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PloS One 2024This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment. (Meta-Analysis)
Meta-Analysis Comparative Study
OBJECTIVES
This study aimed to evaluate the effectiveness of topical clascoterone (TC) compared to oral spironolactone for acne vulgaris treatment.
METHODS
A computerized search through PubMed/MEDLINE, SCOPUS, and the Cochrane Library was conducted to find relevant papers. We used the "netmeta" and "meta" packages for network meta-analysis (NMA) in RStudio 1.2.5019 (2009-2019 RStudio, Inc.) to conduct all of our statistical tests.
RESULTS
Seven articles (n = 2,006 patients) were included. The fixed-effect size showed that TC 1% bis in die (BID) showed potential effectiveness in reducing the inflammatory and non-inflammatory lesion count compared to placebo (Standardized mean difference, SMD = -0.27, 95% CI: -0.36 to -0.17) and (SMD = -0.31, 95% CI: -0.41 to -0.22), respectively. The random-effect size showed that TC 1% BID was significantly associated with a 12-week treatment success compared to placebo (Odds ratio, OR = 2.44, 95% CI: 1.12 to 5.30). Spironolactone 200 mg was associated with a significant reduction in total lesion count (SMD = -4.46, 95% CI: -5.60 to -3.32).
CONCLUSION
TC appears to reduce both inflammatory and non-inflammatory lesion count and may lead to treatment success. Spironolactone at 200 mg showed potential effectiveness in terms of total lesion count reduction. These results suggest that both TC and Spironolactone could be beneficial in treating patients with acne vulgaris.
Topics: Acne Vulgaris; Humans; Spironolactone; Network Meta-Analysis; Treatment Outcome; Administration, Topical; Cortodoxone; Propionates
PubMed: 38814916
DOI: 10.1371/journal.pone.0298155 -
Cureus Apr 2024Acne keloidalis nuchae (AKN) is a rare dermatological condition primarily observed in men of African descent. We present a remarkable case of AKN in a 38-year-old...
Acne keloidalis nuchae (AKN) is a rare dermatological condition primarily observed in men of African descent. We present a remarkable case of AKN in a 38-year-old Caucasian non-Hispanic woman with metabolic syndrome and autoimmune thyroiditis. After appropriate treatment during the one-year follow-up (including oral antibiotics, insulin sensitizers, levothyroxine, spironolactone and liraglutide), the patient demonstrated a visible reduction in plaque size and improvement of overall symptoms. Importantly, this improvement persisted even in the absence of topical treatment, further supporting the notion that hormonal abnormalities may play a significant role in the pathogenesis of AKN. This case report highlights the potential link between AKN and endocrinologic disorders, such as metabolic syndrome and autoimmune thyroiditis. However, further research is warranted to elucidate the underlying mechanisms and establish the causative relationship. Early recognition, appropriate management of associated conditions, and tailored treatment strategies may lead to better outcomes and improved quality of life.
PubMed: 38803744
DOI: 10.7759/cureus.59119 -
Frontiers in Endocrinology 2024Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with...
BACKGROUND
Gender-affirming hormone therapy (GAHT) is a common medical intervention sought by transgender and gender diverse (TGD) individuals. Initiating GAHT in accordance with clinical guideline recommendations ensures delivery of high-quality care. However, no prior studies have examined how current GAHT initiation compares to recommended GAHT initiation.
OBJECTIVE
This study assessed guideline concordance around feminizing and masculinizing GAHT initiation in the Veterans Health Administration (VHA).
METHODS
The sample included 4,676 veterans with a gender identity disorder diagnosis who initiated feminizing (=3,547) and masculinizing (=1,129) GAHT between 2007 and 2018 in VHA. Demographics and health conditions on veterans receiving feminizing and masculinizing GAHT were assessed. Proportion of guideline concordant veterans on six VHA guidelines on feminizing and masculinizing GAHT initiation were determined.
RESULTS
Compared to veterans receiving masculinizing GAHT, a higher proportion of veterans receiving feminizing GAHT were older (≥60 years: 23.7% vs. 6.3%), White non-Hispanic (83.5% vs. 57.6%), and had a higher number of comorbidities (≥7: 14.0% vs. 10.6%). A higher proportion of veterans receiving masculinizing GAHT were Black non-Hispanic (21.5% vs. 3.5%), had posttraumatic stress disorder (43.0% vs. 33.9%) and positive military sexual trauma (33.5% vs.16.8%; all p-values<0.001) than veterans receiving feminizing GAHT. Among veterans who started feminizing GAHT with estrogen, 97.0% were guideline concordant due to no documentation of contraindication, including venous thromboembolism, breast cancer, stroke, or myocardial infarction. Among veterans who started spironolactone as part of feminizing GAHT, 98.1% were guideline concordant as they had no documentation of contraindication, including hyperkalemia or acute renal failure. Among veterans starting masculinizing GAHT, 90.1% were guideline concordant due to no documentation of contraindications, such as breast or prostate cancer. Hematocrit had been measured in 91.8% of veterans before initiating masculinizing GAHT, with 96.5% not having an elevated hematocrit (>50%) prior to starting masculinizing GAHT. Among veterans initiating feminizing and masculinizing GAHT, 91.2% had documentation of a gender identity disorder diagnosis prior to GAHT initiation.
CONCLUSION
We observed high concordance between current GAHT initiation practices in VHA and guidelines, particularly for feminizing GAHT. Findings suggest that VHA clinicians are initiating feminizing GAHT in concordance with clinical guidelines. Future work should assess guideline concordance on monitoring and management of GAHT in VHA.
Topics: Humans; Female; United States; Male; Middle Aged; Practice Guidelines as Topic; Transgender Persons; Adult; United States Department of Veterans Affairs; Veterans; Sex Reassignment Procedures; Guideline Adherence; Aged; Gender Dysphoria; Transsexualism; Veterans Health; Hormone Replacement Therapy; Practice Patterns, Physicians'
PubMed: 38800485
DOI: 10.3389/fendo.2024.1086158 -
MedRxiv : the Preprint Server For... May 2024Randomized clinical trials (RCTs) are the standard for defining an evidence-based approach to managing disease, but their generalizability to real-world patients remains...
IMPORTANCE
Randomized clinical trials (RCTs) are the standard for defining an evidence-based approach to managing disease, but their generalizability to real-world patients remains challenging to quantify.
OBJECTIVE
To develop a multidimensional patient variable mapping algorithm to quantify the similarity and representation of electronic health record (EHR) patients corresponding to an RCT and estimate the putative treatment effects in real-world settings based on individual treatment effects observed in an RCT.
DESIGN
A retrospective analysis of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT; 2006-2012) and a multi-hospital patient cohort from the electronic health record (EHR) in the Yale New Haven Hospital System (YNHHS; 2015-2023).
SETTING
A multicenter international RCT (TOPCAT) and multi-hospital patient cohort (YNHHS).
PARTICIPANTS
All TOPCAT participants and patients with heart failure with preserved ejection fraction (HFpEF) and ≥1 hospitalization within YNHHS.
EXPOSURES
63 pre-randomization characteristics measured across the TOPCAT and YNNHS cohorts.
MAIN OUTCOMES AND MEASURES
Real-world generalizability of the RCT TOPCAT using a multidimensional phenotypic distance metric between TOPCAT and YNHHS cohorts. Estimation of the individualized treatment effect of spironolactone use on all-cause mortality within the YNHHS cohort based on phenotypic distance from the TOPCAT cohort.
RESULTS
There were 3,445 patients in TOPCAT and 11,712 HFpEF patients across five hospital sites. Across the 63 TOPCAT variables mapped by clinicians to the EHR, there were larger differences between TOPCAT and each of the 5 EHR sites (median SMD 0.200, IQR 0.037-0.410) than between the 5 EHR sites (median SMD 0.062, IQR 0.010-0.130). The synthesis of these differences across covariates using our multidimensional similarity score also suggested substantial phenotypic dissimilarity between the TOPCAT and EHR cohorts. By phenotypic distance, a majority (55%) of TOPCAT participants were closer to each other than any individual EHR patient. Using a TOPCAT-derived model of individualized treatment benefit from spironolactone, those predicted to derive benefit and receiving spironolactone in the EHR cohorts had substantially better outcomes compared with predicted benefit and not receiving the medication (HR 0.74, 95% CI 0.62-0.89).
CONCLUSIONS AND RELEVANCE
We propose a novel approach to evaluating the real-world representativeness of RCT participants against corresponding patients in the EHR across the full multidimensional spectrum of the represented phenotypes. This enables the evaluation of the implications of RCTs for real-world patients.
KEY POINTS
How can we examine the multi-dimensional generalizability of randomized clinical trials (RCT) to real-world patient populations? We demonstrate a novel phenotypic distance metric comparing an RCT to real-world populations in a large multicenter RCT of heart failure patients and the corresponding patients in multisite electronic health records (EHRs). Across 63 pre-randomization characteristics, pairwise assessments of members of the RCT and EHR cohorts were more discordant from each other than between members of the EHR cohort (median standardized mean difference 0.200 [0.037-0.410] vs 0.062 [0.010-0.130]), with a majority (55%) of RCT participants closer to each other than any individual EHR patient. The approach also enabled the quantification of expected real world outcomes based on effects observed in the RCT. A multidimensional phenotypic distance metric quantifies the generalizability of RCTs to a given population while also offering an avenue to examine expected real-world patient outcomes based on treatment effects observed in the RCT.
PubMed: 38798457
DOI: 10.1101/2024.05.15.24306285 -
Innovations in Pharmacy 2024: Extemporaneous compounding is the preparation of medicines for individual patients when no commercially available authorized form exists. Unlike registered...
: Extemporaneous compounding is the preparation of medicines for individual patients when no commercially available authorized form exists. Unlike registered medications, these products are not subjected to various tests for quality by Regulatory Authorities. Data on compounded medications in Ghana is currently inadequate or unavailable. There is the need to collate data that can be used to influence policy and to regulate preparation of extemporaneous products. : To establish the prevalence, scope and quality of extemporaneously compounded medicines at selected hospitals in Accra, Ghana. : Prescriptions presented at the pharmacies in selected hospitals were reviewed to determine the requests that needed to be extemporaneously prepared as well as the prevalence and the scope of formulations. Three of the most frequently compounded medications were procured and subjected to microbial contamination tests using the pour plate method followed by differential tests if microbes were present. Content analysis of the active ingredients was determined using High Performance Liquid Chromatography (HPLC). : 641 requests comprising 49 different extemporaneous products were collated from the hospitals studied. Hydroxyurea, furosemide and spironolactone suspensions were the three most frequently prescribed. Patients aged from 0-2 years had majority of the prescriptions. : A population of patients still exist who depend on compounding for their drug needs. 49 different formulations were prepared at one of the hospitals visited. Samples of products analyzed were of good quality.
PubMed: 38779112
DOI: 10.24926/iip.v15i1.5971 -
Journal of Medicine and Life Jan 2024Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the...
Heart failure (HF) remains a significant problem for healthcare systems, requiring the use of intervention and multimodal management strategies. We aimed to assess the short-term effect of empagliflozin (EMPA) and metformin on cardiac function parameters, including ventricular dimension-hypertrophy, septal thickness, ejection fraction (EF), and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with HF and mildly reduced EF. A case-control study included 60 newly diagnosed patients with HF. Patients were divided into two groups: Group E received standard HF treatment (carvedilol, bumetanide, sacubitril-valsartan, spironolactone) plus EMPA 10 mg daily, and Group M received standard HF treatment plus metformin 500 mg daily. After three months of treatment, Group E had a significantly higher EF than Group M compared to initial measurements (a change of 9.2% versus 6.1%, respectively). We found similar results in the left ventricular end-systolic dimension (LVESD), with mean reductions of 0.72 mm for Group E and 0.23 mm for Group M. Regarding cardiac indicators, the level of NT-proBNP was considerably decreased in both groups. However, the reduction was significantly greater in group E than in group M compared to the initial level (mean reduction: 719.9 vs. 973.6, respectively). When combined with quadruple anti-heart failure therapy, metformin enhanced several echocardiographic parameters, showing effects similar to those of EMPA when used in the same treatment regimen. However, the benefits of EMPA were more pronounced, particularly regarding improvements in EF and LVESD.
Topics: Humans; Heart Failure; Benzhydryl Compounds; Glucosides; Metformin; Stroke Volume; Male; Female; Case-Control Studies; Middle Aged; Aged; Natriuretic Peptide, Brain; Peptide Fragments; Echocardiography; Sodium-Glucose Transporter 2 Inhibitors
PubMed: 38737651
DOI: 10.25122/jml-2023-0340 -
Heart (British Cardiac Society) May 2024Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70%...
OBJECTIVE
Heart failure (HF) is characterised by collagen deposition. Urinary proteomic profiling (UPP) followed by peptide sequencing identifies parental proteins, for over 70% derived from collagens. This study aimed to refine understanding of the antifibrotic action of spironolactone.
METHODS
In this substudy (n=290) to the Heart 'Omics' in Ageing Study trial, patients were randomised to usual therapy combined or not with spironolactone 25-50 mg/day and followed for 9 months. The analysis included 1498 sequenced urinary peptides detectable in ≥30% of patients and carboxyterminal propeptide of procollagen I (PICP) and PICP/carboxyterminal telopeptide of collagen I (CITP) as serum biomarkers of COL1A1 synthesis. After rank normalisation of biomarker distributions, between-group differences in their changes were assessed by multivariable-adjusted mixed model analysis of variance. Correlations between the changes in urinary peptides and in serum PICP and PICP/CITP were compared between groups using Fisher's Z transform.
RESULTS
Multivariable-adjusted between-group differences in the urinary peptides with error 1 rate correction were limited to 27 collagen fragments, of which 16 were upregulated (7 COL1A1 fragments) on spironolactone and 11 downregulated (4 COL1A1 fragments). Over 9 months of follow-up, spironolactone decreased serum PICP from 81 (IQR 66-95) to 75 (61-90) µg/L and PICP/CITP from 22 (17-28) to 18 (13-26), whereas no changes occurred in the control group, resulting in a difference (spironolactone minus control) expressed in standardised units of -0.321 (95% CI 0.0007). Spironolactone did not affect the correlations between changes in urinary COL1A1 fragments and in PICP or the PICP/CITP ratio.
CONCLUSIONS
Spironolactone decreased serum markers of collagen synthesis and predominantly downregulated urinary collagen-derived peptides, but upregulated others. The interpretation of these opposite UPP trends might be due to shrinking the body-wide pool of collagens, explaining downregulation, while some degree of collagen synthesis must be maintained to sustain vital organ functions, explaining upregulation. Combining urinary and serum fibrosis markers opens new avenues for the understanding of the action of antifibrotic drugs.
TRIAL REGISTRATION NUMBER
NCT02556450.
PubMed: 38729636
DOI: 10.1136/heartjnl-2023-323796 -
Frontiers in Endocrinology 2023The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an... (Review)
Review
The most common cause of infertility and metabolic problems among women of reproductive age is polycystic ovary syndrome (PCOS), a multifaceted disorder. It is an endocrine disorder that occurs in approximately one in seven women. Among these PCOS patients, two thirds will not ovulate on a regular basis and seek treatment for ovulation induction. The symptoms vary in their severity, namely ovulation disorders, excessive androgen levels, or polycystic ovarian morphology. All these symptoms require a therapeutic approach. Many drugs are used to eradicate PCOS symptoms, like metformin, clomiphene citrate, spironolactone, and pioglitazone. Long-term treatment is required to achieve the desired outcome, which is often accompanied by significant adverse reactions. Some herbs and phytochemicals are equally effective for treating PCOS and produce minimal side effects. Recently, herbal products are gaining popularity due to their wide biological activities, safety, availability, and efficacy. The present review covers aetiology, current treatment, pathophysiology, and detailed pre-clinical and clinical studies on plants and phytochemicals that are proven to be useful for the treatment of symptoms associated with PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Female; Phytotherapy; Phytochemicals; Animals; Plant Extracts
PubMed: 38725974
DOI: 10.3389/fendo.2023.1294406 -
Cureus Apr 2024In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This... (Review)
Review
In India, around 234 million adults (one in three) suffer from hypertension (HTN). An average of 10% of these cases are likely to be resistant hypertension (RH). This load of 23 million patients is expected to expand further with revisions in diagnostic criteria. The treatment and control rates of hypertension in India average around 30% and 15%, respectively. Pharmacological management involves a stepwise approach starting with optimizing the A-C-D (angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs), and thiazide-like diuretics) triple-drug combination, followed by substitution with a thiazide-like diuretic and use of spironolactone as a next step (fourth drug). The subsequent steps are suggestions based on expert input and must be individualized. These include using a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when target blood pressure (BP) values are not achieved. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are likely to be helpful in managing RH due to their renal and cardiovascular protection as well as mortality benefits. SGLT2i lowers BP independent of the dosage and concomitant anti-hypertensive medications. Patient education and tools to monitor BP and treatment compliance will improve outcomes with these medications. In addition to therapeutic intervention, a preventive approach for RH mandates a need to identify patients at risk and use appropriate preventive and optimal therapy to prevent uncontrolled hypertension in patients with cardiovascular disorders.
PubMed: 38721164
DOI: 10.7759/cureus.57804 -
Translational Pediatrics Apr 2024Pleural effusion, pericardial effusion, and pulmonary arterial hypertension have been shown to have potential associations with the use of dasatinib in adults. However,...
BACKGROUND
Pleural effusion, pericardial effusion, and pulmonary arterial hypertension have been shown to have potential associations with the use of dasatinib in adults. However, due to the limited data regarding the efficacy and safety of tyrosine kinase inhibitors (TKIs) in pediatric patients necessities reliance on clinical experience gained from treating adults.
CASE DESCRIPTION
We present a case of a 12-year-old female patient with chronic myelogenous leukemia (CML) who developed significant right-sided pleural effusion, moderate pericardial effusion, and pulmonary arterial hypertension during dasatinib therapy. Dasatinib was promptly discontinued upon identification of these adverse events. This was followed by the use of bosentan for pulmonary hypertension, furosemide and spironolactone diuretics, prednisone anti-inflammatory, and especially a bold attempt to improve pulmonary endothelial permeability with acetyl cysteine aerosolization. At the same time, according to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data reported by the patient and combined with the actual situation, the appropriate TKI was selected for the patient to continue the CML treatment.
CONCLUSIONS
FAERS data gathered on OpenVigil indicates that the signal associated with pericardial effusion is stronger among individuals under the age of 18 when imatinib is used instead of dasatinib (exactly the reverse of the results in the adult group). However, this does not imply that dasatinib is safer for the smaller group. In our situation, dasatinib-induced adverse effects include pericardial effusion. As a result, while administering TKIs to pediatric patients, we still need to increase monitoring-particularly for pulmonary and cardiovascular toxicity-and take swift action in the event that a major adverse reaction occurs. In addition, it is important to report these adverse effects as much as possible in order to give pediatric patients utilizing TKIs more helpful information.
PubMed: 38715671
DOI: 10.21037/tp-23-517