Asunto(s)
Alopurinol , Supresores de la Gota , Gota , Humanos , Alopurinol/uso terapéutico , Alopurinol/administración & dosificación , Gota/tratamiento farmacológico , Gota/complicaciones , Supresores de la Gota/administración & dosificación , Supresores de la Gota/uso terapéutico , Masculino , Manía/tratamiento farmacológico , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/complicaciones , Persona de Mediana EdadRESUMEN
INTRODUCTION: Gout is one of the most common forms of arthritis worldwide. Gout is particularly prevalent in Aotearoa/New Zealand and is estimated to affect 13.1% of Maori men, 22.9% of Pacific men and 7.4% of New Zealand European men. Effective long-term treatment requires lowering serum urate to <0.36 mmol/L. Allopurinol is the most commonly used urate-lowering medication worldwide. Despite its efficacy and safety, the allopurinol dose escalation treat-to-target serum urate strategy is difficult to implement and there are important inequities in allopurinol prescribing in Aotearoa. The escalation strategy is labour intensive, time consuming and costly for people with gout and the healthcare system. An easy and effective way to dose-escalate allopurinol is required, especially as gout disproportionately affects working-age Maori men and Pacific men, who frequently do not receive optimal care. METHODS AND ANALYSIS: A 12-month non-inferiority randomised controlled trial in people with gout who have a serum urate ≥ 0.36 mmol/l will be undertaken. 380 participants recruited from primary and secondary care will be randomised to one of the two allopurinol dosing strategies: intensive nurse-led treat-to-target serum urate dosing (intensive treat-to-target) or protocol-driven dose escalation based on dose predicted by an allopurinol dosing model (Easy-Allo). The primary endpoint will be the proportion of participants who achieve target serum urate (<0.36 mmol/L) at 12 months. ETHICS AND DISSEMINATION: The New Zealand Northern B Health and Disability Ethics Committee approved the study (2022 FULL 13478). Results will be disseminated in peer-reviewed journals and to participants. TRIAL REGISTRATION NUMBER: ACTRN12622001279718p.
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Alopurinol , Supresores de la Gota , Gota , Ácido Úrico , Humanos , Alopurinol/administración & dosificación , Alopurinol/uso terapéutico , Gota/tratamiento farmacológico , Gota/sangre , Nueva Zelanda , Supresores de la Gota/administración & dosificación , Supresores de la Gota/uso terapéutico , Ácido Úrico/sangre , Masculino , Relación Dosis-Respuesta a Droga , Adulto , Estudios de Equivalencia como Asunto , FemeninoRESUMEN
Gout is the second largest metabolic disease worldwide after diabetes, with acute gouty arthritis as most common symptom. Xanthine oxidase (XOD) and the NOD like receptor-3 (NLRP3) inflammasome are the key targets for acute gout treatment. Chlorogenic acid has been reported with a good anti-inflammatory activity, and Apigenin showed an excellent potential in XOD inhibition. Therefore, a series of chlorogenic acid-apigenin (CA) conjugates with varying linkers were designed and synthesized as dual XOD/NLRP3 inhibitors, and their activities both in XOD and NLRP3 inhibition were evaluated. An in vitro study of XOD inhibitory activity revealed that the majority of CA conjugates exhibited favorable XOD inhibitory activity. Particularly, the effects of compounds 10c and 10d, with an alkyl linker on the apigenin moiety, were stronger than that of allopurinol. The selected CA conjugates also demonstrated a favorable anti-inflammatory activity in RAW264.7 cells. Furthermore, compound 10d, which showed the optimal activity both in XOD inhibition and anti-inflammatory, was chosen and its inhibitory ability on NLRP3 and related proinflammatory cytokines was further tested. Compound 10d effectively reduced NLRP3 expression and the secretion of interluekin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) with an activity stronger than the positive control isoliquiritigenin (ISL). Based on these findings, compound 10d exhibits dual XOD/NLRP3 inhibitory activity and, therefore, the therapeutic effects on acute gout is worthy of further study.
Asunto(s)
Apigenina , Ácido Clorogénico , Supresores de la Gota , Proteína con Dominio Pirina 3 de la Familia NLR , Animales , Ratones , Apigenina/farmacología , Apigenina/química , Apigenina/síntesis química , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Células RAW 264.7 , Ácido Clorogénico/farmacología , Ácido Clorogénico/química , Ácido Clorogénico/síntesis química , Supresores de la Gota/farmacología , Supresores de la Gota/síntesis química , Supresores de la Gota/química , Supresores de la Gota/uso terapéutico , Relación Estructura-Actividad , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismo , Estructura Molecular , Gota/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Antiinflamatorios/síntesis química , Antiinflamatorios/farmacología , Antiinflamatorios/químicaRESUMEN
Low back pain is the most common musculoskeletal complaint accounting for over 30 million visits to primary care physicians annually. Serious pathology is found in less than 1% of these visits. Therefore it is often a challenge to distinguish worrisome findings requiring further workup and treatment from common complaints of pain. Gout is an inflammatory arthritis that most commonly affects the appendicular skeleton. It is characterized by the saturation of uric acid and deposition of monosodium urate crystals in joints and tissues. Spinal involvement is rare and is not typically considered on the differential diagnosis for a patient presenting with acute low back pain. We present such a case of a 35-year-old male who presented with intractable back pain, highlighting the need to recognize signs and symptoms that raise suspicion for spinal gout.
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Gota , Dolor de la Región Lumbar , Humanos , Masculino , Dolor de la Región Lumbar/etiología , Adulto , Gota/complicaciones , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/complicaciones , Diagnóstico Diferencial , Supresores de la Gota/uso terapéuticoRESUMEN
Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.
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Supresores de la Gota , Gota , Humanos , Gota/diagnóstico , Gota/terapia , Gota/tratamiento farmacológico , Supresores de la Gota/uso terapéutico , Factores de Riesgo , Ácido Úrico/sangre , Colchicina/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéuticoRESUMEN
Although patients with hyperuricemia and gout often have dyslipidemia, the effects of febuxostat, a xanthine oxidase inhibitor, on their lipid profiles are unclear. Thus, we performed a sub-analysis of the randomized PRIZE study in which the effects of febuxostat on carotid atherosclerosis were investigated in patients with hyperuricemia. The participants were randomized to the febuxostat or control group. The primary endpoint of this sub-analysis was changes in the patients' non-high-density lipoprotein cholesterol (HDL-C) levels from baseline to 6-month follow-up. Correlations between the changes in lipid profiles and cardiometabolic parameters were also evaluated. In total, 456 patients were included. From baseline to 6 months, non-HDL-C levels were significantly reduced in the febuxostat group (-5.9 mg/dL, 95% confidence interval [CI]: -9.1 to -2.8 mg/dL, p < 0.001), but not in the control group (-1.3 mg/dL, 95% CI: -4.4 to 1.8, p = 0.348). The reduction in non-HDL-C levels was more pronounced in women and correlated with changes in serum uric acid and estimated glomerular filtration rate levels only in the febuxostat group. In patients with hyperuricemia, febuxostat treatment was associated with reduced non-HDL-C levels from baseline to the 6-month follow-up compared to the control treatment, suggesting that the lipid-lowering effect of febuxostat should be considered when targeting dyslipidemia.
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Febuxostat , Hiperuricemia , Lípidos , Xantina Oxidasa , Humanos , Febuxostat/uso terapéutico , Febuxostat/farmacología , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Xantina Oxidasa/antagonistas & inhibidores , Masculino , Femenino , Persona de Mediana Edad , Lípidos/sangre , Anciano , Ácido Úrico/sangre , Supresores de la Gota/uso terapéutico , Supresores de la Gota/farmacología , HDL-Colesterol/sangre , Enfermedades de las Arterias Carótidas/tratamiento farmacológico , Enfermedades de las Arterias Carótidas/sangre , Dislipidemias/tratamiento farmacológico , Dislipidemias/sangre , Tasa de Filtración Glomerular/efectos de los fármacosRESUMEN
Gout is characterized by monosodium urate (MSU) crystal deposition secondary to hyperuricemia. Gout is associated with metabolic syndrome (MetS) and its related comorbid conditions such as cardiovascular disease (CVD). Major advances have been made in the comprehension of the link between MetS and gout. Despite observational studies suggesting an association between MetS-related conditions and hyperuricemia, there is no proof of causality. Most studies using Mendelian randomization did not find hyperuricemia as a causal factor for MetS-related conditions. In contrast, these conditions were found associated with hyperuricemia, which suggests a reverse causality. Among patients with gout, this high CVD risk profile implies the need for systematic screening for MetS-related conditions. Most international guidelines recommend systematic screening for and care of CVD and related risk factors in patients with gout. Some anti-hypertensive agents, such as losartan and calcium channel blockers, are able to decrease serum urate (SU) levels. However, there are potential interactions between gout management therapies and the treatment of metabolic diseases. Some data suggest that anti-inflammatory drugs used for gout flare treatment, such as colchicine or canakinumab, might have benefits for CVD. Regarding the impact of urate-lowering therapies on CVD risk, recent studies found a similar CVD safety profile for allopurinol and febuxostat. Finally, sodium-glucose cotransporter-2 inhibitors are promising for gout because of their ability to decrease SU levels and risk of recurrent flares. In this review, we focus on the clinical challenge of managing MetS in patients with gout, particularly older patients with co-medications.
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Gota , Síndrome Metabólico , Humanos , Gota/tratamiento farmacológico , Gota/complicaciones , Síndrome Metabólico/complicaciones , Supresores de la Gota/uso terapéutico , Enfermedades Cardiovasculares/etiología , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicacionesRESUMEN
BACKGROUND/PURPOSE: Patients with gout are at risk for increased serum uric acid (SUA) levels and gout attacks in the short term after undergoing bariatric surgery, and the purpose of this study was to evaluate the benefits of short-term treatment with uric acid-lowering medication after bariatric surgery for the control of gout attacks and SUA levels in patients with gout. METHODS: 71 patients who underwent SG from January 2020 to December 2022 were prospectively included. These patients were diagnosed with hyperuricemia before surgery and had a history of gout attacks. Patients were classified into a drug-treatment group (DTG, n = 32) and a non-drug-treatment group (NDTG, n = 39) according to whether they took uric acid-lowering medication after surgery. Changes in the number of gout attacks, body mass index (BMI), and SUA levels at 1 week, 1 month, 3 months, and 6 months after bariatric surgery were measured in both groups. RESULTS: In the DTG, 22 patients (68.8%) experienced an increase in SUA within 1 week, 3 patients (9.4%) had an acute attack of gout within the first month, and no patients had a gout attack thereafter. In the NDTG, 35 patients (89.7%) experienced an increase in SUA within 1 week, 7 patients (17.9%) had an acute gout attack within the first month, and 4 patients (10.3%) experienced gout attacks between month 1 and month 3 postoperatively. Both groups were free of gout attacks between the 3rd and 6th postoperative month and showed a significant decrease in SUA and BMI by the sixth month. CONCLUSION: In patients with gout, continued use of uric acid-lowering medication after bariatric surgery is beneficial in reducing the number of gout attacks and the risk of rising SUA.
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Cirugía Bariátrica , Supresores de la Gota , Gota , Ácido Úrico , Humanos , Gota/sangre , Cirugía Bariátrica/métodos , Masculino , Femenino , Persona de Mediana Edad , Ácido Úrico/sangre , Supresores de la Gota/uso terapéutico , Adulto , Estudios Prospectivos , Hiperuricemia/sangre , Hiperuricemia/etiología , Índice de Masa Corporal , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Elevated serum uric acid (sUA) is associated with heart failure (HF). HYPOTHESIS: Urate-lowering therapy (ULT) in HF is associated with lower risk of HF hospitalization (hHF) and mortality. METHODS: Data on patients with HF and gout or hyperuricemia in the Clinical Practice Research Datalink database linked to the Hospital Episode Statistics and the Office for National Statistics in the United Kingdom were analyzed. Risks of hHF and all-cause mortality or cardiovascular-related mortality by ULT exposure (ULT initiated within ≤6 months of gout or hyperuricemia diagnosis) were analyzed in a propensity score-matched cohort using adjusted Cox proportional hazards regression models. RESULTS: Of 2174 propensity score-matched pairs, patients were predominantly male, aged >70 years, with mean ± standard deviation sUA 9.3 ± 1.8 (ULT-exposed) and 9.4 ± 1.9 mg/dL (ULT-unexposed). At 5 years, ULT-exposed patients had a 43% lower risk of hHF or all-cause mortality (adjusted hazard ratio [HR]: 0.57; 95% confidence interval [CI]: 0.51-0.65) and a 19% lower risk of hHF or cardiovascular-related mortality (adjusted HR: 0.81; 95% CI: 0.71-0.92) versus no ULT exposure. CONCLUSION: ULT was associated with reduced risk of adverse clinical outcomes in patients with HF and gout or hyperuricemia over 5 years.
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Supresores de la Gota , Insuficiencia Cardíaca , Hiperuricemia , Ácido Úrico , Humanos , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/sangre , Hiperuricemia/epidemiología , Hiperuricemia/complicaciones , Masculino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Femenino , Anciano , Reino Unido/epidemiología , Estudios Retrospectivos , Ácido Úrico/sangre , Supresores de la Gota/uso terapéutico , Factores de Riesgo , Persona de Mediana Edad , Biomarcadores/sangre , Resultado del Tratamiento , Gota/tratamiento farmacológico , Gota/sangre , Gota/complicaciones , Gota/epidemiología , Factores de Tiempo , Bases de Datos Factuales , Estudios de SeguimientoRESUMEN
BACKGROUND Hyperuricemia, which is common in chronic kidney disease and diabetes mellitus patients, raises health concerns. Febuxostat, a first-line urate-lowering agent, prompts cardiovascular risk questions, especially in high-risk patients. This study compared the effects of febuxostat and allopurinol on cardiovascular risk in diabetes mellitus and chronic kidney disease patients. MATERIAL AND METHODS This retrospective observational cohort study, conducted using Taiwan's National Health Insurance Research Database, focused on patients diagnosed with chronic kidney disease and diabetes between January 2012 and December 2017. The study population was divided into 2 groups: allopurinol users (n=12 901) and febuxostat users (n=2997). We performed 1: 1 propensity score matching, resulting in subgroups of 2997 patients each. The primary outcomes were assessed using a competing risk model, estimating hazard ratios (HR) for long-term outcomes, including the risks of all-cause hospitalization, hospitalization for heart failure, and hospitalization for cardiovascular interventions. RESULTS Febuxostat users, compared to allopurinol users, had higher all-cause hospitalization (HR: 1.33; 95% confidence interval [CI]: 1.25 to 1.42; P<.001), hospitalization for heart failure (HR: 1.62; 95% CI: 1.43 to 1.83; P<.001), and hospitalization for cardiovascular interventions (HR: 1.51; 95% CI: 1.32 to 1.74; P<.001). Moreover, the adverse effects of febuxostat on cardiac health were consistent across most subgroups. CONCLUSIONS Use of febuxostat in patients with diabetes mellitus and chronic kidney disease is associated with higher cardiovascular risks compared to allopurinol. Prudent evaluation is essential when recommending febuxostat for this at-risk group.
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Alopurinol , Enfermedades Cardiovasculares , Febuxostat , Supresores de la Gota , Hiperuricemia , Insuficiencia Renal Crónica , Humanos , Febuxostat/uso terapéutico , Febuxostat/efectos adversos , Alopurinol/uso terapéutico , Alopurinol/efectos adversos , Masculino , Femenino , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Taiwán/epidemiología , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/complicaciones , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Diabetes Mellitus/tratamiento farmacológico , Factores de Riesgo , Adulto , HospitalizaciónRESUMEN
Xanthine oxidase inhibitors, including allopurinol and febuxostat, are the first-line treatment of hyperuricemia. This meta-analysis investigated the association between urate-lowering therapy and all-cause mortality in different chronic diseases to match its users and non-users in a real-world setting. Overall, 11 studies were included, which reported adjusted hazard ratios for all-cause mortality over at least 12 months. Meta-analysis of all included studies showed no effect of the therapy on all-cause mortality. However, subgroup analyses showed its beneficial effect in patients with chronic kidney disease (14% risk reduction) and hyperuricemia (14% risk reduction), but not in patients with heart failure (28% risk increase). Urate-lowering therapy reduces all-cause mortality among patients with hyperuricemia and chronic kidney disease, but it seems to increase mortality in patients with heart failure and should be avoided in this subgroup.
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Causas de Muerte , Hiperuricemia , Xantina Oxidasa , Humanos , Xantina Oxidasa/antagonistas & inhibidores , Hiperuricemia/tratamiento farmacológico , Hiperuricemia/mortalidad , Hiperuricemia/sangre , Causas de Muerte/tendencias , Inhibidores Enzimáticos/uso terapéutico , Factores de Riesgo , Alopurinol/uso terapéutico , Supresores de la Gota/uso terapéutico , Febuxostat/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/mortalidad , Ácido Úrico/sangre , Insuficiencia Renal Crónica/mortalidad , AdultoAsunto(s)
Gota , Ácido Úrico , Humanos , Masculino , Persona de Mediana Edad , Gota/sangre , Gota/tratamiento farmacológico , Gota/enfermería , Gota/prevención & control , Supresores de la Gota/uso terapéutico , Recurrencia , Ácido Úrico/sangre , Brote de los Síntomas , Riesgo , Prevención Secundaria , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
OBJECTIVE: To compare the clinical efficacy of febuxostat combined with a low-purine diet versus allopurinol combined with a low-purine diet in the treatment of gout. METHODS: In this prospective controlled trial, 98 gout patients admitted to our hospital from February 2021 to December 2022 were enrolled as study subjects. Patients were randomly assigned to the study group (febuxostat combined with a low-purine diet) and the control group (allopurinol combined with a low-purine diet), with 49 patients in each group. The therapeutic effect was evaluated based on joint function and serum uric acid levels after treatment, and classified into three levels: markedly effective, effective, and ineffective. The levels of inflammatory factors, including tumor necrosis factor-a (TNF-a), cytokine interleukin-1beta (IL-1ß), and interleukin (IL)-18 (IL-18), were collected. The Numeric Rating Scale (NRS) was used to assess the degree of pain in patients. Clinical indicators before and 6 months after treatment were compared between the two groups. RESULTS: There was no statistically significant difference in age and gender between the two groups. After 6 months of treatment, the effective rate in the study group (48 cases, 97.96%) was higher than that in the control group (42 cases, 85.71%), with a statistically significant difference (p = .027). At the same time, the study group had significantly lower levels of serum uric acid (162.39 µmol/L ± 17.23 µmol/L vs. S198.32 µmol/L ± 18.34 µmol/L, p < .001), creatinine (87.39 mmol/L ± 9.76 mmol/L vs. 92.18 mmol/L ± 9.27 mmol/L, p = .014), total cholesterol (3.65 mmol/L ± 0.65 mmol/L vs. 4.76 mmol/L ± 0.73 mmol/L, p < .001), and triglycerides (1.76 mmol/L ± 0.32 mmol/L vs. 2.28 mmol/L ± 0.41 mmol/L, p < .001) compared to the control group, with statistically significant differences (p < .05). After treatment, the levels of inflammatory factors and degree of pain in the study group were significantly lower than those in the control group (all p < .05). During the treatment process, the incidence of adverse reactions in the study group (2 cases, 4.08%) was lower than that in the control group (9 cases, 18.37%), with a statistically significant difference (p = .025). CONCLUSION: Febuxostat combined with a low-purine diet can reduce inflammatory factors and alleviate the degree of pain in gout patients, significantly improving their clinical symptoms.
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Alopurinol , Febuxostat , Supresores de la Gota , Gota , Ácido Úrico , Humanos , Febuxostat/uso terapéutico , Febuxostat/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Alopurinol/uso terapéutico , Gota/tratamiento farmacológico , Gota/sangre , Gota/diagnóstico , Supresores de la Gota/uso terapéutico , Supresores de la Gota/efectos adversos , Estudios Prospectivos , Resultado del Tratamiento , Ácido Úrico/sangre , Anciano , Purinas/uso terapéutico , Biomarcadores/sangre , Terapia Combinada , Factores de Tiempo , Adulto , Mediadores de Inflamación/sangreRESUMEN
INTRODUCTION: Gout management remains suboptimal despite safe and effective urate-lowering therapy. Self-monitoring of urate may improve gout management, however, the acceptability of urate self-monitoring by people with gout is unknown. The aim of this study was to explore the experiences of urate self-monitoring in people with gout. METHODS: Semistructured interviews were conducted with people taking urate-lowering therapy (N = 30) in a 12-month trial of urate self-monitoring in rural and urban Australia. Interviews covered the experience of monitoring and its effect on gout self-management. Deidentified transcripts were analysed thematically. RESULTS: Participants valued the ability to self-monitor and gain more understanding of urate control compared with the annual monitoring ordered by their doctors. Participants indicated that self-monitoring at home was easy, convenient and informed gout self-management behaviours such as dietary modifications, hydration, exercise and medication routines. Many participants self-monitored to understand urate concentration changes in response to feeling a gout flare was imminent or whether their behaviours, for example, alcohol intake, increased the risk of a gout flare. Urate concentrations were shared with doctors mainly when they were above target to seek management support, and this led to allopurinol dose increases in some cases. CONCLUSION: Urate self-monitoring was viewed by people with gout as convenient and useful for independent management of gout. They believed self-monitoring achieved better gout control with a less restricted lifestyle. Urate data was shared with doctors at the patient's discretion and helped inform clinical decisions, such as allopurinol dose changes. Further research on implementing urate self-monitoring in routine care would enable an evaluation of its impact on medication adherence and clinical outcomes, as well as inform gout management guidelines. PATIENT OR PUBLIC CONTRIBUTION: One person with gout, who was not a participant, was involved in the study design by providing feedback and pilot testing the semistructured interview guide. In response to their feedback, subsequent modifications to the interview guide were made to improve the understandability of the questions from a patient perspective. No additional questions were suggested.