PLoS One. 2023 Sep 13;18(9):e0290630. doi: 10.1371/journal.pone.0290630. eCollection 2023.

ABSTRACT

INTRODUCTION: 2,4-dinitrophenol (DNP) is a mitochondrial toxin sometimes used as a weight loss agent. Reports of fatalities from DNP have been increasing since 2000, suggesting an increase in use. Our understanding of DNP toxicity in humans comes from reports to Poison Control and postmortem analyses, sources that are biased to more extreme presentations. This leads to a gap in our knowledge about the adverse effects of DNP at nonlethal doses. Here we investigate the doses and effects of DNP as reported online.

METHODS: We analyzed publicly available Internet posts that we collected from 2017-2019. The posts came from anonymous users or users who voluntarily self-identified. We collected data from websites whose terms of use allow for the secondary analysis of data that their users agree to make public. We used natural language processing techniques that we had previously developed to extract doses, effects, and substances mentioned in each post.

RESULTS: We collected 1,630 posts across 5 online forums and the Reddit forum r/DNP. The posts were from 1,234 unique usernames. The most commonly reported doses were between 150 to 300 mg each day followed by 300 to 450 mg each day. At those doses, the most reported adverse effects were profuse sweating and fatigue. Reports of thermoregulatory (sweating, feeling hot flashes or flushed), fatigue-related, and neurologically related symptoms were statistically significantly more frequent at reported daily doses greater than 150 mg than doses below 150 mg (post-hoc χ2-test with Bonferroni correction). The effects were judged as plausible by two board-certified medical toxicologists. Triiodothyronine, clenbuterol, testosterone, and trenbolone, an androgenic anabolic steroid were the most significantly co-mentioned substances.

CONCLUSIONS: Fatigue, increased body temperature, and paresthesias from DNP are reported more frequently at doses greater than 150 mg each day than at doses less than 150 mg each day. Online discussions of DNP frequently mention androgenic anabolic steroids and other weight loss agents.

PMID:37703241 | PMC:PMC10499234 | DOI:10.1371/journal.pone.0290630

Methods Mol Biol. 2024;2716:137-152. doi: 10.1007/978-1-0716-3449-3_6.

ABSTRACT

Computational methods in modern drug discovery have become ubiquitous, with methods that cover most of the discovery stages: from hit finding and lead identification to lead optimization. The overall aim of these computational methods is to obtain a more efficient discovery process, by reducing the number of "wet" experiments required to produce therapeutics that have higher probability of succeeding in clinical development and subsequently benefitting end patients by developing highly effective therapeutics having minimal side effects. Virtual Screening is usually applied at the early stage of drug discovery, looking to find chemical matter having desired properties, such as molecular shape, electrostatics, and pharmacophores at desired three-dimensional positions. The aim of this stage is to search in a wide chemical space, including chemistry available from commercial suppliers and virtual databases of predicted reaction products, to identify molecules that would exert a particular biochemical response. This initial stage of the discovery process is very important since the subsequent stages will use the initial chemical motifs that have been found at the hit finding stage, and therefore the most suitable the compound is found, the more likely it is that subsequent stages will be successful and less time and resource consuming. This chapter provides a summary of various Virtual Screening methods, including shape match and molecular docking, and these methods are used in a Virtual Screening workflow that is provided as an example which is described to be run automatically in cloud resources. This automatic in-depth exploration of the chemical space using validated Virtual Screening methods can lead to a more streamlined and efficient discovery process, aiming to deliver chemical matter of high quality and maximizing the required biological effects while minimizing adverse effects. Surely, Virtual Screening pipelines of this nature will continue to play a central role in producing much needed therapeutics for the health challenges of the future.

PMID:37702938 | DOI:10.1007/978-1-0716-3449-3_6

Rev Med Suisse. 2023 Sep 13;19(841):1642-1646. doi: 10.53738/REVMED.2023.19.841.1642.

ABSTRACT

Detecting, treating and controlling hypertension remains a primary goal in health policy. New recommendations in the management of hypertension were published in 2023 to withhold its global pandemic. The first step is to initiate dual antihypertensive therapy in most of the cases by combining 2 molecules from different classes in a single tablet. Subsequent steps involve ensuring blood pressure control and, if indicated, combining other drug classes, again as a single pill combination (SPC). These polypills make it possible to reduce blood pressure more effectively, to offer earlier cardioprotection and to increase patient's compliance while simplifying their treatment and eliminating adverse effects. In this article, we will focus on the combination of antihypertensive classes as a revolutionary paradigm.

PMID:37702465 | DOI:10.53738/REVMED.2023.19.841.1642

Trans Am Clin Climatol Assoc. 2023;133:69-80.

ABSTRACT

Despite the advent of more targeted therapies, glucocorticoids (steroids) remain in chronic use (defined as > 3 months or more) by an estimated 0.5% of the population. Steroids yield symptomatic benefits for systemic and local inflammation as well as disease-modifying properties in rheumatoid arthritis, the most common disorder for their chronic use. Despite their many benefits, steroids have been associated with a myriad of common side effects. Observational studies of steroid safety are limited by confounding by indication, and randomized controlled trials have been too short and too small to understand their true safety profile. Glucocorticoid-induced osteoporosis (GIOP) occurs in a time- and dose-dependent way and is associated with both a reduction in bone formation and an increase in bone resorption. Numerous anti-osteoporotic therapies have efficacy for improving bone health among chronic glucocorticoid users, but implementation science approaches are needed to achieve adequate GIOP prevention and to reduce fracture outcomes.

PMID:37701582 | PMC:PMC10493762

Am Heart J. 2023 Sep 11:S0002-8703(23)00274-0. doi: 10.1016/j.ahj.2023.09.002. Online ahead of print.

ABSTRACT

BACKGROUND: The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients.

METHODS: The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit.

IMPLICATIONS: PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted.

PMID:37703948 | DOI:10.1016/j.ahj.2023.09.002

Front Pharmacol. 2023 Aug 28;14:1176980. doi: 10.3389/fphar.2023.1176980. eCollection 2023.

ABSTRACT

Purpose: To conduct a real-world evaluation of the efficacy and safety of combined Chinese and Western medicine in treating knee osteoarthritis (KOA). Methods: A multicenter, prospective cohort study design was employed, enrolling 450 KOA patients (Kellgren-Lawrence score of 3 or less). The patients were divided into a Western medicine treatment group (WM group) and a combined Western and traditional Chinese medicine treatment group (WM-CM group). A 6-week treatment plan was administered, and follow-up visits occurred at 2 weeks, 4 weeks, and 6 weeks after initiating treatment. The primary outcome indicator was the total Western Ontario and McMaster Universities Arthritis Index (WOMAC) score after 6 weeks of treatment. Secondary outcome indicators included WOMAC subscales for pain, stiffness, and joint function, visual analogue scale (VAS) score, physical component summary (PCS), mental component summary (MCS), and clinical effectiveness. The incidence of drug-related adverse events was used as a safety evaluation indicator. Results: A total of 419 patients were included in the final analysis: 98 in the WM group and 321 in the WM-CM group. The baseline characteristics of the two groups were comparable, except for the incidence of stiffness symptoms and stiffness scores. After 6 weeks of treatment, the WM-CM group exhibited superior results to the WM group in improving the total WOMAC score (24.71 ± 1.38 vs. 16.36 ± 0.62, p < 0.001). The WM-CM group also outperformed the WM group in WOMAC pain and joint function scores, VAS score, PCS score, MCS score, and clinical effectiveness (p < 0.05), which was consistent with the findings of the main evaluation index. Subgroup analysis indicated that the combined Chinese and Western medicine treatment showed more pronounced benefits in patients under 65 years of age and in those with a Kellgren-Lawrence (K-L) classification of 0-I. Throughout the study, no adverse effects were observed in either group. Conclusion: The combination of Chinese and Western medicine demonstrated superiority over Western medicine alone in relieving knee pain symptoms, improving knee function, and enhancing the quality of life for KOA patients with a K-L score of 3 or less. Moreover, the treatment exhibited a good safety profile. Clinical Trial Registration: (https://www.chictr.org.cn/), identifier (ChiCTR1900027175).

PMID:37701040 | PMC:PMC10494435 | DOI:10.3389/fphar.2023.1176980

Orphanet J Rare Dis. 2023 Sep 12;18(1):286. doi: 10.1186/s13023-023-02905-0.

ABSTRACT

BACKGROUND: The Covid pandemic seems to have had several detrimental effects on managing patients affected by inherited metabolic diseases (IMD), although published data about the impact of COVID-19 on patients suffering from IMD are very scarce. The scope of our work was to evaluate adherence to the vaccination plan, the side effects experienced by our adult IMD patients, and the symptoms of the SARS-CoV-2 infection.

RESULTS: Sixty-seven patients agreed to respond to a phone interview. The mean age was 36.5 (± 11.6 SD). Regarding the vaccination campaign, fifty-five patients (82%) joined it, of whom ten had received two doses and the remaining forty-five, three. Forty-two patients (76%) reported adverse events following vaccination, the most frequent being local reaction, fever, and asthenia, which lasted an average of two days and resolved without sequelae. Regarding SARS-CoV-2 infection, twenty-seven out of sixty-seven patients (40%) tested positive for the virus; seven of them were not vaccinated at the time of infection; on the other hand, twenty had already had at least two doses. Regarding the prevalence of long-Covid, as many as 12 patients (44%) reported symptoms that persisted after the nasopharyngeal swab tested negative and lasted an average of 81 (± 74 SD) days. There were no statistically significant differences in BMI of patients who contracted the infection and patients who did not (25.15 vs. 25.20, p = .861), between those who had adverse reactions to the vaccine and those who did not (24.40 vs. 25.75, p = .223), between those who had long-Covid and those who did not (25.9 vs. 27.7, p = .183). No relation was observed between metabolic inherited disease, SARS-CoV-2 infection symptoms and adverse vaccine reactions.

CONCLUSIONS: The data indicate that IMD patients adhered to the vaccination campaign comparably to the general Italian population. Adverse events to the vaccine were negligible. SARS-CoV-2 infection, which occurred in most cases after receiving at least two doses of the vaccine, did not cause serious symptoms and never required hospitalisation. A non-negligible share of patients suffered from long-Covid symptoms.

PMID:37700355 | DOI:10.1186/s13023-023-02905-0

Public Health Res Pract. 2023 Sep 13;33(3):3332325. doi: 10.17061/phrpp3332325.

ABSTRACT

OBJECTIVE: Due to the negative connotations around radiation, there is a great deal of angst in the community regarding radiation exposure and health; especially electromagnetic radiation (EMR) sources such as powerlines, mobile phone towers and the rollout of the 5G network. As such, it is important for health authorities to provide the public with information and assurances regarding radiation safety. The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) set up community engagement programs to address community concerns. Type of program or service: From 2003 until April 2022, ARPANSA operated a Health Complaints Register, which collected reports of health complaints from members of the public related to possible EMR exposures.

METHODS: Collected data was used to produce annual statistical summaries on the nature and level of complaints received. Since 2016, ARPANSA has also run the Talk to a Scientist program, which allows the public to communicate directly with scientists on issues about radiation exposure, health and protection in Australia. Data is collected on the type of radiation and radiation source.

RESULTS: There was a low level of interest in the Register, with only 180 reports received over the duration of its operation. Smart meters were the most common source of EMR exposure reported to be responsible for adverse health effects. The most common adverse health effect reported was headaches. The Register was closed in April 2022 due to a lack of interest. In contrast, the Talk to a Scientist program has responded to 6546 enquiries since 2016, most of which have been on EMR sources and the success of the Talk to a Scientist program, which rendered the Register obsolete.

LESSONS LEARNT: The EMR Health Complaints Register never received much interest from the public, potentially due to a perceived lack of engagement with authorities. The Talk to a Scientist program, which facilitated direct interaction with subject matter experts, has been much more successful in engaging with the public and addressing community concerns on radiation safety.

PMID:37699766 | DOI:10.17061/phrpp3332325

BMJ Open. 2023 Sep 12;13(9):e073735. doi: 10.1136/bmjopen-2023-073735.

ABSTRACT

OBJECTIVES: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.

DESIGN: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.

SETTING: The phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023.

PARTICIPANTS: The initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22).

RESULTS: Spearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach's alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r's=0.208-0.774) and discriminant (r's=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability.

CONCLUSIONS: The SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations.

TRIAL REGISTRATION NUMBERS: NCT05122260 and NCT05437029.

PMID:37699630 | DOI:10.1136/bmjopen-2023-073735

BMJ Open. 2023 Sep 12;13(9):e070645. doi: 10.1136/bmjopen-2022-070645.

ABSTRACT

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting side effects of chemotherapeutic drugs. Numerous clinical trials of various targeted drugs for the prevention or treatment of CIPN have been conducted; however, previous systematic reviews with direct comparisons have failed to demonstrate the efficacy of these drugs in the prevention or treatment of CIPN. In addition, no systematic reviews have indirectly compared CIPN prevention and treatment. This article describes a protocol for evaluating the efficacy and safety of drug therapy for the prevention and treatment of CIPN. The results of the proposed systematic review with network meta-analysis (NMA) will provide new insights into the prevention and treatment of CIPN.

METHODS AND ANALYSIS: We will conduct a literature search in MEDLINE, PubMed, Embase, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov to find relevant articles published through January 2023. We will include studies that investigated the efficacy and safety of vitamin B12, goshajinkigan, non-steroidal anti-inflammatory analgesics, opioids, calcium and magnesium, antidepressants and anticonvulsants on CIPN. Two authors will individually screen the retrieved reports and review the full text based on the selection criteria. The primary outcome is the incidence and severity of CIPN. The risk of bias will be assessed using V.2.0 of the Cochrane risk-of-bias tool. We will apply a frequentist random-effects NMA model to pool effect sizes across trials using risk ratios and mean differences with their 95% CIs. Competing interventions will be ranked using the surface under cumulative ranking probabilities. Heterogeneity will be assessed using the heterogeneity variance τ2, Cochran's Q test and I² statistic.

ETHICS AND DISSEMINATION: This review does not require ethical approval. The research will be published in a peer-reviewed journal.

PROSPERO REGISTRATION NUMBER: CRD42022371829.

PMID:37699621 | DOI:10.1136/bmjopen-2022-070645

PLoS One. 2023 Sep 12;18(9):e0291482. doi: 10.1371/journal.pone.0291482. eCollection 2023.

ABSTRACT

BACKGROUND: Adverse Drug Reactions (ADRs) can occur with all medicines even after successful extensive clinical trials. ADRs result in more than 10% of hospital admissions worldwide. In Ghana, there has been an increase of 13 to 126 ADR reports per million population from 2012 to 2018. ADR Surveillance System (ADRSS) also known as pharmacovigilance has been put in place by the Ghana Food and Drugs Authority (FDA) to collect and manage suspected ADR reports and communicate safety issues to healthcare professionals and the general public. The ADRSS in Ho Municipality was evaluated to assess the extent of reporting of ADRs and the system's attributes; determine its usefulness, and assess if the ADRSS is achieving its objectives.

METHODS: We evaluated the ADRSS of the Ho Municipality from January 2015 to December 2019. Quantitative data were collected through interviews and review of records. We adapted the updated CDC guidelines to develop interview guides and a checklist for data collection. Attributes reviewed included simplicity, data quality, acceptability, representativeness, timeliness, sensitivity, predictive value positive and stability.

RESULTS: We found a total of 1,237 suspected ADR during the period, of which only 36 (3%) were reported by healthcare professionals in the Ho Municipality to the National Pharmacovigilance Centre (NPC). Only 43.9% of health staff interviewed were familiar with the ADRSS and its reporting channel. Staff who could mention at least one objective of the ADRSS were 34.2%, and 12.2% knew the timelines for reporting ADR. Reports took a median time of 41 (IQR = 25, 81) days from reporter to NPC. Reports sent on time constituted 37.5%. Fully completed case forms constituted 77.1% and the predictive value positive (PVP) was 20%. About 53% of ADRs were reported for female patients. Up to 88.9% of ADRs were classified as drug related. Anti-tuberculosis agents and other antibiotics constituted (40.6%) and (18.8%) of all reports. The ADRSS was not integrated into the disease surveillance and response system of Ghana's Health Service and so was not flexible to changes. A dedicated ADR surveillance officer in regions helped with the system's stability. Data from Ghana feeds into a WHO database for global decision making.

CONCLUSIONS: There was under-reporting of ADRs in the Ho Municipality from January 2015 to December 2019. The ADR surveillance system was simple, stable, acceptable, representative, had a strong PVP but was not flexible or timely. The ADRSS was found useful and partially met its objectives.

PMID:37699058 | PMC:PMC10497160 | DOI:10.1371/journal.pone.0291482

J Med Internet Res. 2023 Sep 12;25:e45437. doi: 10.2196/45437.

ABSTRACT

BACKGROUND: Mobile health (mHealth) technology has great potential for addressing the epidemic of chronic noncommunicable diseases (CNCDs) by assisting health providers (HPs) with managing these diseases. However, there is currently limited evidence regarding the acceptance of mHealth among HPs, which is a key prerequisite for harnessing this potential.

OBJECTIVE: This review aimed to investigate the perceptions and experiences of HPs regarding the barriers to and facilitators of mHealth use for CNCDs.

METHODS: A systematic search was conducted in MEDLINE (via Ovid), Embase, Web of Science, Google Scholar, and Cochrane Library (via Ovid) for studies that assessed the perceptions and experiences of HPs regarding the barriers to and facilitators of mHealth use for CNCDs. Qualitative studies and mixed methods studies involving qualitative methods published in English were included. Data synthesis and interpretation were performed using a thematic synthesis approach.

RESULTS: A total of 18,242 studies were identified, of which 24 (0.13%) met the inclusion criteria. Overall, 6 themes related to facilitators were identified, namely empowering patient self-management, increasing efficiency, improving access to care, increasing the quality of care, improving satisfaction, and improving the usability of the internet and mobile software. Furthermore, 8 themes related to barriers were identified, namely limitation due to digital literacy, personal habits, or health problems; concern about additional burden; uncertainty around the value of mHealth technology; fear of medicolegal risks; lack of comfortable design and experience; lack of resources and incentives; lack of policy guidance and regulation; and worrisome side effects resulting from the use of mHealth.

CONCLUSIONS: This study contributes to the understanding of the beneficial factors of and obstacles to mHealth adoption by HPs for CNCDs. The findings of this study may provide significant insights for health care workers and policy makers who seek ways to improve the adoption of mHealth by HPs for CNCDs.

PMID:37698902 | DOI:10.2196/45437

Anesthesiology. 2023 Oct 1;139(4):511-522. doi: 10.1097/ALN.0000000000004669.

ABSTRACT

The traditional paradigm of oncologic treatment centered on cytotoxic chemotherapy has undergone tremendous advancement during the last 15 yr with the advent of immunotherapy and targeted cancer therapies. These agents, including small molecule inhibitors, monoclonal antibodies, and immune-checkpoint inhibitors, are highly specific to individual tumor characteristics and can prevent cell growth and tumorigenesis by inhibiting specific molecular targets or single oncogenes. While generally better tolerated than traditional chemotherapy, these therapies are associated with unique constellations of adverse effects. Of particular importance in the perioperative and periprocedural settings are hematologic abnormalities, particularly antiplatelet effects with increased risk of bleeding, and implications for wound healing. This narrative review discusses targeted cancer therapies and provides recommendations for physicians managing these patients' care as it relates to procedural or surgical interventions.

PMID:37698434 | DOI:10.1097/ALN.0000000000004669

Anesthesiology. 2023 Oct 1;139(4):523-536. doi: 10.1097/ALN.0000000000004673.

ABSTRACT

Chronic pain is a public health concern that affects approximately 1.5 billion people globally. Conventional therapeutic agents including opioid and non-opioid analgesics have been associated with adverse side effects, issues with addiction, and ineffective analgesia. Novel agents repurposed to treat pain via different mechanisms are needed to fill the therapeutic gap in chronic pain management. Psychedelics such as lysergic acid diethylamide and psilocybin (the active ingredient in psychedelic mushrooms) are thought to alter pain perception through direct serotonin receptor agonism, anti-inflammatory effects, and synaptic remodeling. This scoping review was conducted to identify human studies in which psychedelic agents were used for the treatment of pain. Twenty-one articles that assessed the effects of psychedelics in treating various pain states were included. The present scarcity of clinical trials and small sample sizes limit their application for clinical use. Overall, psychedelics appear to show promise for analgesia in patients with certain headache disorders and cancer pain diagnoses. Future studies must aim to examine the combined effects of psychotherapy and psychedelics on chronic pain.

PMID:37698433 | DOI:10.1097/ALN.0000000000004673

East Mediterr Health J. 2023 Aug 31;29(8):657-663. doi: 10.26719/emhj.23.050.

ABSTRACT

BACKGROUND: Complementary and alternative medicine is widely used in Saudi Arabia. One of the common practices is the use of camel urine alone or mixed with camel milk for the treatment of cancer, which is often supported by religious beliefs.

AIMS: To observe and follow-up cancer patients who insisted on using camel urine, and to offer some clinically relevant recommendations.

METHODS: We observed 20 cancer patients (15 male, 5 female) from September 2020 to January 2022 who insisted on using camel urine for treatment. We documented the demographics of each patient, the method of administering the urine, reasons for refusing conventional treatment, period of follow-up, and the outcome and side effects.

RESULTS: All the patients had radiological investigations before and after their treatment with camel urine. All of them used a combination of camel urine and camel milk, and treatment ranged from a few days to 6 months. They consumed an average of 60 ml urine/milk per day. No clinical benefit was observed after the treatment; 2 patients developed brucellosis. Eleven patients changed their mind and accepted conventional antineoplastic treatment and 7 were too weak to receive further treatment; they died from the disease.

CONCLUSION: Camel urine had no clinical benefits for any of the cancer patients, it may even have caused zoonotic infection. The promotion of camel urine as a traditional medicine should be stopped because there is no scientific evidence to support it.

PMID:37698221 | DOI:10.26719/emhj.23.050

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