Cognitive Outcomes in Nonacute Patients With Schizophrenia Treated With Long-Acting Injectable Antipsychotics Versus Oral Antipsychotics.

BACKGROUND: Patients with schizophrenia often face challenges related to cognitive function, affecting their daily functioning and overall quality of life. The choice of antipsychotic treatment may play a crucial role in determining cognitive outcomes. STUDY QUESTION: Our study aimed to investigate whether there was a difference in cognitive ability between the patients with schizophrenia receiving oral antipsychotics (OAP) versus long-acting injectable antipsychotics (LAI-APs). STUDY DESIGN: We conducted a cross-sectional study using analytical methods between January 1, 2020, and January 1, 2022. Participants were divided into 2 groups: patients undergoing treatment with OAP and patients undergoing treatment with LAI-AP. All participants underwent version A of Brief Assessment of Cognition in Schizophrenia (BACS). MEASURES AND OUTCOMES: The primary objective was to compare cognitive function in patients with schizophrenia treated with LAI antipsychotics versus OAP using BACS. Primary outcome measures include overall BACS score, with secondary measures focusing on specific cognitive domains. This study contributes to the understanding of the cognitive effects of different antipsychotic formulations in schizophrenia treatment. RESULTS: Although there was a slightly higher intelligence quotient in the LAI-AP group (102.2 vs. 101.32, P = 0.5401), it was not statistically significant. Olanzapine was the most commonly prescribed antipsychotic, with 48% of patients in the LAI-AP group and 40% in the OAP group. The LAI-AP group outperformed in all BACS evaluations. The most notable difference was in the token motor task (57.78 ± 17.03 vs. 50.04 ± 18.82, P = 0.0335), while the Tower of London test showed the smallest difference (17.26 ± 2.61 vs. 15.48 ± 3.47, P = 0.0046). Regression analysis revealed no significant variance in intelligence quotient scores; however, a significant discrepancy in BACS scores was evident, favoring the LAI treatment for better cognitive outcomes. CONCLUSIONS: The use of long-acting antipsychotic treatment in individuals with schizophrenia offers promising advantages in preserving cognitive function.

Edaravone Oral Suspension: A Neuroprotective Agent to Treat Amyotrophic Lateral Sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is characterized by loss of motor neurons due to degeneration of nerve cells within the brain and spinal cord. Early symptoms include limb weakness, twitching or muscle cramping, and slurred speech. As the disease progresses, difficulty breathing, swallowing, and paralysis can lead to death. Currently, there are no medications that cure ALS, and guidelines recommend treatments focused on symptom management. Intravenous (IV) edaravone was approved by the US Food and Drug Administration (FDA) in 2017 as a treatment to slow the progression of ALS. In May 2022, the FDA approved an oral suspension (ORS) formulation of edaravone. MECHANISM OF ACTION: The mechanism of action of edaravone is not well defined. However, its neuroprotective effects are thought to result from antioxidant properties occurring through elimination of free radicals. PHARMACOKINETICS: Edaravone ORS (105 mg) has a bioavailability of 57% when compared with edaravone IV (60 mg). The ORS should be taken on an empty stomach in the morning, with water and no food or beverages, for 1 hour. Edaravone is bound to albumin (92%), has a mean volume of distribution of 63.1 L, a half-life of 4.5-9 hours, and a total clearance of 35.9 L/h after intravenous administration. Edaravone is metabolized into nonactive sulfate and glucuronide conjugates. CLINICAL TRIALS: The FDA approval was based on studies of the pharmacokinetics, safety, tolerability, and bioavailability of edaravone ORS. A phase III, global, multicenter, open-label safety study was conducted on edaravone ORS in 185 patients with ALS over 48 weeks. The most reported treatment-emergent adverse events were falls, muscular weakness, and constipation. Serious treatment-emergent adverse events included disease worsening, dysphagia, dyspnea, and respiratory failure. THERAPEUTIC ADVANCE: Oral edaravone is an ALS treatment that can be self-administered or administered by a caregiver, precluding the need for administration by a health care professional in an institutional setting.

Breast milk-mediated exposure to dioxins and antigen in infancy enhances antigen-specific antibody production capacity in adulthood in mice.

The immune system is sensitive to many chemicals. Among dioxin compounds, 2,3,7,8-tetrachlorodizenzo-p-dioxin (TCDD) is the most toxic environmental pollutant. The effects of perinatal maternal exposure to dioxins may persist into childhood. However, there have been no reports to date on the effects of exposure to dioxins during infancy, when the immune organs are developing. Therefore, we investigated the effects of TCDD and antigen exposure during lactation on immune function, especially antibody production capacity, in adult mice. Beginning the day after delivery, lactating mothers were orally administered TCDD or a mixture of TCDD and ovalbumin (OVA) daily for 4 weeks, until the pups were weaned. At 6 weeks of age, progeny mice were orally administered OVA daily for 10 weeks, while non-progeny mice were orally administered OVA or a mixture of TCDD and OVA daily for 10 weeks. Production of serum OVA-specific IgG was examined weekly. The amount of TCDD transferred from the mother to the progeny via breast milk was determined by measuring TCDD in the gastric contents of the progeny. A trend toward increasing IgA titer was observed in TCDD-treated mice, and production of IgE was observed only in progeny whose mothers were treated with TCDD and OVA. The results suggest that exposure to TCDD and OVA in breast milk can affect immune function in newborns.

[Evaluation of Solubility and Membrane Permeability of Middle-Molecule Compounds Using Artificial Membranes and Living Cells].

In contrast to small molecules, middle molecules present a promising therapeutic modality owing to their elevated specificity, minimal adverse effects, capacity to target protein-protein interactions, and, unlike antibody-based drugs, their suitability for oral administration and intracellular target engagement. Post-oral administration, the paramount considerations encompass solubility and membrane permeability during the initial phase until the drug attains systemic circulation. Furthermore, penetration of the cell membrane is essential to accessing intracellular targets. We evaluated the solubility and membrane permeability of 965 compounds sourced from middle molecule libraries affiliated with Hokkaido University, Kitasato University, and the University of Tokyo. To gauge membrane permeability, we employed both the parallel artificial membrane permeability assay (PAMPA) and Caco-2 cell monolayers. Notably, while membrane permeability in Caco-2 cells exhibited an approximate threefold increase in comparison to PAMPA measurements, certain compounds demonstrated permeability levels less than one-third of those observed in Caco-2 cells. Recognizing the potential involvement of efflux transporters expressed in Caco-2 cells in these variations, we conducted additional assessments involving directional transport in the presence of a transporter inhibitor. Our findings suggest that nearly 80% of these compounds serve as substrates for efflux transporters. Considering the relevance of intracellular targets, we shifted our focus from membrane permeation to intracellular uptake, conducting simulations tailored to assess cellular uptake.

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries.

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

The prevalence of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants is very low: a retrospective cohort register study.

BACKGROUND: Current guidelines from Scandinavian Neuro Committee mandate a 24-hour observation for head trauma patients on anticoagulants, even with normal initial head CT scans, as a means not to miss delayed intracranial hemorrhages. This study aimed to assess the prevalence, and time to diagnosis, of clinically relevant delayed intracranial hemorrhage in head trauma patients treated with oral anticoagulants. METHOD: Utilizing comprehensive two-year data from Region Skåne's emergency departments, which serve a population of 1.3 million inhabitants, this study focused on adult head trauma patients prescribed oral anticoagulants. We identified those with intracranial hemorrhage within 30 days, defining delayed intracranial hemorrhage as a bleeding not apparent on their initial CT head scan. These cases were further defined as clinically relevant if associated with mortality, any intensive care unit admission, or neurosurgery. RESULTS: Out of the included 2,362 head injury cases (median age 84, 56% on a direct acting oral anticoagulant), five developed delayed intracranial hemorrhages. None of these five cases underwent neurosurgery nor were admitted to an intensive care unit. Only two cases (0.08%, 95% confidence interval [0.01-0.3%]) were classified as clinically relevant, involving subdural hematomas in patients aged 82 and 87 years, who both subsequently died. The diagnosis of these delayed intracranial hemorrhages was made at 4 and 7 days following initial presentation to the emergency department. CONCLUSION: In patients with head trauma, on oral anticoagulation, the incidence of clinically relevant delayed intracranial hemorrhage was found to be less than one in a thousand, with detection occurring four days or later after initial presentation. This challenges the effectiveness of the 24-hour observation period recommended by the Scandinavian Neurotrauma Committee guidelines, suggesting a need to reassess these guidelines to optimise care and resource allocation. TRIAL REGISTRATION: This is a retrospective cohort study, does not include any intervention, and has therefore not been registered.

Effects of a Low Dose of Orally Administered Creatine Monohydrate on Post-Fatigue Muscle Power in Young Soccer Players.

The use of creatine monohydrate (Cr) in professional soccer is widely documented. However, the effect of low doses of Cr on the physical performance of young soccer players is unknown. This study determined the effect of a low dose of orally administered Cr on muscle power after acute intra-session fatigue in young soccer players. Twenty-eight young soccer players (mean age = 17.1 ± 0.9 years) were randomly assigned to either a Cr (n = 14, 0.3 g·kg-1·day-1 for 14 days) or placebo group (n = 14), using a two-group matched, double-blind, placebo-controlled design. Before and after supplementation, participants performed 21 repetitions of 30 m (fatigue induction), and then, to measure muscle power, they performed four repetitions in half back squat (HBS) at 65% of 1RM. Statistical analysis included a two-factor ANOVA (p ˂ 0.05). Bar velocity at HBS, time: p = 0.0006, ŋp2 = 0.22; group: p = 0.0431, ŋp2 = 0.12, time × group p = 0.0744, ŋp2 = 0.02. Power at HBS, time: p = 0.0006, ŋp2 = 0.12; group: p = 0.16, ŋp2 = 0.06, time × group: p = 0.17, ŋp2 = 0.009. At the end of the study, it was found that, after the induction of acute intra-session fatigue, a low dose of Cr administered orally increases muscle power in young soccer players.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

Medicinal Cannabis (MedCan 3): a randomised, multicentre, double-blind, placebo-controlled trial to assess THC/CBD (1:20) to relieve symptom burden in patients with cancer-a study protocol for a randomised controlled trial.

BACKGROUND: Distressing symptoms are common in advanced cancer. Medicinal cannabinoids are commonly prescribed for a variety of symptoms. There is little evidence to support their use for most indications in palliative care. This study aims to assess a 1:20 delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) cannabinoid preparation in the management of symptom distress in patients with advanced cancer undergoing palliative care. METHODS AND DESIGN: One hundred and fifty participants will be recruited across multiple sites in Queensland, Australia. A teletrial model will facilitate the recruitment of patients outside of major metropolitan areas. The study is a pragmatic, multicenter, randomised, placebo-controlled, two-arm trial of escalating doses of an oral 1:20 THC/CBD medicinal cannabinoid preparation (10 mg THC:200 mg CBD/mL). It will compare the efficacy and safety outcomes of a titrated dose range of 2.5 mg THC/50mgCBD to 30 mg THC/600 mg CBD per day against a placebo. There is a 2-week patient-determined titration phase, to reach a dose that achieves symptom relief or intolerable side effects, with a further 2 weeks of assessment on the final dose. The primary objective is to assess the effect of escalating doses of a 1:20 THC/CBD medicinal cannabinoid preparation against placebo on change in total symptom distress score, with secondary objectives including establishing a patient-determined effective dose, the effect on sleep quality and overall quality of life. Some patients will be enrolled in a sub-study which will more rigorously evaluate the effect on sleep. DISCUSSION: MedCan-3 is a high-quality, adequately powered, placebo-controlled trial which will help demonstrate the utility of a THC:CBD 1:20 oral medicinal cannabis product in reducing total symptom distress in this population. Secondary outcomes may lead to new hypotheses regarding medicinal cannabis' role in particular symptoms or in particular cancers. The sleep sub-study will test the feasibility of using actigraphy and the Insomnia Severity Index (ISI) in this cohort. This will be the first large-scale palliative care randomised clinical trial to utilise the teletrial model in Australia. If successful, this will have significant implications for trial access for rural and remote patients in Australia and internationally. TRIAL REGISTRATION: ANZCTR ACTRN12622000083796 . Protocol number 001/20. Registered on 21 January 2022. Recruitment started on 8 August 2022.

Experiences of oral pre-exposure prophylaxis use among heterosexual men accessing sexual and reproductive health services in South Africa: a qualitative study.

INTRODUCTION: South African men face a substantial burden of HIV and are less likely to test for HIV and initiate antiretroviral therapy if tested positive and more likely to die from AIDS-related causes than women. In addition to condoms and circumcision, guidelines provide for the use of daily oral pre-exposure prophylaxis (PrEP) as an HIV prevention intervention for any men who recognize their need and request PrEP. However, heterosexual men have not been a focus of PrEP programmes, and since its introduction, there is limited literature on PrEP use among men in South Africa. This study explores the experiences, motivators and barriers to oral PrEP use among heterosexual men accessing primary healthcare services in South Africa. METHODS: This study forms part of a mixed-methods implementation science study aimed at generating evidence for oral PrEP introduction and conducted in primary healthcare clinics in South Africa since 2018. Men aged ≥15 years who initiated oral PrEP and enrolled in a parent cohort study were purposefully invited to participate in an in-depth interview (IDI). Between March 2020 and May 2022, 30 men participated in IDIs exploring their motivators for PrEP use, and experiences with accessing health services. Interviews were audio recorded, transcribed and analysed thematically. RESULTS: The final analysis included 28 heterosexual men (18-56 years old). Motivations to initiate PrEP included fear of acquiring HIV, self-perceived vulnerability to HIV and mistrust in relationships; health systems factors which motivated PrEP use included the influence of healthcare providers, educational materials and mobile services. Perceived reduction in HIV vulnerability and changing proximity to partners were reasons for PrEP discontinuation. Side effects, daily-pill burden and stigma were noted as challenges to PrEP use. Health system barriers to PrEP use included limited PrEP availability, school and work demands, and inconsistent mobile clinic schedules. CONCLUSIONS: Our study reports on the experiences of heterosexual men accessing oral PrEP in real-world settings and contributes to the limited literature among this population. We highlight multiple levels which could be strengthened to improve men's PrEP use, including individual support, education among partners and communities, and addressing health system barriers to access.

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.

OBJECTIVE: To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice. DESIGN: Cohort study emulating a comparative effectiveness trial (target trial). SETTING: Linked primary care, hospital, and death data in England, 2015-21. PARTICIPANTS: 75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin. MAIN OUTCOME MEASURES: Primary outcome was absolute change in glycated haemoglobin A1c (HbA1c) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA1c at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures. RESULTS: 75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA1c values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA1c change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43). CONCLUSIONS: This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA1c, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure (v DPP-4 inhibitors) and kidney disease progression (v sulfonylureas), with no evidence of differences in other clinical endpoints.

In Vivo Pro-Inflammatory Effects of Silver Nanoparticles on the Colon Depend on Time and Route of Exposure.

Nanosilver is a popular nanomaterial, the potential influence of which on humans is of serious concern. Herein, we exposed male Wistar rats to two regimens: a repeated oral dose of 30 mg/kg bw silver nanoparticles (AgNPs) over 28 days and a single-dose injection of 5 mg/kg bw of AgNPs. At three different time points, we assessed antioxidant defense, oxidative stress and inflammatory parameters in the colon, as well as toxicity markers in the liver and plasma. Both experimental scenarios showed increased oxidative stress and inflammation in the colon. Oral administration seemed to be linked to increased reactive oxygen species generation and lipid peroxidation, while the effects induced by the intravenous exposure were probably mediated by silver ions released from the AgNPs. Repeated oral exposure had a more detrimental effect than the single-dose injection. In conclusion, both administration routes had a similar impact on the colon, although the underlying mechanisms are likely different.

Impact of the Oral Administration of Polystyrene Microplastics on Hepatic Lipid, Glucose, and Amino Acid Metabolism in C57BL/6Korl and C57BL/6-Lepem1hwl/Korl Mice.

The impact of microplastics (MPs) on the metabolic functions of the liver is currently unclear and not completely understood. To investigate the effects of the administration of MPs on the hepatic metabolism of normal and obese mice, alterations in the lipid, glucose (Glu), and amino acid regulation pathways were analyzed in the liver and adipose tissues of C57BL/6Korl (wild type, WT) or C57BL/6-Lepem1hwl/Korl mice (leptin knockout, Lep KO) orally administered polystyrene (PS) MPs for 9 weeks. Significant alterations in the lipid accumulation, adipogenesis, lipogenesis, and lipolysis pathways were detected in the liver tissue of MP-treated WT and Lep KO mice compared to the vehicle-treated group. These alterations in their liver tissues were accompanied by an upregulation of the serum lipid profile, as well as alterations in the adipogenesis, lipogenesis, and lipolysis pathways in the adipose tissues of MP-treated WT and Lep KO mice. Specifically, the level of leptin was increased in the adipose tissues of MP-treated WT mice without any change in their food intake. Also, MP-induced disruptions in the glycogenolysis, Glu transporter type 4 (GLUT4)-5' AMP-activated protein kinase (AMPK) signaling pathway, levels of lipid intermediates, and the insulin resistance of the liver tissues of WT and Lep KO mice were observed. Furthermore, the levels of seven endogenous metabolites were remarkably changed in the serum of WT and Lep KO mice after MP administrations. Finally, the impact of the MP administration observed in both types of mice was further verified in differentiated 3T3-L1 adipocytes and HepG2 cells. Thus, these results suggest that the oral administration of MPs for 9 weeks may be associated with the disruption of lipid, Glu, and amino acid metabolism in the liver tissue of obese WT and Lep KO mice.

Efficacy and Safety of Oral Supplementation with Liposomal Iron in Non-Dialysis Chronic Kidney Disease Patients with Iron Deficiency.

INTRODUCTION: Iron deficiency is common in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). Oral iron supplementation is recommended in these patients, but it is associated with a higher incidence of gastrointestinal adverse reactions. Liposomal iron therapy has been proposed as a new iron formulation, improving iron bioavailability with less side effects; however, few data are available in patients with NDD-CKD. METHODS: We designed a single-arm pilot study to evaluate the efficacy of liposomal iron administered for six months in correcting iron deficiency (defined as serum ferritin < 100 ng/mL and/or transferrin saturation < 20%) in patients with NDD-CKD stages 1-5. The primary endpoints were the achievement of serum ferritin ≥ 100 ng/mL and transferrin saturation ≥ 20%. Secondary outcomes were hemoglobin (Hb) changes and the safety of liposomal iron. RESULTS: The efficacy population included 34/38 patients, who completed at least one visit after baseline. Liposomal iron increased the achievement of transferrin saturation targets from 11.8% at baseline to 50.0% at month 6 (p = 0.002), while no significant correction of serum ferritin (p = 0.214) and Hb was found (p = 0.465). When patients were stratified by anemia (Hb < 12 g/dL in women and Hb < 13 g/dL in men), a significant improvement of transferrin saturation was observed only in anemic patients (from 13.3 ± 5.8% to 20.2 ± 8.1%, p = 0.012). Hb values slightly increased at month 6 only in anemic patients (+0.60 g/dL, 95%CI -0.27 to +1.48), but not in those without anemia (+0.08 g/dL, 95%CI -0.73 to +0.88). In patients taking at least one dose of liposomal iron (safety population, n = 38), the study drug was discontinued in eight patients due to death (n = 2), a switch to intravenous iron (n = 2), and the occurrence of side effects (n = 4). CONCLUSIONS: The use of liposomal iron in patients with NDD-CKD is associated with a partial correction of transferrin saturation, with no significant effect on iron storage and Hb levels.

Preparation of orodispersible tablets of bosentan using xylitol and menthol as dissolution enhancers.

Bosentan is a drug used to treat pulmonary hypertension via dual endothelial receptor antagonism. Bosentan has a restricted oral bioavailability, a problem that's mostly due to poor solubility and hepatic metabolism. It is extensively used for the elderly and children who require a friendly dosage form like orodispersible tablets. So, the goal of this research work was to hasten the dissolution rate of bosentan to produce an orodispersible tablet with immediate drug release. Bosentan was exposed to ethanol-assisted kneading with a rise of xylitol or menthol concentrations (1:1 and 1:2 molar ratio of bosentan with excipient). In addition to observing the dissolution behavior, the resulting dry products were investigated using Fourier transform infrared spectroscopy (FTIR), differential thermal analysis (DTA), and X-ray diffraction (XRD). The FTIR reflected possible hydrogen bonding with xylitol and menthol. DSC studies reflected a reduction in the enthalpy and Tm. These results with XRD data reflected partial co-amorphization in the case of xylitol and eutaxia in the case of menthol. These modifications were related to an accelerated dissolving rate. The developed systems were fabricated as orodispersible tablets which exhibited immediate release of bosentan. Thus, the current study offered simple co-processing for the preparation of orodispersible bosentan tablets.

Pregnancy outcomes in pregnant women taking oral probiotic undergoing cerclage compared to placebo: two blinded randomized controlled trial.

AIM: The purpose of this study is to evaluate the oral probiotic effect on pregnancy outcomes in pregnant women undergoing cerclage compared to placebo. METHODS: This study was a double-blind randomized clinical trial undertaken in Yasuj, Iran. 114 eligible participants who have undergone cerclage were randomly divided to either receive probiotic adjuvant or 17α-OHP (250 mg, IM) with placebo from the 16th -37th week of pregnancy by "block" randomization method. Our primary outcomes were preterm labor (PTB) (late and early) and secondary outcomes were other obstetrical and neonatal outcomes included preterm pre-labor rupture of membranes (PPROM), pre-labor rupture of membranes (PROM), mode of delivery, and neonatal outcomes including anthropometric characterize and Apgar score (one and fifth-minute). RESULTS: Results show that there are no statistically significant differences between the two groups in terms of PTB in < 34th (15.51% vs. 17.86%; P = 0.73) and 34-37th weeks of pregnancy (8.7% vs. 16.1%; P = 0.22), and mode of delivery (P = 0.09). PPROM (8.7% vs. 28.5%; P = 0.006) PROM (10.3% vs. 25%; P = 0.04) was significantly lower in patients receiving probiotic adjuvant compared to the control group. After delivery, the findings of the present study showed that there were no significant differences in newborn's weight (3082.46 ± 521.8vs. 2983.89 ± 623.89), head circumstance (36.86 ± 1.53vs. 36.574 ± 1.52), height (45.4 ± 5.34 vs. 47.33 ± 4.92) and Apgar score in one (0.89 ± 0.03 vs. 0.88 ± 0.05) and five minutes (0.99 ± 0.03vs. 0.99 ± 0.03) after birth. CONCLUSION: Our result has shown that the consumption of Lactofem probiotic from the 16th week until 37th of pregnancy can lead to a reduction of complications such as PPROM and PROM.

Clinical use and efficacy of Chinese patent medicines for external use containing pyritum, a mineral medicine mainly used for oral administration: A systematic review.

BACKGROUND: Pyritum, a mineral drug, has been used primarily orally in traditional medicine to treat traumatic injuries, broken tendons, and fractures. Due to growing concerns about the accumulation of heavy metals in the body, this systematic review aims to evaluate the efficacy and safety of Chinese patent medicine containing pyritum for external use (CPMPE) to determine the effectiveness of external use of pyritum. METHODS: A literature search was performed through China National Knowledge Infrastructure, Wanfang, EMBASE, Cochrane Library, and PubMed from inception to February 2023. "Pyrite," "pyritum," "zirantong," "traditional medicine," "oriental medicine," etc, were the keywords from the database. In this systematic review, RCTs and case reports were referred to analyze the efficacy rate and clinical status of CPMPE. RESULTS: About 36 studies were reviewed. Of 36 studies, 23 were RCTs and 13 were case reports. The total effective rate in 34 studies was used to evaluate the efficacy of CPMPE for various disease classifications. The effectiveness of CPMPE was confirmed in case reports, and RCTs showed that using CPMPE as a single or combined treatment had a more significant effect than not using CPMPE in anorectal diseases, orthopedic diseases, obstetrics and gynecology diseases, and skin diseases. CONCLUSIONS: This review concluded that CPMPE might be a safe and effective alternative treatment method for various diseases and has potential benefits in preventing postoperative complications, reducing pain, relieving symptoms, and accelerating healing compared to the control group, which employs unused CPMPE.