological Phenomena , Pregnancy , Risk Factors , Young Adult
7.
BMC Urol ; 20(1): 84, 2020 Jul 02.
Article in English | MEDLINE | ID: mdl-32616076

ABSTRACT

BACKGROUND: Several phase 3 studies reported positive results for combinations of Immune-Oncology (IO) and Vascular Endothelial Growth Factor (VEGF) targeted therapies in patients with metastatic clear cell Renal Cell Carcinoma (ccRCC). However, there are limited data on outcomes to systemic therapy after IO-VEGF combinations. METHODS: A retrospective analysis was performed on patients with metastatic ccRCC treated at the Memorial Sloan Kettering Cancer Center and Cleveland Clinic who initiated systemic therapy post IO-VEGF including combinations with VEGF receptor (VEGFR) tyrosine kinase inhibitors (IO-TKI) and combinations with the anti-VEGF monoclonal antibody bevacizumab (IO-Bev). The study objectives were to evaluate the objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) on systemic therapy post IO-VEGF. RECIST v1.1 criteria were used to determine radiological responses and progression. Survival estimates were evaluated with the Kaplan-Meier methods and the log-rank test from the start of systemic therapy post IO-VEGF to the event of interest. RESULTS: A total of fifty-nine patients were treated post discontinuation of IO-VEGF regimens which included IO-Bev (n = 35; 59%) and IO-TKI (n = 24; 41%). Fifty-eight patients (98%) received IO-VEGF regimens as part of a clinical trial. Subsequent therapies included cabozantinib (n = 22; 37%), axitinib (n = 18; 31%), pazopanib (n = 4; 7%), lenvatinib and everolimus (n = 4; 7%), mTOR inhibitor monotherapy (n = 3; 5%), axitinib and dalantercept (n = 2; 3%), sunitinib (n = 1; 2%), sorafenib (n = 1; 2%), and treatment with agents on unreported clinical trials (n = 4; 7%). Patients treated on unreported clinical trials were excluded from the efficacy analysis. Post IO-VEGF, the ORR was 25% and median PFS was 12.0 months (95% CI, 8.2-24.5). Median OS was 24.5 months (95% CI, 12-NE) and 12 months OS rate was 63.3% (95% CI, 48.6-74.9). We observed no differences post IO-VEGF OS when comparing IO- TKI vs IO-Bev (Log-rank p = 0.73). CONCLUSIONS: Post IO-VEGF, most patients received VEGFR-TKIs. In this setting, VEGFR-TKIs demonstrated clinical activity and remain a viable option for salvage therapy after progression on IO-VEGF.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Adult , Aged , Combined Modality Therapy , Female , Humans , Immunotherapy , Male , Middle Aged , Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors , Retrospective Studies , Withholding Treatment
8.
J Ren Nutr ; 30(6): 503-508, 2020 11.
Article in English | MEDLINE | ID: mdl-32247648

ABSTRACT

OBJECTIVE: Sparse data exist on population distributions of serum fibroblast growth factor-23 (FGF23) levels from developing, middle-income economies. FGF23 levels may differ substantially across regions based on differences in diet and urbanization. In a population-based study from North India, we tested the hypothesis that urinary phosphate excretion and FGF23 levels are lower among rural compared with urban participants, and among vegetarian compared with nonvegetarian participants. METHODS: We measured 24-hour urinary phosphate, and serum parathyroid hormone and FGF23 in a subsample of the population-based Cardiometabolic Risk Reduction in South Asia and Indian Council of Medical Research Coronary Heart Disease surveys. We categorized participants according to diet and residence: urban nonvegetarians (n = 70), urban vegetarians (n = 564), and rural vegetarians (n = 558). Using least square means, we compared the groups' 24-hour urinary phosphate (with urban vegetarians as reference) and FGF23 levels after accounting for age, sex, diabetes, and body mass index. RESULTS: Among 1,192 study participants, mean FGF23 was 41 ± 18 pg/mL, median parathyroid hormone was 44 (interquartile range [IQR] 31-60) pg/mL, and median 24-hour urinary phosphate excretion was 419 (IQR: 47-622) mg/day. Urinary phosphate was significantly higher in rural compared with urban vegetarians (median, 503; IQR, 334-543 versus 365; IQR, 199-399 mg/day), but adjusted mean FGF23 levels did not differ across study groups. CONCLUSION: In rural and urban India, urinary phosphate excretion was low, but FGF23 levels did not differ by residence or dietary preference. Homogenously low dietary phosphate intake across different settings and diets may partly explain the lack of differences in FGF23.


Subject(s)
Diet, Vegetarian/methods , Fibroblast Growth Factors/blood , Parathyroid Hormone/blood , Phosphates/urine , Adult , Diet/methods , Female , Fibroblast Growth Factor-23 , Humans , India , Male , Middle Aged , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data
9.
Natl Med J India ; 33(3): 137-145, 2020.
Article in English | MEDLINE | ID: mdl-33904416

ABSTRACT

Background: . The pattern of dyslipidaemia in South Asia is believed to be different from that in other parts of the world. Nonetheless, limited population-based data are available from the region. We assessed the prevalence, types of, and factors associated with dyslipidaemia among South Asians. Methods: . We used baseline data (2010-11) of the Center for Cardiometabolic Risk Reduction in South Asia (CARRS) cohort of 16 287 representative urban adults aged ≥20 years from Chennai and Delhi in India and Karachi in Pakistan. Total cholesterol (TC) was measured by the enzymatic-cholesterol oxidase peroxidase method, high-density lipoprotein-cholesterol (HDL-C) by the direct homogeneous method and triglycerides (TG) by enzymatic methods. Low-density lipoprotein-cholesterol (LDL-C) was calculated using Friedewald's formula. We defined high TC ≥200 mg/dl or on medication; hypertriglyceridaemia ≥150 mg/dl, high LDL-C ≥130 mg/dl or on medication and low HDL-C <40 mg/dl for males, <50 mg/dl for females. Multivariate logistic regression was carried out to assess the factors associated with dyslipidaemia. Results: . The prevalence of any dyslipidaemia was 76.4%, 64.3% and 68.5% among males and 89.3%, 74.4% and 79.4% among females in Chennai, Delhi and Karachi, respectively. The prevalence of elevated TC was higher in Chennai compared to Delhi and Karachi (31.3%, 28.8% and 22.9%, respectively); males had a significantly greater prevalence of high TG, whereas females had a greater prevalence of low HDL-C in all the three cities. The most common lipid abnormality in all three cities was low HDL-C, which was seen in 67.1%, 49.7% and 61.3% in Chennai, Delhi and Karachi, respectively. Only 2% of the participants were on lipid-lowering drugs. Adjusted for other factors, dyslipidaemia was positively associated with age, female sex, obesity, hypertension, diabetes and tobacco use. Discussion: . Overall, almost seven in ten adults in urban South Asia have some form of dyslipidaemia, and the predominant subtypes were low HDL-C and high TG.


Subject(s)
Dyslipidemias , Hypertension , Adult , Asia , Asian People , Cohort Studies , Dyslipidemias/epidemiology , Female , Humans , India/epidemiology , Male , Prevalence , Risk Factors , Risk Reduction Behavior
10.
Invest New Drugs ; 37(2): 331-337, 2019 04.
Article in English | MEDLINE | ID: mdl-30402678

ABSTRACT

Background Mammalian target of rapamycin (mTOR) pathway and angiogenesis through vascular endothelial growth factor (VEGF) have been shown to play important roles in prostate cancer progression. Preclinical data in prostate cancer has suggested the potential additive effect dual inhibition of VEGF and mTOR pathways. In this phase I/II trial we assessed the safety and efficacy of bevacizumab in combination with temsirolimus for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC). Methods In the phase I portion, eligible patients received temsirolimus (20 mg or 25 mg IV weekly) in combination with a fixed dose of IV bevacizumab (10 mg/kg every 2 weeks). The primary endpoint for the phase II portion was objective response measured by either PSA or RECIST criteria. Exploratory endpoints included changes in circulating tumor cells (CTC) and their correlation with PSA response to treatment. Results Twenty-one patients, median age 64 (53-82), with pre-treatment PSA of 205.3 (11.1-1801.0), previously treated with a median of 2 (0-5) lines of therapy for mCRPC received the combination of temsirolimus weekly at 20 mg (n = 4) or 25 mg (n = 17) with bevacizumab 10 mg/kg every 2 weeks (n = 21). Median time to progression was 2.6 months (95% CI, 1.2-3.9) and the median best PSA change from baseline to 12 weeks was a 32% increase (-40-632%) which met the predefined futility rule and led to early termination of the study. Nine patients (43%) had ≥ grade 3 toxicity that included fatigue (24%), anorexia (10%), nausea/vomiting (5%) and lymphopenia (5%). In exploratory analysis, a decrease in CTC levels was observed in 9 out of 11 patients. No association between PSA levels and CTC levels was detected. Conclusions The combination of temsirolimus and bevacizumab showed limited clinical activity in mCRPC patients previously treated with chemotherapy and was associated with significant adverse events (AEs). Transient decrease in CTC levels was independent from PSA response. NCT01083368.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gene Expression Regulation, Neoplastic/drug effects , Neoplasm Recurrence, Local/drug therapy , Prostatic Neoplasms, Castration-Resistant/drug therapy , Salvage Therapy , TOR Serine-Threonine Kinases/antagonists & inhibitors , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Benzodiazepines/chemistry , Bevacizumab/administration & dosage , Biomarkers, Tumor/metabolism , Disease Progression , Drug Resistance, Neoplasm/drug effects , Follow-Up Studies , Humans , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Prognosis , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , Pyrroles/chemistry , Sirolimus/administration & dosage , Sirolimus/analogs & derivatives , Tissue Distribution
11.
Invest New Drugs ; 37(3): 559-566, 2019 06.
Article in English | MEDLINE | ID: mdl-31037562

ABSTRACT

Background Despite definitive local therapy, patients with high-risk prostate cancer have a significant risk for local and distant failure. To date, no systemic therapy given prior to surgery has been shown to improve outcomes. The phosphatidilinositol 3-kinase/AKT/mTOR pathway is commonly dysregulated in men with prostate cancer. We sought to determine the clinical efficacy and safety of the mTOR/TORC1 inhibitor everolimus in men with high-risk prostate cancer undergoing radical prostatectomy. Methods This is a randomized phase II study of everolimus at two different doses (5 and 10 mg daily) given orally for 8 weeks before radical prostatectomy in men with high-risk prostate cancer. The primary endpoint was the pathologic response (histologic P0, margin status, extraprostatic extension) and surgical outcomes. Secondary endpoints included changes in serum PSA level and treatment effects on levels of expression of mTOR, p4EBP1, pS6 and pAKT. Results Seventeen patients were enrolled: nine at 10 mg dose and eight at 5 mg dose. No pathologic complete responses were observed and the majority of patients (88%) had an increase in their PSA values leading to this study being terminated early due to lack of clinical efficacy. Treatment-related adverse events were similar to those previously reported with the use of everolimus in other solid tumors and no additional surgical complications were observed. A significant decrease in the expression of p4EBP1 was noted in prostatectomy samples following treatment. Conclusions Neoadjuvant everolimus given at 5 mg or 10 mg daily for 8 weeks prior to radical prostatectomy did not impact pathologic responses and surgical outcomes of patients with high-risk prostate cancer. Trial registration NCT00526591 .


Subject(s)
Antineoplastic Agents/therapeutic use , Everolimus/therapeutic use , Neoadjuvant Therapy/mortality , Neoplasm Recurrence, Local/drug therapy , Prostatic Neoplasms/drug therapy , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Prognosis , Prostatic Neoplasms/pathology , Risk Factors , Survival Rate
12.
Int J Hyperthermia ; 36(1): 302-312, 2019.
Article in English | MEDLINE | ID: mdl-30729822

ABSTRACT

Controlling the magnetic properties of a nanoparticle efficiently via its particle size to achieve optimized heat under alternating magnetic field is the central point for magnetic hyperthermia-mediated cancer therapy (MHCT). Here, we have shown the successful use of stevioside (a natural plant-based glycoside) as a promising biosurfactant to control the magnetic properties of Fe3O4 nanoparticles by controlling the particle size. The biocompatibility and cellular uptake efficiency by rat C6 glioma cells and calorimetric magnetic hyperthermia profile of the nanoparticles were further examined. Our finding suggests superior properties of stevioside-coated magnetite nanoparticles in comparison to polysorbate-80 and oleic acid coated nanomagnets as far as particle size reduction, biocompatibility, hyperthermic effect, and cellular uptake by the glioblastoma cancer cells are concerned. The stevioside-coated nanomagnets exhibiting the maximum temperature rise were further investigated as heating agents in in vitro magnetic hyperthermia experiments (405 kHz, 168 Oe), showing their efficacy to induce cell death of rat C6 glioma cells after 30 min at a target temperature T = 43 °C.


Subject(s)
Diterpenes, Kaurane/therapeutic use , Glucosides/therapeutic use , Hyperthermia, Induced/methods , Magnetite Nanoparticles/chemistry , Sweetening Agents/therapeutic use , Animals , Diterpenes, Kaurane/pharmacology , Glucosides/pharmacology , Humans , Rats
13.
Public Health Nutr ; 22(9): 1606-1614, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30591086

ABSTRACT

OBJECTIVE: To assess the knowledge, attitudes and practices related to salt consumption among adults in rural and urban North India. DESIGN: Data for the study were obtained from a community-based cross-sectional survey using an interviewer-administered questionnaire and 24 h urine samples. SETTING: Data collection was conducted during March-October 2012 in rural Haryana and urban Delhi in North India. PARTICIPANTS: Adults (n 1635) aged ≥20 years (701 in rural Haryana; 934 in urban Delhi). RESULTS: Twenty-four per cent of rural and 40·5 % of urban participants knew that a high-salt diet causes high blood pressure. Nearly one-fifth of both rural and urban participants knew that there should be a maximum daily limit for consumption of salt. In rural and urban areas, 46·6 and 45·1 %, respectively, perceived it important to reduce the salt content of their diet; however, only 3·7 and 10·2 %, respectively, reported taking some actions. Participants reported they were consuming 'too little salt', 'just the right amount of salt' or 'too much salt', but their corresponding mean (95 % CI) actual salt consumption (g/d; as measured by 24 h urinary Na excretion) was higher, especially among rural participants (rural: 9·2 (8·13, 10·22), 8·5 (8·19, 8·77) or 8·4 (7·72, 8·99); urban: 5·6 (4·67, 6·57), 5·7 (5·32, 6·01) or 4·6 (4·10, 5·14), respectively). CONCLUSIONS: Knowledge about the deleterious health impact of excess salt consumption is low in this population. Tailored public education for salt reduction is warranted with a particular focus on rural residents.

14.
Nutr J ; 17(1): 15, 2018 02 08.
Article in English | MEDLINE | ID: mdl-29422041

ABSTRACT

BACKGROUND: Dietary patterns (DPs) in India are heterogenous. To date, data on association of indigenous DPs in India with risk factors of nutrition-related noncommunicable diseases (cardiovascular disease and diabetes), leading causes of premature death and disability, are limited. We aimed to evaluate the associations of empirically-derived DPs with blood lipids, fasting glucose and blood pressure levels in an adult Indian population recruited across four geographical regions of India. METHODS: We used cross-sectional data from the Indian Migration Study (2005-2007). Study participants included urban migrants, their rural siblings and urban residents and their urban siblings from Lucknow, Nagpur, Hyderabad and Bangalore (n = 7067, mean age 40.8 yrs). Information on diet (validated interviewer-administered, 184-item semi-quantitative food frequency questionnaire), tobacco consumption, alcohol intake, physical activity, medical history, as well as anthropometric measurements were collected. Fasting-blood samples were collected for estimation of blood lipids and glucose. Principal component analysis (PCA) was used to identify major DPs based on eigenvalue> 1 and component interpretability. Robust standard error multivariable linear regression models were used to investigate the association of DPs (tertiles) with total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides, fasting-blood glucose (FBG), systolic and diastolic blood pressure (SBP and DBP) levels. RESULTS: Three major DPs were identified: 'cereal-savoury' (cooked grains, rice/rice-based dishes, snacks, condiments, soups, nuts), 'fruit-vegetable-sweets-snacks' (Western cereals, vegetables, fruit, fruit juices, cooked milk products, snacks, sugars, sweets) and 'animal food' (red meat, poultry, fish/seafood, eggs) patterns. High intake of the 'animal food' pattern was positively associated with levels of TC (ß = 0.10 mmol/L; 95% CI: 0.02, 0.17 mmol/L; p-trend = 0.013); LDL-C (ß = 0.07 mmol/L; 95% CI: 0.004, 0.14 mmol/L; p-trend = 0.041); HDL-C (ß = 0.02 mmol/L; 95% CI: 0.004, 0.04 mmol/L; p-trend = 0.016), FBG: (ß = 0.09 mmol/L; 95% CI: 0.01, 0.16 mmol/L; p-trend = 0.021) SBP (ß = 1.2 mm/Hg; 95% CI: 0.1, 2.3 mm/Hg; p-trend = 0.032); DBP: (ß = 0.9 mm/Hg; 95% CI: 0.2, 1.5 mm/Hg; p-trend = 0.013). The 'cereal-savoury' and 'fruit-vegetable-sweets-snacks' patterns showed no association with any parameter except for a positive association with diastolic blood pressure for high intake of 'fruits-vegetables-sweets-snacks' pattern. CONCLUSION: Our results indicate positive associations of the 'animal food' pattern with cardio-metabolic risk factors in India. Further longitudinal assessments of dietary patterns in India are required to validate the findings.


Subject(s)
Blood Glucose , Blood Pressure , Cholesterol/blood , Diet/methods , Transients and Migrants/statistics & numerical data , Triglycerides/blood , Adult , Cross-Sectional Studies , Female , Humans , India , Male , Rural Population/statistics & numerical data , Urban Population/statistics & numerical data
15.
BMC Pediatr ; 18(1): 261, 2018 08 04.
Article in English | MEDLINE | ID: mdl-30077178

ABSTRACT

BACKGROUND: Evidence suggests a strong association between nutrition during the first 1000 days (conception to 2 years of life) and cognitive development. Maternal docosahexaenoic acid (DHA) supplementation has been suggested to be linked with cognitive development of their offspring. DHA is a structural component of human brain and retina, and can be derived from marine algae, fatty fish and marine oils. Since Indian diets are largely devoid of such products, plasma DHA levels are low. We are testing the effect of pre- and post-natal DHA maternal supplementation in India on infant motor and mental development, anthropometry and morbidity patterns. METHODS: DHANI is a double-blinded, parallel group, randomized, placebo controlled trial supplementing 957 pregnant women aged 18-35 years from ≤20 weeks gestation through 6 months postpartum with 400 mg/d algal-derived DHA or placebo. Data on the participant's socio-demographic profile, anthropometric measurements and dietary intake are being recorded at baseline. The mother-infant dyads are followed through age 12 months. The primary outcome variable is infant motor and mental development quotient at 12 months of age evaluated by Development Assessment Scale in Indian Infants (DASII). Secondary outcomes are gestational age, APGAR scores, and infant anthropometry. Biochemical indices (blood and breast-milk) from mother-child dyads are being collected to estimate changes in DHA levels in response to supplementation. All analyses will follow the intent-to-treat principle. Two-sample t test will be used to test unadjusted difference in mean DASII score between placebo and DHA group. Adjusted analyses will be performed using multiple linear regression. DISCUSSION: Implications for maternal and child health and nutrition in India: DHANI is the first large pre- and post-natal maternal dietary supplementation trial in India. If the trial finds substantial benefit, it can serve as a learning to scale up the DHA intervention in the country. TRIAL REGISTRATION: The trial is retrospectively registered at clinicaltrials.gov ( NCT01580345 , NCT03072277 ) and ctri.nic.in ( CTRI/2013/04/003540 , CTRI/2017/08/009296 ).


Subject(s)
Child Development , Dietary Supplements , Docosahexaenoic Acids/therapeutic use , Neurodevelopmental Disorders/prevention & control , Adolescent , Adult , Anthropometry , Breast Feeding , Double-Blind Method , Fatty Acids, Omega-3/analysis , Female , Humans , India , Infant , Infant, Newborn , Lactation , Milk, Human/chemistry , Pregnancy , Prenatal Care , Research Design , Young Adult
16.
Am J Perinatol ; 33(6): 600-4, 2016 05.
Article in English | MEDLINE | ID: mdl-26731179

ABSTRACT

Objective This study aims to determine the frequency that umbilical venous catheters (UVCs) and peripherally inserted central catheters (PICCs) migrate into the cardiothymic silhouette after initial verification of correct placement. Study Design This is a single-center, retrospective study in neonates in whom a PICC or UVC was placed. The frequency of catheter tip migration into the cardiothymic silhouette requiring catheter manipulation was determined radiographically at 1 and 24 hours, respectively, after insertion. Results At 1 and 24 hours, 36 and 23% of UVCs (n = 41) migrated into the cardiothymic silhouette, respectively. At 1 and 24 hours, 23 and 11% of PICCs (n = 63) migrated into the cardiothymic silhouette, respectively. Migration was not associated with birth weight, weight at insertion, or postnatal age at insertion. Conclusion UVCs and PICCs frequently migrate into the cardiothymic silhouette increase the risk for development of a pericardial effusion. Serial radiographic assessment of catheter tip location is needed to assess catheter migration within the first 24 hours of line placement.


Subject(s)
Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Central Venous Catheters/adverse effects , Foreign-Body Migration/diagnostic imaging , Foreign-Body Migration/epidemiology , Catheterization, Central Venous/methods , Catheterization, Peripheral/methods , Female , Foreign-Body Migration/therapy , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Male , Pericardial Effusion/etiology , Radiography, Thoracic , Retrospective Studies , Tertiary Care Centers , Time Factors , Umbilical Veins , Wisconsin
17.
Kidney Int ; 88(1): 178-85, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25786102

ABSTRACT

India is experiencing an alarming rise in the burden of noncommunicable diseases, but data on the incidence of chronic kidney disease (CKD) are sparse. Using the Center for Cardiometabolic Risk Reduction in South Asia surveillance study (a population-based survey of Delhi and Chennai, India) we estimated overall, and age-, sex-, city-, and diabetes-specific prevalence of CKD, and defined the distribution of the study population by the Kidney Disease Improving Global Outcomes (KDIGO) classification scheme. The likelihood of cardiovascular events in participants with and without CKD was estimated by the Framingham and Interheart Modifiable Risk Scores. Of the 12,271 participants, 80% had complete data on serum creatinine and albuminuria. The prevalence of CKD and albuminuria, age standardized to the World Bank 2010 world population, was 8.7% (95% confidence interval: 7.9-9.4%) and 7.1% (6.4-7.7%), respectively. Nearly 80% of patients with CKD had an abnormally high hemoglobin A1c (5.7 and above). Based on KDIGO guidelines, 6.0, 1.0, and 0.5% of study participants are at moderate, high, or very high risk for experiencing CKD-associated adverse outcomes. The cardiovascular risk scores placed a greater proportion of patients with CKD in the high-risk categories for experiencing cardiovascular events when compared with participants without CKD. Thus, 1 in 12 individuals living in two of India's largest cities have evidence of CKD, with features that put them at high risk for adverse outcomes.


Subject(s)
Diabetes Mellitus/epidemiology , Renal Insufficiency, Chronic/epidemiology , Urban Population/statistics & numerical data , Adult , Age Factors , Aged , Albuminuria/epidemiology , Cardiovascular Diseases/epidemiology , Female , Glycated Hemoglobin/metabolism , Humans , India/epidemiology , Male , Middle Aged , Practice Guidelines as Topic , Prevalence , Renal Insufficiency, Chronic/complications , Risk Assessment , Sex Factors , Young Adult
18.
BMC Public Health ; 15: 636, 2015 Jul 11.
Article in English | MEDLINE | ID: mdl-26163294

ABSTRACT

BACKGROUND: Harmful effects of alcohol abuse are well documented for drinkers, and adverse effects are also reported for the physical and emotional well-being of family members, with evidence often originating from either drinkers or their families in clinic-based settings. This study evaluates intra-household associations between alcohol abuse in men, and depression and suicidal attempts in women, in community-based settings of Chennai, India. METHODS: This community-based cross-sectional study of chronic disease risk factors and outcomes was conducted in n = 259 households and n = 1053 adults (aged 15 years and above) in rural and urban Chennai. The Alcohol Use Disorder Identification Test (AUDIT) score was used to classify alcohol consumption into 'low-risk', 'harmful', 'hazardous' and 'alcohol dependence' drinking and the Patient Health Questionnaire (PHQ-9) score to classify depression as 'mild', 'moderate', 'moderate-severe' and 'severe'. Multivariate logistic regression models estimated the association of depression in women with men's drinking patterns in the same household. RESULTS: A significant 2.5-fold increase in any depression (PHQ-9 ≥ 5) was observed in men who were 'alcohol-dependent' compared to non-drinkers (OR = 2.53; 95% CI: 1.26, 5.09). However, there was no association between men's drinking behavior and depression in women of the same household, although suicidal attempts approached a significant dose-response relationship with increasing hazard-level of men's drinking (p = 0.08). CONCLUSION: No significant intra-household association was observed between men's alcohol consumption and women's depression, though an increasing (non-significant) trend was associated with suicidal attempts. Complex relationships between suicidal attempts and depression in women and male abusive drinking require further exploration, with an emphasis on intra-household mechanisms and pathways.


Subject(s)
Alcoholism/epidemiology , Alcoholism/psychology , Depressive Disorder/epidemiology , Depressive Disorder/psychology , Suicide/psychology , Suicide/statistics & numerical data , Adult , Comorbidity , Cross-Sectional Studies , Female , Humans , India/epidemiology , Logistic Models , Male
19.
BMC Public Health ; 14: 1239, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25438835

ABSTRACT

BACKGROUND: Indians may be particularly vulnerable to cardiometabolic disease, potentially due to higher body fat for a given BMI, or a tendency towards depositing abdominal adiposity. The aim of the study is to assess whether different measures of the distribution of adiposity (abdominal versus whole body) or amount of adiposity (DXA versus traditional anthropometric) are better at predicting prevalent cardiometabolic risk markers in an Indian population. METHODS: Participants were recruited from the Indian Migration Study (IMS) and the Andhra Pradesh Children and Parent Study (APCAPS). Participants attended a clinic in Hyderabad, India, January 2009-December 2010. Adiposity was measured by conventional anthropometry (including weight, height, waist) and DXA scanning (whole body and abdominal). Blood samples were taken and assessed for fasting plasma glucose, insulin, cholesterol, and triglycerides and blood pressure was measured. Lifestyle data were collected by questionnaire. RESULTS: We invited 4 617 participants to the clinic (1 995 IMS; 2 622 APCAPS) and examined 918 from IMS (46%) and 1 451 from APCAPS (55%). There were strong and consistent relationships between adiposity and cardiometabolic risk factors. Cardiometabolic risk factors did not appear to be more strongly associated with DXA measures as opposed to BMI, or skinfold measures of body fat. There was some evidence that WHR was more closely related to diabetes than total body adiposity, but this was not apparent for the other measures of abdominal adiposity (DXA measures, waist circumference) or other cardiometablic risk factors. CONCLUSIONS: No strong evidence supports that DXA measures or abdominal measures of adiposity are better at predicting the prevalence of cardiometabolic risk factors in comparison to BMI.


Subject(s)
Cardiovascular Diseases/epidemiology , Child Welfare/statistics & numerical data , Intra-Abdominal Fat/physiopathology , Obesity, Abdominal/epidemiology , Absorptiometry, Photon , Adiposity , Anthropometry , Blood Glucose/analysis , Body Height , Body Mass Index , Cardiovascular Diseases/diagnosis , Child , Comorbidity , Female , Humans , India , Male , Obesity, Abdominal/diagnosis , Prevalence , Risk Factors , Triglycerides/blood , Waist Circumference
20.
ACS Nano ; 18(26): 17145-17161, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38906828

ABSTRACT

The induction of heat stress response (HSR) mediated by the generation of heat shock proteins (HSPs) on exposure to magnetic hyperthermia-mediated cancer therapy (MHCT) decreases the efficacy of localized heat treatment at the tumor site, and thus therapy remains a significant challenge. Hence, the present study examined differential HSR elicited in glioma cells post-MHCT under different tumor microenvironment conditions (2D monolayers, 3D monoculture, and coculture spheroids) to recognize target genes that, when downregulated, could enhance the therapeutic effect of MHCT. Gene expression analysis following MHCT revealed that HSP90 was upregulated as compared to HSP70. Hence, to enhance the efficacy of the treatment, a combinatorial strategy using 17-DMAG as an inhibitor of HSP90 following MHCT was investigated. The effects of combinatorial therapy in terms of cell viability, HSP levels by immunofluorescence and gene expression analysis, oxidative stress generation, and alterations in cellular integrity were evaluated, where combinatorial therapy demonstrated an enhanced therapeutic outcome with maximum glioma cell death. Further, in the murine glioma model, a rapid tumor inhibition of 65 and 53% was observed within 8 days at the primary and secondary tumor sites, respectively, in the MCHT + 17-DMAG group, with abscopal effect-mediated complete tumor inhibition at both the tumor sites within 20 days of MHCT. The extracellularly released HSP90 from dying tumor cells further suggested the induction of immune response supported by the upregulation of IFN-γ and calreticulin genes in the MHCT + 17-DMAG group. Overall, our findings indicate that MHCT activates host immune systems and efficiently cooperates with the HSP90 blockade to inhibit the growth of distant metastatic tumors.


Subject(s)
Benzoquinones , Glioma , HSP90 Heat-Shock Proteins , Hyperthermia, Induced , Lactams, Macrocyclic , HSP90 Heat-Shock Proteins/antagonists & inhibitors , HSP90 Heat-Shock Proteins/metabolism , Glioma/therapy , Glioma/pathology , Glioma/immunology , Glioma/drug therapy , Animals , Mice , Lactams, Macrocyclic/pharmacology , Lactams, Macrocyclic/chemistry , Humans , Benzoquinones/pharmacology , Benzoquinones/chemistry , Cell Line, Tumor , Cell Survival/drug effects , Tumor Microenvironment/drug effects
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