Medicines, Volume 10, Issue 1 (January 2023) – 13 articles

Background: Edoxaban is a novel oral anticoagulant which may decrease the risk of stroke and systemic embolism in patients suffering from atrial fibrillation (AF). However, the decreased efficacy of edoxaban versus warfarin for the avoidance of stroke and systemic embolism in AF with creatinine clearance (CrCl) > 95 mL/min has been reported. The purpose of this meta-analysis is to further clarify the safety (major bleeding) and efficacy (stroke or systemic embolism) of edoxaban for AF patients with various CrCl. Methods: A systematic search of studies on edoxaban and warfarin in AF patients related to renal function was conducted in PubMed, Medline, Web of Science databases, EBSCO, Embase, and the Cochrane Central Register of Controlled Trials. In this meta-analysis (protocol number: PROSPERO CRD 42021245512), we included studies that provide specific data on three outcomes: ischemic stroke or systemic embolism (S/SE), bleeding, and all-cause mortality. Results: This meta-analysis enrolled two randomized controlled trials (RCTs) studies and two retrospective studies that enrolled 28,065 patients. According to CrCl, subjects are divided into three groups (CrCl 30–50 mL/min, CrCl 50–95 mL/min, CrCl > 95 mL/min). In AF patients with CrCl 30–50 mL/min, edoxaban 30 mg daily is similar to warfarin in the prevention of ischemic S/SE and all-cause mortality, resulting in lower bleeding rate and better net clinical outcome (ischemic S/SE: hazard ratio (HR), 0.85, 95% confidence interval (CI), 0.19–1.87; all-cause mortality: HR, 0.65, 95% CI, 0.35–1.19; bleeding: HR, 0.75, 95% CI, 0.60–0.93; net clinical outcome: HR, 0.75, 95% CI, 0.63–0.90). In the group of CrCl 50–95 mL/min, the net clinical outcome was more favorable with edoxaban 60 mg daily than warfarin (HR, 0.81, 95% CI: 0.68–0.96), and there was no significant difference between edoxaban 60 mg daily and warfarin in terms of prevention of bleeding, ischemic S/SE, and all-cause mortality. For AF patients with CrCl > 95 mL/min, there was a statistically significant difference in lower bleeding rate between edoxaban 60 mg daily and warfarin (bleeding: HR: 0.70, 95% CI: 0.58–0.84). There was no differential safety in ischemic S/SE, all-cause mortality, and net clinical outcome. Conclusion: Overall, edoxaban was superior to warfarin in terms of net clinical outcome in various groups of CrCl with AF patients. Although there was no significant difference in net clinical outcome between edoxaban and warfarin for AF patients with CrCl > 95 mL/min, edoxaban is not inferior to warfarin in safety and effectiveness in the various levels of CrCl. Edoxaban may be a more effective and safe treatment than warfarin for patients with chronic kidney disease (CKD) who require anticoagulation. More high-quality and long-term clinical research are needed to further estimate the effects of edoxaban. Full article

Introduction. Cataract is the leading cause of blindness. About 90% of cataract blindness occurs in low- and middle-income countries. The prevalence of blindness and low vision in any country depends on the socioeconomic status, the availability of medical and healthcare facilities, and the literacy of the population. Aim: This paper aims to estimate the cataract surgery rate (CSR) at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang (Cataract Operation Centre), and provide descriptive assessments of the patients who received eye treatments in the center. Methods: The data were retrieved from the clinical database from 2013 to 2016. Information on the patient’s sociodemographic and clinical and treatment history was collected. Results: The cataract surgery rate for 2013 was about 27 and increased to 37.3 in 2014. However, it declined to 25 in 2015 before it resumed to 36 in 2016. For female patients who received eye treatments at Pusat Pembedahan Katarak, MAIWP-Hospital Selayang, the rate was higher (53.7%) compared to male patients (46.3%). The mean duration of cataract surgery from 2013 to 2016 was 21.25 ± 11.071 min. Conclusion: The increased cataract surgery rate for MAIWP-HS through smart partnerships for day care cataract surgery proved that better accessibility makes the short- and long-term strategies for the reduction and prevention of blindness in Malaysia possible to achieve. Full article

Choroidal melanoma is a rare malignant tumour, yet it is the most common primary intra-ocular neoplasm and second on the list of top ten most malignant melanoma sites in the body. Clinical presentation can be non-specific and includes photopsia, floaters, progressive visual field loss, and blurry vision. The tumour is quite often diagnosed clinically during fundus examination; however, the most valued diagnostic tests are A- and B-scan ultrasonography (US). Several factors affect prognosis, including the patient’s age, tumour size, histological features, and presence of metastases. Still, with primary treatment and tight surveillance, around 50% of choroidal melanoma patients metastasise. Full article

Patients with Human Immunodeficiency Virus (HIV), and especially Acquired Immunodeficiency Syndrome (AIDS), can present in a multitude of ways with a variety of possible pathologies. This can prove to be a challenge to a clinician. The patient, in this case, was found to have disseminated Mycobacterium-avium-intracellulare (MAI), despite compliance with antiretroviral therapy (ART), who presented with right upper quadrant pain, isolated elevated alkaline phosphatase, and sepsis. Imaging revealed multiple splenic lesions, bilateral psoas abscesses, abdominal lymphadenopathy, and a large right pleural effusion with a mediastinal shift to the left. Psoas abscesses were drained and the cultures grew acid-fast bacilli. The patient was treated with azithromycin, ethambutol and rifabutin. Classically, MAI infections of patients compliant with ART therapy present with localized disease. This case offers a different presentation of MAI despite compliance with ART therapy. Full article

Background: We have recently proposed an alternative strategy of free gingival graft (FGG) and connective tissue graft (CTG) using micronized-gingival connective tissues (MGCTs). The advantage of this strategy is that MGCTs from a small piece of maxillary tuberosity can regenerate the keratinized tissue band. However, safety and efficacy have not yet been established in patients. This clinical study was a pilot case series, and the objective was to assess the safety and the preliminary efficacy of MGCTs on peri-implant mucosa regeneration. Methods: This was a pilot interventional, single-center, first-in-human (FIH), open (no masking), uncontrolled, and single-assignment study. A total of 4 patients who needed peri-implant soft tissues reconstruction around dental implants received transplantation of atelocollagen-matrix with MGCTs micronized by the tissue disruptor technique. The duration of intervention was 4 weeks after surgery. Results: This first clinical study demonstrated that using MGCTs did not cause any irreversible adverse events, and it showed the preliminary efficacy for peri-implant soft tissues reconstruction in dental implant therapy. Conclusions: Though further studies are needed on an appropriate scale, as an alternative strategy of FGG or CTG, MGCTs might be promising for peri-implant mucosa reconstruction without requiring a high level of skills and morbidity to harvest graft tissues. Full article

Objectives: Regulatory clinical Phase I studies are aimed at establishing the human safety of an active pharmaceutical agent to be later marketed as a drug. Since homeopathic medicines are prepared by a potentizing method using alcohol, past a certain dilution, their toxicity/infectivity is assumed to be unlikely. We aimed to develop a bridge study between homeopathic pathogenetic trials and clinical trials. The primary purpose was to evaluate the safety of a nosode, developed from clinical samples of a COVID-19 patient. The secondary objectives were to explore whether a nosode developed for a specific clinical purpose, such as use during an epidemic, may elicit laboratory signals worthy of further exploration. Methods: An open-label study was designed to evaluate the safety and immune response of the Coronavirus nosode BiosimCovex, given orally on three consecutive days to ten healthy volunteers. Clinical examinations, laboratory safety and immune parameters were established. Interferon–gamma, Interleukin-6, and CD 4 were measured. (CTRI registration number: CTRI/2020/05/025496). Results: No serious/fatal adverse events were reported. Laboratory tests to measure safety were unchanged. Three subjects showed elevated Interleukin-6 (IL-6) on day 17 in comparison to the baseline, and ten subjects showed elevated IL-6 on day 34. A significant difference between IL-6 observations, calculated by repeated measures ANOVA, was found to be highly significant. On day 60, the IL-6 values of nine subjects were found to return to normal. Corresponding CD4 cell elevation was observed on day 60, when compared to day 34. Conclusions: HPT may potentially extend into physiological changes with regards to immune response and should encourage future studies. Full article

Background: The prevention of preterm delivery (PTD) represents one of the major topics in modern obstetrics. The aim was to design a prospective study and investigate if mid-trimester serum and amniotic fluid levels of MCP-1 could predict the occurence of spontaneous PTD. Methods: The study involved 198 women who underwent genetic amniocentesis and blood sampling in the middle of their trimester. After applying the criteria for inclusion in the study, there were 16 respondents in the study group, and 38 respondents in the control group. Level of MCP-1 in amniotic fluid and serum was measured with commercially available enzyme-linked immunosorbent assays (ELISA) and statistical analysis was conducted. Results: There was no statistically significant difference in serum or amniotic fluid MCP1 levels between PTD and the control groups. Conclusion: The results suggest that MCP-1 is probably not the most relevant marker for predicting PTD. This study provides new normative data for MCP-1 levels in amniotic fluid and maternal sera and is a valuable tool for future diagnostic and comparative studies. Full article

Introduction: The management of osteoporotic fractures is sometimes rather challenging for spinal surgeons, and considering the longer life expectancy induced by improved living conditions, their prevalence is expected to increase. At present, the approaches to osteoporotic fractures differ depending on their severity, location, and the patient’s age. State-of-the-art treatments range from vertebroplasty/kyphoplasty to hardware-based spinal stabilization in which screw augmentation with cement is the gold standard. Case presentation: We describe the case of a 74-year-old man with an L5 osteoporotic fracture. The patient underwent a vertebroplasty (VP) procedure, which was complicated by a symptomatic cement leakage in the right L4–L5 neuroforamen. We urgently decompressed the affected pedicle via hemilaminectomy. At that point, the column required stability. The extravasation of cement had ruled out the use of cement-augmented pedicle screws but leaving the pedicular screws alone was not considered sufficient to achieve stability. We decided to cover the screws with a polyethylene terephthalate sleeve (OGmend^®) to avoid additional cement leakage and to reinforce the screw strength required by the poor bone quality. Conclusion: In the evolving technologies used for spinal surgery, screws sleeve implants such as OGmend^® are a useful addition to the surgeon’s armamentarium when an increased pull-out strength is required and other options are not available. Full article

(1) Background: There is no specific treatment for concussion in modern medicine, and existing treatment is only limited to resting and restoring cognition. For centuries, Mongolians have used traditional Mongolian medicine (TMM) methods to treat a variety of diseases such as Baria zasal. In this study, we aimed to explore the treatment parents and guardians seek when their children have suffered a concussion. (2) Methods: In this study, we used an online questionnaire. The study participants (n = 400) were randomly selected parents and guardians. The definition of bariachi is an advanced practitioner of baria zasal, which covers most of the massage therapy techniques mentioned in this study. (3) Results: In total, 72% of the parents and guardians went to a bariachi when their children suffered a concussion, while only 10.3% chose western medical hospitals. When asked what they did after the initial treatment was not effective, 47.8% of the participants responded that they went to the bariachi. Based on the days of treatment result, 11.8% reported on the beneficial effects of the treatment appearing in one day, and 60.3% in 1–3 days, which shows that the participants suffered a healing effect of the baria zasal shortly after application to their children. In the regression analysis, visiting a Bariachi was independent of age, gender, or even religion. (4) Conclusions: Although Western medicine is highly developed in Mongolia, the baria zasal of TMM has not lost its appeal in treating concussion. This suggests that baria zasal could be a unique method of concussion treatment even today. This also suggests that the techniques of Baria zasal should be further studied, and as in modern medicine. Full article

It has been shown that the risk of developing obesity, a serious modern health problem, increases with air pollution. However, the molecular links are yet to be fully elucidated. Herein, we propose a hypothesis via which air pollution-induced DNA damage would be the mechanistic link between air pollution and the enhanced risk of obesity and overweight. Indeed, whereas air pollution leads to DNA damage, DNA damage results in inflammation, oxidative stress and metabolic impairments that could be behind energy balance changes contributing to obesity. Such thoughts, worth exploring, seems an important starting point to better understand the impact of air pollution on obesity development independently from the two main energy balance pillars that are diet and physical activity. This could possibly lead to new applications both for therapies as well as for policies and regulations. Full article

Background: Polycystic ovary syndrome (PCOS) is a chronic disorder and is one of the most common endocrine disorders in women of a reproductive age. The prevalence of PCOS is growing globally; 52% of women in Southeast Asia alone suffer from this disorder. This disorder is caused by chronic hyperandrogenism, which hinders folliculogenesis. There is also a close relationship between hyperandrogenism and hyperinsulinemia/insulin resistance (IR), and it is estimated that 40–80% of PCOS patients suffer from insulin resistance (IR). Mesenchymal stem cells (MSCs) and their secretomes have been shown to alleviate PCOS symptoms by decreasing IR and androgen secretion by reducing inflammation. This study aimed to systematically review the literature to study the reported potential of MSCs and their secretomes in decreasing inflammation markers in PCOS treatment. Methods: A systematic literature search was performed on EMBASE, PubMed (MEDLINE), and the Cochrane Library with the terms insulin-resistant PCOS, mesenchymal stem cells, and secretome or conditioned medium as the search keywords. A total of 317 articles were reviewed. Four articles were identified as relevant for this systematic review. Results: The results of this study supported the use of mesenchymal stem cells and their secretions in decreasing inflammatory markers in the treatment of polycystic ovary syndrome. Conclusions: This review provided evidence that treatment with mesenchymal stem cells and their secretomes has the potential to treat PCOS due to its ability to downregulate androgen levels and increase insulin sensitivity, which thereby lowers the level of proinflammatory factors. Full article

Background: Air rescue crew members work equally in aviation and medicine, and thus occupy an important interface between the two work environments of aviation and medicine. The aim of this study was to obtain responses from participants to a validated online-based questionnaire regarding whether hospitals may benefit from the commitment of a medical hospital staff which is also professionally involved in the aviation system as emergency physicians and Helicopter Emergency Medical Services Technical Crew Members (HEMS TC). Furthermore, it focused on the question of whether the skills acquired through Crew Resource Management (CRM) training in the air rescue service might also be used in the ground-based rescue service and, if so, whether they may have a positive effect. Methods: Medical air rescue staff of 37 German air rescue stations was included. Between 27 November 2020 and 03 March 2021, 253 out of 621 employees (response rate: 40.7%) participated voluntarily in a validated anonymized online survey. A quantitative test procedure was performed using the modified questionnaire on teamwork and patient safety (German version). Results: The examination and interpretation of the internal consistency (Cronbach’s alpha) resulted in the following reliabilities: Factor I (Cooperation): α = 0.707 (good); Factor II (Human factors): α = 0.853 (very good); Factor III (Communication): α = 0.657 (acceptable); and Factor IV (Safety): α = 0.620 (acceptable). Factor analysis explained 53.1% of the variance. Conclusions: The medical clinicians participating in this online survey believed that the skills they learned in human factors training such as CRM are helpful in their daily routine work in hospitals or other medical facilities, as well as in their ground-based rescue service activities. These findings may result in the recommendation to make CRM available on a regular to the medical staff in all medical facilities and also to ground-based rescue service staff aiming to increase patient safety and employee satisfaction. Full article

Background: The proportion of women Veterans are increasing and, as such, access to high-quality breast cancer care is important. Prior studies have shown that rural location, age, and a mental health diagnosis negatively impact breast cancer screening rates. Methods: We aimed to retrospectively assess the impact of these risk factors on breast cancer screening adherence rates among Veterans at our institution. Women who were eligible for breast cancer screening per the United States Preventative Services Taskforce guidelines were included. Results: Of 2321 women, overall adherence was 78.2%. There were no significant differences in screening rates between races, various age groups, geographical distribution, and having anxiety or post-traumatic stress disorder (PTSD). However, Veterans with a diagnosis of depression were more likely to adhere to screening guidelines. Having multiple mental health diagnoses was also not a negative risk factor. Conclusions: Our Veteran population’s adherence rates are higher than the national average and rural location, race, age, and certain mental health disorders did not negatively affect adherence to screening mammography. Though more research is needed, screening reminders from our women’s health coordinator may have improved adherence rates and lowered disparities. Full article