Safe Alternatives For Patients Research Articles

Behavioral interventions for improving sleep outcomes in menopausal women: a systematic review and meta-analysis.

Perimenopausal and postmenopausal women commonly report sleep disruption and insomnia. Behavioral interventions may be safe alternatives for patients who are unwilling to begin pharmacological treatments because of adverse effects, contraindications, or personal preference. The primary objective is to assess the efficacy of behavioral interventions on sleep outcomes among perimenopausal and postmenopausal women, as measured using standardized scales and objective methods (polysomnography, actigraphy). The secondary objective is to evaluate the safety of these methods through occurrence of adverse events. Searches were performed within MEDLINE (OVID interface, 1946 onward), Embase (OVID interface, 1974 onward), Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Web of Science (Core collection) using a search strategy developed in consultation with a health sciences librarian. Title/abstract and full-text screenings were performed in duplicate, and relevant studies were selected based on inclusion and exclusion criteria set to identify randomized controlled trials evaluating the effects of behavioral interventions on sleep quality. Risk of bias assessments were done using the Cochrane Risk of Bias 2 tool, and the Grading of Recommendations Assessment, Development and Evaluation approach was used to assess the certainty of the body of evidence. Data were pooled in a meta-analysis using a random-effects model. Nineteen articles reporting results from 16 randomized controlled trials were included, representing a total of 2,108 perimenopausal and postmenopausal women. Overall, behavioral interventions showed a statistically significant effect on sleep outcomes (standardized mean difference [SMD], -0.62; 95% confidence interval [CI], -0.88 to -0.35; I2 = 93.4%). Subgroup analyses revealed that cognitive behavioral therapy (SMD, -0.40; 95% CI, -0.70 to -0.11; I2 = 72.7%), physical exercise (SMD, -0.57; 95% CI, -0.94 to -0.21; I2 = 94.0%), and mindfulness/relaxation (SMD, -1.28; 95% CI, -2.20 to -0.37; I2 = 96.0%) improved sleep, as measured using both subjective (eg, Pittsburg Sleep Quality Index) and objective measures. Low-intensity (SMD, -0.91; 95% CI, -1.59 to -0.24; I2 = 96.8) and moderate-intensity exercise (SMD, -0.21; 95% CI, -0.34 to -0.08; I2 = 0.0%) also improved sleep outcomes. No serious adverse events were reported. Overall risk of bias ranged from some concern to serious, and the certainty of the body of evidence was assessed to be of very low quality. This meta-analysis provides evidence that behavioral interventions, specifically, cognitive behavioral therapy, physical exercise, and mindfulness/relaxation, are effective treatments for improving sleep outcomes among perimenopausal and postmenopausal women.

Selective COX-2 inhibitor continues to be a safe alternative in patients with nonselective NSAIDs hypersensitivity

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) cause different types of allergic and pseudo allergic reactions. This results in difficulties in clinical practice. Most cases of NSAID hypersensitivity are mediated by the inhibition of cyclooxygenase-1 enzyme (COX-1), which results in depletion of the protective prostaglandin E2, and promotes the unrestrained synthesis of inflammatory mediators from mast cells. Selective COX-2 inhibitors are considered safe alternatives in patients with NSAID allergy, although hypersensitivity reactions to COX-2 inhibitors have also been reported. Our study aimed to report the experience in Qatar for using COX2 inhibitors as an alternative treatment for nonselective NSAID allergy.Methods: Data of patients who underwent open challenge with a single dose of oral celecoxib 200 mg were retrieved from the procedure log of the Allergy and immunology Division in Hamad medical corporation, Doha, Qatar, from 2013 to 2022. The challenge was considered positive if the patient developed cutaneous or respiratory symptoms.Results: A total of 31 patients were identified; 4 with a history of celecoxib allergy. The remaining 27 (23 females and 4 males); with mean ( ± SD, range) age of 42 ( ± 12, 20–65) years had hypersensitivity to one (n = 11) or more than one (n = 16) nonselective NSAID, manifested as cutaneous, respiratory, or anaphylactic symptoms. Those 4 patients with celecoxib allergy were challenged and only one with a historical reaction of anaphylaxis developed anaphylaxis during the challenge. Celecoxib was well tolerated in all 27 patients with hypersensitivity reactions to nonselective NSAIDs. Also, patients were contacted by telephone call at 24 hours and after 1 week with no evidence of delayed reactions.Conclusions: Selective COX-2 and nonselective NSAIDs have similar overall efficacy as analgesic, anti-inflammatory, and antipyretic agents. Hypersensitivity reaction to COX-2 inhibitors has been reported; however, it is rare. So, it is safer to challenge the patients with COX-2 inhibitors before prescribing them as alternative medication in patients with Nonselective NSAID allergies. We plan to conduct a single-/double-blind placebo-controlled study for more patients, especially using graded challenges for high-risk profile candidates. Also, it may be of significance to test more than one type of selective COX-2 to avoid drug-specific reactions.

Cross-reactive hypersensitivity to NSAIDs: Experience of a Tunisian allergology center

BackgroundThe accurate diagnosis of cross-reactive reactions (CRR) to nonsteroidal anti-inflammatory drugs (NSAIDs) depends on a careful history and oral drug challenge. In this study, we report the result of a new procedure implemented in Tunisian allergology center to explore CRR to NASIDs in patients with immediate hypersensitivity (IHS) to NSAIDs. MethodsOur structured protocol using oral provocation tests (OPTs) was based on the latest advances in the literature. This protocol was tested in patients with a clinical history of IHS reactions to one or more NSAIDs and referred to the pharmacology department of Sfax (Tunisia) between 2012 and 2018. Patients were classified into 5 subgroups: an ASA subgroup, a multiple NSAIDs subgroup, a single non-selective NSAID subgroup, a paracetamol subgroup, and a celecoxib subgroup. ResultsA total of 34 patients were enrolled. Personal history of atopy was found in 26 (76.5%). A diagnosis of CRR to NSAIDs was made in 24 patients (70.6%): 6 patients in the ASA subgroup, 12 patients in the multiple NSAIDs subgroup, 4 patients in the single non-selective NSAID subgroup, 1 patient in the paracetamol subgroup and 1 patient in the celecoxib subgroup. Regarding safe alternatives in patients with CRR to NSAIDs (n=24), prevalence of cross-reactivity to paracetamol or celecoxib was found in 20% and 27.3% of patients with confirmed CRR to NSAIDs, respectively. ConclusionOur structured protocol based on standardized oral provocation tests helps physicians to prescribe a suitable drug in patients with a history of IHS reactions to NSAIDs.

Retrospective analysis of adverse events with topical onychomycosis medications reported to the United States Food and Drug Administration.

Topical onychomycosis therapy is commonly prescribed due to its tolerability and low incidence of side effects. There are limited data on adverse events associated with the newer topical onychomycosis drugs. The objectives of this study is to classify the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. The United States Food and Drug Administration Adverse Event Reporting (FAERS) database was analyzed for the most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution. Google Trends was used to examine public interest in these drugs and these data were compared with yearly adverse events in the FAERS database. The most common adverse reactions associated with ciclopirox 8% solution, efinaconazole 10% solution, and tavaborole 5% solution were drug ineffectiveness. Application site erythema and nail discoloration were reported with all three medications. Increased Google searches for efinaconazole and tavaborole were associated with increased in reporting of adverse events to the FDA. Topical antifungals are safe alternatives for patients who have contraindications to oral medications. For improved efficacy, physicians should confirm the diagnosis of onychomycosis and choose appropriate candidates before starting topical therapy. Patients should be given clear instructions on drug usage and counseled about the more common side effects, including application site reactions and nail discoloration.

Is Surgical or Catheter-based Interventions an Option After an Unsuccessful Mitral Clip?

The objective of this study was to assess the results of catheter-based and surgical reinterventions in primary mitral regurgitation after failed MitraClip therapy. We report on 21 consecutive symptomatic patients with primary mitral regurgitation (median age 78 years) who underwent either repeat MitraClip therapy (n = 7) or mitral valve surgery (n = 14) after failure of the index procedure with 1-2 MitraClip implantations. At the time of reinterventions, 193 (interquartile range [IQR]: 32-622) days after the index procedure, patients had recurrent or persistent grade 3 mitral regurgitation. Early mortality at 30 days was 4.8%. Cardiac-related survival at 2 years was 85.4% (4 cardiac and 4 noncardiac deaths). Three of 7 patients with percutaneous reintervention were converted to surgery at 34, 52, and 56 days because repeat MitraClip therapy was ineffective because of pre-existing clip detachment or leaflet tear. Final therapy was biological mitral valve replacement in 14 of 21 patients (66.7%); 4 were treated with percutaneous repeat MitraClip repair (19%), and in 3 patients, surgical repairs were performed (14.3%). At follow-up with a median of 708 days, New York Heart Association class had improved significantly to class 2 (IQR: 1.0-2.5) (P = 0.0004), and the left ventricular end-diastolic diameter had decreased from 56 (IQR: 52-59) mm to 51 (48-58) mm (P = 0.0378), respectively. Recurrence of significant mitral regurgitation was absent in all but 1 patient with unsuccessful repeat MitraClip therapy who was deemed inoperable. Our data show that both repeat MitraClip and also mitral valve surgery are feasible and safe alternatives in patients without an excessively increased perioperative risk. We conclude that whenever leaflet insertion is not compromised, repeat catheter-based repair is a reasonable redo concept; in the remaining cases, surgery should be offered to the patient.

Are drug provocation tests still necessary to test the safety of COX-2 inhibitors in patients with cross-reactive NSAID hypersensitivity?

BackgroundCOX-2 inhibitors are safe alternatives in patients with cross-reactive non-steroidal anti-inflammatory drug (NSAID) hypersensitivity. These drugs are recommended to these patients after negative drug provocation tests (DPTs). However, cumulative data on encouraging results about the safety of COX-2 inhibitors in the majority of these patients bring the idea as to whether a DPT is always mandatory for introducing these drugs in all patients with cross-reactive NSAID hypersensitivity. ObjectiveTo document the safety of COX-2 inhibitors currently available and to check whether or not any factor predicts a positive response. MethodsThis study included the retrospective analysis of cases with cross-reactive NSAID hypersensitivity who underwent DPTs with COX-2 inhibitors in order to find safe alternatives. DPTs were single-blinded and placebo controlled. ResultsThe study group consisted of 309 patients. COX-2 inhibitors were well tolerated in the majority of the patients [nimesulide: 91.9%; meloxicam: 90.2%; rofecoxib: 94.9%; and celecoxib: 94.9%)]. Twenty-five patients (30 provocations) reacted to COX-2 inhibitors. None of the factors were found be associated with positive response. ConclusionOur results suggest to follow the traditional DPT method to introduce COX-2 inhibitors for finding safe alternatives in all patients with cross-reactive NSAID hypersensitivity before prescription as uncertainty of any predictive factor for a positive response continues. However, these tests should be performed in hospital settings in which emergency equipment and experienced personnel are available.

Severe cutaneous adverse reactions to antiepileptic drugs in Asians

Ethnicity has been shown to be a contributing risk factor regarding antiepileptic drug (AED)-induced severe cutaneous adverse drug reactions (SCARs). To increase the clinical and epidemiologic information in Asians, we investigated the characteristics, outcome, and tolerability toward alternative drugs for AED-induced SCARs. A total of 154 patients with AED-induced SCARs, including Stevens-Johnson syndrome (SJS), toxic epidermal necrosis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), were analyzed for demographic characteristics, causative AEDs, latent period, organ involvement, complications, and mortality. Tolerability toward alternative AEDs was followed for patients after AED-SCARs episodes. Carbamazepine (CBZ) and phenytoin (PHT) were the most common causative AEDs for SJS/TEN (67.8%) and DRESS (43.6%), respectively. No SCARs case was caused by nonaromatic AEDs, e.g., valproic acid (VPA) and topiramate (TPM). The liver was the most frequently involved internal organ in AED-DRESS, whereas ocular complications were more commonly seen in AED-SJS/TEN. The mortality of AED-SJS/TEN and -DRESS was 6.1% and 7.7%, respectively. By following alternative AED usage of patients after AED-SCARs episodes, we noted that most patients were tolerant of nonaromatic AEDs. One case of oxcarbazepine-SJS had cross-hypersensitivity to lamotrigine (LTG) and further developed into DRESS. CBZ, PHT, and LTG were the major causative AEDs for SCARs. The mortality of PHT-SCARs was higher than CBZ-SCARs due to complicated comorbidity in patients. Nonaromatic AEDs were safe alternatives for patients with aromatic AED-induced SCARs.

Endovascular repair compared with surveillance for patients with small abdominal aortic aneurysms

Although repair of large abdominal aortic aneurysms (AAAs) is well accepted, randomized clinical trials have failed to demonstrate benefit for early surgical repair of small aneurysms compared with surveillance. Endovascular repair has been shown to be safer than open surgical repair in patients with large aneurysms, prompting a randomized trial of early endovascular repair vs surveillance in patients with small aneurysms. We randomly assigned 728 patients (13.3% women; mean age, 71 +/- 8 years) with 4 to 5 cm AAAs to early endovascular repair (366 patients) or ultrasound surveillance (362 patients). Rupture or aneurysm-related death and overall mortality in the two groups were compared during a mean follow-up of 20 +/- 12 months. Among patients randomized to treatment, 89% underwent aneurysm repair. Among patients randomized to surveillance, 31% underwent aneurysm repair during the course of the study. After a mean follow-up of 20 +/- 12 months (range, 0-41 months), 15 deaths had occurred in each group (4.1%). The unadjusted hazard ratio (95% confidence interval) for mortality after early endovascular repair was 1.01 (0.49-2.07, P = .98). Aneurysm rupture or aneurysm-related death occurred in two patients in each group (0.6%). The unadjusted hazard ratio was 0.99 (0.14-7.06, P = .99) for early endovascular repair. Early treatment with endovascular repair and rigorous surveillance with selective aneurysm treatment as indicated both appear to be safe alternatives for patients with small AAAs, protecting the patient from rupture or aneurysm-related death for at least 3 years.

Ceftriaxone-Induced Fixed Drug Eruption

Fixed drug eruption (FDE) is an unusual type of cutaneous adverse drug reaction that is characterized by recurrent site-specific lesions each time the drug responsible is taken. FDE from cephalosporins has been rarely reported, and to the best of our knowledge there is no published report of ceftriaxone-induced FDE in the literature. We report the first case of a 54-year-old Turkish woman who presented with ceftriaxone-induced FDE. Topical provocation with ceftriaxone sodium salt (1% in water [aq.], 5% aq., 10% in petrolatum [pet.], 20% pet.) remained negative both at previously affected sites and in the unaffected skin of the back. Therapeutic re-exposure with intravenous ceftriaxone 1 g confirmed the diagnosis. The patient tolerated amoxicillin and cefazolin, suggesting that the sensitizing portion was not the beta-lactam ring. Identification of the antigenic determinants of FDE-inducing drugs will make predicting safe alternatives in patients with FDE an easier task.

Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance. We searched MEDLINE (1966–2006), the COCHRANE LIBRARY (4th Issue 2006) and EMBASE (1966–2006) up to December 9, 2006, and analysed all publications included using a predefined evaluation sheet. Symptoms and severity of adverse events to coxibs were analysed based on all articles comprising such information. Subsequently, the probability for adverse events triggered by coxibs was determined on analyses of double-blind prospective trials only. Among 3,304 patients with NSAID intolerance, 119 adverse events occurred under coxib medication. All adverse events, except two, have been allergic/urticarial in nature; none was lethal, but two were graded as life-threatening (grade 4). The two non-allergic adverse events were described as a grade 1 upper respiratory tract haemorrhage, and a grade 1 gastrointestinal symptom, respectively. In 13 double-blind prospective studies comprising a total of 591 patients with NSAID intolerance, only 13 adverse reactions to coxib provocations were observed. The triggering coxibs were rofecoxib (2/286), celecoxib (6/208), etoricoxib (4/56), and valdecoxib (1/41). This review documents the good tolerability of coxibs in patients with NSAID intolerance, for whom access to this class of drugs for short-term treatment of pain and inflammation is advantageous.

Insulin allergy; desensitization with crystalline zinc-insulin and steroid tapering

The insulin analogues, aspart and lispro, have been considered safe alternatives for patients with insulin allergy, because of their decreased immunogenicity. However, recent several reports showed that neither of them was completely free from allergic reactions. We also experienced a patient with insulin allergy not only to human regular insulin but also to both of the insulin analogues. Interestingly, the insulin analogues, which readily dissociate from polymer to monomer, induced the most severe allergic reaction among several types of human insulin reagents in the present case. Allergy to crystalline zinc-insulin, the three-dimensional structure of which results in delayed dissociation and absorption, was negative on intradermal tests. However, its large subcutaneous injection caused local allergic reaction. These results suggested that the allergic reaction might depend on the rapidity of insulin monomerization and absorption, and thus that the immunogenic residue of insulin is concealed when insulin is polymerized. Based on the intradermal tests, we speculated that the antigenic epitope might be B30-Thr in the present case. We also report here the modified method of insulin desensitization using crystalline zinc-insulin with prednisolone tapering. This might be a simple and useful treatment for insulin allergy.