Drugs in Context

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Authors: Coral González Fernández, Jose Antonio Ros Lucas, Maria Molina Molina, Juan Rigual Bobillo, Rogelio Alejandro García Montenegro, Raquel Fernández González, Ana Jaureguiza Oriol, Jose Abal Arca

Background: Occupational exposure to silica is related to autoimmune diseases and features of autoimmunity, mainly autoantibodies. The study objectives were to estimate the prevalence of silicosis with associated autoimmune findings or diagnosed autoimmune diseases in Spain, and to assess the clinical and functional characteristics of affected patients. Methods: This is a multicentre prospective study in patients diagnosed with silicosis. Autoantibodies analysed were antinuclear antibodies, isotypes IgA, IgM and IgG, rheumatoid factor, anticyclic citrullinated peptide, anti-Scl70, anti-Ro, and anti-LA. Pulmonary function tests were performed. Results: Autoimmunity was assessed in 105 patients. Autoimmune findings were recorded in 29 (27%) patients, including antinuclear antibodies (n=21), anti-Ro (n=7), rheumatoid factor (n=5) and anti-Scl70 (n=3). Autoimmune disease was diagnosed in 16 (15%) patients, mainly rheumatoid arthritis (n=7) and systemic lupus erythematosus (n=4). Patients with silicosis and autoimmune findings had a lower mean time of exposure to silica and showed a trend toward lower values in pulmonary function tests. Conclusions: Autoimmune findings and diagnosis of autoimmune diseases were frequent in patients with silicosis in Spain.

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Authors: Francesco Angelico

Chronic liver disease (CLD) is a significant global health concern and generally leads to fibrosis, cirrhosis and hepatocellular carcinoma. Various factors, such as metabolic abnormalities, viral infections, alcoholism, genetics and autoimmune responses, contribute to liver damage. CLD is characterized by different phenotypes, including non-alcoholic fatty liver disease, metabolic-associated fatty liver disease, drug-induced liver injury and alcoholic liver disease. These conditions have seen an increase in comorbidities and hospitalizations over the past decade, imposing a substantial burden on patients and healthcare systems. Understanding the underlying mechanisms of liver injury is crucial for effective management and reducing the clinical and economic burden of CLD. Although several attempts have been evaluated to find a drug therapy option for the management of non-alcoholic fatty liver disease and metabolic-associated fatty liver disease, there is no effective drug approved to date. However, different studies have demonstrated that silymarin, the milk thistle extract, could exert hepatoprotective, antioxidant, anti-inflammatory and antifibrotic properties and should therefore be considered an efficacious, tolerable and promising herbal product for the management of liver activity in CLDs. This review discusses the clinical features, diagnosis and available treatments for major liver diseases, acting as an introduction to a clinical case collection based on the management and treatment of major liver diseases with silymarin. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series

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Authors: Emanuele Grassedonio, Lorena Incorvaia, Marco Guarneri, Fabio Guagnini, Massimo Midiri

Post-contrast acute kidney injury is defined as a nephropathy with an increase in serum creatinine of >0.3 mg/dL (or >26.5 μmol/L) or >1.5-times the baseline within 48–72 h of intravascular administration of a contrast medium. Patients with cancer have an increased risk of post-contrast acute kidney injury not only related to the frequent use of contrast medium for computed tomography scans but also to other factors, including the type of tumour, age, oncological therapies, use of other nephrotoxic agents and dehydration. Preventive strategies were developed and may be applied to different risk profiles. Patients at risk may be detected by recently published risk scores.

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Authors: Dhyuti Gupta, Prithpal Singh Matreja, Shilpa Patrick, Meenu Thomas, Pooja Agarwal, Preeti Singh

Background: Fixed-dose combinations (FDCs) were brought into the market with the intent of providing benefits primarily to patients and physicians. Nevertheless, despite their multiple advantages, they have their own set of drawbacks, especially regarding irrational FDCs. If physicians continue to prescribe them, prohibiting their sale would become all the more challenging. This cross-sectional survey study was planned to comprehend the level of knowledge, attitude and practice of physicians regarding such FDCs at a tertiary care teaching institute of western Uttar Pradesh, India. Methodology: A pre-validated questionnaire was communicated electronically to all the attending physicians. For data analysis, descriptive statistics were applied and a χ2 test was performed for inter-group comparison. Results: Amongst the 108 respondents, participation was almost comparable from both medical and surgical branches, with most participants being junior residents (58%). Even with sound knowledge of FDCs, only 46.30% of them were aware of banned FDCs. Similarly, only 6.48% could correctly identify the disadvantages associated with the use of FDCs, and 33.18% could correctly recognize irrational FDCs. This finding was consistently reflected in their attitude and practice and only 15.74% of respondents cross-referenced FDCs with the available literature. Furthermore, despite 88.89% of respondents checking for rationality of FDCs before prescribing them, a compendium of irrational FDCs is routinely prescribed. Conclusion: To amend these shortcomings in prescribing of irrational FDCs, some recommendations are proposed by the authors herein.

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Authors: Jenna Januszka, Emily Drwiega, Rodrigo Burgos, Renata Smith, Melissa Badowski

Background: Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as first-line treatment in 2017. Reported national surveillance data in the USA estimated INSTI-R to be 6.3% as of 2018. This article aims to describe estimated prevalence of INSTI-R within a single clinic network in Chicago, IL, USA, and identify risk factors for resistance and virological failure (VF). Methods: This was a retrospective, single-centre study of adults with HIV starting an INSTI-containing regimen between September 2017 and 2020. The primary endpoint was the difference in INSTI-R of the sample population compared with the national prevalence. Other outcomes included VF and documented INSTI-R mutations. Results: Of 948 participants screened, 321 were included. Eight people had baseline INSTI-R testing results available, of which five had INSTI-R at baseline for an estimated prevalence of 1.6%. This estimation was significantly less than the national estimated prevalence of 6.3% (p<0.001). VF occurred in 26 (7.8%) individuals. Because no participants acquired INSTI-R during the study period, investigators were unable to identify risk factors associated with the development of INSTI-R. People with high pre-treatment viral loads had 1.21 (95% CI 1.05–1.39) higher odds of VF. Conclusions: Amongst participants on INSTI-containing regimens, INSTI-R rates were estimated to be lower than the estimated national prevalence. Detectable preswitch viral loads were more associated with VF than undetectable viral loads.

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Authors: Tirsit Ketsela Zeleke, Bekalu Dessie Alamirew, Zegaye Agmassie Bazezew, Muluken Adela Alemu, Abdisa Gemedi Jara, Rahel Belete Abeb

Background: Low levels of living standards amongst street dwellers worldwide limit their access to conventional healthcare services, resulting in self-medication use for the treatment of an illness. Nevertheless, self-medication use has risks, including adverse drug reactions, increased polypharmacy, drug resistance, drug dependence, drug interactions and incorrect diagnosis. Ethiopia has a large street-dwelling community; however, there are no studies conducted in Ethiopia assessing self-medication use amongst street dwellers. This study provides insight into self-medication use and predictors amongst street dwellers in Ethiopia. Methods: A community-based, multicentre cross-sectional study was conducted amongst street dwellers from 1 September 2022 to 1 February 2023 at community drug-retail outlets in the three major cities in the Amhara region of Ethiopia. The data were obtained using an interviewer-administered questionnaire. Frequencies and percentages of descriptive statistics were calculated. Bivariable and multivariable logistic regression analyses were employed to indicate predictors of self-medication use. To determine statistical significance, a 95% confidence interval with a p value below 0.05 was utilized. Results: The prevalence of self-medication use was 67.4%. Time and financial savings were reported as the reasons for most self-medication use. The most commonly reported illnesses for which people sought self-medication were gastrointestinal diseases. Low monthly income (adjusted OR 3.72, 95% CI 2.34–5.91) and residing near sewage areas (adjusted OR 3.37, 95% CI 2.03–5.58) were significantly associated with self-medication use. Conclusion: Street dwellers had a high rate of self-medication use. Residing near sewage areas and having a low level of income were factors in self-medication use. Gastrointestinal diseases, respiratory ailments and dermatological conditions were the most frequently reported complaints, whereas antimicrobials and anthelmintics were the most commonly used medications. We recommend that healthcare services enhance outreach programmes to the most vulnerable people, such as street dwellers, especially those with lower monthly incomes and who live near sewage areas, to reduce self-medication rates.

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Authors: Michael Langworthy, Peter Lascarides, Wilson Ngai, Kevin Steele, Yili Huang

Background: Clinical trials on the use of viscosupplementation with hyaluronic acid (HA) in patients with knee osteoarthritis (KOA) are inconsistent, making it challenging to determine its value in clinical practice. One issue is the availability of various HA products on the market; differences in their chemical features can impact patient outcomes. Herein, we assess the efficacy and safety of three once-weekly intra-articular (IA) injections of Hylan G-F 20, a high-molecular-weight and highly crosslinked HA product, in patients with KOA. We hypothesized that Hylan G-F 20 would provide significant pain relief with no increased safety risk compared with IA saline (placebo). Methods: This was a 26-week, patient-blinded and evaluator-blinded, single-centre, randomized placebocontrolled trial. Men or women ≥18 years of age with Larsen grade II or III KOA were included. Patients received IA injections of either Hylan G-F 20 or placebo once a week for 3 weeks. The primary endpoints were the week 12 and 26 visits. Primary efficacy outcomes included visual analogue scale (VAS) pain scores, patient activity level and an overall assessment of clinical condition. Secondary outcomes included adverse events (AEs) that emerged during treatment. The primary analysis included the intention-to-treat population. An alpha level of 0.05 was used in the statistical analysis. Results: Thirty patients were included in the intentionto- treat population (15 per group). All efficacy outcomes were statistically significant in favour of Hylan G-F 20, except night pain and inactivity stiffness, for both patientassessed (all p=0.0001 at week 12) and evaluator-assessed (all p=0.0001 at week 12 and p=0.0004–0.0180 at week 26) measurements. There was also a greater proportion of symptom-free patients and those with a >50% improvement in their VAS scores, except night pain, in the Hylan G-F 20 group (p=0.001–0.003 in patient-assessed scores and p<0.0001 to 0.002 in evaluator-assessed scores at week 12). Two patients, one in each group, experienced an AE; no sequelae occurred, and no special treatment was required for either AE. No patients withdrew from the study prematurely due to an AE. Conclusion: In patients with chronic idiopathic KOA, Hylan G-F 20 provides significant improvements in pain relief compared with placebo with no added safety concerns.

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Authors: Rahel Belete Abebe, Bezawit Mulat Ayal, Muluken Adela Alemu, Tirsit Ketsela Zeleke

Background: Antibiotics are drugs of natural or synthetic origin used to treat various infections. The practice of excessive and inappropriate antibiotics use is the main global cause of bacterial resistance, which is one of the most serious global public health threats. It is estimated that about 50% of global antibiotic prescriptions are inappropriate. This study assesses the prevalence and pattern of inappropriate prescriptions of antibiotics amongst ambulatory care visits in Ethiopia. Methods: A facility-based, cross-sectional study with a quantitative approach was conducted amongst randomly selected prescriptions issued for outpatients from May to June 2022 at Debre Markos Specialized Comprehensive Hospital, Northwest Ethiopia. Descriptive statistics, such as frequencies and percentages, were computed. For group comparisons, χ2 and independent sample t-tests were computed. The statistical significance of the association was considered at p<0.05. Results: A total of 2640 antibiotics were prescribed for patients in the outpatient setting with various bacterial infections via 911 prescriptions, of which 49.5% were non-compliant with the national treatment guideline. Guideline non-compliant prescriptions increased remarkably amongst patients in the outpatient setting diagnosed with community-acquired pneumonia (38.8% versus 30.1%; p=0.006) and peptic ulcer disease (14.9% versus 9%; p=0.006). Moreover, inappropriate prescription was significantly higher amongst patients taking amoxicillin/clavulanic acid (33.2% versus 48.2%; p<0.001) and cephalexin (17.8% versus 24.3%; p=0.016). Conclusion: Large proportions of antibiotic prescriptions for outpatients were non-compliant with the national treatment guideline, suggesting that prescribers need to give special attention to outpatients whilst ordering antibiotics such as amoxicillin/clavulanic acid and cephalexin. Antibiotic stewardship efforts to optimize outpatient antibiotic prescriptions and reduce the use of potentially inappropriate antibiotics are needed in Ethiopia.

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Authors: Niklas Garde, Markus Heibel

Spasticity and its related symptoms of spasms, pain, sleep disturbance and bladder dysfunction are common in persons with multiple sclerosis (MS) and may be interconnected through a common pathophysiology and/or may trigger and worsen each other. Tetrahydrocannabinol–cannabidiol (nabiximols) oromucosal spray (Sativex) is an add-on treatment for adults with moderate-to-severe MS spasticity who fail to respond adequately to conventional oral medications. There is evidence that nabiximols can ameliorate spasticity-associated symptoms irrespective of its effect on spasticity. This case series describes 12 adults with MS spasticity who were evaluated for symptom evolution before and during adjunctive nabiximols treatment. Nabiximols reduced spasticity severity in 11 patients, of whom 8 had a clinically important ≥30% improvement in 0–10 Numeric Rating Scale scores during treatment. In 7 patients who reported spasms, severity was reduced or spasms were absent/unnoticeable during nabiximols treatment. Walking distance was improved in 8 patients. Pain severity was reduced in 11 patients, and sleep disorder was completely resolved in 3 patients and improved in 8. Bladder dysfunction was improved in 6 of 7 patients with baseline symptoms. Two patients arguably should have discontinued nabiximols sooner: one had a limited response and experienced adverse effects throughout 6 months of treatment; the other was a non-responder who suffered a fall due to dizziness after 7 weeks of use. Overall, this case series shows, at an individual patient level, that the benefits of nabiximols extend beyond spasticity to include spasticity-related symptoms.

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Authors: David Gómez-Ulloa, M Chris Runken, Wilton I Rodriguez, Basilio Hernández, Montserrat Chivite, E Anne Davis, Paul Nisbet

Background: As research continues towards improved treatments for Alzheimer disease (AD), there is growing interest in the views and needs from patients and caregivers on AD treatments. Methods: In this study, we surveyed patients with AD and caregivers to determine the treatment goals that are most important to them. Patients with AD and caregivers were independently recruited in Europe and North America to complete a web-based survey. Eligible participants were ≥18 years old and diagnosed with mild cognitive impairment or mild-to-moderate AD (patient-reported group) or persons involved in the care of patients with AD (caregiver-reported group). A total of 322 patients and 614 caregivers completed the survey. Results: The demographic characteristics of patients in the patient-reported and the caregiver-reported groups were similar. Disease severity of patients was greater in the caregiver-reported group compared with the patient-reported group (72.1% versus 46.9% moderate AD). The most important goal of AD treatment in both groups was maintenance of quality of life (QoL) (patient-reported group 31.1% and caregiver-reported group 38.8%; p=0.01). This was consistent across disease stages or symptom severity except for patients with mild cognitive impairment in the caregiver-reported group where slowing the progression of memory loss was the most important treatment goal. Conclusions: Patient QoL was consistently the most relevant treatment goal for patients with AD and caregivers. In AD clinical trials, patient-relevant outcomes, for example, QoL, should be given high priority to reflect the needs and demands of patients with AD and their caregivers. A preliminary report of this work was presented at the 14th Clinical Trials on Alzheimer’s Disease meeting (November 9–12, 2021).

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Authors: José Antonio Magaña Serrano, José Angel Cigarroa López, Adolfo Chávez Mendoza, Juan Betuel Ivey-Miranda, Genaro Hiram Mendoza Zavala, Luis Olmos Domínguez, Sergio Armando Chávez Leal, José Ernesto Pombo Bartelt, Eduardo Heberto Herrera-Garza, Gerardo Mercado Leal, Rodolfo Parra Michel, Luisa Fernanda Aguilera Mora, Patricia Lenny Nuriulu Escobar

Acute heart failure (HF) is associated with poor prognosis. After the acute event, there is a vulnerable period during which the patient has a marked risk of readmission or death. Therefore, early optimization of treatment is mandatory during the vulnerable period. The objective of this article is to provide recommendations to address the management of patients with HF during the vulnerable period from a practical point of view. A group of Mexican experts met to prepare a consensus document. The vulnerable period, with a duration of up to 6 months after the acute event – either hospitalization, visit to the emergency department or the outpatient clinic/day hospital – represents a real window of opportunity to improve outcomes for these patients. To best individualize the recommendations, the management strategies were divided into three periods (early, intermediate and late vulnerable period), including not only therapeutic options but also evaluation and education. Importantly, the recommendations are addressed to the entire cardiology team, including physicians and nurses, but also other specialists implicated in the management of these patients. In conclusion, this document represents an opportunity to improve the management of this population at high risk, with the aim of reducing the burden of HF.