The Benefits of the Post-Transplant Cyclophosphamide in Both Haploidentical and Mismatched Unrelated Donor Setting in Allogeneic Stem Cells Transplantation.

Allogeneic hematopoietic cell transplantation (alloHSCT) is a standard therapeutic approach for acute leukemias and many other hematologic malignancies. The proper choice of immunosuppressants applicable to different types of transplantations still requires strict and careful consideration, and data in this regard are divergent. For this reason, in this single-centered, retrospective study, we aimed to compare the outcome of 145 patients who received post-transplant cyclophosphamide (PTCy) for MMUD and haplo-HSCT or GvHD prophylaxis for MMUD-HSCT alone. We attempted to verify if PTCy is an optimal strategy in MMUD setting. Ninety-three recipients (93/145; 64.1%) underwent haplo-HSCT while 52 (52/145; 35.9%) underwent MMUD-HSCT. There were 110 patients who received PTCy (93 in haplo and 17 in MMUD group) and 35 patients received conventional GvHD prophylaxis based on antithymocyte globulin (ATG), cyclosporine (CsA), and methotrexate (Mtx) in the MMUD group only. Our study revealed that patients receiving post-transplant cyclophosphamide (PTCy) show decreased acute GvHD rates and CMV reactivation as well as a statistically lower number of CMV copies before and after antiviral treatment compared to the CsA + Mtx + ATG group. Taking into account chronic GvHD, the main predictors are donor age, ≥40 years, and haplo-HSCT administration. Furthermore, the survival rate of patients following MMUD-HSCT and receiving PTCy with tacrolimus and mycophenolate mofetil was more than eight times greater in comparison to patients receiving CsA + Mtx + ATG (OR = 8.31, p = 0.003). These data taken together suggest that the use of PTCy displays more benefits in terms of survival rate compared to ATG regardless of the type of transplantation performed. Nevertheless, more studies with a larger sample size are required to confirm the conflicting results in the literature studies.

Phytochemicals in Gynecological Cancer Prevention.

Gynecological cancer confers an enormous burden among women worldwide. Accumulating evidence points to the role of phytochemicals in preventing cervical, endometrial, and ovarian cancer. Experimental studies emphasize the chemopreventive and therapeutic potential of plant-derived substances by inhibiting the early stages of carcinogenesis or improving the efficacy of traditional chemotherapeutic agents. Moreover, a number of epidemiological studies have investigated associations between a plant-based diet and cancer risk. This literature review summarizes the current knowledge on the phytochemicals with proven antitumor activity, emphasizing their effectiveness and mechanism of action in gynecological cancer.

In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment.

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose-methotrexate conjugate (GLU-MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter-1 (GLUT1). GLU-MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU-MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU-MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU-MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.

The Effect of a New Glucose-Methotrexate Conjugate on Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma Cell Lines.

Patients with hematologic malignancies require intensive therapies, including high-dose chemotherapy. Antimetabolite-methotrexate (MTX) has been used for many years in the treatment of leukemia and in lymphoma patients. However, the lack of MTX specificity causes a significant risk of morbidity, mortality, and severe side effects that impairs the quality of patients' life. Therefore, novel targeted therapies based on the malignant cells' common traits have become an essential treatment strategy. Glucose transporters have been found to be overexpressed in neoplastic cells, including hematologic malignancies. In this study, we biologically evaluated a novel glucose-methotrexate conjugate (Glu-MTX) in comparison to a free MTX. The research aimed to assess the effectiveness of Glu-MTX on chosen human lymphoma and leukemia cell lines. Cell cytotoxicity was verified by MTT viability test and flow cytometry. Moreover, the cell cycle and cellular uptake of Glu-MTX were evaluated. Our study reveals that conjugation of methotrexate with glucose significantly increases drug uptake and results in similar cytotoxicity of the synthesized compound. Although the finding has been confined to in vitro studies, our observations shed light on a potential therapeutic approach that increases the selectivity of chemotherapeutics and can improve leukemia and lymphoma patients' outcomes.

Glycoconjugation as a Promising Treatment Strategy for Psoriasis.

Despite the progress in the development of novel treatment modalities, a significant portion of patients with psoriasis remains undertreated relative to the severity of their disease. Recent evidence points to targeting the glucose transporter 1 and sugar metabolism as a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases. In this review, we discuss glycoconjugation, an approach that facilitates the pharmacokinetics of cytotoxic molecules and ensures their preferential influx through glucose transporters. We propose pathways of glycoconjugate synthesis to increase effectiveness, cellular selectivity, and tolerability of widely used antipsoriatic drugs. The presented approach exploiting the heightened glucose requirement of proliferating keratinocytes bears the potential to revolutionize the management of psoriasis. SIGNIFICANCE STATEMENT: Recent findings concerning the fundamental role of enhanced glucose metabolism and glucose transporter 1 overexpression in the pathogenesis of psoriasis brought to light approaches that proved successful in cancer treatment. Substantial advances in the emerging field of glycoconjugation highlight the rationale for the development of glucose-conjugated antipsoriatic drugs to increase their effectiveness, cellular selectivity, and tolerability. The presented approach offers a novel therapeutic strategy for the treatment of psoriasis and other hyperproliferative skin diseases.

Clinical validation of nuclear factor kappa B expression in invasive breast cancer.

Breast cancer is the most commonly diagnosed cancer in Polish women. The expression of transcription nuclear factor kappa B, a key inducer of inflammatory response promoting carcinogenesis and cancer progression in breast cancer, is not well-established. We assessed the nuclear factor kappa B expression in a total of 119 invasive breast carcinomas and 25 healthy control samples and correlated this expression pattern with several clinical and pathologic parameters including histologic type and grade, tumor size, lymph node status, estrogen receptor status, and progesterone receptor status. The data used for the analysis were derived from medical records. An immunohistochemical analysis of nuclear factor kappa B, estrogen receptor, and progesterone receptor was carried out and evaluation of stainings was performed. The expression of nuclear factor kappa B was significantly higher than that in the corresponding healthy control samples. No statistical difference was demonstrated in nuclear factor kappa B expression in relation to age, menopausal status, lymph node status, tumor size and location, grade and histologic type of tumor, and hormonal status (estrogen receptor and progesterone receptor). Nuclear factor kappa B is significantly overexpressed in invasive breast cancer tissues. Although nuclear factor kappa B status does not correlate with clinicopathological findings, it might provide important additional information on prognosis and become a promising object for targeted therapy.

Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide.

The study was designed to evaluate the potential use of insulin for cancer-specific treatment. Insulin-induced sensitivity of MCF-7 breast cancer cells to chemotherapeutic agents 5-fluorouracil and cyclophosphamide was evaluated. To investigate and establish the possible mechanisms of this phenomenon, we assessed cell proliferation, induction of apoptosis, activation of apoptotic and autophagic pathways, expression of glucose transporters 1 and 3, formation of reactive oxygen species, and wound-healing assay. Additionally, we reviewed the literature regarding theuse of insulin in cancer-specific treatment. We found that insulin increases the cytotoxic effect of 5-fluorouracil and cyclophosphamide in vitro up to two-fold. The effect was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and overexpression of glucose transporters 1 and 3 as well as inhibition of cell proliferation and motility. We propose a model for insulin-induced sensitization process. Insulin acts as a sensitizer of cancer cells to cytotoxic therapy through various mechanisms opening a possibility for metronomic insulin-based treatments.

Osteopontin splice variants are differential predictors of breast cancer treatment responses.

BACKGROUND: Osteopontin is a marker for breast cancer progression, which in previous studies has also been associated with resistance to certain anti-cancer therapies. It is not known which splice variants may mediate treatment resistance. METHODS: Here we analyze the association of osteopontin variant expression before treatment, differentiated according to immunohistochemistry with antibodies to exon 4 and to the osteopontin-c splice junction respectively, with the ensuing therapy responses in 119 Polish breast cancer patients who presented between 1995 and 2008. RESULTS: We found from Cox hazard models, logrank test and Wilcoxon test that osteopontin exon 4 was associated with a favorable response to tamoxifen, but a poor response to chemotherapy with CMF (cyclophosphamide, methotrexate, fluorouracil). Osteopontin-c is prognostic, but falls short of being a significant predictor for sensitivity to treatment. CONCLUSIONS: The addition of osteopontin splice variant immunohistochemistry to standard pathology work-ups has the potential to aid decision making in breast cancer treatment.

The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors.

Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential.

Optimizing Outcomes in Mismatched Unrelated Donor Allogeneic Transplantation: Post-Transplant Cyclophosphamide's Dual Impact on Graft versus Host Disease Incidence and Overall Survival: Retrospective Analysis on Behalf of Polish Adult Leukemia Group.

Allogeneic hematopoietic cell transplantation (allo-HSCT) stands as an effective treatment method for various hematologic malignancies. However, graft-versus-host disease (GvHD), an intricate immunological phenomenon where donor immune cells target recipient tissues, remains a significant challenge, particularly in mismatched unrelated donors (MMUD). Post-transplant cyclophosphamide (PTCy) has emerged as a promising immunosuppressive strategy, revolutionizing haploidentical transplantation and demonstrating promise in MMUD settings. Background/Objectives: This study aimed to evaluate the impact of PTCy on MMUD allo-HSCT outcomes, specifically its effects on GvHD incidence and overall survival, compared to anthitymocyte globulin (ATG). Methods: One hundred seventy-four patients were classified into three groups based on the type of transplantation: PTCy-haplo (114/174; 65.5%), PTCy-MMUD (23/174; 13.2%), and ATG-MMUD (37/174; 21.2%). Results: Our findings showed that PTCy-MMUD significantly reduced acute GvHD occurrence compared to PTCy-haplo and ATG-MMUD approaches (p = 0.006). The delayed onset of acute GvHD in the PTCy-MMUD group suggests a more controlled immune reconstitution, contributing to the lower incidence. Importantly, PTCy-MMUD exhibited enhanced five-year overall survival rates, aligning with the notion that reduced GvHD correlates with improved patient outcomes (p = 0.032). Conclusions: We believe that this study contributes valuable insights into PTCy-MMUD's management, underscoring its potential to significantly reduce GvHD incidence and enhance survival outcomes. Although further investigations and clinical trials are warranted, this research underscores the promising role of PTCy-based GvHD prophylaxis in improving MMUD allo-HCT success.

Evaluation of AI-Driven LabTest Checker for Diagnostic Accuracy and Safety: Prospective Cohort Study.

Background: In recent years, the implementation of artificial intelligence (AI) in health care is progressively transforming medical fields, with the use of clinical decision support systems (CDSSs) as a notable application. Laboratory tests are vital for accurate diagnoses, but their increasing reliance presents challenges. The need for effective strategies for managing laboratory test interpretation is evident from the millions of monthly searches on test results' significance. As the potential role of CDSSs in laboratory diagnostics gains significance, however, more research is needed to explore this area. Objective: The primary objective of our study was to assess the accuracy and safety of LabTest Checker (LTC), a CDSS designed to support medical diagnoses by analyzing both laboratory test results and patients' medical histories. Methods: This cohort study embraced a prospective data collection approach. A total of 101 patients aged ≥18 years, in stable condition, and requiring comprehensive diagnosis were enrolled. A panel of blood laboratory tests was conducted for each participant. Participants used LTC for test result interpretation. The accuracy and safety of the tool were assessed by comparing AI-generated suggestions to experienced doctor (consultant) recommendations, which are considered the gold standard. Results: The system achieved a 74.3% accuracy and 100% sensitivity for emergency safety and 92.3% sensitivity for urgent cases. It potentially reduced unnecessary medical visits by 41.6% (42/101) and achieved an 82.9% accuracy in identifying underlying pathologies. Conclusions: This study underscores the transformative potential of AI-based CDSSs in laboratory diagnostics, contributing to enhanced patient care, efficient health care systems, and improved medical outcomes. LTC's performance evaluation highlights the advancements in AI's role in laboratory medicine.

Application and efficacy of transcutaneous electrical acupoint stimulation (TEAS) in clinical practice: A systematic review.

Transcutaneous electrical acupoint stimulation (TEAS) is an emerging therapeutic approach that combines the effects of transcutaneous electrical nerve stimulation (TENS) with acupuncture point stimulation. Due to its noninvasive nature, it possesses relative advantages over traditional acupuncture and needle-based electrostimulation. Despite the large number of randomized clinical trials (RCTs) describing the effectiveness of TEAS in different applications, its role and mechanism are still not fully understood. The aim of this study was to systematically compare and summarize the latest studies examining a variety of TEAS applications in clinical practice. Databases, including Medline (PubMed), Cochrane Library and Google Scholar were searched without any time restrictions (as of March 2021). The analysis was performed according to the Cochrane Collaboration criteria. Out of 637 studies, only 22 RCTs were selected. Nine studies evaluated the impact of TEAS on nausea and vomiting (NV), showing beneficial effects compared to standard therapy. Eight RCTs examined the effectiveness of TEAS in pain management, reporting pain alleviation described using the visual analog scale (VAS) and lowering of total opioid doses. Improvement of postoperative recovery, in vitro fertilization and pregnancy outcomes, as well as display of cardioprotective properties were found to positively correlate with TEAS. As a noninvasive modality with advantages over classical acupuncture and needle-based electrostimulation, TEAS may be a valuable tool in clinical practice, particularly for pain and NV management. However, considering the methodological quality of the RCTs, rigorous large-scale clinical trials are required to evaluate the clinical utility of this method.

Identification of Factors Affecting the Increased Percentage of CGA Recommendations among Patients on Geriatric Ward.

In Poland, the elderly population is noticeably increasing every year. Therefore, the current healthcare system has to rise to the challenge of treatment and prevention strategies targeting elderly persons. Based on the Vulnerable Elders Survey (VES-13 scale), consisting of international and validated scales, we put effort into identifying the factors affecting the increased percentage of CGA (Comprehensive Geriatric Assessment) recommendations by healthcare system physicians. The study group involved 78 patients from the Department of Geriatrics, Wroclaw Medical University, Poland, aged 60-91 (median Me = 81 years old). Of the studied patients, 51 were recommended for CGA (51/78; 64.6%). A statistically significant association was observed between CGA recommendation and age (p < 0.001); the likelihood of a CGA recommendation increased with age. Furthermore, the increased CGA recommendation was observed among geriatric patients with: (a) frailty syndrome (OR = 11.2, CI95% 2.88-43.5, p < 0.001), (b) high risk of malnutrition or malnutrition (OR = 3.87; CI95%, 1.00-14.9, p = 0.04), (c) low mental status (OR = 3.32, CI95% 1.22-9.09, p = 0.029), (d) low ability to perform basic daily duties (according to ADL scale-OR = 12.6, CI95% 1.57-101, p = 0.004 and IADL scale-OR = 4.71, CI95% 1.72-12.9, p = 0.003), and (e) fall risk (OR = 15.0, CI95% 4.67-48.3, p < 0.001). Moreover, homocysteine levels increased with age (p = 0.003) and decreased with sleep duration (p = 0.043). Taken together, all these factors seem to be important when implementing treatment programs adjusted to the individual geriatric patient.

Evaluation of the Approach towards Vaccination against COVID-19 among the Polish Population-In Relation to Sociodemographic Factors and Physical and Mental Health.

Due to the rapid development of COVID-19 vaccines, the world has faced a huge challenge with their general acceptance, including Poland. For this reason, we attempted to determine the sociodemographic factors influencing the decision of positive or negative attitudes toward COVID-19 vaccination. The analysis included 200,000 Polish participants-80,831 women (40.4%) and 119,169 men (59.6%). The results revealed that the most common reasons for vaccine refusal and hesitancy were the fear of post-vaccination complications and their safety (11,913/31,338, 38.0%; 9966/31,338, 31.8%). Negative attitudes were observed more often among male respondents with primary or secondary education (OR = 2.01, CI95% [1.86-2.17] and OR = 1.52, CI95% [1.41-1.63], respectively). On the other hand, older age ≥ 65 (OR = 3.69; 95%CI [3.44-3.96]), higher education level (OR = 2.14; 95%CI [2.07-2.22]), living in big cities with a range of 200,000-499,999 inhabitants and more than 500,000 inhabitants (OR = 1.57, CI95% [1.50-1.64] and OR = 1.90, CI95% [1.83-1.98], respectively), good physical conditions (OR = 2.05; CI95% [1.82-2.31]), and at last normal mental health conditions (OR = 1.67, CI95% [1.51-1.85]) were significantly associated with COVID-19 vaccine acceptance. Our study indicates which population group should be further supplied with data and information by health education, the government, and healthcare professionals to alleviate the negative attitude toward COVID-19 vaccines.

The Impact of Different Types of Diet on the Prevention of Diseases among Polish Inhabitants, Including COVID-19 Disease.

Proper nutrition may help in preventing deaths or at least alleviating the symptoms of many chronic diseases. While the COVID-19 disease was still taking its toll, the world had to adjust to new life conditions, which could change nutritional habits. In this observational, cross-sectional study, we aimed to identify the potential correlations between sociodemographic factors and diet and the presence of common chronic diseases among Polish inhabitants. Furthermore, we tried to determine whether the COVID-19 pandemic led to changes in nutritional habits. Therefore, based on the online study (the National Test for Poles' Health (NTPH), we collected data from 376,102 and 200,000 respondents in two different time frames (before the COVID-19 pandemic: 2019-2020 and during the COVID-19 pandemic: 2021-2022, respectively). Despite the rapid global rise of the COVID-19 pandemic, among our study group, hypertension was still the most commonly occurring disease in both time frames (32.33% in 2019-2020 and 34.95% in 2021-2022, p < 0.001). Furthermore, more chronic diseases were reported during the COVID-19 pandemic than in 2019-2020. Regarding sociodemographic factors, male respondents were more likely to develop hypertension and diabetes (OR = 1.35 CI 95% (1.28-1.43), p < 0.001; and OR = 1.20 CI 95% (1.11-1.30), p < 0.001). Vegetarian diet decreases the likelihood of hypertension, neurological disease, and diabetes (OR = 0.69, CI 95% (0.60-0.81), p < 0.001; OR = 0.72, CI 95% (0.59-0.88), p = 0.001; and OR = 0.73, CI 95% (0.55-0.96), p = 0.026). In line with this, consuming meat meals increases the risk of hypertension (OR = 1.09, CI 95% (1.02-1.17), p = 0.009). Interestingly, a reduced-sodium diet has an association with decreased morbidity of COVID-19 disease (OR = 0.72, CI 95% (0.63-0.82), p < 0.001). This result brings new light to more research to be done to allow efficient prevention of this disease. In conclusion, our study shows the beneficial role of a balanced diet in reducing the incidence rate of common chronic diseases. Our findings may be educational for those who would like to change their nutritional habits and/or for public health professionals to suggest the implementation of proper diets to their patients.

Identification of Barriers Limiting the Use of Preventive Vaccinations against Influenza among the Elderly Population: A Cross-Sectional Analysis.

Older adults are at a high risk of experiencing severe complications of influenza. Receiving a vaccination is a beneficial strategy to prevent the disease and reduce the severity of influenza illnesses. This cross-sectional questionnaire-based study aimed to evaluate the influence of sociodemographic, clinical, and mental parameters as well as other potential risk factors on refusal to vaccinate against influenza among the elderly population in Poland. Furthermore, due to the prevailing COVID-19 pandemic, we put efforts into finding any statistical correlations between the fear of COVID-19 infection in patients and their attitudes toward receiving an influenza vaccination. The study was conducted in November−December 2020 in Poland on a representative nationwide sample of 500 individuals aged > 60. Of the respondents, 62 (12.4%) and 51 (10.2%) underwent influenza vaccination in 2019 and 2020, respectively. Out of ten different factors analyzed in this study, three were significantly associated with attitudes towards influenza vaccination. Participants with net income below the national average of PLN 3000 (OR = 2.37, CI 95% [1.26−4.47]), compared to those earning more than PLN 3000, had significantly higher odds of having a negative attitude towards influenza vaccination. Furthermore, respondents with <174 cm height (OR = 2.56, CI 95% [1.51−4.33]) and those with strong fear of COVID-19 infection (OR = 1.65, CI95% [1.02−2.66]) were also more likely to refrain from influenza vaccination. We believe the identification of factors limiting the willingness to receive influenza vaccination is an effective way to help clinicians focus their efforts on educating the groups of patients with the highest odds of refusing to receive the vaccine. Moreover, it may aid the design and enforcement of national solutions or the implementation of novel legislative measures and preventive programs, increasing public confidence and promoting vaccination, especially among groups at high risk of developing this disease.

Sociodemographic and Health-Related Factors Influencing Drug Intake among the Elderly Population.

Excessive drugs intake among the elderly population, including self-medication, constitutes an important public health problem. Polypharmacy may lead to numerous adverse health effects, which become more prevalent when combined with biological changes in seniors. In this cross-sectional study, 500 Polish adults aged ≥60 years (M = 67.9 ± 4.2) were asked to complete a questionnaire via telephone calls, allowing us to identify sociodemographic and health-related factors influencing the daily medications consumption. Our findings revealed that all of the participants were receiving medications; 60.2% of them receive at least 1 to 3 drugs per day (301/500). The most commonly used medications included antihypertensive drugs and analgesics (51.0% and 46.0%, respectively). Taking into account clinical conditions, independent predictors of receiving over 3 medications per day turned out to be (1) coronary artery disease (OR = 6.77; CI 95%, 2.86-16.1), (2) diabetes (OR = 3.23, CI 95%, 1.75-5.95), (3) asthma (OR = 4.87, CI 95%, 2.13-11.1), (4) heart failure (OR = 3.38, CI 95%, 1.59-7.19) and (5) gastroesophageal reflux disease (OR = 1.93, CI 95%, 1.03-3.62). Participants suffering from depression were more likely to take drugs for hypertension (OR = 1.70, CI 95%, 1.04-2.78), while those with anxiety and social loneliness took more painkillers (OR = 2.59, CI 95%, 1.58-4.26 and OR = 2.08, CI 95%, 1.38-3.13, respectively). The most significant sociodemographic factors increasing the drugs intake among the population included in our study were high body mass and subsequent increased BMI values (OR = 2.68, CI 95%, 1.50-4.77). Furthermore, living in a city with over 400,000 inhabitants increased the likelihood of taking antidepressants (OR = 2.18, CI 95%, 1.20-3.94). Our study revealed factors increasing the risk of excessive medications intake and hence, increased susceptibility to some iatrogenic diseases among the elderly population. These factors should be considered by primary care physicians while prescribing appropriate drugs to elderly patients.

Correction: Agrawal et al. The Assessment of Fear of COVID-19 among the Elderly Population: A Cross-Sectional Study. J. Clin. Med. 2021, 10, 5537.

In the original publication [...].

Transcutaneous electrical acupoint stimulation to reduce opioid consumption in patients undergoing inguinal hernia repair: protocol for a randomized controlled trial.

BACKGROUND: The purpose of this study is to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) in the postoperative treatment of patients undergoing inguinal hernia repair compared with sham and no treatment group. METHODS: This study is a protocol for a three-armed, single-blinded, placebo-controlled randomized controlled trial. Ninety participants scheduled for inguinal hernia repair will be randomly assigned to the TEAS group (n = 30), sham group (n = 30), and control group (n = 30). The TEAS group will receive treatment using four portable coin-sized electro-stimulators at both local and distal acupuncture points. The sham group will receive sham treatment with mock electrostimulation. The treatment groups will receive mixed frequency stimulation (alternating at 2 and 100 Hz every 3 s) in continuous mode for 30 min at intervals of 2 h for 24 h postoperatively. The control group will receive postoperative pain control using patient-controlled analgesia (PCA) device. The primary outcome is the total morphine dose received in the postoperative period (mg) using PCA 24 h after surgery. The number of PCA demands (i.e., times the button will be pressed) and delivered bolus doses, score on the Visual Analogue Scale, opioid-related side effects, the requirement for supplemental medications, score on the Hospital Anxiety and Depression Scale (HADS), and blood levels of stress hormones cortisol and prolactin. DISCUSSION: The results of this trial will determine whether TEAS with intensified stimulation protocol is a safe and effective option for reducing analgesic consumption and postoperative pain. TRIAL REGISTRATION: ISRCTN76428396. Registered on 05 October 2020. https://www.isrctn.com/ISRCTN76428396.