Archives of Clinical and Biomedical Research

Commercially available disposable products such as cell culture utensils and catheters do not necessarily possess sufficient quality for in vitro fertilization (IVF), from the perspective of pyrogen contamination. We aimed to comprehensively analyze the pyrogen contamination status, including bacterial endotoxins, of the products used for IVF in assisted reproductive technology (ART) and improve their cleanliness using a new sterilization technology. Pyrogen contamination levels were evaluated using a direct human cell-based pyrogen test that is not affected by the recovery ratio, unlike bacterial endotoxin tests. Pyrogen inactivation tests were performed using low-temperature ozone/hydrogen peroxide gas treatment. The residual hydrogen peroxide was colorimetrically quantified, and the effectiveness of its removal by drying treatment was evaluated using germ cell viability as an indicator. Significant amounts of pyrogen, from 0.014 to 1.110 EU/product, were detected in seven of the twenty products. Pyrogen contamination levels were reduced below the detection limit by ozone/hydrogen peroxide gas sterilization. Hydrogen peroxide remained on the surface of the GPS dish but was reduced to a level that did not affect human sperm viability and embryo development after drying at 80{degrees}C for 24 h following sterilization. These products may carry a potential risk of reducing ART success rates, and pyrogen contamination levels may exceed the previously reported allowable level of 0.01-0.02 EU/mL in human IVF during actual use. Our study suggests that the manufacturing of products free from pyrogens and without adverse effects on germ cells is possible using ozone/hydrogen peroxide gas sterilization and subsequent drying technologies.

IntroductionPrescribing naloxone is recommended by the Centers for Disease Control and Prevention to reduce the risk of death from an opioid overdose. Naloxone is rarely prescribed, even when indicated; improving our understanding of how primary care providers (PCP) perceive their role in naloxone prescribing is essential to increase opioid medication safety. The objectives of this study were to: (1) describe how PCPs perceive their role in prescribing naloxone for patients who are at high risk of an overdose and (2) describe PCP-reported barriers and facilitators of naloxone prescribing. MethodsCurrently practicing providers completed semi-structured interviews, based on Theory of Planned Behavior, to understand their attitudes toward naloxone, their perceived role in naloxone prescribing, and facilitators/barriers to prescribing naloxone. ResultsEleven interviews were conducted with physicians (n=2), physician assistants (n=8), and a nurse practitioner (n=1). Providers held generally positive attitudes toward naloxone as a rescue medication. Negative attitudes toward naloxone include the perception of facilitating risky opioid use. Providers suggested that whomever prescribes the opioid pain medication should be primarily responsible for prescribing naloxone. Providers noted that stigma may prevent them from discussing naloxone during clinic visits. Increasing visit time and receiving support/education from organizational and professional society leadership were identified as important facilitators of naloxone prescribing. ConclusionsWhile providers were aware of what naloxone was used for, there was reticence in discussing this medication with patients. Providers reported that whomever prescribes a pain medication should be primarily responsible for ensuring medication safety. If primary care organizations would like to improve opioid medication safety, ensuring that providers feel supported and receive needed education are essential.

The use of combination therapies*, as well as FDA-approved drugs for off-label indications, to treat advanced cancer, is widespread. While much is known about their clinical effectiveness, there exists no examination of the relative cost of novel multidrug combinations vs. traditional available therapy options, or study as to how knowledge about comparative therapy costs at the point-of-care can be leveraged by doctors, health systems, and payers. We found that: O_LIcombination multidrug cancer regimens may be less costly than monotherapies or other standard options; C_LIO_LInovel, multidrug combinations are often better financial values than monotherapies or other standard options; C_LIO_LIhaving treatment cost and value data, at the point of care, enables the prompt selection of more cost-effective medications and the avoidance of expensive low-value therapies that are financially wasteful. C_LI We conclude that the effectiveness of value-based purchasing initiatives may be amplified if physicians and payers use comparative treatment cost/value data to enhance their cancer drug-selection decision making. * Including combinations of immunotherapies, chemotherapies, targeted drugs with distinct mechanisms of action, etc. SO_SCPLOWTUDYC_SCPLOW HO_SCPLOWIGHLIGHTSC_SCPLOWWhat Is The Current Knowledge On The Topic? {ballotcheck}The effectiveness of molecularly targeted multidrug therapies used to treat advanced cancer is well established; 1-4 that few clinicians are aware of the cost of the medications they prescribe, or which are more cost-effective, deliver a better return-on-investment or represent a financial value; 8 and, that it is intuitive to believe that a combination of multiple high-cost medications is more expensive than a single-drug or other standard therapy options. What Question Did This Study Address? {ballotcheck}Although studies on the clinical impact of multidrug cancer treatments abound, 1-4 there are no examinations of the relative cost or value of combination therapies vs. that of traditional monotherapies, or how knowledge of how this data can be used in practice. A systematic method to calculate, evaluate and compare the relative cost of mono-therapies, 2- and 3-drug combination cancer therapy options is presented for use by physicians, health systems and payers to better manage their oncology specialty pharmacy spend and drive better medical outcomes. 3 What Does This Study Add To Our Knowledge? {ballotcheck}We show that multidrug cancer therapies are not necessarily more costly than single-drug or other standard therapy options; and that furnishing physicians and payers with comparative treatment cost and value data to augment their complex medication selection decision making enables them to identify drugs that are a value, avoid those that are wasteful, and create better targeted novel combination cancer therapies that represent a value, which incorporates both clinical and financial aspects. How Might This Change Combination Therapy Drug Selection Or Value-Based Oncology Management? {ballotcheck}Clinicians have the tools, information, and data with which to confidently prescribe novel drug combinations that customize molecular targeting, and lower treatment costs. Payers now have a framework within which to drive value-based purchasing to gain control of their oncology specialty drug risk. Patients will benefit from more personalized, efficient and effective therapies and less financial toxicity (i.e., distress).

IntroductionPhysiological oocyte activation requires a synergy between the oocyte and sperm to release calcium (Ca2+) through oscillations. The absence of such synergy between the oocyte and sperm leads to a negative impact on oocyte activation. Studies have shown that Artificial oocyte activation (AOA) is helpful in cases with failed or low fertilization rates. Studies present mixed opinions about increasing blastocyst rate. MethodsA retrospective cohort single-center study was performed between January 2018 and October 2023, including 54 couples with suboptimal blastocyst development. The study compared intracytoplasmic sperm injection (ICSI) AOA cycles with previous conventional ICSI cycles and conventional ICSI without AOA cycles with previous conventional ICSI cycles in couples with failed or low blastocyst rates (< 30%) in the original ICSI cycle. ResultsWe compared 22 AOA cycles to previous conventional ICSI cycles in the same patients and 32 conventional ICSI cycles without AOA to previous conventional ICSI cycles in the same patients. After AOA, the blastocyst rate was not significantly higher than the control group (48% vs 29% p=0.19). Conversely, the blastocyst rate was significantly higher in the conventional ICSI without AOA cycles than in the control group (48% vs 24% p=0.04). The fertilization rate was not statistically significant between the first and second cycles in both groups. ConclusionThe literature still lacks strong evidence for AOA overcoming impaired embryonic development. Therefore, AOA remains reserved for couples with a failed or low fertilization history to improve fertilization results. Optimal laboratory conditions and ovarian stimulation modifications without AOA may improve blastocyst rates.

Vertebral compression fractures secondary to osteoporosis can be treated with vertebral augmentation. Since intraprocedural pain is common during vertebral body endplate manipulation, these procedures are often carried out using conscious sedation or general anesthesia. Research has shown that the vertebral endplates are innervated by the basivertebral nerve, which has been successfully targeted via radiofrequency ablation to treat chronic vertebrogenic lower back pain. With this physiology in mind, we treated ten patients with vertebral compression using intraosseous basivertebral nerve block as the primary intraprocedural analgesia. In this case series, we describe our successful experience with this novel approach.

This study investigates the impact of progesterone resistance on endometrial receptivity and evaluates the efficacy of pituitary downregulation combined with hormone replacement therapy (HRT) in improving pregnancy outcomes following frozen embryo transfer (FET). A retrospective analysis was conducted on 147 patients with recurrent implantation failure (RIF) who underwent secretory-phase endometrial biopsy and subsequent FET treatments at the Reproductive Center of the First Affiliated Hospital of Guangxi Medical University between April 2019 and May 2022. Based on biopsy results and endometrial preparations, patients were categorized into four groups: secretory phase + non-downregulated protocol group (n=29), secretory phase + GnRH-a + HRT Protocol group (n=20), proliferative phase + non-downregulated protocol group (n=59), proliferative Phase + GnRH-a + HRT Protocol group (n=39). Endometrial preparation regimens and pregnancy outcomes during the first FET cycle after biopsy were compared. The results showed that there was no statistical difference in the outcome of assisted pregnancy between the different endometrial preparation protocols in the four groups. These findings suggest that the prioritization of down-regulation protocols may not be essential for FET in patients with RIF, even when endometrial biopsy during the implantation window reveals proliferative-phase characteristics.

The selection of competent human sperm influences the successful outcome of Assisted Reproductive Technology. Conventionally used techniques like density gradient and swim-up, use motility-based separation, which may not correlate with the maturity and quality of the sperm. Existing techniques that select mature sperm based on hyaluronic acid binding ability, select very small numbers of sperm, rendering them unsuitable for intra-uterine insemination. We report the development of a new method, USelect that selects and isolates millions of mature sperms based on their ability to bind to hyaluronic acid. Validation of Uselect was done on semen samples (n=40) compared with the conventional methods, like density gradient, and swim up. Subsequently, Uselect selected sperms were used for intra-uterine insemination in a clinical trial (n=50 female patients). Sperm isolated using USelect showed similar mean sperm count and rapid progressive motility compared to SU, but lower than the density gradient method. However, the DNA fragmentation index and hyaluronic acid binding capacity were statistically significant in the USelect sperms that promoted the fertilization rate and showed a higher percentage of biochemical pregnancy (32%, n=16) than density gradient (18%, n=9).

BACKGROUNDSotalol loading intravenously enables achieving blood levels of sotalol that are observed at maximal steady-state concentration (Cmax ss) in one-day permitting the measurement of maximum QTc effects. Rapid evaluation of the QTc effects permits determination of arrhythmic risk and thus permits discharge in 24-hours instead of the usual three-day oral load hospitalization. Given the expense of IV Sotalol an oral loading test strategy is presented that also achieves Cmax ss blood levels rapidly, permitting a one-day hospitalization for QTc evaluation. METHODPharmacokinetic parameters referred to in the literature derived from normals as well as patients was utilized for population pharmacokinetic modeling and simulation.to obtain the Cmax ss concentrations for patients with normal renal function, creatinine clearance (CrCl) > 90 ml/min), as well as for patients with a CrCl of 60-89, 30-59, and 10-29 ml/min). Using pharmacokinetic simulations, an oral loading dose, as well as a second oral dose were determined that would reach the estimated Cmax ss in each of the groups based on renal function. RESULTSFor target dosing of 120 mg oral sotalol BID in patients with a CrCl >90 ml/min an oral loading dose of 200 mg provides a peak sotalol level of 1,420 ng/ml in 3-4 hours post dosing. The Cmax ss target is 1,299 ng/ml resulting in a 9% overshoot. The Cmax ss concentration provides a means of evaluating QTc effects within 24-hours. Oral loading regimens are described for varying additional renal function levels (CrCl 60-90, 30-59 and 10-29 ml/min) along with the time to first oral dose and follow-up dosing. The initial test dose can be based on an 80 or 120 mg oral sotalol maintenance dosing strategy. CONCLUSIONSEmploying an oral loading strategy may permit QTc evaluation and one-day discharge, preserving the pharmacoeconomic advantage of a Cmax ss test strategy. Clinical PerspectiveO_ST_ABSWhat is Known?C_ST_ABSO_LIIntravenously loading of sotalol enables achieving blood levels that are observed at maximal steady-state concentration (Cmax ss) in one-day permitting the measurement of maximum QTc effects. C_LIO_LIRapid evaluation of the QTc effects permits determination of arrhythmic risk and thus permits discharge in 24-hours instead of the usual three-day oral load hospitalization C_LI What the Study AddsO_LIWith oral sotalol loading, the Cmax ss can also be achieved in one-day permitting the measurement of maximum QTc effects and discharge from the hospital in 24-hours instead of the usual three-day inpatient initiation of oral sotalol. C_LI

BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus responsible for the ongoing Covid-19 pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine(HCQ) could prevent SARS CoV-2 in healthcare workers(HCW) at high-risk of exposure. MethodThis voluntary observational study for the prevention and treatment of COVID-19 was conducted at a tertiary care center, from 12th June to 12th October 2020(total 16 weeks). All consented asymptomatic HCWs of CIMS hospital were administered 400 mg HCQ twice a day on day one followed by 400 mg once weekly to be taken with meals up to 16 weeks. Data collected included OPD registration, risk assessment, medical and family history (related to COVID), physical examination and vitals, pulse oximetry, ECG (pre and post HCQ), drug adherence, side effects, adverse drug reactions. ResultThe study enrolled 927 full-time, hospital-based HCWs ((including doctors, nurses, paramedical, lab technicians, sanitary workers and others), of whom 731(78.85%) initially started HCQ while 196 (21.14%) did not volunteer. The median age and weight of the study population was 27.5 years and 69.5 kg respectively. No major associated co-morbidities were present in these HCWs. There was an increased trend towards non adherence to HCQ with each proceeding week more so after week 11. Of the 731 HCWs taking HCQ a total of 167(22.8%) tested COVID positive at different intervals of time as against 30 HCW (15.3%) out of 196 not taking HCQ. The rate of COVID-19 positive was statistically significantly higher in the HCWs taking HCQ (p=0.0220; 95% CI: 1.14% to 12.94%), as compared to those not on HCQ. Thus HCQ was not prophylactically effective against COVID 19 infection. No participants in this study experienced grade 3 or 4 adverse events. No significant difference in the median of ECG changes in QTc between pre and post HCQ administration of 46 HCWs was observed. ConclusionsThis clinical study did not detect a reduction in SARS CoV-2 transmission with prophylactic administration of 400 mg/HCQ in HCWs. All participants who did contract SARSCoV-2 were either asymptomatic or had mild disease courses with full recoveries. All adverse events were self-limiting and no serious cardiovascular events were reported with use of HCQ. In the absence of robust data, it seems premature to recommend HCQ as a prophylactic panacea for COVID-19.

BackgroundFor the acquisition of intraoperative fluoroscopic images, standard projections have to be manually adjusted. This process resembles a trial-and-error process and is therefore time-consuming and leads to increased radiation exposure for both patient and staff. In addition, the standard projections adjusted are subject to intra- and interindividual variance. However, to date, only very limited data exist in the literature quantifying the time and radiation exposure caused by the process of manually setting standard projections as well as the intra- and interindividual variance for the manual adjustment of standard projections. Material and MethodsA.p. and lateral standard projections of the vertebral bodies of two fresh-frozen specimen were manually adjusted by two examiners with a different level of experience using a mobile C-arm. The time needed for manual adjustment as well as the number of X-ray shots acquired and the radiation dose caused during this process were documented. Intra- and interindividual variance of the central beam, the orbital rotation and angulation of the C-arm was analyzed. ResultsThe median time needed was 75.9s, with no significant difference between the examiners (p=0.13). 7.1 x-ray images were acquired in average to reach subjective satisfaction with the standard projection with significantly more x-ray shots for the lateral standard (p=0.04) and for the examiner with less experience (p<0.001). Accordingly, the dose caused was more than 50% higher than for the experienced examiner (p=0.01). Mean interindividual variance of the central beam was 7.6{degrees} while the intraindividual variance was 4.2{degrees}. ConclusionIn summary, this study investigated the interrater and intrarater variance for standard manual level setting in the thoracic and lumbar spine. Additionally, we were able to quantify the time and number of radiographs required for this procedure for different levels of experience, as well as the resulting radiation dose.

BackgroundPrecise prediction of residual tumour size following neoadjuvant systemic therapy for breast cancer is crucial in assessing response and surgical decision making. Our study is aimed at assessing the performance of conventional imaging modalities like ultrasound and mammography in predicting the residual tumour size after neoadjuvant systemic therapy and in evaluating the impact of imaging on the surgical outcomes. MethodsWe retrospectively compared the tumour size measured by ultrasonography and mammography and the residual tumour size on final histopathology in 109 patients. Concordance was defined as a size difference within 25% of the histopathology size. We also looked at the distribution of concordance between different T status and molecular subtypes, accuracy of USG in predicting pathological complete response and axillary lymph nodal metastasis and also surgical outcomes in the discordant cases. ResultsThe concordance rates of mammography and ultrasonography were 68.2% and 52.3% respectively without statistically significant difference between the two modalities (p = 0.081). Combination of both the modalities had a concordance rate of 57.8%. Ultrasonography had accuracy of 81.7% for predicting pathological complete response and 79.8% for predicting axillary nodal metastasis. We did not identify any influence of histologic subtype on the associations between preoperative measurements and pathology size or the accuracy for detecting pathological complete response (p values 0.43 and 0.46 respectively). In 12 cases, the radiology-pathology discordance could have led to large excision volume surgeries. In the overall cohort, recurrence free survival and overall survival rates at median follow up of 19.1 month were 87.2% and 95.4% respectively. ConclusionsUltrasound and mammography showed moderate concordance with pathology for estimation of the residual tumour size without any significant difference in the performance between the two. Despite the moderate concordance, surgical outcomes were fairly well managed in the discordant cases with the oncoplastic surgical techniques. Our study highlights the usefulness of the cheaper and widely available conventional imaging modalities in the developing countries where the cost of treatment is to be contained.

The newly proposed method of processing cell suspensions for spermatozoa recovery is based on differential centrifugation and allows obtaining male germ cells from biopsy samples and using them for fertilization, especially if they are critically low in number and conventional methods for sperm recovery do no work or are inefficient.

The emergence and the widespread of Coronavirus disease 2019 (COVID-19) demands an accurate detection method to establish a diagnosis. Real-time polymerase chain reaction (real-time PCR) is accounted for the perfect point of reference in detecting this virus. The notion that this virus also invades the male reproductive tract requires further investigation to prove the presence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in the semen. This investigation was designed to detect SARS-CoV-2 in COVID-19 survivors semen. This study design was a cross-sectional examination and conducted between November 2020 and March 2021 in the Andrology Unit of Dr. Soetomo General Hospital and Professor Nidom Foundation, both located in the City of Surabaya, Indonesia. The sample was 34 male participants aged above 18 years old and had been confirmed COVID-19 by nasopharyngeal swab PCR test. Part of the semen was taken for real-time PCR testing with the QuantStudio 5 Applied Biosystem (AB) PCR machine and the kits utilized were the STANDARD M nCOV Real-Time Detection Kit and mBioCov-19 RT-PCR Kit. Furthermore, the mean of participants ages was 35.74 years old with 25% of them had had a history of primary infertility and 21.8% of secondary infertility. From the real-time PCR COVID-19 of the semen examination, this investigation found that 27 participants had been negatives (74.4%), six inconclusive (17.6%), and one positive (3%) of SARS CoV-2. In summary, SARS-CoV-2 could be found in the semen of COVID-19 survivors. This should be a concern for the potential impact of COVID-19 in male fertility and the possibility of transmission reproductively.

BackgroundDue to its antioxidative, anti-inflammatory, anti-apoptosis, and antifatigue properties, molecular hydrogen (H2) is potentially a novel therapeutic gas for acute coronavirus disease 2019 (COVID-19) patients. AimTo determine the efficacy and safety profile of hydrogen rich water (HRW) to reduce the risk of progression of COVID-19. Design and settingsWe conducted a phase 3, triple-blind, randomized, placebo-controlled trial to evaluate treatment with HRW started within 5 days after the onset of signs or symptoms in primary care patients with mild-to-moderate, laboratory-confirmed COVID-19 and at least one risk factor for severe COVID-19 illness. MethodParticipants were randomly assigned to receive HRW or placebo twice daily for 21 days. The composite primary endpoint was the incidence of clinical worsening (dyspnea, fatigue) associated with a need for oxygen therapy, hospitalization or death at day-14; the incidence of adverse events was the primary safety end point. ResultsA total of 675 participants were followed up until day-30. 337 in the HRW group and 338 in the placebo group. Baseline characteristics were similar in the two groups. HRW was not superior to placebo in preventing clinical worsening at day-14: in H2 group, 46.1% met a clinical deterioration, 43.5% in the placebo group, Hazard Ratio 1.09, 90% confidence interval [0.90-1.31]. One death was reported in the H2 group and 2 in the placebo group at day-30. Adverse events were reported in 91 (27%) and 89 (26.2%) participants respectively. ConclusionTwice-daily ingestion of HRW from the onset of COVID-19 symptoms for 21 days did not reduce clinical worsening. How this fits inO_LIOnly a few molecules specially developed against SARS-CoV-2 can limit impact of COVID-19 (vaccines, monoclonal antibodies or antiviral drugs) C_LIO_LIUsing their multiple properties, H2 may play a key role in preventing the severe and post-acute forms of COVID-19 C_LIO_LITaking twice daily Hydrogen Rich Water (HRW) was not efficacious to prevent severe COVID-19 in at risk COVID-19 patients. C_LIO_LIHRW confirmed a very safe profil C_LI

ObjectiveDetermine whether hormone-associated venous thromboembolism (VTE) risk varies by exposure route and formulation in 50-64 year-old US women. DesignNested case-control study. SettingLarge US commercially-insured population with patient-level claims data. ParticipantsWomen aged 50-64 years with at least one year of enrollment. Controls were matched to incident cases (10:1) on VTE date and cases age (+/- 2yrs). Exclusions included prior VTE, intravascular vena cava (IVC) filter within twelve months, and anticoagulant exposure within 14 days. ExposuresAll estrogen and progestogen prescriptions (with route and formulation) filled within 12 months prior to index date were coded as current (0-60 days), past (61-365 days), or none. Contraceptives were categorized separately. OutcomeAcute VTE cases were identified with ICD codes plus anticoagulant, IVC filter, or death within 30 days. ResultsConditional logic regression analyses controlled for differences between cases (n=20,359) and controls (n=203,590) in Elixhauser comorbidities and VTE risk factors. Odds ratios (OR) were as follows: for current oral, unopposed estradiol 1.24 (95% CI: 1.09 to 1.40) or conjugated equine estrogen (CEE) 1.46 (95% CI: 1.28 to 1.68); for progestogens with estradiol 1.14 (95% CI: 0.95 to 1.37), with CEE 1.52 (95% CI: 1.25 to 1.84), or with ethinyl estradiol 2.35 (95% CI: 1.71 to 3.25). Current transdermal estradiol had the lowest ORs, whether unopposed, 0.70 (95% CI: 0.59 to 0.83) or combined with progestogens, 0.73 (95% CI: 0.56 to 0.96), but varied by progestogen. The OR for estrogen-progestogen contraceptives was 5.22 (95% CI: 4.67 to 5.84) compared to no exposure and 4.24 (95% CI: 3.64 to 4.98) compared to combined MHT. ConclusionsIn 50-64-year-old women, transdermal menopausal hormone therapy (estradiol with or without progestogens) did not elevate VTE risk. In contrast, contraceptives markedly increased VTE risk. Summary Boxes What is already known on this topic?O_LIRandomized controlled trials indicate that relative risk for venous thromboembolism (VTE) is approximately twice as high with menopausal hormone therapy (MHT) containing conjugated equine estrogen (CEE) with or without medroxyprogesterone acetate compared to no hormone exposure. C_LIO_LIRecent large, observational studies in the UK and Europe suggest that estradiol is lower risk than CEE and transdermal estradiol does not raise VTE risk compared to no hormone exposure, but results may not generalize to the United States because of differences in formulary, prescribing patterns, and background VTE incidence. C_LI What this study addsO_LIUsing a large medical record database for US commercially-insured women 50-64 years of age, results confirmed that VTE risk was higher for oral compared to transdermal MHT and transdermal MHT (unopposed estrogen or combined with a progestogen) did not increase risk for VTE compared to no hormone exposure. However, unique US prescribing patterns included MHT with transdermal estradiol plus oral progestogens and MHT with ethinyl estradiol. C_LIO_LIMHT estrogen formulation affected VTE risk: ethinyl estradiol had higher risk than CEE, and CEE had higher risk than estradiol. C_LIO_LICombined hormonal contraceptives (oral, vaginal, transdermal) had a markedly higher increase in VTE compared to MHT. C_LI

IntroductionThe adoption of biologic therapies imposes a substantial financial burden on the Jordanian healthcare system. Ranibizumab is prescribed for various retinal disorders, and its associated costs are considerable. The introduction of biosimilars is beneficial in retaining desired clinical parameters while providing cost relief and enhanced access to patients. ObjectiveTo examine the budget impact and expanded access of switching to ranibizumabs biosimilar for the management of retinal diseases in guideline-based practice and in real-world practice in Jordan. MethodA 4-year budget impact analysis from Jordanian public sector payers sector was performed (2023 to 2026) that included patient prevalence and incidence, average ranibizumab dose per year, and anticipated shifts in the market share of ranibizumab and aflibercept. The model took into account the anticipated price erosion of the biosimilar in 2025 and 2026. Sensitivity analyses were performed to assess the effect of changes in uptake rates, price, and market share. ResultsThe annual cost savings per patient when switching from aflibercept to ranibizumabs biosimilar were from 20.55 JOD (Jordanian Dinar) to 1519.93 JOD, translating to a percentage saving of 2.68% to 35.12% across the various scenarios and indications. The total budget impact ranged widely from 6.9 M JOD to 21.2 M JOD based on treatment regimens adjusted to current practice, PRN (Pro re nata), or T&E (Treat and extend). Patient access improved between 2.75% to 124.76% in the different scenarios. ConclusionThe introduction of ranibizumabs biosimilar significantly reduces the expenditures and enhances treatment access.

BackgroundThis study has assessed the protective effect of a new Anti-COVID-19 SA58 Nasal Spray (SA58 Nasal Spray) against SARS-CoV-2 infection under continuous exposure. MethodsThis is an exploratory open-label, single-arm trial. To evaluate the safety and effectiveness of SA58 against SARS-CoV-2 family transmission, SA58 was administered to all enrolled family contacts at 3[~]6-hour intervals. The frequency of administration and adverse events (AEs) were self-reported by online questionnaire, and RT-PCR tests were used to diagnose SARS-CoV-2 infection. The effectiveness was assessed in comparison to a contemporaneous control group whose information was collected through three follow-up visits. Total effectiveness and single-day effectiveness were calculated. ResultsThe incidence of SARS-CoV-2 infection was 62.9% (44/70) in the experimental group and 94.8% (343/362) in the control group. Using SA58 nasal spray at least three times per day could possibly reduce the risk of household transmission of SARS-CoV-2 by 46.7%[~]56.5%. The incidence of AEs was 41.4% and the severity of all AEs was mild. ConclusionEven under the scenario of continuous exposure to SARS-CoV-2, SA58 nasal spray remained effective in blocking viral transmission and was well tolerated.

Introduction: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine disorder affecting women of reproductive age. Besides reproductive and metabolic disturbances, PMOS negatively impacts psychological well-being and quality of life. Despite available treatment options, there remains a need for safe and effective therapies that improve both clinical symptoms and fertility outcomes. Aim: To compare the efficacy of VAMHA and MYRHA tablet combination therapy with standard non-hormonal therapy in restoring regular menstruation. Secondary objectives included assessment of ovulation, menstrual symptoms, polycystic ovarian morphology, hormonal and metabolic parameters, anthropometric measures, and skin manifestations. Study Design: Open-label, randomized, multicentre, prospective comparative clinical study. Methods: Seventy-one women with PMOS were randomized to Group A (n=37) or Group B (n=34). Group A received VAMHA and MYRHA tablets (2 tablets each), while Group B received Metformin 500 mg plus Myoinositol 600 mg (1 tablet), twice daily for 180 days. Data were recorded in Case Report Forms. Statistical Analysis: Continuous variables were summarized using mean and standard deviation, while categorical variables were expressed as frequencies and percentages. Appropriate statistical tests, including Chi-square, were used. A p-value [&le;]0.05 was considered significant. Results: Significantly more participants in Group A achieved regular menstrual cycles than Group B (31 vs. 22; p<0.05). Ovulation occurred in 16 participants in Group A compared with 6 in Group B (p<0.05). Both groups showed significant improvement in menstrual irregularity and related symptoms. Significant reductions in Anti-Mullerian Hormone (AMH), fasting insulin, and body mass index (BMI) were observed in both groups (p<0.05). Resolution of polycystic ovarian morphology occurred in 13 participants (38.23%) in Group A and 10 (33.33%) in Group B. Both treatments were well tolerated with no major safety concerns. Conclusions: VAMHA and MYRHA combination therapy was superior to standard non-hormonal therapy in improving menstrual regularity and ovulation. It also produced favourable metabolic, hormonal, and ultrasonographic outcomes, suggesting its potential as a safe and effective option for comprehensive PMOS management and fertility enhancement.

BackgroundCell and gene therapies (CGT) represent a transformative class of medical interventions, yet their high production costs limit patient access. Understanding the structure of manufacturing costs is essential for informing policies that can expand access to these therapies. ObjectiveThis study develops and applies a cost-of-goods-sold (COGS) model to analyze the contributors to manufacturing costs for mRNA-based CGT, with application to a wide range of current and future therapies. MethodsAn Excel-based COGS model was constructed based on cost categories for CGT. Two mRNA-based products at commercial scale were used to populate the model: an mRNA vaccine and a therapeutic mRNA gene therapy. Cost inputs were drawn from vendor pricing, peer-reviewed and grey literature, and expert consultation with CGT manufacturing specialists. Three scenarios (worst, base, and best case) were modeled across six cost categories: materials, consumables, capital, labor, licenses, and royalties. A tornado diagram sensitivity analysis was conducted to identify key cost drivers. The mRNA vaccine was used to build and validate the model strucutre using publicly available data sources. The therapeutic mRNA therapy was used as the main use case for illustration and sensitivity analysis. ResultsUnder base-case assumptions, the estimated cost per dose for the therapeutic mRNA product is $56.09, ranging from $3.68 (best case) to $383.22 (worst case). Licensing and royalty fees together account for approximately 83% of total base-case COGS ($6,996,000 and $6,960,000 per production run, respectively, out of $16,825,597 total). Excluding these fees, material costs represent the largest remaining share (61%), followed by consumables (34%), capital (4%), and labor (1%). Sensitivity analysis confirms that licensing and royalty assumptions are the dominant source of uncertainty in the model. ConclusionsLicensing and royalty fees are the primary driver of mRNA-based CGT production costs and represent the greatest opportunity for cost reduction through policy intervention. Strategic priorities for cost reduction should focus on optimizing reagent utilization, increasing platform potency, and expanding use of contract development and manufacturing organizations (CDMOs) to reduce capital and labor costs. Key PointsProducing an example mRNA gene therapy costs about $56 per dose to manufacture, driven almost entirely driven by fees paid to patent holders for the underlying technology. Licensing and royalty fees cost roughly 83 cents of every dollar spent on these new biopharmaceutical products. Until that changes, the gap between what therapies cost to make and what patients and payers are charged will remain very wide.

BackgroundCarpal Tunnel Syndrome (CTS) is the most common compressive neuropathy, accounting for 90% of all neuropathies. Its prevalence ranges from 3.8% - 7.8% in the population. The gold standard for its diagnosis is the neurophysiological study (85% sensitivity and 95% specificity), with the disadvantage of being invasive, complex and expensive, which means an increase in cost and time for the diagnosis of the disease. The main objective of this diagnostic test evaluation study is to investigate the value of ultrasound in the diagnosis of CTS, and among the secondary objectives, to establish the ultrasound parameters that are predictors of CTS in comparison with neurophysiological studies, attempting to standardize a protocol and reference values that determine the presence or absence of CTS. MethodsProspective, cross-sectional study. The reference test with which we compared the ultrasound is the neurophysiological test (NPT). Patients will come consecutively from the Neurophysiology Department of the Virgen Macarena Hospital, with clinical suspicion of CTS and fulfilling the inclusion/exclusion criteria. To calculate the sample size (EPIDAT program) we proposed a sensitivity of 78% and specificity of 87% with a confidence level of 95%, requiring 438 patients (264 NPT positive, 174 NPT negative). We followed an ultrasound study protocol that included the ultrasound variables: cross-sectional area at the entrance and exit of the tunnel, range of nerve thinning, wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and the existence of adjacent wrists or masses. We propose a timeline for the study to be performed between 2020 and 2023. Finally, we propose a cost-effectiveness analysis. DiscussionUltrasound not only allows to objectify the alterations of the median nerve but also the underlying pathological mechanisms in CTS. A multitude of ultrasound parameters have been described that should be regarded in syndromes study, among which we included the cross-sectional area, the range of nerve thinning, the wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and assessment of anatomical alterations. The use of ultrasound as a diagnostic tool in CTS has many advantages for both doctors and the patients, as it is a non-invasive, convenient, and fast tool increasingly accessible to professionals. Administrative information O_TBL View this table: org.highwire.dtl.DTLVardef@1972c1borg.highwire.dtl.DTLVardef@1d0defaorg.highwire.dtl.DTLVardef@1df09a9org.highwire.dtl.DTLVardef@1f3624aorg.highwire.dtl.DTLVardef@1b9fbbd_HPS_FORMAT_FIGEXP M_TBL C_TBL