INTRODUCTION

While a 600 mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300 mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether higher clopidogrel LD regimen in percutaneous coronary intervention (PCI) outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease.

A systematic literature search for randomized clinical trials (RCTs) was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov and HerdinPH. Studies included those between 2010 and 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects.

Nine RCTs involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only eight studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced the incidence of overall MACE (OR: 0.82, 95% CI: 0.74-0.91, p = 0.0002), nonfatal myocardial infarction (OR: 0.56; 95% CI: 0.32-0.99, p = 0.15) and target vessel revascularization (OR: 0.63; 95% CI: 0.41-0.95, p = 0.03), without significant difference in terms of cardiac death (OR: 0.89; 95% CI: 0.76-1.04, p = 0.15) and stroke (OR: 0.92; 95% CI: 0.67-1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR: 1.27; 95% CI: 1.08-1.49, p = 0.005] without significant difference in minor bleeding (OR: 1.05; 95% CI: 0.94-1.17, p = 0.35).

The administration of 600 mg clopidogrel LD reduces the overall risk of MACE with associated increased risk of major bleeding.

BACKGROUND OF THE STUDY

Coronary artery disease (CAD) poses a significant global health challenge. In the Philippines, despite increased availability of coronary artery bypass grafting (CABG), cost remains a barrier to access. This research evaluates key factors such as all-cause death, cardiovascular death, repeat revascularization and quality of life post-CABG under the Philippine Health Z Benefit Package (PZBP). Its findings provide critical insights for shaping clinical practices, policymaking and advocating for broader implementation of the PZBP to improve healthcare access and quality of life for post-CABG patients.

This retrospective cross-sectional study explores the outcomes of post-coronary artery bypass grafting (CABG) patients enrolled under the PZBP. The study, conducted at Perpetual Succour Hospital in Cebu City from December 2018 to September 2023, included patients diagnosed with CAD based on ACC/AHA 2021 guidelines. Using a complete enumeration strategy, the research employed descriptive statistics for demographic and clinical profiling, and measured quality of life using the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) tool.

The study analyzed 29 patients who underwent CABG through the PZBP, presenting detailed demographic and clinical data. Most patients (41.4%) fell within the 51-60 age range, with males comprising 75.9%. Diabetes mellitus type II was prevalent (58.6%) and 86.2% had three-vessel diseases. The quality of life assessed with WHOQOL-BREF yielded positive scores across physical, mental, social and environmental domains, indicating favorable outcomes. Notably, no cardiovascular deaths, all-cause deaths, or repeat revascularizations were reported during the study, highlighting the effectiveness of CABG under PZBP.

The study on post-CABG patients under the PZBP shows promising outcomes with no all-cause death, cardiovascular death, or repeat revascularization. This indicates the program's effectiveness in delivering accessible, high-quality healthcare, enhancing long-term survival rates and overall well-being. However, addressing underutilization is crucial, highlighting the importance of raising awareness and utilization to further improve post-CABG patients' outcomes and quality of life.

Pain is one of the common non-motor symptoms in patients with Parkinson disease and is characterized by early onset， a high incidence rate， and diverse types of discomfort， which seriously affects the quality of life of patients. Based on the related concepts of pain in Parkinson disease and the current status of research in China， this article reviews the commonly used non-pharmaceutical interventions for alleviating pain in patients and their mechanisms， in order to provide a basis for developing pain management regimens.
Parkinson Disease ; Pain

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

Objective To investigate the state of anxiety and depression in patients with Parkinson disease due to high-altitude exposure in Tibet， China and its impact on quality of life. Methods A total of 93 patients with Parkinson disease who attended Tibet Autonomous Region People’s Hospital from February 2023 to November 2024 were enrolled， and basic information and assessment scales were collected. The Unified Parkinson’s Disease Rating Scale Part Ⅲ （UPDRS-Ⅲ） and Hoehn-Yahr （H-Y） stage were used to evaluate disease severity； Parkinson’s Disease Quality of Life Questionnaire （PDQ-39） was used to evaluate the quality of life of patients； the diagnostic criteria for depression and anxiety in Parkinson disease were used for the diagnosis of depression and anxiety in patients with Parkinson disease； Hamilton Depression Scale （HAMD） and Hamilton Anxiety Scale （HAMA） were used to assess the severity of depression and anxiety. Results Among the 93 patients with Parkinson disease， the prevalence rates of depression and anxiety were 59.1% and 44.1%， respectively. There were significant differences between the depression group and the non-depression group in the somatization， despair， cognitive impairment， block factor， and day-night changes of anxiety， but there were no significant differences in sleep disorders and body weight between the two groups. The depression group had significantly higher PDQ-39 scores than the non-depression group， and the anxiety group had significantly higher PDQ-39 scores than the non-anxiety group. Depressive state was negatively correlated with folate and was positively correlated with blood homocysteine. Anxiety state was positively correlated with H-Y stage and UPDRS Ⅲ score. Conclusion There are relatively high prevalence rates of depression and anxiety in patients with Parkinson disease in Tibetan plateau area， which significantly affects the quality of life of patients.
Parkinson Disease ; Depression ; Anxiety

Objective To investigate the clinical features of dyskinesia and related risk factors in female patients with Parkinson disease （PD）. Methods A cross-sectional study was conducted among the female patients who met the diagnostic criteria for PD at the outpatient service of PD in Aerospace Center Hospital， and demographic data and clinical data were collected and compared between groups， including levodopa equivalent daily dose （LEDD）， Unified Parkinson’s Disease Rating Scale-Ⅲ（UPDRS-Ⅲ）， UPDRS-Ⅳ， scores of non-motor symptoms （cognition and depression）， presence or absence of dyskinesia， and single levodopa dose （LD） during the onset of dyskinesia. A binary logistic regression analysis was used to investigate the influencing factors for dyskinesia in female patients with PD. Results A total of 146 female PD patients were enrolled， among whom 30 patients had dyskinesia， with an incidence rate of 20.5%. Compared with the non-dyskinesia group in terms of clinical features， the dyskinesia group had a significantly younger age of onset [（54.3±12.5） years vs （62.7±10.0） years， P<0.001]， a significantly longer disease duration [（9.9±3.7） years vs （4.5±3.7） years， P<0.001]， a significantly higher severity of disease [H-Y stage： （2.65±0.58） vs （2.35±0.83）， P=0.03]， a significantly longer duration of LD administration [（7.5±3.2） years vs （3.2±2.6） years， P<0.001]， a significantly higher LEDD [（703.2±203.9） mg vs （442.1±226.3） mg， P<0.001]， and significantly lower body weight [（54.1±8.2） kg vs （60.0±8.7） kg， P=0.001] and BMI [（20.9±3.1） kg/m2 vs （23.4±3.1） kg/m2， P<0.001]. The multivariate logistic regression analysis showed that high BMI （OR=0.770， P=0.005） was a protective factor against dyskinesia in female PD patients， while long disease duration （OR=1.304， P=0.001） and high LEDD （OR=1.003， P=0.012） were risk factors for dyskinesia. Conclusion There is a relatively high incidence rate of dyskinesia in female PD patients， which should be taken seriously in clinical practice， and high BMI is a protective factor， while long disease duration and high LEDD are risk factors for dyskinesia in female PD patients.
Parkinson Disease ; Dyskinesias ; Levodopa

Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression

Parkinson disease (PD) is a complex neurodegenerative disorder characterized by a variety of motor and non-motor symptoms. Many studies have shown that the transmembrane protein 175 (TMEM175) gene may be a potential target for the treatment of PD and other neurodegenerative disorders, but the specific pathogenic mechanism remains unclear. TMEM175 is a lysosomal protein-coding gene that encodes a lysosomal proton channel protein. This article reviews the research advances in the characterization of the TMEM175 gene and its encoded proteins, the clinical features of mutant PD, and related pathogenic mechanism. It is shown that the TMEM175 gene has an impact on the pathogenesis of PD, and patients with different mutation sites tend to have different ages of onset and clinical features. Compared with the patients without TMEM175 mutations, the patients with TMEM175 mutations tend to have an earlier age of onset, more severe motor symptoms, and more susceptibility to cognitive impairment and non-motor symptoms. This article systematically reviews the TMEM175 gene, in order to assist in the early diagnosis of PD and the discovery of new disease-modifying therapies and treatment strategies.
Parkinson Disease

Parkinson disease is a neurodegenerative disorder with motor and cognitive impairments as the main clinical symptoms. The disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the formation of Lewy bodies， which are eosinophilic inclusions composed of α-synuclein， in the remaining dopaminergic neurons. The disease predominantly affects middle-aged and elderly individuals. Oxidative stress caused by mitochondrial dysfunction can lead to the loss of dopaminergic neurons， so mitochondrial dysfunction is considered as the main cause of Parkinson disease. Mitochondrial biogenesis has an important effect on the function of mitochondria. Therefore， abnormality of the regulation system of mitochondrial biogenesis is closely related to the occurrence and development of Parkinson disease. This review focuses on the regulatory mechanism of mitochondrial biogenesis control system and aims to provide promising therapeutic targets for Parkinson disease.
Parkinson Disease

Parkinson disease （PD） is the second most prevalent neurodegenerative disorder and predominantly impacts the extrapyramidal system. This condition arises from the degeneration of the dopaminergic nigrostriatal pathway. In recent years， studies have shown that PD pathology and lesions are not limited to the center nervous system， and that PD is a systemic and multisystem disease. The concurrence of PD with peripheral neuropathy （PN） has been increasingly acknowledged， although its pathogenesis remains elusive. The motor symptoms in PD patients often mask the symptoms of PN， leading to relatively low clinical recognition of PD coexisting with PN. This poses challenges in the clinical diagnosis and treatment of PD. This review comprehensively summarize the pathogenesis of PD coexisting with PN.
Parkinson Disease