Stud Health Technol Inform. 2023 Sep 12;307:110-116. doi: 10.3233/SHTI230701.

ABSTRACT

BACKGROUND: In Germany, patients are entitled to a medication plan. While the overview is useful, it does not contain explicit information on various potential adverse drug events (ADEs). Therefore, physicians must continue to seek information from various sources to ensure medication safety.

OBJECTIVE: In this project a first functional prototype of a medication therapy tool was developed that focuses on visualizing and highlighting potential ADEs. A usability analysis about the tool's functionality, design and usability was conducted.

METHODS: A web application tool was developed using the MMI Pharmindex as database. ADEs are color coded and can be displayed in three different ways - as a list, a table, or a graph. To test the tool, an online survey was conducted amongst healthcare professionals (n = 9). The test included two real medication plans to check ADEs through the tool.

RESULTS: The survey results indicated that the web tool was clear and self-explanatory. It scored overall "good" (score: 76.5) on the System Usability Scale questionnaire. Due to the free-text information of the database used, there were some inconsistencies in the visualized ADEs.

CONCLUSION: There is a demand for a visualization tool for medications. The high quality of the database is crucial in order to correctly visualize all necessary information, such as drug-drug interactions and inclusion of patient data. This is essential to provide a trustworthy tool for medical professionals.

PMID:37697844 | DOI:10.3233/SHTI230701

J Pak Med Assoc. 2023 Aug;73(8):1771. doi: 10.47391/JPMA.8248.

NO ABSTRACT

PMID:37697794 | DOI:10.47391/JPMA.8248

J Pak Med Assoc. 2023 Aug;73(8):1592-1597. doi: 10.47391/JPMA.6885.

ABSTRACT

OBJECTIVES: To assess the short-term adverse effects of two inactivated coronavirus disease-2019 vaccines, and the demographic factors associated with such events.

METHODS: The cross-sectional study was conducted in Karachi from August to October 2021 after approval from the ethics review board of Dow University of Health Sciences, Karachi, and comprised adults of either gender who had received at least one dose of either Sinopharm or CoronaVac vaccine. Data was collected using online and printed survey forms. The questionnaire investigated the symptoms experienced by the participants after the administration of the vaccine dose. Data was analysed using SPSS 22.

RESULTS: Of the 1000 survey forms filled, 896 were analysed; 505(56.4%) women and 391(43.6%) men were included in the study. Most of the participants were aged 18-30 years 644(71.9%). Overall, 581(64.8%) subjects had received Sinopharm vaccine, and 315(35.2%) received CoronaVac. The incidence of side effects after the first and second dose respectively was 63.3% (368 out of 581) and 55.2% (239 out of 433) for Sinopharm and 65.4% (206 out of 315) and 61.4% (89 out of 145) for CoronaVac. The factors associated with a higher risk of side effects were female gender and young age (p<0.05).

CONCLUSIONS: Most of the reported symptoms were minor in nature, like pain at the injection site, and women and those of young age reported such symptoms more than men and the elderly.

PMID:37697748 | DOI:10.47391/JPMA.6885

Microbiol Spectr. 2023 Sep 12:e0180023. doi: 10.1128/spectrum.01800-23. Online ahead of print.

ABSTRACT

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio. This subset analysis included only neonates and young infants < 3 mo of age. The microbiologic modified intent-to-treat population (mMITT) included 20 patients (ceftolozane/tazobactam, n = 14; meropenem, n = 6). All patients had pyelonephritis at baseline; two patients in each treatment group had bacteremia (overall 4/20, 20%). Escherichia coli was the most common baseline pathogen (overall 16/20, 80%). Safety and efficacy results were similar between treatment groups and consistent with the overall pediatric population. There were no serious drug-related adverse events (AEs), no discontinuations due to AEs, and no AEs leading to death in either treatment group. For the ceftolozane/tazobactam and meropenem treatment groups, clinical cure rates in the mMITT population were 92.9% and 100%, respectively. The population PK analysis of neonates and young infants demonstrated similar ceftolozane and tazobactam exposures to those of adults, achieving pharmacodynamic targets associated with clinical and microbiologic cure. Ceftolozane/tazobactam has a favorable safety profile and achieves high clinical cure and microbiologic eradication rates in neonates and young infants < 3 mo of age with cUTI and pyelonephritis. IMPORTANCE Extrapolation of antibacterial agent pharmacokinetics from adults to newborns and young infants may not be appropriate; similarly, the clinical manifestations of infectious diseases and outcomes following antibacterial treatment may not be similar. Ceftolozane/tazobactam is an antibacterial drug combination active against Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacteria. A clinical study led to the approval for ceftolozane/tazobactam in patients from birth to 18 y of age who have complicated urinary tract infections, including those with serious kidney infections. Based on data collected during that clinical study, we compared newborns and young infants who were treated with ceftolozane/tazobactam (14 patients) and those who were treated with meropenem (6 patients). We found that ceftolozane/tazobactam treatment of newborns and young infants up to 3 mo of age who have complicated urinary tract infections demonstrated a favorable safety profile and high clinical cure and microbiologic eradication rates, similar to meropenem.

PMID:37698430 | DOI:10.1128/spectrum.01800-23

BMJ Case Rep. 2023 Sep 11;16(9):e255632. doi: 10.1136/bcr-2023-255632.

ABSTRACT

A woman in her 50s with metastatic hormone receptor positive breast cancer developed rhabdomyolysis and subsequent acute kidney injury while on a combination of ribociclib and rosuvastatin therapy. She had been taking both medications long term and had recently recommenced her ribociclib at her usual dose after a routine 1 week break. Cyclin-dependent kinase 4/6 inhibitors have been implicated in causing rhabdomyolysis by potentiating statin effect by way of inhibition of cytochrome P450 enzymatic action and decreasing hepatic membrane transporter function. This is the first case in which the combination of ribociclib and rosuvastatin has been shown to cause this adverse effect. It is also one of the first to demonstrate this effect occurring years after commencement of therapy. Continued vigilance for this side effect should be maintained long term.

PMID:37696610 | PMC:PMC10496681 | DOI:10.1136/bcr-2023-255632

Orv Hetil. 2023 Sep 10;164(36):1406-1415. doi: 10.1556/650.2023.32861. Print 2023 Sep 10.

ABSTRACT

In developed countries, osteoporosis is one of the most common debilitating conditions in the population over the age of 50. Unfortunately, the pathomechanism of the disease is still not fully understood. Nowadays, the administration of antiresorptive drugs blocking osteoclastic activity is the most commonly used medication to slow down the speed of the bone loss. One of the uncommon side effects of such drugs is the medication-related osteonecrosis of the jaw (MRONJ). Recently, a number of alternative therapeutic approaches has been tested and published, amongst them the recombinant human parathyroid hormone (rhPTH, teriparatide) use, which is turning into a promising treatment modality. According to certain meta-analyses, its pharmacological effect on increasing bone mineral density and controlling pathological vertebral fractures is superior to antiresorptive drugs; however, the so-called "off-label" application of teriparatide remains controversial. As intermittent administration of teriparatide stimulates bone formation, several animal and clinical studies indicated that systemic application of teriparatide shortened fracture healing time and improved quality of the callus and the newly formed bone. Furthermore, recently several clinical studies showed the beneficial effect of the intermittent rhPTH administration in the management of MRONJ. This article reviews the history of the anabolic effect of the low-dose rhPTH discovery, provides evidence-based data from animal and human studies, summarizes its biological mechanisms and the clinical benefits of the anabolic therapy and also their possible role in the management of MRONJ. The majority of the clinical data indicates that, in the case of therapy-resistant osteonecrosis, it may be worthwhile to apply short-term intermittent teriparatide therapy. Notwithstanding, more randomized clinical trials are necessary in order to confirm the efficacy and the safety of the use of teriparatide in the treatment of MRONJ. Orv Hetil. 2023; 164(36): 1406-1415.

PMID:37695713 | DOI:10.1556/650.2023.32861

Asian J Anesthesiol. 2023 Jun 1;61(2):89-101. doi: 10.6859/aja.202306_61(2).0006. Epub 2023 Jan 1.

ABSTRACT

BACKGROUND: We explored the analgesic efficacy of two non-opioid adjuvants (midazolam and dexmedetomidine) with ropivacaine in children undergoing infraumbilical surgeries.

METHODS: In this parallel group randomized controlled trial, 135 children aged between 2 and 8 years were recruited. Children were randomly allocated to one of three groups: RD received 1 mL/kg of ropivacaine (0.2%) with dexmedetomidine 1 μg/kg, RM received 1 mL/kg of ropivacaine (0.2%) with midazolam 30 µg/kg, and R received 1 mL/kg of ropivacaine (0.2%) with 1 mL normal saline. The primary outcome of the present study was to determine the duration of postoperative analgesia. Secondary outcomes were assessing postoperative face, leg, activity, cry, consolability (FLACC) pain score, rescue analgesics, hemodynamics, sedation scores, and adverse effects.

RESULTS: The analgesia duration was significantly prolonged in the RD and RM group (600.0 [480.0-720.0] minutes and 600.0 [480.0-720.0] minutes, respectively) compared to the R group 360.0 (300.0-480.0) minutes (P < 0.001). The FLACC score was comparatively higher in the R group compared to the RD and RM groups postoperatively. Time for the first rescue analgesia was more prolonged in RD and RM groups when compared with the R group. Postoperative sedation was higher in the RM group up to 120 minutes postoperatively compared to the RD and R groups.

CONCLUSION: The combination of dexmedetomidine or midazolam with local anesthetics significantly increases the analgesia duration while minimizing adverse effects.

PMID:37694514 | DOI:10.6859/aja.202306_61(2).0006

Asian J Anesthesiol. 2023 Jun 1;61(2):46-60. doi: 10.6859/aja.202306_61(2).0002. Epub 2023 Jan 1.

ABSTRACT

The main objective of this systematic review and meta-analysis was to determine the safety and effectiveness of VivaSight double-lumen tubes (VS-DLTs) in one-lung ventilation (OLV) compared to conventional DLTs (c-DLTs). The study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement's guidelines. From the database's inception to December 2022, we searched seven different databases. We included 364 patients from six randomized controlled trials who were scheduled to undergo surgery requiring OLV. The Cochrane risk of bias assessment tool was utilized to determine the risk of bias. The odds ratio (OR) was estimated for categorical variables, while the mean difference was calculated for continuous variables. Patients were randomly assigned to the VS-DLT or c-DLT group. The results revealed that patients in the c-DLT group have longer intubation time than the VS-DLT patients (mean difference [MD] = -90.01; 95% confidence interval [CI], -161.33 to -18.69; P = 0.01). Significantly, more secretions were present in the VS-DLT group than in the c-DLT group (OR = 4.24; CI, 1.96 to 9.13; P = 0.0002). Also, the fiberoptic bronchoscope was used more frequently in the c-DLT group compared to the VS-DLT group (OR = 0.01 [0.00, 0.07]; P < 0.00001). We found that VS-DLT was safe as the pooled analysis showed no significant difference according to side effects such as hoarseness and sore throat. The other outcomes, such as dislodgement, the clearance of secretions, and the quality of lung deflation (excellent), were non-significant between the two groups.

PMID:37694513 | DOI:10.6859/aja.202306_61(2).0002

Int J Nanomedicine. 2023 Sep 4;18:4949-4967. doi: 10.2147/IJN.S425013. eCollection 2023.

ABSTRACT

BACKGROUND: Near-infrared cyanine dyes have high sensitivity and spatial resolution imaging capabilities, but they also have unavoidable drawbacks such as photobleaching, low water solubility, fluorescence quenching, and toxic side effects. As an effective biologic drug carrier, albumin combines with cyanine dyes to form albumin@dye nanoparticles. These nanoparticles can alleviate the aforementioned issues and are widely used in tumor imaging and photothermal therapy.

METHODS: Herein, a newly synthesized near-infrared dye IR-817 was combined with bovine serum albumin (BSA) to create BSA@IR-817 nanoparticles. Through the detection of fluorescence emission and absorption, the optimal concentration and ratio of BSA and IR-817 were determined. Subsequently, dynamic light scattering (DLS) measurements and scanning electron microscopy (SEM) were used for the physical characterization of the BSA@IR-817 nanoparticles. Finally, in vitro and in vivo experiments were conducted to assess the fluorescence imaging and photothermal therapeutic potential of BSA@IR-817 nanoparticles.

RESULTS: IR-817 was adsorbed onto the BSA carrier by covalent conjugation and supramolecular encapsulation, resulting in the formation of dispersed, homogeneous, and stable nanoparticles with a particle size range of 120-220 nm. BSA@IR-817 not only improved the poor water solubility, fluorescence quenching, and toxic side effects of IR-817 but also enhanced the absorption and fluorescence emission peaks in the near-infrared region, as well as the fluorescence in the visible spectrum. In addition, BSA@IR-817 combined with laser 808 irradiation was able to convert light energy into heat energy with temperatures exceeding 50 °C. By creating a mouse model of subcutaneous melanoma, it was discovered that the tumor inhibition rate of BSA@IR-817 was greater than 99% after laser irradiation and that it achieved nearly complete tumor ablation without causing significant toxicity.

CONCLUSION: Our research, therefore, proposes the use of safe and effective photothermal nanoparticles for the imaging, diagnosis, and treatment of melanoma, and offers a promising strategy for future biomedical applications.

PMID:37693889 | PMC:PMC10488832 | DOI:10.2147/IJN.S425013

Pan Afr Med J. 2023 Jun 21;45:92. doi: 10.11604/pamj.2023.45.92.36496. eCollection 2023.

ABSTRACT

Polyarteritis nodosa (PAN) is a systemic vasculitis affecting medium and small-sized vessels resulting in multiple organ involvement. Refractory PAN requires a different therapeutic approach. We herein report the case of a 42-year-old male presenting a non-virus-related refractory PAN with a favorable outcome on rituximab. He presented significant weight loss, muscle weakness, peripheral axonal neuropathy, and medium-sized cutaneous vessel necrotizing vasculitis. The patient received high-dose corticosteroids and cyclophosphamide with no significant clinical improvement while developing adverse side effects such as hypertension and diabetes. Rituximab was prescribed as an alternative therapy at 1000 mg on day 0 and day 15. This allowed for complete and rapid control of disease activity with regression of cutaneous injury and substantial improvement of neurological symptoms. In conclusion, using chimeric anti-CD20 monoclonal antibodies, such as rituximab, although rarely reported in refractory non-virus-related PAN, may be an effective alternative therapy, as portrayed in our case.

PMID:37692987 | PMC:PMC10491718 | DOI:10.11604/pamj.2023.45.92.36496

F1000Res. 2023 Jun 30;12:337. doi: 10.12688/f1000research.130939.2. eCollection 2023.

ABSTRACT

Idiopathic chronic eosinophilic pneumonia (ICEP) is a rare interstitial lung disease of unknown cause. It usually responds well to systemic corticosteroid therapy, but relapses are frequent. We describe two cases of 21- and 27-year-old patients, presenting with dyspnea. The diagnosis of steroid-relapsing and steroid-dependent ICEP was made respectively. Mepolizumab was prescribed to both patients. This treatment resulted in successful long-term disease management with much fewer side effects than a traditional corticosteroid therapy.

PMID:37691733 | PMC:PMC10483178 | DOI:10.12688/f1000research.130939.2

J Clin Oncol. 2023 Sep 11:JCO2301361. doi: 10.1200/JCO.23.01361. Online ahead of print.

ABSTRACT

PURPOSE: Trastuzumab deruxtecan (T-DXd) 5.4 and 6.4 mg/kg showed robust antitumor activity in multiple cancer indications; however, T-DXd 5.4 mg/kg has not been evaluated in patients with previously treated human epidermal growth factor receptor 2-mutant (HER2m; defined as single-nucleotide variants and exon 20 insertions) metastatic non-small-cell lung cancer (mNSCLC).

METHODS: DESTINY-Lung02, a blinded, multicenter, phase II study, investigated T-DXd 5.4 mg/kg once every 3 weeks for the first time in previously treated (platinum-containing therapy) patients with HER2m mNSCLC and further assessed T-DXd 6.4 mg/kg once every 3 weeks in this population. The primary end point was confirmed objective response rate (ORR) per RECIST v1.1 by blinded independent central review.

RESULTS: One hundred fifty-two patients were randomly assigned 2:1 to T-DXd 5.4 or 6.4 mg/kg once every 3 weeks. As of December 23, 2022, the median duration of follow-up was 11.5 months (range, 1.1-20.6) with 5.4 mg/kg and 11.8 months (range, 0.6-21.0) with 6.4 mg/kg. Confirmed ORR was 49.0% (95% CI, 39.0 to 59.1) and 56.0% (95% CI, 41.3 to 70.0) and median duration of response was 16.8 months (95% CI, 6.4 to not estimable [NE]) and NE (95% CI, 8.3 to NE) with 5.4 and 6.4 mg/kg, respectively. Median treatment duration was 7.7 months (range, 0.7-20.8) with 5.4 mg/kg and 8.3 months (range, 0.7-20.3) with 6.4 mg/kg. Grade ≥ 3 drug-related treatment-emergent adverse events occurred in 39 of 101 (38.6%) and 29 of 50 (58.0%) patients with 5.4 and 6.4 mg/kg, respectively. 13 of 101 (12.9%) and 14 of 50 (28.0%) patients had adjudicated drug-related interstitial lung disease (2.0% grade ≥ 3 in each arm) with 5.4 and 6.4 mg/kg, respectively.

CONCLUSION: T-DXd demonstrated clinically meaningful responses at both doses. Safety profile was acceptable and generally manageable, favoring T-DXd 5.4 mg/kg.

PMID:37694347 | DOI:10.1200/JCO.23.01361

Am J Cancer Res. 2023 Aug 15;13(8):3668-3678. eCollection 2023.

ABSTRACT

Children and young adult with high grade gliomas (HGG) have dismal prognoses and treatment options remain limited. We present 19 patients diagnosed with anaplastic astrocytoma (AA) or glioblastoma (GBM) treated with concomitant and adjuvant 20-30 mg/m2/dose of vinorelbine and 30 mg/kg/day valproic acid (VA) in combination to consolidated TMZ and focal RT after maximal surgery. We evaluated the feasibility of treating children diagnosed with HGG. The median follow-up time was 51.4 months (range, 6.2-106.6 months). The 5-year OS was 57.9% (CI 95%, 33.2-76.3) and the 5-year PFS was 57.9% (CI 95%, 33.2-76.3). Eight patients (42.1%) have progressed so far, with a median time to progression of 9 months from diagnosis (range, 4.6-34.7 months). All of them died for disease progression. At time of analysis, 11 patients were still alive with no evidence of disease. It is notable that all events occurred within 35 months from the start of therapy. All 19 treated patients reported low-grade drug-related adverse events (AEs). The treatment was well tolerated in our limited cohort of patients without significant toxicity. Further studies of the efficacy and safety of combination of vinorelbine/VA to consolidated RT/TMZ therapy in children with HGG are underway in a clinical trial setting.

PMID:37693163 | PMC:PMC10492125

Cureus. 2023 Aug 9;15(8):e43230. doi: 10.7759/cureus.43230. eCollection 2023 Aug.

ABSTRACT

The increasing use of immune checkpoint inhibitors, such as nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, for advanced neoplastic disease has revealed significant cutaneous immune-related adverse effects. Herein, we report a case of bullous pemphigoid (BP) secondary to nivolumab therapy for recurrent metastatic oropharyngeal squamous cell carcinoma. In this patient, the time to development of BP was three years, which represents the most delayed onset of BP secondary to a PD-1 inhibitor that has been reported in the literature. Symptoms were initially controlled on low-dose oral prednisone but recurred after two years. The patient was subsequently treated with a several-month taper of high-dose oral prednisone, during which he was able to resume nivolumab without recurrence of skin lesions. Although immune checkpoint inhibitor-induced BP remains rare, physicians should be aware of this serious cutaneous immune-related adverse event as the use of this drug class continues to expand.

PMID:37692698 | PMC:PMC10491457 | DOI:10.7759/cureus.43230

Endocr Metab Immune Disord Drug Targets. 2023 Sep 7. doi: 10.2174/1871530323666230907112453. Online ahead of print.

ABSTRACT

BACKGROUND: Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (HR-NSAIDs) are common adverse events related to the widespread use of over-the-counter NSAIDs for the treatment of a variety of inflammatory conditions. Urticaria is the most commonly reported immediate cutaneous clinical sign of HR-NSAIDs, but it can be a manifestation of pathophysiologically different clinical entities that require different therapeutic strategies. The aim of this study is to ease the identification of the correct phenotype of HR-NSAIDs in patients reporting urticaria associated with the intake of NSAIDs and provide updated information about their diagnosis and management.

METHODS: The study is a narrative review conducted by collecting the most relevant and up-to-date data related to the classification, pathophysiology, severity, and prognosis of NSAID hypersensitivity reactions. PubMed and Embase scientific databases were used as search engines to select relevant articles.

RESULTS: Patients developing HR-NSAIDs can be divided into two categories: selective responders (SR), who develop reactions after the administration of a single specific NSAID due to an underlying IgE or T-cell mediated hypersensitivity mechanism, or cross-intolerant (CI), who develop reactions to more than one chemically unrelated NSAIDs due to abnormalities in the biochemical pathways related with prostaglandin metabolism, independently from an underlying immunological mechanism. Five major different categories of HR-NSAIDs have been identified: NSAIDs-exacerbated cutaneous disease (NECD), NSAIDs-induced urticaria/angioedema with/without respiratory and systemic symptoms of anaphylaxis (NIUAA), and NSAIDs-exacerbated respiratory disease (NERD), which are developed by CI patients, and single NSAIDs-induced urticaria, angioedema and/ or anaphylaxis (SNIUAA) and single NSAIDs-induced delayed hypersensitivity reactions (SNIDHR), which are developed by CI patients. In vivo and in vitro diagnostic tests have rarely been shown to be reliable in all these entities and therefore are not routinely used in clinical practice. The management in SR patients consists of strict avoidance of the culprit drug, while for cross-intolerance reactions oral tolerance tests with safe alternative drugs (e.g. weak COX-1 inhibitors or selective COX-2 inhibitors) can be performed.

CONCLUSION: HR-NSAIDs are being observed with increasing frequency, however, the pathogenesis behind some NSAIDS-associated clinical entities is still unclear. Diagnosis is mostly based on a thorough clinical history and confirmed by a drug challenge test. Clinical management is based on strict avoidance and use of alternative tolerated medications. Overall, all therapeutic decisions depend on the correct identification of the type of reaction the patient experienced.

PMID:37691219 | DOI:10.2174/1871530323666230907112453

Eur Respir J. 2023 Sep 9;62(3):2300198. doi: 10.1183/13993003.00198-2023. Print 2023 Sep.

ABSTRACT

BACKGROUND: Current guidelines recommend 20-40 mg·day-1 of oral prednisolone for treating pulmonary sarcoidosis. Whether the higher dose (40 mg·day-1) can improve outcomes remains unknown.

METHODS: We conducted an investigator-initiated, single-centre, open-label, parallel-group, randomised controlled trial (ClinicalTrials.gov identifier NCT03265405). Consecutive subjects with pulmonary sarcoidosis were randomised (1:1) to receive either high-dose (40 mg·day-1 initial dose) or low-dose (20 mg·day-1 initial dose) oral prednisolone, tapered over 6 months. The primary outcome was the frequency of relapse or treatment failure at 18 months from randomisation. Key secondary outcomes included the time to relapse or treatment failure, overall response, change in forced vital capacity (FVC, in litres) at 6 and 18 months, treatment-related adverse effects and health-related quality of life (HRQoL) scores using the Sarcoidosis Health Questionnaire and Fatigue Assessment Scale.

FINDINGS: We included 86 subjects (43 in each group). 42 and 43 subjects completed treatment in the high-dose and low-dose groups, respectively, while 37 (86.0%) and 41 (95.3%), respectively, completed the 18-month follow-up. 20 (46.5%) subjects had relapse or treatment failure in the high-dose group and 19 (44.2%) in the low-dose group (p=0.75). The mean time to relapse/treatment failure was similar between the groups (high-dose 307 days versus low-dose 269 days, p=0.27). The overall response, the changes in FVC at 6 and 18 months and the incidence of adverse effects were also similar. Changes in HRQoL scores did not differ between the study groups.

INTERPRETATION: High-dose prednisolone was not superior to a lower dose in improving outcomes or the HRQoL in sarcoidosis and was associated with similar adverse effects.

PMID:37690784 | DOI:10.1183/13993003.00198-2023

BMC Womens Health. 2023 Sep 9;23(1):478. doi: 10.1186/s12905-023-02630-7.

ABSTRACT

INTRODUCTION: In 2018, the Malawi Ministry of Health adopted the recommendation to switch first-line antiretroviral therapy (ART) from an efavirenz (EFV)-based to a dolutegravir (DTG)-based regimen. Little is known about patients' experience during this transition. We conducted a qualitative study to explore DTG-related counselling challenges among providers of HIV care and factors influencing regimen switching or non-switching among women living with HIV in Lilongwe, Malawi.

METHODS: Between February-July 2020, we recruited participants who took part in DTG counselling on reasons to switch, side effects, and benefits from two government health facilities providing HIV care: Area 18 health centre and Bwaila district hospital in Lilongwe, Malawi. We purposively sampled and interviewed 8 women living with HIV who remained on an EFV-based regimen after counselling, 10 women who switched to a DTG-based regimen, and 10 HIV care providers who provided counselling about ART switching. In-depth interviews were used to explore patient's perceptions of DTG, factors affecting the decision to switch, and both patient and provider experience with counselling. Interview data was coded for themes using inductive and deductive codes. Interviews were conducted until thematic saturation was achieved. Data matrices were used for analysis and thematic extraction.

RESULTS: Most women in both groups were well versed on DTG's potential side effects and felt well counselled on the benefits of switching, such as quicker viral load suppression. Many women associated DTG with birth defects and expressed concern. However, the primary reason for not switching was concern with how the new medication would be tolerated, especially when they were satisfied with their current regimen. Almost all providers expressed difficulty providing DTG counselling. Primary reasons included feeling inadequately trained and/or not having resources to use during counselling, such as diagrams or brochures.

CONCLUSION: DTG counselling was well accepted by women; however, some felt that their concerns were not fully addressed. Providers reflected this sentiment in that they did not feel adequately trained or well-equipped to provide adequate counselling. Training on counselling for new ART regimens should be intensified and utilize patient-centered educational materials to address the concerns raised by both patients and health care providers.

PMID:37689628 | PMC:PMC10492391 | DOI:10.1186/s12905-023-02630-7

Ned Tijdschr Geneeskd. 2023 Aug 30;167:D7604.

ABSTRACT

BACKGROUND: Oral nicotine pouches are pouches that contain varying amounts of nicotine. The use of nicotine pouches by adolescents has increased since 2020. Subsequently, there has been an increase in the amount of reports of nicotine intoxications. Acute nicotine intoxications have a biphasic clinical course, during which the initial symptoms may include agitation, tachycardia and vomiting. When large enough doses are used more serious symptoms may emerge. As well as the acute side effects, studies have shown that the use of oral nicotine pouches with tobacco is associated with a younger age at which cigarette smoking is initiated.

PATIENT DESCRIPTION: A 9 year-old boy presented at the Emergency Department with symptoms of nausea, dizziness and shivering following the oral use of one nicotine pouch. Aside from tachycardia the physical examinations showed no abnormalities. The patient was diagnosed with an acute nicotine intoxication and was admitted to the paediatric department for 24 hours.

CONCLUSION: Oral nicotine pouches are commonly used by adolescents. Aside from the addictive nature of nicotine, it is important that clinicians are aware of the symptoms of acute and late-phase intoxications.

PMID:37688459

Molecules. 2023 Aug 24;28(17):6229. doi: 10.3390/molecules28176229.

ABSTRACT

Breast cancer, due to its high incidence and mortality, is a public health problem worldwide. Current chemotherapy uses non-specific cytotoxic drugs, which inhibit tumor growth but cause significant adverse effects. (-)-Epicatechin (EC) is part of a large family of biomolecules called flavonoids. It is widely distributed in the plant kingdom; it can be found in green tea, grapes, and cocoa. Several studies in animals and humans have shown that EC induces beneficial effects in the skeletal muscle and the cardiovascular system, reducing risk factors such as arterial hypertension, endothelial dysfunction, damage to skeletal muscle structure, and mitochondrial malfunction by promoting mitochondrial biogenesis, with no adverse effects reported. Recently, we reported that EC had an antitumor effect in a murine triple-negative mammary gland tumor model, decreasing tumoral size and volume and increasing survival by 44%. This work aimed to characterize the effects of flavanol EC on proliferation, migration, and metastasis markers of triple-negative murine breast (4T1) cancer cells in culture. We found proliferation diminished and Bax/Bcl2 ratio increased. When the migration of culture cells was evaluated, we observed a significant reduction in migration. Also, the relative expression of the genes associated with metastasis, Cdh1, Mtss1, Pten, Bmrs, Fat1, and Smad4, was increased. In conclusion, these results contribute to understanding molecular mechanisms activated by EC that can inhibit metastatic-associated proliferation, migration, and invasion of murine breast cancer cells.

PMID:37687058 | PMC:PMC10488497 | DOI:10.3390/molecules28176229

Nutrients. 2023 Aug 30;15(17):3788. doi: 10.3390/nu15173788.

ABSTRACT

Inadequate sleep is a global health concern. Sleep is multidimensional and complex; new multi-ingredient agents are needed. This study assessed the comparative effects of two multi-ingredient supplements on sleep relative to placebo. Adults (N = 620) seeking better sleep were randomly assigned to receive one of three study products. Sleep A (contained lower (0.35 mg THC and higher levels of botanicals (75 mg each hops oil and valerian oil), Sleep B (contained higher THC (0.85 mg) and lower botanicals (20 mg each hops oil and valerian oil) or placebo) for 4 weeks. Sleep disturbance was assessed at baseline and weekly using NIH's Patient-Reported Outcomes Measurement Information System (PROMIS™) Sleep Disturbance SF 8A survey. Anxiety, stress, pain, and well-being were assessed using validated measures at baseline and weekly. A linear mixed-effects regression model was used to assess the change in health outcome score between active product groups and the placebo. There was a significant difference in sleep disturbance, anxiety, stress, and well-being between Sleep A and placebo. There was no significant difference in any health parameter between Sleep B and placebo. Side effects were mild or moderate. There were no significant differences in the frequency of side effects between the study groups. A botanical blend containing a low concentration of THC improved sleep disturbance, anxiety, stress, and well-being in healthy individuals that reported better sleep as a primary health concern.

PMID:37686820 | PMC:PMC10490534 | DOI:10.3390/nu15173788