BACKGROUND

Observational studies have increasingly reported transthyretin amyloid cardiomyopathy (ATTR-CM) as an under-recognized cause of heart failure. We report the first ATTR-CM diagnosed via multi-modality imaging in the Philippines signifying an important milestone in recognition and management of this formerly believed rare disease, locally. Utilization of non-invasive imaging such as echocardiography, cardiac MRI and technetium-99m pyrophosphate scintigraphy (PYP) demonstrates the potential for accurate diagnosis as well as timely and appropriate treatment strategies.

An 81/M Filipino with a history of carpal tunnel surgery, post-percutaneous coronary intervention (PCI), had three months’ history of refractory heart failure symptoms despite optimized medical treatment. His 2D-echo showed an ejection fraction (EF): 45%-50%, increased left ventricular (LV) posterior wall thickness with mild basal inferior wall hypokinesia and ECG: atrial fibrillation with low voltage. Speckle tracking imaging showed average global longitudinal strain: - 6.5% with cherry-on-top pattern on polar strain map. Cardiac MRI demonstrated diffuse late gadolinium enhancement from endocardial to transmural layers of biventricular and biatrial walls, highly suggestive of cardiac amyloidosis (CA). Light-chain amyloidosis was excluded by negative serum/urine protein electrophoresis/immunofixation. Tc-99m PYP scan revealed greater myocardial-than-bone uptake with a Perugini score 3 and calculated heart-to-contralateral ratio of 1.7. Congestion was controlled with intravenous loop diuretics and he was discharged stable with metoprolol succinate, dapagliflozin and apixaban. At the time of paper submission, he is currently being evaluated for tafamidis treatment.

The case highlighted the advantage of multi-modality imaging for noninvasive yet accurate identification of the disease. A tailored approach is required in slowing the disease progression and improving outcomes.

Objective: To analyze the efficacy and safety of the sodium channel blockers (SCB) antiseizure medication in the treatment of focal epilepsy in infants under 6 months of age. Methods: This was a case series study. Infants with focal epilepsy with onset within 6 months of age and treated with SCB attending the Department of Neurology of Beijing Children's Hospital from June 2016 to April 2022 were collected. The clinical data, auxiliary examinations, SCB application, efficacy, adverse reactions, and prognosis were analyzed retrospectively. Patients were grouped according to type of seizure and epileptic syndrome, age of onset and etiology. Chi square test and Fisher exact test were used to analyze the differences between groups statistically. Results: A total of 118 infants were enrolled, 65 males and 53 females, with an age of epilepsy onset of 56 (4, 114) days. Developmental and epileptic encephalopathy was diagnosed in 60 infants, 39 had self-limited neonatal and (or) infantile epilepsy, and 19 had non-syndromic focal epilepsy. Application of SCB: 106 used oxcarbazepine, 2 used lacosamide, 9 switched from oxcarbazepine to lacosamide or a combination of 2 SCB, and 1 used oxcarbazepine, lacosamide, and lamotrigine successively; oxcarbazepine was the first choice in 46 cases. The age at which SCB was applied was 103 (53, 144) days. The children were followed up for 6 months to 6 years. SCB was effective in 89 cases (75.4%), including 70 cases (59.3%) who achieved seizure freedom. The seizure-free rate was higher in the focal epilepsy only group than in the group with other seizure types (64.4% (65/101) vs. 4/17, χ²=9.99, P<0.05). The responder and seizure-free rates were all higher in the group with the onset age of >3-6 months than the group >1-3 months (84.4% (38/45) vs. 62.5% (20/32), 73.3% (33/45) vs. 46.9% (15/32), χ²=4.85 and 5.58, both P<0.05). With the exception of variants in the PRRT2 gene, those with variants in sodium or potassium channels had higher responder and seizure-free rates than those with variants in other genes(86.2% (25/29) vs. 45.5% (10/22), 62.1% (18/29) vs. 22.7% (5/22), χ²=9.65 and 7.82,both P<0.05). The most common adverse event was transient hyponatremia, which happened in 66 cases (55.9%). There were 9 cases of rash, which subsided in 6 cases after discontinuing oxcarbazepine and switching to lacosamide, and 7 cases of electrocardiogram abnormalities, which improved after withdrawing oxcarbazepine and changing to lacosamide in 1 case. Conclusion: SCB are effective and tolerable in the treatment of focal epilepsy in infants under 6 months of age, with better efficacy in patients with genetic variants of the sodium or potassium channel, focal seizures only, and seizure onset >3-6 months of age.
Child ; Female ; Male ; Infant, Newborn ; Humans ; Infant ; Sodium Channel Blockers/adverse effects* ; Oxcarbazepine ; Lacosamide ; Retrospective Studies ; Epilepsies, Partial/drug therapy* ; Seizures ; Sodium ; Anticonvulsants/adverse effects*

BACKGROUND: Hypertension is considered an important risk factor for the coronavirus disease 2019 (COVID-19). The commonly anti-hypertensive drugs are the renin-angiotensin-aldosterone system (RAAS) inhibitors, calcium channel blockers (CCBs), and beta-blockers. The association between commonly used anti-hypertensive medications and the clinical outcome of COVID-19 patients with hypertension has not been well studied. METHODS: We conducted a retrospective cohort study that included all patients admitted with COVID-19 to Huo Shen Shan Hospital and Guanggu District of the Maternal and Child Health Hospital of Hubei Province, Wuhan, China. Clinical and laboratory characteristics were extracted from electronic medical records. Hypertension and anti-hypertensive treatment were confirmed by medical history and clinical records. The primary clinical endpoint was all-cause mortality. Secondary endpoints included the rates of patients in common wards transferred to the intensive care unit and hospital stay duration. Logistic regression was used to explore the risk factors associated with mortality and prognosis. Propensity score matching was used to balance the confounders between different anti-hypertensive treatments. Kaplan-Meier curves were used to compare the cumulative recovery rate. Log-rank tests were performed to test for differences in Kaplan-Meier curves between different groups. RESULTS: Among 4569 hospitalized patients with COVID-19, 31.7% (1449/4569) had a history of hypertension. There were significant differences in mortality rates between hypertensive patients with CCBs (7/359) and those without (21/359) (1.95% vs. 5.85%, risk ratio [RR]: 0.32, 95% confidence interval [CI]: 0.13-0.76, χ2 = 7.61, P = 0.0058). After matching for confounders, the mortality rates were similar between the RAAS inhibitor (4/236) and non-RAAS inhibitor (9/236) cohorts (1.69% vs. 3.81%, RR: 0.43, 95% CI: 0.13-1.43, χ2 = 1.98, P = 0.1596). Hypertensive patients with beta-blockers (13/340) showed no statistical difference in mortality compared with those without (11/340) (3.82% vs. 3.24%, RR: 1.19, 95% CI: 0.53-2.69, χ2 = 0.17, P = 0.6777). CONCLUSIONS In our study, we did not find any positive or negative effects of RAAS inhibitors or beta-blockers in COVID-19 patients with hypertension, while CCBs could improve prognosis.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; COVID-19 ; Calcium Channel Blockers/therapeutic use* ; Child ; China ; Humans ; Hypertension/drug therapy* ; Prognosis ; Retrospective Studies ; SARS-CoV-2

Objective: Explore the usage of anti-hypertension drugs and the rationality of hypertension prescription among the primary health centers in Dongcheng District, Beijing. Method: This cross-sectional and retrospective study was applied to analyze the hypertension prescriptions from the 8 community health centers in Dongcheng District. The anatomical, therapeutic and chemical classification (ATC) codes were used to determine the drug category. ATC information was used to filter data containing antihypertensive drugs, and group the number and proportion of ATC categories. The type of drug was judged by its generic name. According to the diagnosis information in the prescription, the prescription containing the Western medicine diagnosis of hypertension was screened out. The comorbidities of hypertension in the study included 7 types of diseases including diabetes, chronic kidney disease, coronary heart disease, heart failure, atrial fibrillation, stroke, and dyslipidemia. The analysis of prescription rationality included rationality of combination medication, rationality of drug dosage and rationality of drug price. The agreed daily dose (DDD) method was used to analyze the rationality of drug dosage. The drug utilization index (DUI) was used as a quantitative indicator to estimate the rationality of medication, and overdose was expressed by DUI>1. The reasonableness of the drug price was judged based on the price of the drug and whether it was a drug in the "4+7" plan. Results: A total of 658 140 prescriptions were extracted as the final data set, involving 7 categories and 60 commonly used anti-hypertensive drugs, and the corresponding cost of medication was ￥96.58 million. Drugs were prescribed according to comorbidities, and the choice followed the international guidelines. Calcium channel blockers (CCB) were the most prescribed drugs in the prescriptions of patients with comorbidities, and α-adrenergic receptor antagonists were the least prescribed drugs. The proportion of diuretics prescribed in hypertensive patients complicating with heart failure was 21.17% (505/2 385), which was much higher than that of patients complicating with other comorbidities (P<0.05). The proportion of diuretics prescribed in hypertension patients complicating with dyslipidemia was lower than that of patients with other comorbidities (2 639 (0.94%), P<0.05), and β-blockers (BB) or angiotensin Ⅱreceptor blockers (ARB) were more likely to be selected (BB: 59 348 (21.08%), ARB: 51 356 (18.24%))in these patients. The proportion of BB in prescriptions for hypertension patients with chronic kidney disease was lower than that of patients with other comorbidities (P<0.05). The proportion of BB in prescriptions for hypertension patients with coronary heart disease was higher than that of other comorbidities (P<0.05). Hypertension patients with atrial fibrillation or stroke accounted for a higher proportion of CCB prescriptions (P<0.05). Single antihypertensive drug prescriptions accounted for the highest proportion, 61.19% (402 745/658 140). Two-combination prescriptions accounted for the highest proportion of combination prescriptions, 72.19% (184 392/255 395). CCB based two-combination prescriptions accounted for the highest proportion, 122 350(66.36%). ARB-based tri-combination prescriptions accounted for the highest proportion, 48 915(89.50%),followed by CCB based tri-combination prescriptions (44 732(81.85%)).There were 2 174 (0.33%) prescriptions with unreasonable combination therapies and DUI>1 were found in 48 out of 60 commonly used drugs. In all possible antihypertensive drugs, only 40.92% (109 227/266 993)followed the "4+7" plan. Conclusions: The anti-hypertensive agents from these prescriptions in the primary health centers are diverse, and the choice is generally complied with the guidelines, but some unreasonable situations existed, especially on the combined anti-hypertensive medication, overdose, and"4+7"plan is not followed completely.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Beijing/epidemiology* ; Calcium Channel Blockers/therapeutic use* ; Community Health Centers ; Cross-Sectional Studies ; Humans ; Hypertension/drug therapy* ; Prescriptions ; Retrospective Studies

OBJECTIVE: Cardiovascular diseases are associated with an increased risk of depression, but it remains unclear whether treatment with cardiovascular agents decreases or increases this risk. The effects of drugs on individual usage are also often unknown. This review aimed to examine the correlation between depression and common cardiovascular drugs, develop more potent interventions for depression in cardiovascular patients, and further research on the bio-behavioural mechanisms linking cardiovascular drugs to depression. DATA SOURCES: The data in this review were obtained from articles included in PubMed, EMBASE, and Web of Science. STUDY SELECTION: Clinical trials, observational studies, review literature, and guidelines about depression and cardiovascular drugs were selected for the article. RESULTS: We systematically investigated whether the seven most used cardiovascular drugs were associated with altered risk of incident depression in this literature review. Statins have been proven to have antidepressant effects. Some studies believe angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARB) can exert an antidepressant influence by acting on the renin-angiotensin system, but further clinical trials are needed to confirm this. Beta-blockers have previously been associated with depression, but the current study found no significant association between beta blockers and the risk of depression. Aspirin may have antidepressant effects by suppressing the immune response, but its role as an antidepressant remains controversial. calcium channel blockers (CCBs) can regulate nerve signal transduction by adjusting calcium channels, but whether this effect is beneficial or harmful to depression remains unclear. Finally, some cases have reported that nitrates and diuretics are associated with depression, but the current clinical evidence is insufficient. CONCLUSIONS Statins have been proven to have antidepressant effect, and the antidepressant effects of ACEIs/ARB and aspirin are still controversial. CCBs are associated with depression, but it is unclear whether it is beneficial or harmful. No association has been found with β-blockers, diuretics, and nitrates.
Angiotensin Receptor Antagonists/therapeutic use* ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use* ; Antihypertensive Agents/therapeutic use* ; Calcium Channel Blockers/therapeutic use* ; Cardiovascular Agents/therapeutic use* ; Cardiovascular Diseases/drug therapy* ; Depression/drug therapy* ; Humans ; Hypertension/drug therapy* ; Renin-Angiotensin System

BACKGROUND AND OBJECTIVES: 2018 ESC/ESH Hypertension guideline recommends 2-drug combination as initial anti-hypertensive therapy. However, real-world evidence for effectiveness of recommended regimens remains limited. We aimed to compare the effectiveness of first-line anti-hypertensive treatment combining 2 out of the following classes: angiotensin-converting enzyme (ACE) inhibitors/angiotensin-receptor blocker (A), calcium channel blocker (C), and thiazide-type diuretics (D).METHODS: Treatment-naïve hypertensive adults without cardiovascular disease (CVD) who initiated dual anti-hypertensive medications were identified in 5 databases from US and Korea. The patients were matched for each comparison set by large-scale propensity score matching. Primary endpoint was all-cause mortality. Myocardial infarction, heart failure, stroke, and major adverse cardiac and cerebrovascular events as a composite outcome comprised the secondary measure.RESULTS: A total of 987,983 patients met the eligibility criteria. After matching, 222,686, 32,344, and 38,513 patients were allocated to A+C vs. A+D, C+D vs. A+C, and C+D vs. A+D comparison, respectively. There was no significant difference in the mortality during total of 1,806,077 person-years: A+C vs. A+D (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.97−1.20; p=0.127), C+D vs. A+C (HR, 0.93; 95% CI, 0.87−1.01; p=0.067), and C+D vs. A+D (HR, 1.18; 95% CI, 0.95−1.47; p=0.104). A+C was associated with a slightly higher risk of heart failure (HR, 1.09; 95% CI, 1.01−1.18; p=0.040) and stroke (HR, 1.08; 95% CI, 1.01−1.17; p=0.040) than A+D.CONCLUSIONS: There was no significant difference in mortality among A+C, A+D, and C+D combination treatment in patients without previous CVD. This finding was consistent across multi-national heterogeneous cohorts in real-world practice.
Adult ; Angiotensin Receptor Antagonists ; Antihypertensive Agents ; Calcium Channel Blockers ; Calcium Channels ; Cardiovascular Diseases ; Cohort Studies ; Diuretics ; Heart Failure ; Humans ; Hypertension ; Korea ; Mortality ; Myocardial Infarction ; Propensity Score ; Stroke

The acrosome reaction is a prerequisite for fertilization, and its signaling pathway has been investigated for decades. Regardless of the type of inducers present, the acrosome reaction is ultimately mediated by the elevation of cytosolic calcium. Inositol 1,4,5-trisphosphate-gated calcium channels are important components of the acrosome reaction signaling pathway and have been confirmed by several researchers. In this study, we used a novel permeabilization tool BioPORTER^® and first demonstrated its effectiveness in spermatozoa. The inositol 1,4,5-trisphosphate type-1 receptor antibody was introduced into spermatozoa by BioPORTER^® and significantly reduced the calcium influx and acrosome reaction induced by progesterone, solubilized zona pellucida, and the calcium ionophore A23187. This finding indicates that the inositol 1,4,5-trisphosphate type-1 receptor antibody is a valid inositol 1,4,5-trisphosphate receptor inhibitor and provides evidence of inositol 1,4,5-trisphosphate-gated calcium channel involvement in the acrosome reaction in human spermatozoa. Moreover, we demonstrated that the transfer of 1,4,5-trisphosphate into spermatozoa induced acrosome reactions, which provides more reliable evidence for this process. In addition, by treating the spermatozoa with inositol 1,4,5-trisphosphate/BioPORTER^® in the presence or absence of calcium in the culture medium, we showed that the opening of inositol 1,4,5-trisphosphate-gated calcium channels led to extracellular calcium influx. This particular extracellular calcium influx may be the major process of the final step of the acrosome reaction signaling pathway.
Acrosome Reaction/physiology* ; Calcimycin/pharmacology* ; Calcium/pharmacology* ; Calcium Ionophores/pharmacology* ; Drug Delivery Systems ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism* ; Male ; Progesterone/pharmacology* ; Spermatozoa/metabolism* ; Zona Pellucida/metabolism*

OBJECTIVE: South Korea made a list of potentially inappropriate medications (PIMs) for elderly patients in 2015 and has prompted medical professionals to prescribe proper medication by using the drug utilization review (DUR) system. It has been three years since the system was introduced, but related studies have rarely been conducted. This study aimed to evaluate the effect of the DUR system on the prescription of PIMs for elderly patients. METHODS: The data on the prescription of PIMs for elderly patients (≥ 65 years) who received medical treatment between March 1st and May 31st in 2015 (before introduction of the DUR system) and who received medical treatment between March 1st and May 31st in 2018 (after introduction of the DUR system) were retrospectively collected from electronic medical records. RESULTS: The prescriptions of PIMs decreased from 3,716 (7.7%) to 3,857 (6.9%) (p < 0.001). The prescription of escitalopram and paroxetine, among selective serotonin reuptake inhibitors, increased significantly, and that of short-acting benzodiazepines also increased significantly from 454 (0.93%) to 624 (1.2%). CONCLUSION: Prescription of PIMs for elderly patients significantly decreased (p < 0.001) after the DUR system was introduced. Further expanded studies of PIMs need to be conducted for the safety of elderly patients.
Aged ; Benzodiazepines ; Citalopram ; Drug Utilization Review ; Drug Utilization ; Electronic Health Records ; Humans ; Korea ; Paroxetine ; Potentially Inappropriate Medication List ; Prescriptions ; Retrospective Studies ; Serotonin Uptake Inhibitors ; Tertiary Care Centers

Rabbit Syndrome is an uncommon side effect of antipsychotic treatment. Although it is usually associated with typical antipsychotics, it can also be related to atypical antipsychotics. Anticholinergics are the most accepted treatment approach in treating Rabbit Syndrome. Fluvoxamine is a member of selective serotonin reuptake inhibitors and it is a potent agonist of sigma 1 receptors. In this article, we report a Rabbit Syndrome case who has benefited from fluvoxamine, in terms of both depressive disorder and Rabbit Syndrome; and present the data on the effects of sigma 1 agonist fluvoxamine on numerous movement disorders.
Antipsychotic Agents ; Cholinergic Antagonists ; Depressive Disorder ; Fluvoxamine ; Movement Disorders ; Receptors, sigma ; Serotonin Uptake Inhibitors

There is considerable overlap in the clinical presentations of apathy and depression. However, differential diagnosis between apathy and other psychiatric conditions, including depression and dementia, is important. In this report, we present the case of a 67-year-old woman with a history of receiving selective serotonin reuptake inhibitor (SSRI) treatment for depression. Differential diagnosis between treatment-resistant depression and SSRI-induced apathy syndrome was required. The symptoms of her apathy syndrome were relieved after the discontinuation of SSRIs and the addition of olanzapine, methylphenidate, and modafinil. Furthermore, we briefly review related literature in this article.
Aged ; Apathy ; Dementia ; Depression ; Diagnosis, Differential ; Female ; Humans ; Methylphenidate ; Serotonin ; Serotonin Uptake Inhibitors