EVALUATION OF AUTONOMIC DYSFUNCTION BY HEART RATE VARIABILITY ANALYSIS IN TYPE 2 DIABETES MELLITUS

Objective: Cardiac autonomic neuropathy (CAN) is a severe and common, yet highly underdiagnosed, complication of Type 2 diabetes mellitus (T2DM). Subclinical CAN may have reduced heart rate variability (HRV) but normal Ewing battery test. This study was performed to evaluate the importance of 5 minutes HRV for the detection of autonomic dysfunction in T2DM without (CAN-T2DM).Methods: This cross-sectional observational study was conducted at the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU) on 30 recently diagnosed T2DM (RT2DM) and 54 long-term CAN-male T2DM patients (LT2DM), aged 45-55 years, from the Endocrinology Out Patient Department of BSMMU, Dhaka. 30 age and body mass index matched apparently healthy male subjects were control. Ewing battery test was used to rule out CAN positive T2DM. HRV data were recorded by a polyrite-D and analyzed by software. HRV was assessed by time domain method. For statistical analysis, ANOVA and unpaired t-test were used.Results: Mean RR, standard deviation of NN intervals (SDNN) (p<0.05), and root mean square of the successive differences (RMSSD) were significantly (p<0.001) lower, and mean HR and SDNN/RMSSD were (p<0.001) significantly higher in LT2DM compared to RT2DM and control. In addition, SDNN was also significantly (p<0.05) lower in RT2DM than that of control.Conclusions: Results conclude that autonomic dysfunction may occur in both LT2DM and RT2DM patients without neuropathy and 5 minutes HRVtest is an important tool for detecting subclinical CAN.Keywords: Type 2 diabetes mellitus, Cardiac autonomic neuropathy, Heart rate variability

Effect of Losartan and Atenolol on heart rate variability in newly diagnosed essential hypertensive patient

Background: Essential hypertension is associated with altered autonomic function. Essential hypertension is treated with drugs which modify the sympatho-parasympathetic balance. Losartan (angioteosin II receptor blocker) and atenolol (beta blocker) is commonly used antihypertensive drugs.Objective: To evaluate the effect of antihypertensive drugs on heart rate variability (HRV) in patients with essential hypertension.Methods: This prospective observational study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from July 2012 to June 2013 on 120 newly diagnosed hypertensive patients without any medication (group B, age 30-55 years). They were selected from the Out Patients Department (OPD) of cardiology, BSMMU, Dhaka. Age, sex and BMI matched 60 apparently healthy norrnotensive subjects were also studied as control (group A). Based on treatment, these study subjects were divided into two groups (BI and B2). Group B1a included 60 patients received Josartan 50 mg daily and B2a included 60 patients received atenolol 50mg daily. They were observed once before the treatment (B1a & B2a), after 3 months medication (B1b & B2b) and after 6 months medication (B1c & B2c). For assessing HRV, Mean heart rate, Mean R-R interval, Max/Min R-R interval, SDNN, RMSSD were recorded by a polyrite. Data were compared among before treatment, after 3 months treatment and after 6 months treatment. For statistical analysis ANOVA, independent sample't' test and paired sample 't' test were performed. Results: Mean resting pulse rate, mean heart rate, systolic blood pressure, diastolic blood pressure were significantly higher and mean R-R interval, Max/Min R-R interval, SDNN, RMSSD were significantly lower in newly diagnosed hypertensive patients in comparison with that of healthy normoten­sive subjects and after treatment. Jn both groups SDNN, RMS SD, mean R-R interval were found significantly higher after 6 months of treatment compared to their values after 3 months treatment. Again these values were found close to the values in normotensive subjects. In addition, mean heart rate was found significantly lower in atenolol treated patients than those of controls. Again in atenolol group these values were found significanLly higher than the corresponding values in losartan treated patients after 6 months treatment. Conclusion: Reduced cardiac vagal tone occurs in newly diagnosed hypertensive patients which is improved by both losartan and atenolol and in particular atenolol was found more effective

Age-related cardiovascular response to tilt test in healthy volunteers of both sexes

This study aimed to assess the age-related changes in the cardiovascular response to tilt test in 90 healthy individuals of both sexes (age range: 18-60 years). Tilting was done at 600 for 10 min using a motorized tilt table. The blood pressure was recorded by a sphygmomanometer. The heart rate and peripheral capillary oxygen saturation were measured by a pulse oximeter. In males, significantly lesser changes in the systolic, diastolic and mean arterial pressure were observed in the old age (47-60 years) than the young (18-32 years) and middle age (33-46 years) groups. Significantly lesser responses in the heart rate and systolic blood pressure change were observed in the old age females compared to young age after tilting. The rise of diastolic blood pressure after tilting was lesser in the old age female compared to both young and middle-age females. In conclusion, the aging process is associated with attenuated cardiovascular response to tilt test in both males and females

Effects of Oral Supplementation of Vitamin E on Fragility of RBC in Hemolytic Anemic Patients with G6PD Deficiency

Background: Vitamin E has role in maintaining the integrity of red cell membrane by preventing oxidation of polyunsaturated fatty acids and thereby protects cells from oxidative stress- induced lysis in G6PD deficiency, which can be reflected by changes in osmotic fragility of RBC and some absolute values like MCV, MCH & MCHC. Objective: To observe the effects of vitamin E supplementation on fragility of RBC in order to evaluate role of this antioxidant vitamin in reducing chronic hemolysis in G6PD deficient patients. Methods: For this, a total number of 102 subjects with age ranged from 5 to 40 years of both sexes were included in the study. Among them 68 were G6PD enzyme deficient patients, of whom 34 were in supplemented group (study group) and 34 were in non-supplemented group (control group). The supplemented group received vitamin E supplementation for 60 consecutive days at a dose of 800 IU/day for adult and 400 IU/day for children < 12 years (in a divided dose i,e. 4 times daily). Age and sex matched 34 apparently healthy subjects with normal blood G6PD level were taken to observe the base line data (healthy control) and also for comparison. All the G6PD deficient patients were selected from Out Patient Department (OPD) of Hematology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh during the period of July 2005 to June 2006 and all the healthy subjects were selected from personal contact. Blood G6PD level, osmotic fragility of RBC were measured by standard techniques and MCV, MCH, and MCHC were obtained by calculation. All the parameters were measured on day 1 (one) of their first visit and also were on day 60 in deficient group. Data were compared among the deficient groups, also in supplemented group just before and after supplementation. Analysis of data was done by appropriate statistical method. Results: Mean starting and completing points of osmotic fragility of RBC were significantly higher but MCV, MCH, MCHC were significantly lower in patients suffering from hemolytic anemia due to G6PD deficiency in comparison to those of the healthy control. After supplementation with vitamin E starting and completing points of osmotic fragility of RBC were significantly decreased whereas, MCV, MCH, MCHC were significantly increased towards those of healthy control in supplemented group of patients in comparison to those of their pre-supplemented (day-1) and non-supplemented groups both on day 1 and day 60. Conclusion: From this study it may be concluded that, disturbances of some of the hematological parameter like higher osmotic fragility of RBC and lower MCV, MCH, MCHC occur in G6PD deficient hemolytic anemic patients, which returned towards normal after supplementation of vitamin E, which clearly indicates the role of this anti-oxidant vitamin in maintaining red cell membrane integrity and thereby decreases the rate of hemolysis in this group of patients. So, vitamin E can be supplemented along with other drugs for better management of the patients. Key words: Osmotic fragility, G6PD, hemolytic anemia, vitamin E.DOI: 10.3329/bsmmuj.v1i1.3688 BSMMU J 2008; 1(1): 6-1

Type 2 Diabetes Mellitus: Cardiovascular Autonomic Neuropathy and Heart Rate Variability

Type 2 Diabetes Mellitus is associated with both macro- and microvascular complications. One among the latter, is cardiovascular autonomic neuropathy (CAN). CAN is attributed to cardiac arrhythmias and sudden death. Underlying pathogenesis of cardiac autonomic neuropathy is chronic hyperglycemia induced oxidative stress causing neuronal necrosis, apoptosis and death, leading to the sympathetic and parasympathetic nerve dysfunction. The balance between sympathetic and parasympathetic nervous system is reflected by heart rate variability (HRV). HRV describes “the variations of both instantaneous heart rate and R-R intervals which in turn reflects the cardiac autonomic nervous control”. HRV measured at rest is a marker of autonomic nerve function status. Thus, HRV test is recommended to diagnose diabetic CAN. Time domain parameters predominantly reflect overall autonomic activity and parasympathetic nervous system (PNS) modulations. Frequency domain parameters either reflect, sympathetic nervous system (SNS) activity, PNS activity, or the balance between the two activities. Nonlinear HRV indices marks PNS influences, SNS influences and sympatho-vagal balance. Almost all these HRV parameters are remarkably reduced in T2DM due to cardiac autonomic dysfunction. HRV is an important simple and noninvasive diagnostic tool to detect CAN

Study of Glucose-6-phosphate Dehydrogenase (G6PD) Status in Preeclampsia

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the common enzymopathy and may be one of the risk factor for complicated pregnancy. Objectives: To measure erythrocyte G6PD level in pregnant women with preeclampsia in order to observe this enzyme status and also to measure Hb, TC of RBC, serum bilirubin, reticulocyte count to observe hemolytic status. In addition, to correlate this enzyme level with all these hematological parameters in order to find out any relationships among them. Methods: This cross sectional study was carried out in the Department of Physiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Shahbag, Dhaka from January to December 2008. For this, 30 pregnant women with preeclampsia, age ranged from 20 to 34 years during their third trimester (>24th weeks) were studied (group B). They were selected from the Obstetric and Gynae Out Patient Department (OPD) of BSMMU and Bangladesh Medical College Hospital (BMCH) of Dhaka City. For comparison age matched 30 apparently normal pregnant women of the same gestational age (control group - group A) were also studied. They were selected by personal contact. Erythrocyte G6PD level was measured by Spectrophotometric method using kit of Randox. Serum bilirubin, hemoglobin concentration, total count of RBC and reticulocyte count were measured by standard laboratory techniques. For statistical analysis ANOVA, independent sample t test, Chi-square test and Pearson's correlation coefficient test were performed by using SPSS for windows version-12 as applicable. Results: In this study, erythrocyte G6PD level was significantly lower in preeclampsia in comparison to that of control but their percentages of involvement was not statistically significant. In addition, hemoglobin concentration and RBC count were significantly lower and serum bilirubin and reticulicyte count were significantly higher in the study group than those of control group. On the other hand, erythrocyte G6PD level was positively correlated with hemoglobin concentration and total count of RBC while negatively correlated with serum bilirubin and reticulocyte count and all these relationships were statistically significant in the study group. Conclusion: Therefore, this study revealed that presence of G6PD deficiency associated with hemolysis in preeclampsia may act as a contributory factor for the development of this complicated pregnancy. Key words: G6PD; preeclampsia DOI: 10.3329/bsmmuj.v2i2.4758 BSMMU J 2009; 2(2): 56-6

Comparison of serum homocysteine level in young and middle-aged adult patients with coronary artery disease

Deaths due to coronary artery disease have been increasing in young people aged 15 mmol/L) was 16.2% in Group I compared to 12.4% in Group II (P=0.001). Therefore, control measures for keeping homocysteine levels within the normal range in young people might be useful. BSMMU J 2022; 15(3): 197-20

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030