Autonomic Response Latency Revisited: Assessment of Repeatability in Healthy Subjects.

Background: Autonomic function assessment provides valuable information regarding the status of the autonomic nervous system. The time lag between the onset of orthostasis and the peak/nadir of heart rate response is a surrogate of the integrity of underlying autonomic neural pathways. Autonomic response latency (ARL) is a relatively novel yet underreported parameter in this context. Test-retest repeatability of this parameter has not been evaluated previously. Materials and Methods: We recruited 31 healthy adults (17 males and 14 females; 29.00 ± 5.44 years) and subjected them to postural challenge tests on five instances - forenoon and afternoon of day 1, the next day, 1 week later, and 1 month later. Tachycardia and bradycardia latencies (TL and BL) were computed using heart rate derived from digital ECG data. Repeatability was assessed using the intraclass correlation coefficient (ICC) and coefficient of variation (CoV). Results: ICCs for TL and BL were 0.69 (0.56, 0.82) and 0.77 (0.66, 0.87), respectively. The CoVs for TL and BL were 14.8% and 12.4%, respectively. Sex-based subgroup analysis revealed ICCs for TL and BL in males to be 0.71 (0.53, 0.86) and 0.74 (0.57, 0.88) and in females to be 0.68 (0.64, 0.86) and 0.82 (0.66, 0.93), respectively. CoVs for TL and BL were 14.4% and 13.8% in male subjects and 15.4% and 10.7% in female subjects, respectively. Conclusion: ARL to orthostatic challenge demonstrated moderate to good test-retest repeatability. Based on our observations, we propose that ARL has potential as a consistent and repeatable index for the assessment of the integrity of autonomic neural pathways and therefore can help in the diagnosis of autonomic neuropathy.

Exploring Ultra-short Heart Rate Variability Metrics in Patients with Diabetes Mellitus: A Reliability Analysis.

Objectives: Ultra-short heart rate variability (HRV) metrics represent autonomic tone parameters derived using small epochs of interbeat interval data. These measures have risen in popularity with the advent of wearable devices that can capture interbeat interval data using electrocardiography (ECG) or photoplethysmography. Autonomic neuropathy in diabetes mellitus (DM) is well established, wherein 5-min HRV is conventionally used. Ultra-short measures have the potential to serve as markers of reduced autonomic tone in this patient population. Methods: Data of patients with Type I and Type II DM who had presented to our laboratory for autonomic neuropathy assessment were chosen for analysis. One-minute and 2-min epochs were chosen from 5 min of ECG data using standard software. Time domain, frequency domain, and nonlinear measures were computed from 1 to 2 min epochs, and reliability was compared with measures derived from 5-min HRV using intraclass correlation coefficients (ICCs). Results: Data of 131 subjects (79 males, 52 females; mean age = 53.3 ± 12.16 years) were analyzed. All ultra-short HRV measures derived from 1 min to 2 min data showed good to excellent reliability (median ICC values ranging from 0.83 to 0.94) when compared with 5-min metrics. The notable exception was very low frequency (VLF) power, which showed poor reliability (median ICC = 0.43). Conclusions: Ultra-short HRV metrics derived from 1 to 2 min epochs of ECG data can be reliably used as predictors of autonomic tone in patients with DM. VLF power is poorly reproducible in these small epochs, probably due to variability in respiratory rates. Our findings have implications for ultra-short HRV estimation using short epochs of ECG data.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Use of Multimodality Intraoperative Neuromonitoring in Tethered Cord Syndrome - Experience from a Tertiary Care Center.

Detethering of the spinal cord is done in nearly all cases of tethered cord syndrome (TCS), which can damage nerve roots, and hence, there is a need to identify filum terminale during surgery. Multimodality intraoperative neuromonitoring (IONM) may be useful in this regard to prevent postoperative morbidity. Twenty-six patients (13 males and 13 females, age range: one year to 56 years) with TCS were recruited for the study. Triggered electromyography (t-EMG), transcranial motor evoked potential (TcMEP) and free-running electromyography (f-EMG) were used in the study on a case-to-case basis. Warning criteria were followed according to the standard guidelines. Nerve roots and filum terminale were successfully identified and detethered in all cases. There was no new postoperative deficit seen. Transcranial motor evoked potentials did not change during surgery and no new limb weakness was seen in any of the investigated cases. Triggered EMG successfully helps in identifying nerve roots and filum terminale, while TcMEP is a good prognostic indicator of motor viability. Multimodality IONM use during tethered cord surgery should be encouraged to prevent postoperative deficits.

Role of Meditation in Ameliorating Examination Stress Induced Changes in Cardiovascular and Autonomic Functions.

Background: Examination stress is a very well-known model of psychological stress in students. It induces changes in systolic (SBP) and diastolic blood pressure (DBP), along with changes in heart rate variability (HRV) and baroreflex sensitivity (BRS), due to autonomic perturbations. Purpose: To find out if Raj Yoga meditation (RYM) practice affects autonomic and cardiovascular function in healthy young subjects during periods of examination stress. Our primary objective was to evaluate the effect of one month of supervised RYM practice on ameliorating examination-induced changes in cardiovascular and autonomic function. The secondary objective was to measure the stress levels of medical students before and after RYM. Methods: Pre-training measurements of SBP, DBP, HRV, and BRS were done, and the Medical Student Stressor Questionnaire (MSSQ) was administered to 80 participants one month before examinations. They were then trained in RYM. Post-training assessment of the same parameters was done after examinations and also after two months. Results: In our study, RYM training decreased DBP (p = 0.01) but not SBP. BRS showed a trend towards an increase after RYM practice, but it was not statistically significant (p = 0.44). The standard deviation of the NN interval (SDNN) (p = 0.03), low-frequency (LF) nu (0.003), and high-frequency (HF) nu (0.04) showed a statistically significant change. Average RR, median RR, average rate, square root of the mean squared differences of successive NN intervals (RMSSD), pRR, total power, LF (µs2), and LF/HF ratio were not statistically significantly different between the three groups. There was a statistically significant decline in MSSQ scores for MSSQ I (p = 0.04), MSSQ II (p = 0.04), and MSSQ IV (p = 0.03). Conclusion: Short-term practice of supervised RYM during stressful periods is protective for the cardiovascular and autonomic systems and decreases stress in medical students.

Treatment Outcome Comparison Between two 3-Dimensional Plates (Y-Shaped Plate Versus Trapezoidal Condylar Plate) in Management of Mandible Condylar Fracture: A Randomized Control Trial.

Aim: To compare the treatment outcomes (clinical, functional and radiographical) using the two different 3-Dimensional plates in open reduction internal fixation of mandibular condylar fracture (MCF). Assessment of ease of fixation and fixation time were also performed. Methodology: 20 MCF patients were divided equally into two groups (Group A: Trapezoidal Condylar Plate and Group B: Y-shaped plate) and the treatment outcomes were compared. Intraoperatively time required for fixation was also compared. The patients were followed up at different timelines till 3 months. Result: Baseline parameters had statistically insignificant distribution in both groups implying effective randomization and balanced confounding factors. Intraoperatively, adequate anatomical reduction was achieved in both groups with statistically insignificant difference in time required for fixation. Postoperatively, no statistically significant difference was found in radiographic and functional parameters. None of the patients in either group reported with facial nerve injury, condylar resorption, Temporomandibular Disorders. However, 02 patients in Group A and 01 patient in Group B presented with infection, parotid fistula, and hardware failure respectively with statistically insignificant difference. Conclusion: This study concluded that the treatment outcomes were satisfactory with the use of both 3-D plate, but further studies with larger sample size and longer follow up are required.

Minocycline in depression not responding to first-line therapy: A systematic review and meta-analysis.

BACKGROUND: Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs). METHODS: We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence. RESULTS: Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy. CONCLUSION: There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens. REGISTRATION: CRD42023398476 (PROSPERO).

Critical Self-Appraisal Towards the Better Use of a Webinar Series as an Online Tool for Postgraduate Teaching.

INTRODUCTION: The current coronavirus disease 2019 (COVID-19) pandemic adversely affected the conventional teaching mode, resulting in an exponential rise in online modalities such as webinars. Simultaneously, the lockdown provided substantial time to pursue potential academic content on the web. It is known that newly admitted postgraduate students of Physiology require a structured program that can guide them to conduct research for the completion of the course. METHODS: Gauging the opportunity, a webinar series was conducted on basic research methodology and thesis writing in Physiology. The series comprised hourly lectures delivered between 4:00 and 5:00 pm for seven consecutive days. Suggestions for future topics for webinars were sought through open-ended questions. Additionally, feedback for increment in students' knowledge at the end of the webinar was also inquired on a Likert scale. Open-ended answers were pooled into fields, and Likert scale scores were evaluated. RESULTS: There were 364 (35.8%) postgraduate students who registered for the webinar. The remaining were faculty (51.6%), research scholars (8.8%), and senior residents (3.8%). Among the postgraduate students who submitted the feedback, a majority (98.4%) of them agreed that their knowledge was enhanced at the end of the series. Most of the postgraduate students (31%) chose Biostatistics for future webinars. CONCLUSION: Webinars are a useful tool for postgraduate teaching. They should be constructed with engaging infrastructure and relevant examples. The availability of recorded content on the online forum is beneficial for asynchronous learners. Having an idea about students' choice for essential topics helps in the advanced planning of a demanding webinar.

Medical Education During the COVID-19 Pandemic: A Single Institution Experience.

Social distancing to curb the COVID-19 pandemic has caused suspension of classroom teaching in all educational institutions. We implemented a novel online classroom platform at our institute to continue medical education. The program attracted encouraging feedback from the students. It may serve as a model for uninterrupted teaching and training during times of crisis.

Effect of Vitamin D status on QTc interval in type 2 diabetes mellitus.

OBJECTIVES: Diabetes mellitus (DM) is associated with autonomic neuropathy and metabolic abnormalities. These predispose the patients to prolongation of QTc and risk of arrhythmias and sudden cardiac death. Vitamin D may also cause QTc prolongation. We hypothesized that concomitant Vitamin D deficiency and Type 2 DM may act in synergy to prolong QTc interval. METHODS: Newly diagnosed Type 2 DM patients were recruited from Department of Endocrinology. Lead II ECG was acquired for 5 min during supine rest using a digital data acquisition system. QTc interval extraction was performed using software. 25-hydroxy Vitamin D estimation was done using Chemiluminescence method. Patients were divided into two groups- Vitamin D deficient and insufficient (VDD/I) and optimal (VDO) as per standard criteria. QTc intervals were compared between the two groups. RESULTS: Sixty-five patients participated in the study. Age was comparable between the groups (p=0.67, Unpaired t-test). There was no significant difference amongst QTc intervals between the groups (p=0.19, Mann Whitney test). Also, there was no significant correlation between Vitamin D levels and QTc intervals assessed using Spearman's correlation coefficient. CONCLUSIONS: While it seems plausible, coexisting Vitamin D deficiency and Type 2 DM probably do not act in synergy to prolong QTc interval. These findings merit future research on larger cohorts to investigate the relationship between Vitamin D status and newly diagnosed Type 2 DM on QTc intervals.

Evaluating exercise challenge to validate cardiac autonomic dysfunction in lean PCOS phenotype.

Background Polycystic ovary syndrome (PCOS) is frequently associated with infertility, obesity, hypertension, and diabetes mellitus. Cardiac autonomic dysfunction is well documented in long-term patients of PCOS, with impairment being proportionate to disease duration. However, there is paucity of literature on cardiac autonomic tone in the "lean" phenotype of PCOS. We used exercise challenge to probe for autonomic dysfunction, as assessed by heart rate variability (HRV), an index of cardiac autonomic tone. Methods Our study population consisted of 27 newly diagnosed PCOS patients and 25 healthy females matched by age and body mass index. Short-term HRV was assessed using time and frequency domain indices. Moderate, isotonic exercise was used as an interventional tool. Indices of both groups were compared in three bins - at baseline, immediate, and late postexercise stages. Results The groups had comparable HRV indices at baseline. However, low-frequency (LF) power was significantly reduced in PCOS patients during immediate and late postexercise phases when compared with controls (p = 0.03 and 0.03, respectively). Time domain indices also exhibited a fall postexercise, although not statistically significant. Conclusions Although "lean" phenotype PCOS patients had comparable HRV parameters as controls at baseline, the administration of exercise challenge led to reduced sympathetic drive, evident by reduced LF power in patient group. This may be due to latent autonomic dysfunction in "lean" PCOS, which is unmasked on exposure to exercise challenge. We propose that the evaluation of HRV response to exercise may serve as a sensitive screening tool to detect early cardiovascular dysfunction in newly diagnosed lean PCOS patients.

VEGF-A and cardiac autonomic function in newly diagnosed type 2 diabetes mellitus: A cross-sectional study at a tertiary care center.

INTRODUCTION: Cardiac autonomic neuropathy (CAN) is a key complication of type 2 diabetes mellitus (Ty2DM). Vascular endothelial-derived growth factor (VEGF-A) plays a key role in diabetic macrovascular and microvascular complications. It is shown to be elevated in diabetic neuropathy and has the potential to serve as a biomarker in Ty2DM. We evaluated VEGF-A levels and cardiac autonomic function in newly diagnosed Ty2DM patients. MATERIALS AND METHODS: Forty-four newly diagnosed patients (with symptoms within 1 year from the date of recruitment) were included in the study. Cardiac autonomic function was assessed using heart rate variability (HRV) and Ewing's battery tests. Ewing's scores were computed and tabulated. VEGF-A levels were estimated using enzyme-linked immunosorbent assay (ELISA). RESULTS: The patients demonstrated normal responses to the reactivity tests. Ewing's scores were 0 (0-0) and 0 (0-0) for sympathetic and parasympathetic parameters, respectively. The autonomic tone was impaired as assessed by HRV parameters. VEGF-A levels were elevated (308.3 ± 167.2 pg/mL) when compared with the previous literature. DISCUSSION: Impaired tone with normal reactivity was suggestive of early stage of autonomic neuropathy. Elevated VEGF-A levels may be attributed to a protective action of the factor seen in early stages of neuropathy in Ty2DM. Serial VEGF-A estimation in large cohorts of newly diagnosed diabetics may validate it as a biomarker in CAN seen in Ty2DM.

A Pilot Study for Evaluation of Digital Systems as an Adjunct to Sphygmomanometry for Undergraduate Teaching.

OBJECTIVES:  Blood pressure estimation is a key skill for medical practitioners. It is routinely taught to undergraduate medical students using an aneroid sphygmomanometer. However, the conceptual understanding in the practical remains limited. We conducted the following study to evaluate the efficacy of digital data acquisition systems as an adjunct to the sphygmomanometer to teach blood pressure. METHODS:  Fifty-seven first-year medical students participated in the study. An MCQ test of 15 questions, consisting of 10 conceptual and five factual questions, was administered twice - pre- and post-demonstration of blood pressure measurement using a digital data acquisition system. In addition, qualitative feedback was also obtained. RESULTS:  Median scores were 7 (6 - 8) and 3 (1.5 - 4) in pre-test sessions for conceptual and factual questions, respectively. Post-test scores showed a significant improvement in both categories (10 (9 - 10) and 4 (4 - 4.5), respectively, Mann-Whitney U test, p < 0.0001). Student feedback also indicated that the digital system enhanced learning and student participation. CONCLUSIONS:  Student feedback regarding the demonstrations was uniformly positive, which was also reflected in significantly improved post-test scores. We conclude that parallel demonstration on digital systems and the sphygmomanometer will enhance student engagement and understanding of blood pressure measurement.

Baroreflex Dysfunction in Prader Willi Syndrome.

Prader-Willi syndrome is a classical hypothalamic insufficiency disorder. This syndrome is often associated with cardiovascular morbidity and mortality - which could probably be attributed to autonomic dysfunction. A 21-year-old Prader Willi syndrome patient was referred for cardiovascular and autonomic function assessment. We performed a battery of tests assessing vascular structure (carotid intima thickness), vascular function (arterial stiffness indices), baroreflex sensitivity (overall integrator of short term regulation of blood pressure), blood pressure variability and autonomic tone (heart rate variability) along with autonomic reactivity tests. We observed impaired baroreflex sensitivity along with orthostatic tachycardia with normal vascular function tests. Prader- Willi syndrome patient have baroreflex dysfunction with probable afferent and/ central autonomic neural defects.