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1.
Expert Opin Drug Saf ; : 1-11, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39152782

RESUMEN

INTRODUCTION: Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder characterized by progressive muscle degeneration and weakness, caused by mutations in the dystrophin gene. DMD has effects in early age with significantly shortened lifespan and deteriorated quality of life in the second decade, creating an urgent need to develop better therapeutic options. Corticosteroid medication therapy is an integral tool for the management of DMD and several therapeutic options have been recently approved for use. AREAS COVERED: A comprehensive literature search was completed to examine efficacy and safety profiles of the three corticosteroid medications available for use in DMD patients. The review presents information about the three agents through clinical trials, significant preclinical trials, and comparative studies. EXPERT OPINION: Managing DMD takes a multidisciplinary approach, although long-term corticosteroid therapy remains a significant therapeutic tool. Based on the available published studies, unequivocal comparison between the benefits of the three medications cannot yet be made. When selecting a medication for a patient, the decision-making process will most likely rely on the minor differences in the adverse effect profiles. Whichever medication is utilized will surely be a part of a larger regimen that includes other novel therapeutic agents.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38977481

RESUMEN

PURPOSE: Antibody therapy for chronic rhinosinusitis with nasal polyps (CRSwNP) has been established in Germany since 2019. With limited long-term data on biologic treatment for CRSwNP, we conducted a comprehensive evaluation of our 4-year data. This monocentric study aims to assess the real-world effects of this treatment on clinical course, quality of life, treatment adherence, biologic switching, dual therapy, and comorbidities. METHODS: We retrospectively analysed biologic therapy data in patients with severe chronic rhinosinusitis with nasal polyps. 191 patients with CRSwNP treated with Dupilumab, Mepolizumab, or Omalizumab were observed for up to 4 years in a real-life setting. RESULTS: We observed clear symptom improvements with few side effects. No loss of efficacy or tolerability was noted during the 4-year period. Patients reported high satisfaction compared to previous therapies, with overall improved quality of life. Revision surgery or oral steroid use during biologic therapy was rare. Some patients prolonged injection intervals or discontinued steroid nasal spray. Biologic switching occurred infrequently due to side effects or inadequate response and was generally well tolerated. Many patients reported additional positive effects such as asthma or allergy symptom improvement and reduced medication intake. CONCLUSION: In summary, this study confirms the potency and tolerability of biologics for CRSwNP treatment, with sustained efficacy over 4 years. Biologic switching is a viable option for inadequate response or intolerable side effects. Therapy positively impacts Th2 comorbidities, corticosteroid requirements, surgery need, and overall compliance remains high. CLINICAL TRIAL REGISTRATION: Project No.: 22-0802. Registry name: Biologika bei Patient*innen mit chronischer Sinusitis mit Nasenpolypen.

3.
J Pak Med Assoc ; 74(6): 1067-1073, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38948973

RESUMEN

Objectives: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. METHODS: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. The study included patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for ≥3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. RESULTS: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinaemia and 70(42%) with hypreprolactinaemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Patients having treatment duration 11-20 months (p=0.006) and >40 months (p=0.001) were at high risk of developing hyperprolactinaemia. CONCLUSIONS: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management.


Asunto(s)
Hiperprolactinemia , Prolactina , Inhibidores de la Bomba de Protones , Humanos , Inhibidores de la Bomba de Protones/uso terapéutico , Inhibidores de la Bomba de Protones/efectos adversos , Femenino , Estudios Transversales , Masculino , Hiperprolactinemia/epidemiología , Hiperprolactinemia/inducido químicamente , Hiperprolactinemia/sangre , Hiperprolactinemia/tratamiento farmacológico , Prolactina/sangre , Adulto , Persona de Mediana Edad , Pakistán/epidemiología , Prevalencia
4.
Prz Gastroenterol ; 19(2): 159-164, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38939068

RESUMEN

Introduction: Proton pump inhibitors (PPIs) are effective drugs used for multiple gastrointestinal complications. They are commonly used in both hospitalised and outpatients. However, little is known about its utilisation pattern in ambulatory patients. Aim: To evaluate the inexpedient continuous use of PPIs in patients with respect to treatment duration. Material and methods: A cross-sectional observational study was conducted from January 2018 to November 2019 in Khyber Pakhtunkhwa, Pakistan. Regular proton pump inhibitor users were identified through patient histories. Results: During the study period, 171 patients were included using a non-probability consecutive sampling technique, who were using regular proton pump inhibitors for a longer duration, i.e. from 3 months to 15 years. The highest proportion (42.8%) were using PPI regularly from 3 months to 1 year followed by 22.9% for 1-2 years, 12.0% for 2-3 years, 7.8% for 3-4 years, 4.2% for 4-5 years, and 10.24% for > 5 years. Omeprazole and esomeprazole were the most commonly used drugs, with 71.1% and 23.5% prevalence, respectively. A total of 33.73% of patients had continued PPI use on their own after initially being prescribed by the physician. Conclusions: It can be deduced that PPIs are used in outpatients beyond standard treatment guidelines. The inexpedient continuous use of proton pump inhibitors is of concern due to the risk of developing adverse effects. Therefore, patient counselling and periodic monitoring must be carried out to prevent the irrational use of PPIs.

5.
Cureus ; 15(11): e48682, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-38090465

RESUMEN

Mandibular advancement devices (MADs) remain a popular non-invasive treatment modality for the management of obstructive sleep apnea (OSA). However, the occlusal side effects from long-term therapy may result in poor patient compliance and patient drop-outs. Hence, knowledge of the possible side effects of these devices on occlusion is necessary. This article attempts to systematically review the evidence available in support of the possible long-term effects of mandibular advancement therapy on occlusion in adult sleep apnea patients. A detailed search was conducted for unpublished and published literature and their references in various electronic databases. A grey literature search was also performed. Studies until June 30, 2022, were selected. Randomized controlled trials, non-randomized trials, and cohort studies investigating the occlusal side effects of MADs for the treatment of snoring or OSA with a follow-up of at least four years were included. Study selection, data extraction, and risk of bias assessment were performed individually and in duplicate. The risk of bias was assessed by Cochrane tools for randomized and non-randomized studies. Fourteen studies were selected for the final qualitative analysis. The side effects reported were upper incisor retroclination, lower incisor proclination, decreased overjet and overbite, and change in the total occlusal contact area. The review concludes that long-term MAD therapy has statistically and clinically significant effects on occlusion.

6.
Int J Mol Sci ; 24(19)2023 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-37833892

RESUMEN

A personalized treatment decision for Gaucher disease (GD) patients should be based on relevant markers that are specific to GD, play a direct role in GD pathophysiology, exhibit low genetic variation, reflect the therapy, and can be used for all patients. Thirty-four GD patients treated with enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were analyzed for platelet count, chitotriosidase, and tartrate-resistant acid phosphatase activity in plasma samples, and quantitative measurement of Lyso-Gb1 was performed in dried blood spots. In our ERT and SRT study cohorts, plasma lyso-GL1 correlated significantly with chito-triosidase (ERT: r = 0.55, p < 0.001; SRT: r = 0.83, p < 0.001) and TRAP (ERT: r = 0.34, p < 0.001; SRT: r = 0.88, p < 0.001), irrespective of treatment method. A platelet count increase was associated with a Lyso-Gb1 decrease in both treatment groups (ERT: p = 0.021; SRT: p = 0.028). The association of Lyso-Gb1 with evaluated markers was stronger in the SRT cohort. Our results indicate that ERT and SRT in combination or in a switch manner could offer the potential of individual drug effectiveness for particular GD symptoms. Combination of the key biomarker of GD, Lyso-Gb1, with other biomarkers can offer improved response assessment to long-term therapy.


Asunto(s)
Enfermedad de Gaucher , Humanos , República Checa , Enfermedad de Gaucher/diagnóstico , Enfermedad de Gaucher/tratamiento farmacológico , Biomarcadores , Terapia de Reemplazo Enzimático , Recuento de Plaquetas
7.
J Dermatolog Treat ; 34(1): 2200868, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37026590

RESUMEN

BACKGROUND: Long-term real-life data on secukinumab use in psoriasis are limited. OBJECTIVES: Determine the long-term effectiveness of secukinumab in moderate-to-severe psoriasis in real-life. METHODS: Multicenter retrospective study analyzing data from adult patients treated with secukinumab for at least 192 weeks and up to 240 weeks in Southern Italy, between 2016 and 2021. Clinical data, including concurrent comorbidities and prior treatments were collected. Effectiveness was assessed by Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), Dermatology Life Quality Index (DLQI) scores at the initiation of secukinumab and at weeks 4, 12, 24, 48, 96, 144, 192, and 240. RESULTS: Two hundred and seventy-five patients (174 males), mean age 50.80 ± 14.78 years, were included; 29.8% had an uncommon localization, 24.4% psoriatic arthritis, 71.6% comorbidities. PASI, BSA, and DLQI improved significantly from week 4 and continued to improve over time. Between weeks 24 and 240, PASI score was mild (≤10) in 97-100% of patients, 83-93% had mild affected BSA (BSA ≤ 3), and 62-90% reported no effect of psoriasis on their quality of life (DLQI 0-1). Only 2.6% of patients reported adverse events and no patient discontinued the treatment during the study period. CONCLUSIONS: Secukinumab effectiveness in the long-term treatment of psoriasis is confirmed in real-world.


Asunto(s)
Anticuerpos Monoclonales , Psoriasis , Adulto , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anticuerpos Monoclonales/efectos adversos , Estudios Retrospectivos , Calidad de Vida , Resultado del Tratamiento , Índice de Severidad de la Enfermedad , Psoriasis/tratamiento farmacológico , Psoriasis/inducido químicamente , Italia
8.
Pharmaceuticals (Basel) ; 16(1)2023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-36678571

RESUMEN

Lithium remains the drug of first choice for prophylactic treatment of bipolar disorder, preventing the recurrences of manic and depressive episodes. The longitudinal experiences with lithium administration greatly exceed those with other mood stabilizers. Among the adverse side effects of lithium, renal, gastrointestinal, neurological, thyroid, metabolic, cognitive, dermatological, cardiologic, and sexual are listed. Probably, the most important negative effect of lithium, occurring mostly after 10-20 years of its administration, is interstitial nephropathy. Beneficial side-effects of long-term lithium therapy also occur such as anti-suicidal, antiviral, and anti-dementia ones. Pharmacokinetic and pharmacodynamic interactions of lithium, mostly those with other drugs, may have an impact on the success of long-term lithium treatment. This paper makes the narrative updated review of lithium-induced side-effects and interactions that may influence its prophylactic effect in bipolar disorder. Their description, mechanisms, and management strategies are provided. The papers appearing in recent years focused mainly on the long-term lithium treatment are reviewed in detail, including recent research performed at Department of Psychiatry, Poznan University of Medical Sciences, Poland. Their own observations on ultra-long lithium treatment of patients with bipolar disorder are also presented. The review can help psychiatrists to perform a successful lithium prophylaxis in bipolar patients.

9.
Front Pharmacol ; 13: 1024046, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36506505

RESUMEN

Due to the Russian invasion, which started on 24 February 2022, the Ukrainian healthcare system is facing multiple challenges. A great number of healthcare facilities have been destroyed, while availability of other ones is often limited due to a lack of qualified medical staff. Certain services, e.g. cancer therapies, have been seriously disrupted. Moreover, millions of Ukrainians with chronic conditions are also suffering as due to war-related problems with execution of their long-term therapies. Availability of drugs is particularly limited in the occupied regions. According to the national statistics, as of 18 August 2022, about 505 pharmacies were damaged in Eastern Ukraine and 47 completely ruined. Moreover, the invaders have been blocking humanitarian aid provided to these territories by the Ukrainian government or other countries. Fortunately, in the areas controlled by the Government of Ukraine, the acute shortage of medicines, observed at the beginning of the war, has already been eliminated. Nevertheless, not all drugs are now fully available, even in the areas where no military attacks occur. The economic availability of drugs is also profoundly influenced by the significant increase in the cost of medications and the fall in average salaries. The Government of Ukraine is trying to minimise the impact of these war-related challenges by adopting a new legislation. This includes, among others, simplification of procedures for licensing, quality control and import of medicinal products to Ukraine. Other measures involve securing displaced people with the option of benefiting from local healthcare facilities, broadening the scope of the ePrescription system, authorizing primary care doctors to issue prescriptions to refugees, increasing the number of drugs reimbursed for long-term therapies, etc. These solutions, however, cannot balance all the harmful consequences the war in Ukraine brings in terms of maintenance of long-term therapies. Therefore, in order to minimise this negative impact, Ukraine still needs urgent international support in this area.

10.
Front Endocrinol (Lausanne) ; 13: 901925, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36225201

RESUMEN

Purpose: This study aimed to investigate the skeletal outcomes of patients with osteogenesis imperfecta (OI) who received bisphosphonate (BP) treatment and entered drug holiday after achieving an age- and sex-specific bone mineral density (BMD) reference. Methods: Patients with OI receiving BP treatment were enrolled when they entered drug holidays of BPs. The skeletal outcomes were evaluated in detail during the drug holiday, including BMD, X-ray of the bone, bone fracture incidence, and bone turnover biomarkers. The pathogenic mutations of OI were identified by next-generation sequencing and confirmed by Sanger sequencing. Results: A total of 149 OI patients (127 juveniles and 22 adults) who entered drug holidays after nearly 4 years of BP treatment were included. Areal BMD at the lumbar spine increased from 0.934 ± 0.151 to 0.990 ± 0.142 g/cm2 and was stable in the second (1.029 ± 0.176 g/cm2) and third years (1.023 ± 0.174 g/cm2) of BP drug holidays, and BMD at the femoral neck, trochanter, and total hip had no significant change, but it was gradually inferior to that of the same-gender juveniles in the second and third years of the drug holiday. BMD at the lumbar spine and proximal hip did not change and was inferior to that of the same-gender adults. The average time of fractures fluctuated from 0.18 to 0.08 per year in juveniles, while only one adult suffered from a fracture during BP drug holidays. Bone turnover markers were in the normal range, except for a mildly high level of ß-carboxy-terminal cross-linked telopeptide of type 1 collagen in the juvenile group. A total of 17 (11.4%) patients received BP retreatment because of bone loss during the drug holiday. OI type III and type IV and COL1A2 mutation were correlated to a longer duration of BP treatment to enter drug holidays (all p < 0.05). Old age at initial treatment (OR, 1.056) and OI type III (OR, 10.880) were correlated to a higher risk of BP retreatment. Conclusions: OI patients will undergo nearly 4 years of BP treatment to achieve drug holidays. During the 3 years of the drug holiday, the patients' BMD is stable, and fracture incidence does not increase significantly. Patients are more inclined to need retreatment during drug holidays owing to the late start of BP treatment and more severe OI phenotypes.


Asunto(s)
Fracturas Óseas , Osteogénesis Imperfecta , Biomarcadores , Colágeno Tipo I/genética , Difosfonatos/uso terapéutico , Femenino , Fracturas Óseas/etiología , Humanos , Masculino , Osteogénesis Imperfecta/tratamiento farmacológico , Osteogénesis Imperfecta/genética
11.
Int J Surg ; 98: 106221, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35026462

RESUMEN

BACKGROUND: The aim of the present study is to present the three years follow-up a randomised controlled trial that compared Hartmann's Procedure (HP) with sigmoidectomy with primary anastomosis (with or without defunctioning ileostomy) (PA) in a randomised design to determine the optimal treatment strategy for perforated diverticulitis with purulent or fecal peritonitis. METHODS: Data were prospectively gathered for the first 12 months after randomization and retrospectively collected up to 36 months. The primary long-term endpoint was stoma free rate 36 months after the index procedure. Secondary outcomes were patients with a stoma at 36 months, percentage of stoma reversals, related reinterventions, parastomal/incisional hernia rates, total in hospital days including all readmissions regardless their relation to the intervention, overall morbidity and mortality. RESULTS: Three years follow-up was completed in 119 of the originally 130 included patients, with 57 (48%) in the PA-group and 62 (52%) patients in the HP-group. 36 months stoma free rate was significantly better for patients undergoing PA compared with HP (PA 92% vs HP 81%, hazard ratio 2.326 [95% CI 1.538-3.517]; log-rank p < 0·0001). Stoma reversal rates did not significantly differ (PA 31/40(78%) versus HP 45/61(74%), p = 0.814). Overall cumulative morbidity (PA 21/57(36%) versus HP 30/62(48%), p = 0.266) and mortality (PA 6/57(11%) versus HP 7/62 (11%), p = 1.000) did not differ between groups. However, more parastomal hernias occurred in the HP-group (HP 10/62(16%) vs PA 1/57(2%), p = 0.009) and the mean total in hospital days after three years follow-up was significantly lower in the PA-group compared to the HP-group (PA 14 days (IQR 9.5-22.5) versus HP 17 days (IQR 12.5-27.5)), p = 0.025). CONCLUSION: Long-term results showed that in haemodynamically stable, immunocompetent patients primary anastomosis is superior to Hartmann's procedure as treatment for perforated diverticulitis with respect to long-term stoma free rate, overall hospitalization and parastomal hernias.


Asunto(s)
Diverticulitis del Colon , Diverticulitis , Perforación Intestinal , Peritonitis , Anastomosis Quirúrgica/efectos adversos , Colostomía , Estudios de Seguimiento , Humanos , Perforación Intestinal/etiología , Perforación Intestinal/cirugía , Peritonitis/etiología , Peritonitis/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
12.
J Dermatolog Treat ; 33(5): 2425-2432, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34694953

RESUMEN

Most patients with psoriasis present with localized mild-to-moderate disease. In this case, the application of topical treatments in the first-line setting is recommended in most cases.Among different topical options, the fixed-dose combination of betamethasone dipropionate (BD) and vitamin D analogue (Cal) aerosol foam (Enstilar®, Leo Pharma) is approved as first-line topical therapy for the treatment of psoriasis in USA and the EU, due to its high efficacy and its favorable administration scheme.The PSO-LONG was the first trial to report on the long-term efficacy and safety of the Cal/DB foam treatment for the proactive management of psoriasis and now, the indications of Cal/BD foam included its use in the psoriasis maintenance treatment. However, the precise role of this treatment and the potential therapeutic schemes in the long-term management of psoriasis need further clarification.This Position Paper, authored by a group of Italian Expert Dermatologists, critically discusses the long-term management of psoriasis with Cal/BD foam in clinical practice. In particular, the biological rationale in the proactive treatment with Cal/BD foam and current evidence regarding this therapeutic approach are presented, along with its application also in patients with moderate-to-severe disease, difficult-to-treat lesions, or within combination regimens. In addition, strategies to improve adherence to long-term treatment of psoriasis are discussed.


Asunto(s)
Fármacos Dermatológicos , Psoriasis , Aerosoles/uso terapéutico , Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapéutico , Combinación de Medicamentos , Humanos , Psoriasis/tratamiento farmacológico , Resultado del Tratamiento
13.
J Control Release ; 335: 422-436, 2021 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-34087247

RESUMEN

Allergic rhinitis (AR), histamine-mediated upper airway inflammatory disorder, is characterized by sneezing, itching, airway hyperreactivity, etc. Though it is clinically well-managed by non-invasive inhaled antihistamines, for example, ketotifen (KT, histamine release inhibitor) and cetirizine (CTZ, histamine receptor antagonist), inherent defects of short mucosal in situ retention, frequent administration resulting in irritation to mucosa, and lack of target-specific sequential release of dual drug systems which have been proven to be more effective are inevitable, urging for alternative therapeutic strategies. Recent advances in nanotechnology may be pivotal to generating muco-adhesive nanosystems, which is desirable to prolong local retention, reduce dosing frequency and relieve mucosal irritation. In this regard, KT incorporated and CTZ decorated hydroxybutyl chitosan nanoparticles (K âŠ‚ CH NPs) were fabricated as nasal adaptive sequential release dual drug system for long-term AR therapy. Nasal adaptive morphology transformation and two-step payload release up to 72 h were achieved in vitro, with ~ 3-fold higher bio-adhesivity over free drugs appeared. K âŠ‚ CH NPs accomplished longer histamine release inhibition (~ 24 h) and histamine H1 receptor antagonism (~ 6 h), compared with free KT&CTZ of ~ 12 h and ~ 2 h, respectively. The nanosystems provided comparable anti-allergic effect to free antihistamines via successive intranasal dropping in AR rat, while encouragingly, significantly (P < 0.05) better therapeutic efficacy at reduced treatment frequency (every 4 days) and dose (half-dose). Therefore, the outcomes establish K âŠ‚ CH NPs as effective low-dose and long-interval administered nanosystems to ameliorate histamine-mediated AR inflammation, which could in principal find extensive utilizations in respiratory allergy intervention.


Asunto(s)
Antialérgicos , Quitosano , Rinitis Alérgica , Animales , Quitosano/uso terapéutico , Histamina , Antagonistas de los Receptores Histamínicos H1/uso terapéutico , Ratas , Rinitis Alérgica/tratamiento farmacológico
14.
Front Vet Sci ; 8: 669815, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33969044

RESUMEN

Osteoarthritis (OA) treatment is a major orthopedic challenge given that there is no ideal drug capable to reverse or stop the progression of the OA. In that regard, bisphosphonates have been proposed as potential disease-modifying drugs due to their possible chondroprotective effect related to obtaining a greater subchondral bone quality. However, their effectiveness in OA is still controversial and additionally, there is little evidence focused on their long-term effect in preclinical studies. The aim of this study was to evaluate the risedronate quantitative effect on articular and subchondral periarticular bone by histomorphometry, in an experimental rabbit model in an advanced stage of OA. Twenty-four adult New Zealand rabbits were included in the study. OA was surgically induced in one randomly chosen knee, using the contralateral as healthy control. Animals were divided into three groups (n = 8): placebo control group, sham surgery group and risedronate-treated group. After 24 weeks of treatment, cartilage and subchondral femorotibial pathology was evaluated by micro-computed tomography (micro-CT) and undecalcified histology. The research results demonstrated that the experimental animal model induced osteoarthritic changes in the operated joints, showing an increased cartilage thickness and fibrillation associated with underlying subchondral bone thinning and decreased trabecular bone quality. These changes were especially highlighted in the medial tibial compartments as a possible response to surgical instability. Regarding the trabecular analysis, significant correlations were found between 2D histomorphometry and 3D imaging micro-CT for the trabecular bone volume, trabecular separation, and the trabecular number. However, these associations were not strongly correlated, obtaining more precise measurements in the micro-CT analysis. Concerning the long-term risedronate treatment, it did not seem to have the capacity to reduce the osteoarthritic hypertrophic cartilage response and failed to diminish the superficial cartilage damage or prevent the trabecular bone loss. This study provides novel information about the quantitative effect of long-term risedronate use on synovial joint tissues.

15.
Tohoku J Exp Med ; 253(4): 261-267, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33853993

RESUMEN

Bisphosphonates have been the first drug of choice for osteoporosis in the recent years because of their known ability to suppress osteoclast activity. The adverse effect of long-term bisphosphonate administration in the fracture-healing process is controversial. The aim of our study was to observe not only morphology but also morphometry of the fracture site of atypical femoral fracture with and without long-term bisphosphonate administration, in a case study of two difficult-to-obtain human samples. The patients with insufficient healing of atypical femoral fracture were treated with valgus wedge osteotomy. Histomorphometrical analysis was performed in bone samples of fracture sites harvested during osteotomy. The thickness of the femoral cortex was measured in the fracture site and the adjacent, non-fracture site. A comparative analysis of the content of hypertrophic osteoclasts in fracture sites, shape and size of osteons, mass, and ratio of the woven bone to the total bone mass was performed, comparing bisphosphonate-treated and untreated samples. In bisphosphonate-treated samples, we observed femoral cortex thickening at the fracture site; the appearance of hypertrophic osteoclasts; decreased bone resorption surface, decreased osteoclast numbers on the bone resorption surface, and increased ratio of multinuclear osteoclasts; osteons were misshapen and thin; and the mass and ratio of the woven bone to the total bone mass were higher. This study demonstrated that long-term bisphosphonate administration can alter the morphological features of the fracture site compared to its physiological state.


Asunto(s)
Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Fracturas del Fémur/inducido químicamente , Curación de Fractura , Osteoporosis/tratamiento farmacológico , Anciano de 80 o más Años , Difosfonatos/administración & dosificación , Difosfonatos/farmacología , Femenino , Fracturas del Fémur/diagnóstico por imagen , Curación de Fractura/efectos de los fármacos , Humanos , Tomografía Computarizada por Rayos X
16.
Epilepsy Res ; 173: 106619, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33774428

RESUMEN

PURPOSE: Epilepsy may be treated with antiepileptic drugs (AEDs), which have been reported to decrease bone mineral density (BMD). Current data is conflicting and variable, and little is known with regard to how duration of AED use or specific AEDs, such as CYP-450 enzyme-inducing (EIAEDs) versus non-enzyme inducing (NEIAEDs) drugs affect BMD. We sought to systematically review BMD changes due to AED use to identify trends in reporting. METHODS: A literature search via Medline (PubMed), EMBASE, and Cochrane databases was performed. Peer-reviewed articles were identified that reported on BMD measurements in conjunction with AEDs. RESULTS: Twenty-six studies met inclusion criteria. Long-term therapy was shown across multiple, well-controlled studies to have the most significant BMD loss. Carbamazepine had the most frequent reporting of unfavorable effects on bone health and Lamotrigine seemed to show the most bone-protective qualities. Serum biochemical markers of bone turnover did not significantly correlate with measured BMD changes. CONCLUSION: The present study provides evidence that long-term AED therapy is the most significant risk factor for BMD loss. Furthermore, there was little compelling evidence to support that EIAEDs, as a class, were more harmful to bone than NEIAEDs, which has been previously suggested in multiple studies. Early clinical concern for significant loss of BMD may not be warranted as lower BMD was less likely to be observed during the initial years of AED therapy. Furthermore, serum markers of bone turnover are not clinically reliable in assessing BMD changes in patients taking AEDs.


Asunto(s)
Anticonvulsivantes , Epilepsia , Anticonvulsivantes/efectos adversos , Densidad Ósea , Carbamazepina/efectos adversos , Epilepsia/tratamiento farmacológico , Humanos , Lamotrigina/farmacología , Lamotrigina/uso terapéutico
17.
Clin Otolaryngol ; 46(4): 758-766, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33534183

RESUMEN

OBJECTIVES: Treatment with botulinum toxin A (BoNT) is the therapy of choice for many patients with facial synkinesis. Repeated injections relieve hypertonicity and hyperkinesis of reinnervated mimic muscles. Aim of the study was to prove if the injection regime and dosage of BoNT change during long-time therapy. DESIGN: Retrospective analysis of patients´ data, who were treated for synkinesis with BoNT from 1998 to 2018. SETTING: Tertiary referral facial nerve centre. PARTICIPANTS: Injection pattern of BoNT was based on clinical symptoms, observations of the specialist and on previous treatment pattern. Onabotulinumtoxin (OnaBoNT), Incobotulinumtoxin (IncoBoNT) and Abobotulinumtoxin (AboBoNT) were available for treatment. Patients consulted our department for following treatment as soon as the symptoms re-occurred. MAIN OUTCOME MEASURES: Change in dosage and injection pattern, the time intervals between treatments over the entire therapy period. RESULTS: Seventy-three patients were repeatedly injected. The median number of treatments was 18, the median treatment interval was 3.0 months. During the initial treatment, orbicularis oculi and the mentalis muscles were the most frequently injected muscles (94%). During repeated treatment, the number of injected muscles increased significantly (P < .0001), whereas the dose per muscle remained stable. The initial dose was 24 U (95%-CI 22-27 U) for OnaBoNT and IncoBoNT; 69 U for AboBoNT(95%-CI 44-94 U). We observed a significant increase in dosage for OnaBoNT and IncoBoNT (P < .0001) during the long-term therapy. The time intervals between treatments were stable for all three BoNT preparations (P > .05). CONCLUSIONS: We observed significant change in treatment dose and injection pattern of BoNT in patients with facial synkinesis. These results provide an orientation in dose finding and injection regimen of BoNT in the long-term course of therapy.


Asunto(s)
Toxinas Botulínicas Tipo A/uso terapéutico , Músculos Faciales/fisiopatología , Fármacos Neuromusculares/uso terapéutico , Sincinesia/tratamiento farmacológico , Sincinesia/fisiopatología , Adolescente , Adulto , Anciano , Femenino , Humanos , Inyecciones Intramusculares , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
18.
Hormones (Athens) ; 20(1): 151-159, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33026609

RESUMEN

BACKGROUND: Reassignment of a female-to-male (FtM) person requires gender-affirming, androgenic hormonal treatment that is planned to induce appropriate structural changes. This therapy must be prolonged long term, even after the sex reassignment surgery (SRS). The purpose of this study is to evaluate the effects of hormone therapy with testosterone in FtM subjects during a 24-month follow-up in order to highlight the occasional need for early decompensation and to make adequate hormone therapy modulations. METHODS: Fifteen out of 23 FtM persons had been previously treated with SRS, while eight were still awaiting surgery. During hormone therapy, both groups were followed for 24 months, with evaluation of desired changes, adverse effects, and functional or metabolic indicators. RESULTS: In the group of operated FtM subjects (15/23), a significant increase of total testosterone (total T) and free testosterone (free T) was found after 24 months. Luteinizing hormone (LH) maintained a low level, decreasing after ovariectomy, while FSH increased. Voice deepening, facial and body hair variation, male-pattern balding, and body mass index (BMI) increase are all physical changes due to androgenization. In both groups of patients who have been closely monitored, the side effects and thromboembolic, metabolic, and cardiovascular risks of androgen therapy, even in the long term, appear to be irrelevant. CONCLUSION: Total T, free T, and LH dosages are shown to be reliable markers of correct androgenization. Strict monitoring of lipid profile, evaluation of BMI and hematocrit, avoidance of self-initiated therapeutic modifications, adherence to a healthy lifestyle, and avoidance of excessive daily calorie intake can limit risks linked to long-term testosterone administration. TRIAL REGISTRATION: Retrospectively registered.


Asunto(s)
Andrógenos/farmacología , Testosterona/farmacología , Personas Transgénero , Adulto , Andrógenos/administración & dosificación , Femenino , Humanos , Masculino , Testosterona/administración & dosificación
19.
Cult Med Psychiatry ; 45(2): 218-233, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32725439

RESUMEN

Patients often adhere to intrathecal opioid therapy (IOT) for many years, despite the lack of scientific evidence for its efficacy and the scarce knowledge about long-term effects. Moreover, there is no knowledge on how the efficacy of IOT is influenced by cultural factors. We assessed the long-term efficacy and frequency of side effects of IOT in two culturally different patient samples. A chart review was conducted of all patients with IOT, who had been treated in interdisciplinary pain centers in Freiburg and in Tehran in a 15-year span. Personal data, diagnosis, duration of pain disease, pump type in use, revision operations, and opioid doses were recorded. Patients completed a questionnaire containing pain scores, pain-related disability (PDI), anxiety, depression, and unwanted side effects. Fourteen Iranian and 36 German patients (32 m/18 f) were studied. Mean duration of IOT was 10.2 years. Pain levels prior to IOT were 7.64 (NRS) (range 4-10, SD 1.64), 3.86 (range 0-9, SD 2.32) directly after pump implantation, and 4.17 (range 0-10, SD 2.11) at time of follow-up. Iranian patients had significantly lower pain levels directly after implantation, depression scores, and pain-related disability. Frequent side effects were obstipation, sexual dysfunction, urinary retention, and fatigue. Most side effects were significantly less frequent in the Iranian sample. There were no severe complications or permanent neurological deficit. Our study demonstrates the effectiveness of IOT also for long-term application. Differences in clinical efficacy are partially due to cultural factors. Side effects are frequent but not limiting patient satisfaction.


Asunto(s)
Analgésicos Opioides , Comparación Transcultural , Analgésicos Opioides/efectos adversos , Humanos , Inyecciones Espinales , Irán , Encuestas y Cuestionarios
20.
Pediatr Dermatol ; 38(2): 464-468, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33382463

RESUMEN

Blue rubber bleb nevus syndrome is a rare vascular syndrome characterized by continuous eruption of vascular nodules in the skin, mucous membranes, and solid organs due to somatic activating mutations of the angiopoietin receptor TEK gene. It may be complicated by acute life-threatening hemorrhage and localized intravascular coagulation. We report an 11-year-old girl with complicated blue rubber bleb nevus syndrome treated with sirolimus since the age of 2. We review the literature on sirolimus therapy for children with blue rubber bleb nevus syndrome.


Asunto(s)
Neoplasias Gastrointestinales , Nevo Azul , Neoplasias Cutáneas , Niño , Femenino , Neoplasias Gastrointestinales/tratamiento farmacológico , Humanos , Nevo Azul/diagnóstico , Nevo Azul/tratamiento farmacológico , Sirolimus/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico
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