RESUMEN
BACKGROUND: Asthma is a common respiratory disease, which may be associated with an increased risk of herpes zoster (HZ), often a debilitating disease associated with severe pain. This is the first systematic review with the objective of summarising evidence on HZ burden in adults with asthma. METHODS: A global systematic literature review and meta-analysis was conducted (MEDLINE and Embase, 2003-2024) on HZ burden (incidence, risk and complications) in adults (≥18â years) with asthma. RESULTS: There were 19 studies included on HZ outcomes in adults with asthma. Pooled HZ incidence per 1000 person-years was 5.71 (95% CI 4.68-6.96) in adults aged ≥18â years (4.20 (95% CI 3.09-5.70) in those aged <60â years versus 10.33 (95% CI 9.17-11.64) in those aged ≥60â years). The pooled rate ratio for developing HZ was 1.23 (95% CI 1.11-1.35) in those aged ≥18â years and 1.36 (95% CI 1.15-1.61) in those aged ≥50â years. The risk of HZ was higher in people with asthma using systemic corticosteroids, long-acting ß-agonists plus inhaled corticosteroids and "add-on therapy". Asthma was also associated with an increased risk of post-herpetic neuralgia (OR 1.21, 95% CI 1.06-1.37) and HZ ophthalmicus (OR 1.9, 95% CI 1.1-3.2). Differences in study design, setting, case definitions and follow-up durations led to heterogeneity. CONCLUSIONS: This systematic literature review and meta-analysis found that adults with asthma have an increased risk of HZ, with higher risks in older age groups and in those on certain treatments, such as oral corticosteroids. HZ vaccines are available for adults, including those with comorbidities such as asthma, and can be considered as part of integrated respiratory care.
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Asma , Herpes Zóster , Humanos , Asma/epidemiología , Asma/complicaciones , Asma/tratamiento farmacológico , Herpes Zóster/epidemiología , Herpes Zóster/complicaciones , Adulto , Incidencia , Corticoesteroides/uso terapéutico , Persona de Mediana Edad , Factores de Riesgo , Salud GlobalRESUMEN
OBJECTIVE: To evaluate the impact of a pilot intervention for physicians to support their treatment of patients at risk for opioid abuse. SETTING, DESIGN AND PATIENTS, PARTICIPANTS: Patients at risk for opioid abuse enrolled in Medicare plans were identified from July 1, 2012 to April 30, 2014 (N = 2,391), based on a published predictive model, and linked to 4,353 opioid-prescribing physicians. Patient-physician clusters were randomly assigned to one of four interventions using factorial design. INTERVENTIONS: Physicians received one of the following: Arm 1, patient information; Arm 2, links to educational materials for diagnosis and management of pain; Arm 3, both patient information and links to educational materials; or Arm 4, no communication. MAIN OUTCOME MEASURES: Difference-in-difference analyses compared opioid and pain prescriptions, chronic high-dose opioid use, uncoordinated opioid use, and opioid-related emergency department (ED) visits. Logistic regression compared diagnosis of opioid abuse between cases and controls postindex. RESULTS: Mailings had no significant impact on numbers of opioid or pain medications filled, chronic high-dose opioid use, uncoordinated opioid use, ED visits, or rate of diagnosed opioid abuse. Relative to Arm 4, odds ratios (95% CI) for diagnosed opioid abuse were Arm 1, 0.95(0.63-1.42); Arm 2, 0.83(0.55-1.27); Arm 3, 0.72(0.46-1.13). While 84.7 percent had ≥1 psychiatric diagnoses during preindex (p = 0.89 between arms), only 9.5 percent had ≥1 visit with mental health specialists (p = 0.53 between arms). CONCLUSIONS: Although this intervention did not affect pain-related outcomes, future interventions involving care coordination across primary care and mental health may impact opioid abuse and improve quality of life of patients with pain.
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Analgésicos Opioides/efectos adversos , Dolor Crónico/tratamiento farmacológico , Educación Médica Continua/métodos , Capacitación en Servicio/métodos , Trastornos Relacionados con Opioides/etiología , Manejo del Dolor/efectos adversos , Manejo del Dolor/métodos , Médicos/psicología , Trastornos Relacionados con Sustancias/etiología , Reclamos Administrativos en el Cuidado de la Salud , Anciano , Dolor Crónico/diagnóstico , Dolor Crónico/psicología , Prescripciones de Medicamentos , Consumidores de Drogas/psicología , Femenino , Humanos , Modelos Logísticos , Masculino , Medicare , Persona de Mediana Edad , Análisis Multivariante , Trastornos Relacionados con Opioides/diagnóstico , Trastornos Relacionados con Opioides/prevención & control , Trastornos Relacionados con Opioides/psicología , Proyectos Piloto , Pautas de la Práctica en Medicina , Medición de Riesgo , Factores de Riesgo , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/prevención & control , Trastornos Relacionados con Sustancias/psicología , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
OBJECTIVES: The pregabalin dose-response for pain, Patient Global Impression of Change (PGIC), and sleep quality measures in painful diabetic peripheral neuropathy (pDPN), postherpetic neuralgia (PHN), and fibromyalgia (FM) is relevant for physicians treating these patients. This analysis aimed to demonstrate the dose-response of pregabalin for each indication and describe the onset (incidence), onset/continuation (prevalence), and resolution of adverse events (AEs) occurring during treatment. METHODS: Data from 14 placebo-controlled, fixed-dose pregabalin trials in pDPN, PHN, and FM were pooled within each indication. Patients had mean baseline pain scores ≥6 on an 11-point numeric rating scale. A hyperbolic Emax dose-response model examined the dose-response of pregabalin for pain, PGIC, and sleep quality. Safety assessments included onset and prevalence of common AEs each week, and resolution in the first 2 months of treatment. RESULTS: In all indications, the likelihood of patients experiencing pain relief and improvements in PGIC and sleep quality increased in a dose-dependent manner with increasing doses. In all indications, new incidences of dizziness and somnolence were highest after 1 week of treatment, with few subsequent new reports at a given dose. Prevalence rates decreased steadily after 1 week of treatment. In FM, new onset weight gain emerged 6-8 weeks following treatment; prevalence rates generally increased then remained steady over time. With the exception of weight gain, many AEs resolved in month 1. CONCLUSION: The dose-response of pregabalin for pain, PGIC, and sleep quality was demonstrated, highlighting the benefit of achieving the maximum recommended dose of 300 mg/day for pDPN, 300-600 mg/day for PHN, and 300-450 mg/day for FM. Common AEs are generally seen within 1 week of starting treatment, with few subsequent new reports at a given dose. New onset weight gain occurs after 6 weeks of treatment, reinforcing the need for regular monitoring of weight.
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Analgésicos/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Fibromialgia/tratamiento farmacológico , Neuralgia Posherpética/tratamiento farmacológico , Pregabalina/uso terapéutico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Analgésicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pregabalina/administración & dosificación , Pregabalina/efectos adversos , Sueño/efectos de los fármacos , Adulto JovenRESUMEN
PURPOSE: We performed pooled analyses from 3 small, clinical trials of tanezumab in patients with urological chronic pelvic pain, including chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome, to identify patient subpopulations more likely to benefit from tanezumab treatment. MATERIALS AND METHODS: Pooled analyses included data from 208 patients with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome randomized to placebo (104, 65 [62.5%] female) or tanezumab (104, 63 [60.6%] female) who received 1 dose or more of study medication. Data on tanezumab were from study A4091010 (interstitial cystitis/bladder pain syndrome) on 200 µg/kg intravenous, study A4091019 (chronic prostatitis/chronic pelvic pain syndrome) on 20 mg intravenous and study A4091035 (interstitial cystitis/bladder pain syndrome) on 20 mg subcutaneous. Primary study end points were evaluated using analysis of covariance with gender, study and baseline pain as covariates. RESULTS: For pooled analyses least squares mean (SE) change from baseline in 24-hour pain intensity vs placebo was -0.60 (0.24, 90% CI -0.99, -0.20) overall and -0.99 (0.32, p=0.002) and -0.17 (0.36, p=0.650) for females and males, respectively. The improvement in pain intensity was significant (p=0.011) for patients with symptoms suggesting the concomitant presence of nonurological associated somatic syndromes but not for those with pelvic pain symptoms only (p=0.507). CONCLUSIONS: Women with interstitial cystitis/bladder pain syndrome and patients with symptoms suggesting the concomitant presence of nonurological associated somatic syndromes were more likely to experience significant pain reduction with tanezumab than with placebo therapy. In contrast, no difference was reported in response between tanezumab and placebo therapy for men with chronic prostatitis/chronic pelvic pain syndrome symptoms only.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Cistitis Intersticial/tratamiento farmacológico , Dolor Pélvico/tratamiento farmacológico , Trastornos Somatosensoriales/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The intestinal efflux pump P-glycoprotein (P-gp), the product of the multi-drug resistance-1 (MDR-1) gene, significantly influences the pharmacokinetics of several drugs. Ciclosporin is a substrate for P-gp and is metabolized by cytochrome P450 (CYP) 3A enzymes. P-gp activity is affected by several known single nucleotide polymorphisms (SNPs) and haplotypes. MDR-1 genotypes of SNPs C1236T, G2677T/A and C3435T, as well as haplotypes C-G-C and T-T-T and CYP3A5*1 genotype (predictive of CYP3A5 expression), were related to ciclosporin blood concentrations measured at both 0 and 2 h after drug dosing in 197 stable renal transplant patients. Significant differences (of a magnitude unlikely to be relevant clinically) in dose-normalized blood ciclosporin concentrations were found only between MDR-1 genotypes of the C1236T SNP and between haplotype groups C-G-C and T-T-T in patients that were expressers of CYP3A5. MDR-1 SNPs and haplotypes and also CYP3A5*1 genotype, do not appear to have a major influence on ciclosporin pharmacokinetics.
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Ciclosporina/administración & dosificación , Sistema Enzimático del Citocromo P-450/genética , Genes MDR/genética , Inmunosupresores/administración & dosificación , Trasplante de Riñón/fisiología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Adulto , Anciano , Anciano de 80 o más Años , Ciclosporina/sangre , Ciclosporina/farmacocinética , Citocromo P-450 CYP3A , Femenino , Genotipo , Haplotipos , Humanos , Inmunosupresores/sangre , Inmunosupresores/farmacocinética , Trasplante de Riñón/inmunología , Persona de Mediana EdadRESUMEN
Cytochrome P450 3A5 (CYP3A5) is involved in the biotransformation of many orally administered drugs, some of which are dose optimized using therapeutic drug monitoring. The CYP3A5 gene exhibits variable inter-individual expression, which is related to a single-nucleotide polymorphism. Producers of the enzyme possess at least one CYP3A5*1 allele. Knowledge of patients' CYP3A5 genotype, in conjunction with therapeutic drug monitoring (TDM), may aid patient management. Real-time polymerase chain reaction (PCR) was used to genotype the A6986G mutation of the CYP3A5 gene. Specific primers were employed to generate a DNA product, co-amplified with two internal hybridization probes, using a LightCycler. DNA melt curve analysis readily identified the genotypes CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3. Results were confirmed using DNA sequencing with 100% correlation. Genotypes were determined from 263 individuals and compared with the genotypes of a pseudogene CYP3AP1, which is in disequilibrium with CYP3A5. This is a rapid and reliable method for genotyping the CYP3A5 polymorphism which may be used as an important adjunct to the TDM service offered by laboratories to optimize drug prescription.
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Sistema Enzimático del Citocromo P-450/genética , Reacción en Cadena de la Polimerasa/métodos , Secuencia de Bases , Citocromo P-450 CYP3A , Cartilla de ADN , Monitoreo de Drogas/métodos , Genotipo , HumanosRESUMEN
Immunosuppressant drugs are crucial in order to protect transplanted kidney, heart or liver against the body's natural defence mechanisms. These drugs are used to prevent both acute rejection of the organ as well as chronic deterioration of the graft over longer periods of time. Currently used immunosuppressant drugs are calcineurin inhibitors (cyclosporin and tacrolimus), steroids (prednisolone and methylprednisolone), antimetabolites (azathioprine and mycophenolate mofetil), antiproliferatives (sirolimus) and monoclonal antibodies that are used as an induction therapy (basilximab, daclizumab and muromonab). Over time, we have learnt more about existing immunosuppressive choices and the ways to monitor these drugs, and the current trend in immunosuppression therapy is towards tailoring the therapy according to an individual patient. The major issue that is now emerging is not how to prevent acute rejection, as current drugs are all efficacious, but rather how to avoid the long-term side effects that can harm both the graft and host, and negatively influence compliance. The market in transplantation is considerable and still growing; the whole market including the immuno-suppressants used in autoimmune diseases had sales of approximately pound 1.5 billion in 2001. There are currently 23 new drugs in advanced clinical development intended to be used in either organ transplantation or as treatment of autoimmune diseases. The new drugs that are intended to be used in transplantation are mostly analogues of currently used drugs with improved safety and pharmaceutical profiles.