Ther Innov Regul Sci. 2022 Sep;56(5):839-847. doi: 10.1007/s43441-022-00431-y. Epub 2022 Jul 25.

ABSTRACT

PURPOSE: Scientific information in the drug labeling is expected to be the most up-to-date and consistent information across countries where medicine is approved. The objective of the present study is to investigate the consistency of safety-related information on product labeling for novel therapeutics concurrently approved in Japan and the US.

METHODS: Safety information at the time of initial approval of new drugs approved concurrently both in Japan and the US in the recent 7 years were identified and reviewed for concordance. Factors associated with the discordance were also investigated.

RESULTS: Despite the similar medical practices, population health, and regulation in Japan and the US, the level of concordance of safety information found in the drug labeling of 45 new active substances was low (20.4%). The development strategy of the drugs and having the same MAH were significantly associated with the concordance rate. The mean concordance rate among the 9 drugs with Black Box Warning in both countries was also low (32.9%).

CONCLUSIONS: We found a low level of concordance between Japan and the US even when related to clinically important information raised by Black Box Warnings. The low concordance rate highlighted the need for a greater transparency in decision-making processes about the safety information in a drug labeling by both industry and regulators to take appropriate countermeasures against the discordance.

PMID:35877034 | PMC:PMC9310370 | DOI:10.1007/s43441-022-00431-y

Zhonghua Yi Xue Za Zhi. 2022 Jul 26;102(28):2196-2200. doi: 10.3760/cma.j.cn112137-20211220-02828.

ABSTRACT

Objective: To evaluate the occurrence and recovery of adverse drug reactions (ADRs) of preventive treatment in the elderly population with latent tuberculosis infection (LTBI). Methods: A total of 2 583 elderly patients with LTBI were recruited in Zhongmu, Henan Province from July 1 to October 17, 2015. Face-to-face surveys and physical examinations were used to obtain the basic information of the participants, and the body mass index (BMI) was calculated. Fasting venous blood was collected from the participants for blood biochemical and routine blood tests. The random numbers were generated by Excel 2010, and the participants were divided into group A (1 284 cases) and group B (1 299 cases) by simple randomization. Both group A and group B received combination treatment of isoniazid and rifapentine. Group A was treated for 8 weeks with weekly doses of isoniazid at 15 mg/kg and 900 mg for those with body weight ≤50 and>50 kg, respectively, and the doses of rifapentin were 750 and 900 mg, respectively. Group B was treated twice a week for 6 weeks, the doses of isoniazid in patients with body weight ≤50 and>50 kg were [600-(50-body weight)×15] (rounded up) and 600 mg, respectively, and the doses of rifapentin were 600 and 450 mg, respectively. During the treatment period, doctors observed, inquired about and recorded symptoms related to ADRs, and blood biochemical and routine blood tests were performed at 4 weeks after taking the drug, the end of the treatment, and 3 months after the end of the treatment. The patients with ADRs were treated accordingly by severity. The ADRs and graded treatment outcomes of LTBI patients in group A and group B were compared. Results: The age［M（Q1，Q3）］of the participants was 60 (55,65) years old, and 54.7% (1 412/2 583) were males. There were no statistical differences in age, gender, BMI and baseline biochemical indexes between groups A and B (all P values>0.05). The incidence of ADRs in group A and group B were 18.5% (237/1 279) and 16.3% (209/1 279), respectively, and those with alanine aminotransferase (ALT)≥5 ULN accounted for 0.8% (7/931) and 1.1% (11/987), aspartate aminotransferase (AST)≥5 ULN accounted for 0.3% (3/931) and 0.3% (3/987), respectively, and there were no statistically significant differences (all P values>0.05). There were 7 and 11 patients with ALT≥5 ULN in group A and group B, respectively, and 3 patients with AST≥5 ULN for each group, respectively. After treatment, except for 2 patients with ALT≥5 ULN in group B, ALT and AST levels in all the other patients returned to normal. There were 15 and 10 patients with abnormal white blood cell count in group A and group B, respectively, and 10 and 9 patients returned to normal after treatment. Conclusion: LTBI preventive treatment has a high incidence of adverse drug reactions, but it can be effectively controlled through active monitoring and graded management.

PMID:35872584 | DOI:10.3760/cma.j.cn112137-20211220-02828

BMC Cancer. 2022 Jul 25;22(1):816. doi: 10.1186/s12885-022-09915-4.

ABSTRACT

BACKGROUND: The endothelial activation and stress index (EASIX) score has been reported to predict overall survival (OS) in hematological cancers. However, it has not been validated as a prognostic marker for diffuse large B-cell lymphoma (DLBCL) to date.

METHODS: The records of 265 patients who presented with DLBCL in the Republic of Korea between January 07, 2004, and March 05, 2020 were retrospectively reviewed. For all included patients, EASIX scores were calculated using serum lactate dehydrogenase (LDH) and creatinine levels and the platelet count measured at diagnosis as follows: LDH (U/L) × creatinine (mg/dL)/platelet count (109/L).

RESULTS: The median age of the patients was 64 years. The optimal cutoff value of EASIX according to the receiver operating characteristic analysis for OS was 1.33. All the patients were treated with cyclophosphamide, doxorubicin, vincristine, and prednisone combined with rituximab. The 1-year OS and progression-free survival (PFS) rates were lower in the high-EASIX group than in the low EASIX group (63.8% vs. 84.4%, p < 0.001 and 54.0% vs. 79.6%, p < 0.001, respectively). A high EASIX was an independent poor prognostic factor for OS and PFS (hazard ratio, 1.606; 95% CI, 1.077-2.395; p = 0.020 and hazard ratio, 1.621; 95% CI, 1.066-2.464; p = 0.024, respectively).

CONCLUSIONS: EASIX is a readily available and cheaply obtainable parameter in clinical studies and shows considerable potential as a new prognostic marker for patients with newly diagnosed DLBCL.

PMID:35879680 | DOI:10.1186/s12885-022-09915-4

Curr Issues Mol Biol. 2022 Jul 6;44(7):3089-3099. doi: 10.3390/cimb44070213.

ABSTRACT

Doxorubicin (DOX) and vincristine (VC) are anti-cancer drugs commonly used for lymphoma in veterinary and human medicine. However, there are several side effects caused by these drugs. In this study, the protective effects of sonicated Bordetella bronchiseptica bacterin (sBb) on dendritic cells (DCs) damaged by two anti-cancer drugs were investigated. DCs play important roles in the innate and adaptive immunity of hosts, especially activating T cells that can suppress tumor growth. The metabolic activity of DCs significantly increased after the treatment with sBb compared to that of control DCs. In addition, there was a marked change in mitochondrial integrity between DOX-treated DC and DOX + sBb-treated DCs. Flow cytometric analysis also demonstrated that sBb upregulated the expression of the surface markers of DCs, particularly CD54. In mixed lymphocyte responses, sBb significantly increased the antigen-presenting capability of DCs. In particular, sBb increased the capability of control DCs by approximately 150% and that of VC-treated DCs by 221%. These results suggest that sBb can be used as a potential immunostimulatory agent to protect DCs from anti-cancer drug-induced damage and provide fundamental information about using a combination of DCs and vincristine in immunotherapy.

PMID:35877437 | DOI:10.3390/cimb44070213

Mycoses. 2022 Jul 25. doi: 10.1111/myc.13506. Online ahead of print.

ABSTRACT

BACKGROUND: Acute Generalized Exanthematous Pustulosis (AGEP) is a rash with multiple sterile intraepidermal or sub corneal non-follicular pustules on edematous papules, with a sudden development and rapid evolution, triggered by drugs, vaccination, insect bites, exposure to mercury and allergens.

OBJECTIVES AND METHODS: We describe a female patient who developed extensive and abnormally prolonged AGEP following exposure to terbinafine and Sars-COV Vaccine. A detailed review of terbinafine-induced-AGEP cases was performed, with the aim of evaluating if the AGEP criteria would follow a different pattern when the disease is triggered by this drug. A pubmed search helped retrieve all terbinafine induced AGEP case reports. AGEP specific Sideroff criteria were analyzed in Terbinafine-induced cases, and compared to other trigger causes.

CONCLUSIONS: when AGEP causative drug was terbinafine, a delay in recovery was observed, compared to the existing AGEP criteria when other causes are considered. Terbinafine frequently leads to delayed resolution AGEP probably due to the presence of the drug in the skin during several weeks after exposure, even after discontinuation, and the disease severity may be potentialized by additional factors such as concomitant viral infections or vaccination.

PMID:35876217 | DOI:10.1111/myc.13506

Clin Exp Dermatol. 2022 Jul 25. doi: 10.1111/ced.15343. Online ahead of print.

ABSTRACT

Drug-induced photodistributed telangiectasia (PT) is cutaneous side effects resulting from the interaction of ultraviolet (UV) radiation with pharmacotherapy. Reports of PT in literature are scarce. We report twenty-five cases of drug-induced photodistributed telangiectasias, highlighting the potential relationship between the onset of skin lesions, drug-intake and photo-exposure. We alert practitioners that telangiectasia is a possible dermatological phototoxic side-effect to many drugs.

PMID:35876166 | DOI:10.1111/ced.15343

Amyloid. 2022 Jul 23:1-9. doi: 10.1080/13506129.2022.2091985. Online ahead of print.

ABSTRACT

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy.

METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months.

RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10-12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths.

CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile.

CLINICALTRIALS.GOV: NCT03759379.

PMID:35875890 | DOI:10.1080/13506129.2022.2091985

Front Pharmacol. 2022 Jul 5;13:858345. doi: 10.3389/fphar.2022.858345. eCollection 2022.

ABSTRACT

India confines more than 17% of the world's population and has a diverse genetic makeup with several clinically relevant rare mutations belonging to many sub-group which are undervalued in global sequencing datasets like the 1000 Genome data (1KG) containing limited samples for Indian ethnicity. Such databases are critical for the pharmaceutical and drug development industry where diversity plays a crucial role in identifying genetic disposition towards adverse drug reactions. A qualitative and comparative sequence and structural study utilizing variant information present in the recently published, largest curated Indian genome database (IndiGen) and the 1000 Genome data was performed for variants belonging to the kinase coding genes, the second most targeted group of drug targets. The sequence-level analysis identified similarities and differences among different populations based on the nsSNVs and amino acid exchange frequencies whereas a comparative structural analysis of IndiGen variants was performed with pathogenic variants reported in UniProtKB Humsavar data. The influence of these variations on structural features of the protein, such as structural stability, solvent accessibility, hydrophobicity, and the hydrogen-bond network was investigated. In-silico screening of the known drugs to these Indian variation-containing proteins reveals critical differences imparted in the strength of binding due to the variations present in the Indian population. In conclusion, this study constitutes a comprehensive investigation into the understanding of common variations present in the second largest population in the world and investigating its implications in the sequence, structural and pharmacogenomic landscape. The preliminary investigation reported in this paper, supporting the screening and detection of ADRs specific to the Indian population could aid in the development of techniques for pre-clinical and post-market screening of drug-related adverse events in the Indian population.

PMID:35865963 | PMC:PMC9294532 | DOI:10.3389/fphar.2022.858345

Clin Infect Dis. 2022 Jul 21:ciac585. doi: 10.1093/cid/ciac585. Online ahead of print.

ABSTRACT

BACKGROUND: Higher doses of rifampicin may improve treatment outcomes and reduce the duration of TB therapy, but drug-drug interactions with anti-retroviral therapy (ART) and safety in people living with HIV have not been evaluated.

METHODS: This was a randomized open-label trial where newly diagnosed TB patients were randomized to higher (35 mg/kg) or standard (10 mg/kg) daily dose rifampicin. ART treatment naïve patients were randomized to dolutegravir- or efavirenz-based ART, whilst those already on ART continued existing medications. At week 6, trough dolutegravir or mid-dose efavirenz plasma concentrations were assayed. Sputum was collected for mycobacterial culture collected at week 8, and plasma for HIV viral load at Week 24.

RESULTS: Among 128 patients randomized, the median CD4 count was 191cells/mm3. Geometric mean ratio (GMR) for trough dolutegravir concentrations on higher vs. standard-dose rifampicin was 0.57 [95%CI: 0.34-0.97, p = 0.039] and GMR for mid-dose efavirenz was 0.63 [0.38-1.07, p = 0.083]. There was no significant difference in attainment of targets for dolutegravir trough or efavirenz mid-dose concentrations between rifampicin doses. The incidence of HIV treatment failure at week 24 was similar between rifampicin doses (14.9% vs. 14.0%, p = 0.901), as was the incidence of drug-related grade 3-4 adverse events (9.8% vs 6%). At week 8, fewer patients remained sputum culture positive on higher-dose rifampicin (18.6% vs. 37.0%, p = 0.063).

CONCLUSIONS: Compared to standard-dose rifampicin, high-dose rifampicin reduced dolutegravir and efavirenz exposures but HIV suppression was similar across treatment arms. Higher-dose rifampicin was well-tolerated among people living with HIV, and associated with a trend towards faster sputum culture conversion.

PMID:35861296 | DOI:10.1093/cid/ciac585

Sci Rep. 2022 Jul 20;12(1):12404. doi: 10.1038/s41598-022-16479-7.

ABSTRACT

Identifying medication errors is one method of improving patient safety. Peri operative anesthetic management of patient includes polypharmacy and the steps followed prior to drug administration. Our objective was to identify, extract and analyze the medication errors (MEs) reported in our critical incident reporting system (CIRS) database over the last 15 years (2004-2018) and to review measures taken for improvement based on the reported errors. CIRS reported from 2004 to 2018 were identified, extracted, and analyzed using descriptive statistics and presented as frequencies and percentages. MEs were identified and entered on a data extraction form which included reporting year, patients age, surgical specialty, American Society of Anesthesiologist (ASA) status, time of incident, phase and type of anesthesia and drug handling, type of error, class of medicine, level of harm, severity of adverse drug event (ADE) and steps taken for improvement. Total MEs reported were 311, medication errors were reported, 163 (52%) errors occurred in ASA II and 90 (29%) ASA III patient, and 133 (43%) during induction. During administration phase 60% MEs occurred and 65% were due to human error. ADEs were found in 86 (28%) reports, 58 of which were significant, 23 serious and five life-threatening errors. The majority of errors involved neuromuscular blockers (32%) and opioids (13%). Sharing of CI and a lesson to be learnt e-mail, colour coded labels, change in medication trolley lay out, decrease in floor stock and high alert labels were the low-cost steps taken to reduce incidents. Medication errors were more frequent during administration. ADEs were occurred in 28% MEs.

PMID:35858974 | DOI:10.1038/s41598-022-16479-7

BMJ Case Rep. 2022 Jul 20;15(7):e249411. doi: 10.1136/bcr-2022-249411.

ABSTRACT

Although novel immunotherapy has shown promise for patients with melanoma, a more activated state of the immune system may lead to adverse systemic effects. Immunotherapy-induced meningoencephalitis is a rare and seldom reported adverse effect of immunotherapy but with the expanding role of immunotherapy in cancer treatments it must be recognised. Patients receiving immunotherapy should receive a proper warning about the potential for this life-threatening condition. Herein, we report a patient in his 70s with neurological changes after his second treatment with dual immunotherapy for a primary metastatic melanoma of the bladder neck.

PMID:35858738 | DOI:10.1136/bcr-2022-249411

Riv Psichiatr. 2022 Jul-Aug;57(4):198-202. doi: 10.1708/3855.38385.

ABSTRACT

PURPOSE: Current guidelines, due to potential toxicity and lack of clinical evidence, do not recommend the use of lithium in the treatment of Anorexia Nervosa (AN). Scarce evidence is available on the use, side effects, and tolerability of this drug in children and adolescents with AN, a population characterized by specific clinical, metabolic, and hydro-electrolytic balance features. Here we report a case series of children and adolescents hospitalized for AN and treated with lithium.

METHODS: Case series reporting the use of lithium in 7 female young patients with AN. Reasons for introduction, dosages, formulation, plas-ma levels, adverse drug reactions (ADR) and modifi-cations of electrocardiogram (EKG) and plasma levels of glucose, cholesterol, creatinine, urea, sodium, and thyroid-stimulating hormone (TSH) were assessed. Re-sults. Reasons for the introduction of lithium included unstable mood, insufficient compliance with nutri-tional programs, and psychomotor agitation. In all of the patients an improvement on target symptoms was observed. Lithium was started at 171.4 (+/-56.7) mg/day, up to 600.0 (+/-173.2) mg/day. The most frequent scheme was three times daily. The mean plasmatic concentration was 0.6 (+/-0.3) mmol/L at one month. One pa-tient experienced polyuria, polydipsia and dry mouth, and another showed increased creatinine kinase. No major modifications of EKG, glucose, cholesterol, cre-atinine, urea, sodium emerged.

CONCLUSIONS: In this sample of children and adolescents hospitalized for AN, lithium was administered to improve psychiatric symptoms impairing compliance. All the patients experienced an improvement on these symptoms after being admin-istered lithium. ADR were reported in 2 cases. These data should be investigated in wider populations and controlled studies.

PMID:35856320 | DOI:10.1708/3855.38385

Pharmacol Res Perspect. 2022 Aug;10(4):e00987. doi: 10.1002/prp2.987.

ABSTRACT

The assessment in real-life conditions of the safety and efficacy of new antimalarial drugs is of greatest interest. This study aimed to monitor and evaluate both clinical and biological safety of pyronaridine-artesunate (PA) in real-life conditions in Burkina Faso's health system. This was a single-arm, open-label study, where patients attending Nanoro health facilities with uncomplicated malaria were consented to be part of a cohort event monitoring (CEM). At inclusion (day-0), PA was administered orally once a day for 3 days. Patients spontaneous reported any clinical adverse events (AEs) occurring within 28 days following the treatment. Additionally, the study focused on AEs of special interest (AESI), namely clinical signs related to hepatotoxicity and increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST). A nested subset of patients with blood sample collection at day-0 and day-7 were monitored to investigate the effect of PA on biochemistry parameters. From September 2017 to October 2018, 2786 patients were treated with PA. About 97.8% (2720/2786) of patients did not report any AE. The most commonly reported events were respiratory, thoracic, and mediastinal disorders (8.3 per 1000), infections and infestations (7.9 per 1000), and gastrointestinal disorders (7.2 per 1000). No clinical or biological hepatotoxicity event related to PA was reported during the follow-up. Changes in biochemistry parameters remained within laboratory reference ranges. The study showed that PA is a well-tolerated drug and should be considered as a good option by malaria control programs in countries where existing first-line antimalarial drugs are continuously threatened by the emergence of drug resistance.

PMID:35855566 | DOI:10.1002/prp2.987

AMIA Annu Symp Proc. 2022 May 23;2022:524-533. eCollection 2022.

ABSTRACT

The identification of associations between drugs and adverse drug events (ADEs) is crucial for drug safety surveillance. An increasing number of studies have revealed that children and seniors are susceptible to ADEs at the population level. However, the comprehensive explorations of age risks in drug-ADE pairs are still limited. The FDA Adverse Event Reporting System (FAERS) provides individual case reports, which can be used for quantifying different age risks. In this study, we developed a statistical computational framework to detect age group of patients who are susceptible to some ADEs after taking specific drugs. We adopted different Chi-squared tests and conducted disproportionality analysis to detect drug-ADE pairs with age differences. We analyzed 4,580,113 drug-ADE pairs in FAERS (2004 to 2018Q3) and identified 2,523 pairs with the highest age risk. Furthermore, we conducted a case study on statin-induced ADE in children and youth. The code and results are available at https://github.com/Zhizhen- Zhao/Age-Risk-Identification.

PMID:35854736 | PMC:PMC9285161

AMIA Annu Symp Proc. 2022 May 23;2022:349-358. eCollection 2022.

ABSTRACT

Although pharmaceutical products undergo clinical trials to profile efficacy and safety, some adverse drug reactions (ADRs) are only discovered after release to market. Post-market drug safety surveillance - pharmacovigilance - leverages information from various sources to proactively identify such ADRs. Clinical notes are one source of observational data that could assist this process, but their inherent complexity can obfuscate possible ADR signals. In previous research, embeddings trained on observational reports have improved detection of such signals over commonly used statistical measures. Moreover, neural embedding methods which further encode juxtapositional information have shown promise on analogical retrieval tasks, suggesting proximity-based alternatives to document-level modeling for signal detection. This work uses natural language processing and locality sensitive neural embeddings to increase ADR signal recovery from clinical notes, with AUCs of ~0.63-0.71. Constituting a ~50% increase over baselines, our method sets the state-of-the-art for these reference standards when solely leveraging clinical notes.

PMID:35854716 | PMC:PMC9285153

Sci Transl Med. 2022 Jul 20;14(654):eabo2652. doi: 10.1126/scitranslmed.abo2652. Epub 2022 Jul 20.

ABSTRACT

Hyperinflammation triggered by SARS-CoV-2 is a major cause of disease severity, with activated macrophages implicated in this response. OP-101, a hydroxyl-polyamidoamine dendrimer-N-acetylcysteine conjugate that specifically targets activated macrophages, improves outcomes in preclinical models of systemic inflammation and neuroinflammation. In this multicenter, randomized, double-blind, placebo-controlled, adaptive phase 2a trial, we evaluated safety and preliminary efficacy of OP-101 in patients with severe COVID-19. Twenty-four patients classified as having severe COVID-19 with a baseline World Health Organization seven-point ordinal scale of ≥5 were randomized to receive a single intravenous dose of placebo (n = 7 patients) or OP-101 at 2 (n = 6), 4 (n = 6), or 8 mg/kg (n = 5 patients). All study participants received standard of care, including corticosteroids. OP-101 at 4 mg/kg was better than placebo at decreasing inflammatory markers; OP-101 at 4 and 8 mg/kg was better than placebo at reducing neurological injury markers, (neurofilament light chain and glial fibrillary acidic protein). Risk for the composite outcome of mechanical ventilation or death at 30 and 60 days after treatment was 71% (95% CI: 29%, 96%) for placebo and 18% (95% CI: 4%, 43%; P = 0.021) for the pooled OP-101 treatment arms. At 60 days, 3 of 7 patients given placebo and 14 of 17 OP-101-treated patients were surviving. No drug-related adverse events were reported. These data show that OP-101 was well tolerated and may have potential to treat systemic inflammation and neuronal injury, reducing morbidity and mortality in hospitalized patients with severe COVID-19.

PMID:35857827 | DOI:10.1126/scitranslmed.abo2652

JAMA Dermatol. 2022 Jul 20. doi: 10.1001/jamadermatol.2022.2749. Online ahead of print.

ABSTRACT

IMPORTANCE: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).

OBJECTIVES: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.

DESIGN, SETTINGS, AND PARTICIPANTS: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.

INTERVENTIONS: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.

MAIN OUTCOMES AND MEASURES: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.

RESULTS: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred.

CONCLUSION AND RELEVANCE: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02448381.

PMID:35857290 | DOI:10.1001/jamadermatol.2022.2749

BMC Health Serv Res. 2022 Jul 19;22(1):925. doi: 10.1186/s12913-022-08320-8.

ABSTRACT

BACKGROUND: In China, 85.4% of adverse drug reactions (ADRs) are spontaneously reported by healthcare facilities. As a result, many ADRs are not reported due to lack of mandatory reporting requirements. As healthcare professionals, clinical pharmacists (CPhs) serve as a bridge between clinical work and medication and ensure rational drug use. In China, A team of CPhs implemented an intervention for ADRs reporting, with the goal of improving the number of ADRs reports, the number of unreported ADRs, and the standardized reporting rate.

METHODS: On June 01, 2015, a team of CPhs implemented an intervention for ADRs reporting at a Grade A, Class 3 hospital in China. The drug review catalogue (DRC) was used to screen physician orders for having visible symptoms of ADRs across departments, pooled the ADRs, and submitted them to the Center for Advanced Drug Monitoring (CNCAM). We retrospectively analysed the effect of a CPhs ADRs reporting intervention on the number of clinical ADRs reports, the number of unreported ADRs, and the standardized reporting rate over a 9-year period by interrupted time series (ITS). The method was implemented at the hospital on June 1, 2015, and a segmented regression model was used to analyse the data from January 1, 2010, to December 31, 2019.

RESULTS: After the CPhs ADRs reporting intervention, the number of inpatient ADRs reports submitted to the CNCAM immediately increased by approximately 63 (62.658, P < 0.01) and then decreased by approximately 1 (0.701, P = 0.000151 < 0.01) per month afterward; the number of unreported ADRs was immediately reduced by approximately 44 (44.091, P < 0.01) and remained largely unchanged over time (P > 0.05); the standardized ADRs reporting rate per month immediately increased by 63.634% (P < 0.01) and remained largely unchanged over time (P > 0.05).

CONCLUSION: The CPhs ADRs reporting intervention had an immediate effect on improving ADRs reporting, which highlights the severity of ADRs underreporting in Chinese hospitals. The method is practical and should be used more widely in clinical practice. For example, the method can adjust and establish a DRC catalog that meets the actual situation of the implementing hospital based on the hospital's drug use habits and has the characteristics of good adaptability. However, it does have some limitations; for example, it may be difficult to detect early ADRs without visible symptoms.

PMID:35854263 | DOI:10.1186/s12913-022-08320-8

BMC Geriatr. 2022 Jul 19;22(1):601. doi: 10.1186/s12877-022-03279-x.

ABSTRACT

INTRODUCTION: Polypharmacy is commonly associated with adverse health outcomes. There are currently no meta-analyses of the prevalence of polypharmacy or factors associated with polypharmacy. We aimed to estimate the pooled prevalence of polypharmacy and factors associated with polypharmacy in a systematic review and meta-analysis.

METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies with no restrictions on date. We included observational studies that reported on the prevalence of polypharmacy among individuals over age 19. Two reviewers extracted study characteristics including polypharmacy definitions, study design, setting, geography, and participant demographics. The risk of bias was assessed using the Newcastle-Ottawa Scales. The main outcome was the prevalence of polypharmacy and factors associated with polypharmacy prevalence. The pooled prevalence estimates of polypharmacy with 95% confidence intervals were determined using random effects meta-analysis. Subgroup analyses were undertaken to evaluate factors associated with polypharmacy such as polypharmacy definitions, study setting, study design and geography. Meta-regression was conducted to assess the associations between polypharmacy prevalence and study year.

RESULTS: 106 full-text articles were identified. The pooled estimated prevalence of polypharmacy in the 54 studies reporting on polypharmacy in all medication classes was 37% (95% CI: 31-43%). Differences in polypharmacy prevalence were reported for studies using different numerical thresholds, study setting, and publication year. Sex, study geography, study design and geographical location were not associated with differences in polypharmacy prevalence.

DISCUSSION: Our review highlights that polypharmacy is common particularly among older adults and those in inpatient settings. Clinicians should be aware of populations who have an increased likelihood of experiencing polypharmacy and efforts should be made to review the appropriateness of prescribed medications and occurrence of adverse effects potentially associated with polypharmacy.

CONCLUSIONS AND IMPLICATIONS: Clinicians should be aware of the common occurrence of polypharmacy and undertake efforts to minimize inappropriate polypharmacy whenever possible.

PMID:35854209 | DOI:10.1186/s12877-022-03279-x

AAPS PharmSciTech. 2022 Jul 19;23(6):199. doi: 10.1208/s12249-022-02362-1.

ABSTRACT

Griseofulvin (GF) is used as an antifungal to treat superficial skin fungal infections such as tinea capitis and tinea pedis. Currently, GF is only available in traditional oral dosage forms and suffers from poor and highly variable bioavailability, hepatotoxicity, and long duration of treatment. Therefore, the main objective of this study was to reduce the side effects of the drug and to increase the concentration of the drug retained in the cutaneous stratum corneum (SC) and improve its efficacy through the preparation of drug-laden GF microsponge (GFMS). The emulsification-solvent-diffusion method was used to prepare GFMS, and the prescriptions were screened by a single-factor approach. The optimized formulation (GFF8) had a microsponge particle size (μm) of 28.36 ± 0.26, an encapsulation efficiency (%) of 87.53 ± 1.07, a yield (%) of 86.58 ± 0.42, and drug release (%) from 77.57 ± 3.88. The optimized microsponge formulation was then loaded into a Carbopol 934 gel matrix and skin retention differences between the microsponge gel formulation and normal gels were examined by performing skin retention and fluorescence microscopy tests. Finally, the hepatoprotective and cutaneous stratum corneum retention abilities of microsponge gel formulations compared to oral GF formulations were assessed by hepatotoxicity, pharmacokinetics, and tissue distribution studies. This provides a new perspective on GF dermal stratum corneum retention administration.

PMID:35854184 | DOI:10.1208/s12249-022-02362-1