Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Association of stress and primary hypothyroidism.

Background: Hypothyroidism is the result of impaired production and secretion of thyroid hormones. The cardiovascular system is affected by fluctuations in thyroid hormone levels. Stressful events or stressors can affect the hypothalamic-pituitary-thyroid (HPT) axis and psychological and physiological responses. Stress increases thyroid hormone levels while decreasing TSH levels, which exacerbates autoimmune thyroid disease. Aim: To evaluate the relationship between stress and primary hypothyroidism. Methods: A total of 77 newly diagnosed hypothyroid patients (TSH >5.0 mIU/L) and 77 healthy adults (TSH 0.5-5.0 mIU/L) were enrolled. During a brief general physical examination, the following values were measured: height, weight, blood pressure, pulse, and pulse rate. A brief systemic examination of the cardiovascular system and lungs was also performed to rule out systemic diseases. Heart rate variability (HRV) processing and analysis were performed using Pro LabChart (PowerLab 8Pro) data analysis software from AD Instrument. Results: Mean Avg. RR was significantly higher, RM SSD and pRR50 were significantly lower in cases than in controls. Mean HF was significantly lower and LF/HF (frequency range) was significantly higher in cases than in controls. Mean PSS was significantly higher in cases (25.82 ± 2.83) than in controls (22.47 ± 2.10). The majority of cases (54.5%) had a high stress level. The TSH level showed a highly significant correlation with the LF/HF ratio and with the PSS score. Conclusion: The mean Avg. RR and HF were significantly higher, RM SSD and pRR50 and LF/HF (frequency range) were significantly lower in hypothyroid patients.

Comparison of a Novel Score "NOD-ACLF" to Other Established Prognostic Scores for Prediction of Mortality in APASL-ACLF Patients: A Cohort Study from a Tertiary Care Center of North India.

Background: Commonly used prognostic scores for acute on-chronic liver failure (ACLF) have complex calculations. We tried to compare the simple counting of numbers and types of organ dysfunction to these scores, to predict mortality in ACLF patients. Methods: In this prospective cohort study, ACLF patients diagnosed on the basis of Asia Pacific Association for Study of the Liver (APASL) definition were included. Severity scores were calculated. Prognostic factors for outcome were analysed. A new score, the Number of Organ Dysfunctions in Acute-on-Chronic Liver Failure (NOD-ACLF) score was developed. Results: Among 80 ACLF patients, 74 (92.5%) were male, and 6 were female (7.5%). The mean age was 41.0±10.7 (18-70) years. Profile of acute insult was; alcohol 48 (60%), sepsis 30 (37.5%), variceal bleeding 22 (27.5%), viral 8 (10%), and drug-induced 3 (3.8%). Profiles of chronic insults were alcohol 61 (76.3%), viral 20 (25%), autoimmune 3 (3.8%), and non-alcoholic steatohepatitis 2 (2.5%). Thirty-eight (47.5%) were discharged, and 42 (52.5%) expired. The mean number of organ dysfunction (NOD-ACLF score) was ->4.5, simple organ failure count (SOFC) score was >2.5, APASL ACLF Research Consortium score was >11.5, Model for End-Stage Liver Disease-Lactate (MELD-LA) score was >21.5, and presence of cardiovascular and respiratory dysfunctions were significantly associated with mortality. NOD-ACLF and SOFC scores had the highest area under the receiver operating characteristic to predict mortality among all these. Conclusion: The NOD-ACLF score is easy to calculate bedside and is a good predictor of mortality in ACLF patients performing similar or better to other scores.

Cathepsin S as an early biomarker for cardiovascular disease in chronic kidney disease patients / Catepsina S como um biomarcador precoce para doença cardiovascular em pacientes com doença renal crônica

Abstract Introduction: A high incidence of cardiovascular disease (CVD) events and premature mortality is observed in patients with chronic kidney disease (CKD). Thus, new biomarkers that may help predict the development of CVD in early stages of CKD are being investigated along with other traditional risk factors. Objective: To investigate cathepsin S as an early biomarker for CVD in patients with CKD. Methods: A total of 64 patients with CKD were included and classified into 2 groups: CKD patients with established CVD and CKD patients with non-established CVD. All patients were submitted to routine investigations including complete blood count, random blood sugar, glycated hemoglobin (HbA1c), serum electrolytes, urea, creatinine, total protein, total albumin, calcium total, phosphorous, uric acid, vitamin D, parathormone, lipid profile, liver function test, measurement of serum cathepsin S (Cat S), and 2D Echo of the heart. Results: The level of serum Cat S was increased in CKD patients with CVD (p <0.05) as well as in later stages of CKD (p <0.05). CVD was also more common in patients in early stage CKD. In early stages CKD, Cat S and CVD were positively correlated. Conclusion: These findings suggest that serum Cat S might be useful as an early biomarker for CVD in CKD patients.

Resumo Introdução: Uma alta incidência de eventos de doença cardiovascular (DCV) e mortalidade prematura é observada em pacientes com doença renal crônica (DRC). Assim, novos biomarcadores que podem ajudar a prever o desenvolvimento de DCV nos estágios iniciais da DRC estão sendo investigados juntamente com outros fatores de risco tradicionais. Objetivo: Investigar a catepsina S como um biomarcador precoce para DCV em pacientes com DRC. Métodos: Um total de 64 pacientes com DRC foram incluídos e classificados em 2 grupos: pacientes com DRC com DCV estabelecida e pacientes com DRC com DCV não estabelecida. Todos os pacientes foram submetidos a investigações de rotina incluindo hemograma completo, glicemia aleatória, hemoglobina glicada (HbA1C), eletrólitos séricos, ureia, creatinina, proteína total, albumina total, cálcio total, fósforo, ácido úrico, vitamina D, paratormônio, perfil lipídico, teste de função hepática, medição da catepsina S sérica (Cat S), e Eco 2D do coração. Resultados: O nível de Cat S sérica esteve aumentado em pacientes com DRC com DCV (p <0,05), bem como em estágios posteriores da DRC (p <0,05). A DCV também foi mais comum em pacientes com DRC em estágio inicial. Em estágios iniciais da DRC, a Cat S e a DCV foram positivamente correlacionadas. Conclusão: Estes achados sugerem que a Cat S sérica pode ser útil como um biomarcador precoce para DCV em pacientes com DRC.

COVID-19 cases and their outcome among patients with uncommon co-existing illnesses: A lesson from Northern India.

Introduction: Newer coexisting conditions should be identified in order to modify newer risk factors. Aim was to identify patients with non-classical or less common coexisting conditions in patients infected of COVID 19. Method: Single centred study from June 2020 to May 2021 at a tertiary centre in North India. A preformed questionnaire was used to record clinical and laboratory parameters and to identify cases which are in addition to CDC list and Indian data. Results: 0.67% (46) cases out of 6832 patients were identified to have non-classical coexisting illness. It was divided into 2 groups-infections A (60.1%) and non-infections B (39.9%). Group A included-tuberculosis- pulmonary (14.3%) & extra pulmonary (32.9%), bacterial (25.0%) viral infections [dengue, hepatitis B & C] (14.3%), HIV disease (10.7%) and malaria (3.6%). Group B included- organ transplant (27.8%), autoimmune [myasthenia gravis, polymyositis, psoriasis] (22.6%), haematologic [Haemophilia, ITP, Aplastic anaemia, APML, CML] (27.8%), uncommon malignancies [disseminated sacral chordoma and GTN] (11.1%) and snakebite (11.1%). Serum Procalcitonin was not helpful for diagnosis of bacterial infection in COVID-19 disease. Group A had significantly longer duration of illness, hepatitis and elevated CRP. The mortality in group A & B were 32.1% and 43.8% respectively. Death in non-severe COVID cases was in tetanus and snakebite. 30.7% death among tuberculosis patients. More than 70% of deaths were attributable to COVID 19 in both the groups. Conclusion: In Indian settings, comorbidities like tuberculosis and bacterial infections can precipitate severe COVID 19 unlike other parts of the world where tuberculosis is relatively uncommon.