Treatment Of Acute Attacks Research Articles

Efficacy of Celecoxib Oral Solution in Adults With and Without Baseline Nausea: Post Hoc Analysis of Results From Two Randomized, Double-Blind Placebo-Controlled Trials in the Acute Treatment of Migraine (P14-12.009)

Efficacy of Celecoxib Oral Solution in Adults With and Without Baseline Nausea: Post Hoc Analysis of Results From Two Randomized, Double-Blind Placebo-Controlled Trials in the Acute Treatment of Migraine (P14-12.009)

The Safety of Celecoxib as an Acute Treatment for Migraine: A Narrative Review.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been the first-line choice for the acute treatment of migraine attacks for decades; however, the safety of a particular NSAID is related to its treatment dose, duration, and mechanism of action. Although adverse event (AE) risks differ substantially among individual migraine treatments, increased or prolonged exposure to any NSAID elevates risks and severity of AEs. For this narrative review, we conducted a literature search of PubMed until July 2022, focusing on the history, mechanism of action, and treatment guidelines informing the safety and efficacy of celecoxib oral solution for the acute treatment of migraine attacks. Here we discuss the mechanisms of action of nonselective NSAIDs vs. cyclooxygenase-2 (COX-2) inhibitors, and how these mechanisms underlie the AEs associated with these treatments. We review the clinical trials that influenced the regulatory history of NSAIDs, specifically COX-2 inhibitors, the role of traditional and new formulations of NSAIDs including celecoxib oral solution, and special considerations in the acute treatment of migraine attacks. Low-dose formulations of NSAIDs, such as celecoxib oral solution, provide acute migraine analgesia with similar or fewer associated cardiovascular and gastrointestinal events than previous formulations.

A Comprehensive Management Approach in Pediatric and Adolescent Patients With Hereditary Angioedema.

Hereditary angioedema (HAE) is a rare autosomal-dominant disorder; most cases are characterized by low plasma levels of C1 esterase inhibitor (C1-INH). Clinical manifestations of HAE due to C1-INH deficiency include unpredictable, acute, recurrent episodes of nonpruritic swelling that can affect the face, trunk, limbs, and the respiratory, gastrointestinal, and genitourinary tracts. Attacks can be disfiguring, disabling, painful, and even life-threatening if laryngeal swelling occurs. Symptoms of HAE generally manifest in childhood. Effective medications are available and approved to treat HAE in children. However, evidence informing use of these medications in pediatric clinical practice is limited. Hereditary angioedema management plans are critical to optimize outcomes and should address on-demand treatment for acute attacks and plans to prevent potentially fatal laryngeal attacks. The plan should also comprise a holistic approach to address nonclinical aspects of HAE, including quality of life (QoL) and psychological issues. This article provides an overview of HAE management principles that health care providers can apply to treat pediatric patients to improve their QoL.

Safety and Effectiveness of Magnesium Sulphate for Severe Acute Asthma Management Among Under-five Children: Systematic Review and Meta-analysis.

Asthma is the common chronic inflammatory disease affecting children. It is usually associated with airway hyper-responsiveness. Globally, the prevalence of asthma among pediatrics population varies from 10% to 30%. Its symptoms range from chronic cough to life-threatening bronchospasm. At emergency department, all patients with acute severe asthma should initially receive oxygen, nebulized β2-agonists, nebulized anticholinergic agent, and corticosteroids. Though bronchodilators act within minutes, corticosteroids may require hours. Magnesium sulphate (MgSO4) was first considered for treating asthma about 60 years ago. Several case reports were published on its usefulness in decreasing admission and endotracheal intubation. So far, evidence is conflicting to fully employ MgSO4 for asthma management in children under five. This systematic review was aimed to evaluate the effectiveness and safety of MgSO4 in the treatment of severe acute asthmatic attacks in children. A systematic and comprehensive search of literature was performed to identify controlled clinical trials conducted on IV and nebulized MgSO4 in pediatric patients with acute asthma. Data generated from three randomized clinical trials were included in the final analysis. In this analysis, intravenous MgSO4 did not improve respiratory function (RR=1.09, 95%CI: 0.81-1.45) and not safer than conventional treatment (RR=0.38, 95%CI: 0.08-1.67). Similarly, use of nebulized MgSO4 showed no significant effect on respiratory function (RR=1.05, 95%CI: 0.68-1.64) and more tolerable (RR=0.31, 95%CI: 0.14-0.68). Intravenous MgSO4 may not be superior to conventional treatment in moderate to severe acute asthma among children and neither have significant adverse effects. Similarly, nebulized MgSO4 showed no significant effect on respiratory function in moderate to severe acute asthma in children under five but it seems a safer alternative.

A Review of Randomized Controlled Trials of Hereditary Angioedema Long-Term Prophylaxis with C1 Inhibitor Replacement Therapy: Alleviation of Disease Symptoms Is Achievable.

Through its fluctuating disease activity and unpredictable attacks, hereditary angioedema (HAE) imposes a substantial patient burden. To minimize HAE burden and improve quality of life, treatment should involve individualized management strategies that address on-demand therapy and short-term/long-term prophylaxis. Goals of long-term prophylaxis include reducing the number, severity, and burden of HAE attacks. The best characterized forms of HAE arise from deficiency or dysfunction of C1-inhibitor (C1-INH; types I/II), and C1-INH replacement therapy is a first-line intervention for on-demand (acute) treatment of HAE attacks, short-term prophylaxis before high-risk procedures, and long-term prophylaxis. Randomized, double-blind, placebo-controlled crossover trials have shown dose-dependent efficacy with plasma-derived C1-INH (pdC1-INH) 40-60 IU/kg subcutaneously, pdC1-INH 1000 U intravenously, and recombinant human C1-INH (rhC1-INH) 50 IU/kg (maximum 4200 IU) intravenously, all administered twice weekly, as long-term prophylaxis in patients with a history of 2 to ≥4 attacks/month. Overall, up to 83% (pdC1-INH 60 IU/kg) of patients experienced an HAE attack reduction threshold of ≥70%, and up to 58% (pdC1-INH 60 IU/kg) achieved an attack reduction threshold of ≥90%. Lower-dose intravenous pdC1-INH therapy (1000 U) was seemingly less effective, with 45% of 22 patients experiencing an HAE attack reduction threshold of ≥70%, and up to 23% achieving an attack reduction threshold of ≥90%. Higher-dose intravenous rhC1-INH 50 IU/kg (maximum, 4200 IU) twice weekly was of intermediate benefit. Despite a baseline mean attack frequency of 17.9 (during the 3 months prior to study treatment) and a mean attack frequency during a 4-week placebo period of 7.2, 52% of 23 patients experienced ≥70% reduction in attack frequency and 26% of 23 patients experienced ≥90% reduction in attack frequency. The increasing patient percentages treated with C1-INH replacement therapy as long-term prophylaxis meeting these high thresholds reinforces hopes and expectations that "attack freedom" is achievable, including for those with moderate or severe disease.

Efficacy, safety and indirect comparisons of lasmiditan, rimegepant, and ubrogepant for the acute treatment of migraine: A systematic review and network meta-analysis of the literature.

We performed a random-effects network meta-analysis to study the efficacy and safety of newly developed drugs for the acute treatment of migraine attacks. MEDLINE via PubMed, Embase and The Cochrane Register of Controlled Trials were searched from inception to 11 February 2022. Phase 3 randomized controlled trials examining all formulations of lasmiditan, rimegepant and ubrogepant for the acute treatment of adults with migraine, were included. Data were extracted following the PRISMA guidelines. Seven studies (SAMURAI, SPARTAN, CENTURION, Study 302, Study 303, ACHIEVE I and II) involving n = 12,859 patients were included. All treatments were superior in efficacy to placebo. Lasmiditan 200 mg showed the highest two-hour pain freedom, while two-hour freedom from most bothersome symptom was equally achieved by the higher doses of lasmiditan (100 and 200 mg), rimegepant and the higher doses of ubrogepant (50 and 100 mg). The odds of treatment-emergent adverse events were greatest with all doses of lasmiditan. Lasmiditan 200 mg was the most effective intervention in the treatment of migraine attacks, although it was associated with high degrees of dizziness, nausea and somnolence. Rimegepant showed slightly lower, but similar efficacy rates to lasmiditan. Ubrogepant had overall the best tolerability profile. These conclusions are limited by the absence of head-to-head comparisons, limitations of individual trials and of the meta-analysis methodology itself.PROSPERO trial registration: CRD42022308224.

New medications to mitigate attacks of hereditary angioedema: does one size fit all?

Hereditary angioedema has received renewed attention in the past two decades, with the elucidation of the biochemical pathways resulting in bradykinin overproduction in patients with congenital C1esterase inhibitor (C1INH) deficiency, leading to recurrent attacks of tissue swelling due to uncontrolled vascular permeability. 1 Busse PJ Christiansen SC Hereditary angioedema. N Engl J Med. 2020; 382: 1136-1148 Crossref PubMed Scopus (132) Google Scholar Oedema attacks affecting the lingual or laryngeal area can become lethal as a result of asphyxiation. 2 Minafra FG Gonçalves TR Alves TM Pinto JA The mortality from hereditary angioedema worldwide: a review of the real-world data literature. Clin Rev Allergy Immunol. 2022; 62: 232-239 Crossref PubMed Scopus (4) Google Scholar Several new treatments have emerged, 143 years after Quincke's first description of hereditary angioedema and 15 years after the introduction of the first specific bradykinin B2 receptor inhibitor (icatibant). These drugs specifically target crucial steps in the kallikrein–kinin (contact) cascade downstream of bradykinin production. 3 Fijen LM Bork K Cohn DM Current and prospective targets of pharmacologic treatment of hereditary angioedema types 1 and 2. Clin Rev Allergy Immunol. 2021; 61: 66-76 Crossref PubMed Scopus (0) Google Scholar Many of these agents have shown their efficacy and safety in acute (on-demand) treatment and prophylaxis of hereditary angioedema attacks, saving lives and revolutionising patients’ quality of life. 4 Lumry WR Settipane RA Hereditary angioedema: epidemiology and burden of disease. Allergy Asthma Proc. 2020; 41: S08-S Crossref Google Scholar These modalities fit well into the modern paradigm in hereditary angioedema treatment, supporting patients’ autonomy, recommending self-administration, and reducing reliance on hospital emergency rooms, health-care providers, and medical points of care. 5 Maurer M Magerl M Betschel S et al. The international WAO/EAACI guideline for the management of hereditary angioedema—the 2021 revision and update. Allergy. 2022; 77: 1961-1990 Crossref PubMed Scopus (32) Google Scholar An investigational oral plasma kallikrein inhibitor for on-demand treatment of hereditary angioedema: a two-part, randomised, double-blind, placebo-controlled, crossover phase 2 trialOral administration of sebetralstat was well tolerated and led to rapid suppression of plasma kallikrein activity, resulting in increased time to use of conventional attack treatment and faster symptom relief versus placebo. Based on these results, a phase 3 trial to evaluate the efficacy and safety of two dose levels of sebetralstat in adolescent and adult participants with hereditary angioedema has been initiated ( NCT05259917 ). Full-Text PDF

Observational Analysis of the Costs Associated with Acute Treatment of Breakthrough Migraine Attacks in Medicaid Patients Using Preventive Therapies.

Medications for preventive treatment of migraine reduce migraine frequency, usually measured by a reduction in monthly migraine days (MMD), but generally do not eliminate the need for acute treatment. To assess the economic impact of treatment-related reductions in frequency, methodological guidance recommends capturing cost differences along the spectrum of MMD. Characterize monthly migraine medication costs along the spectrum of MMD for patients using calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) for prevention. Medicaid State Drug Utilization Data (SDUD) were used to identify formulations and per-unit costs for oral, intranasal, and parenteral migraine-specific medications for acute and preventive treatment used by fee-for-service (FFS) Medicaid enrollees in 2020. National drug codes of relevant therapies were used to match SDUD to formulation characteristics including substance, route of administration, and branded/generic marketing status. Mean per-unit cost and the formulation's share of total prescriptions were estimated. Monthly medication costs were modeled based on formulations' per-unit costs and frequency of acute medication use during clinical trials of CGRP mAbs. In the SDUD, there were 563,338 prescriptions for migraine-specific acute medications; triptans accounted for 97.37%. Triptan formulations prescribed were 83.78% oral tablet, 10.89% orally disintegrating tablet, 2.60% intranasal, and 2.73% parenteral. Dihydroergotamine accounted for < 1% of total prescriptions and had the highest per-unit cost ($443.50, branded intranasal). There were 97,119 prescriptions for CGRP mAbs, the majority for erenumab (45.73%) or galcanezumab (45.24%). Modeled monthly acute and preventive medication costs ranged from approximately $550 in patients with the fewest MMD treated with oral triptans to > $1500 in patients with the most MMD treated with dihydroergotamine. In consideration of the migraine-specific acute medications used in FFS Medicaid 2020, for patients using CGRP mAbs for prevention, medication costs may vary significantly with the number of breakthrough attacks treated per month and the type of migraine-specific acute therapy used.

Adding erythropoietin to intravenous methylprednisolone in acute treatment of attacks of neuromyelitis optica spectrum disorders: A randomized controlled trial.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system (CNS) that prompts immediate potent treatment. Delaying treatment could leave debilitating sequelae. As erythropoietin (EPO) has shown neuroprotective effects, we studied the effects of adding EPO to intravenous methylprednisolone (IVMP) in patients with acute attacks of NMOSD. Methods: NMOSD cases with acute attacks were included. Cases of optic neuritis (ON) and those with myelitis were separated. After randomization [with block sizes of 2 (1:1 ratio)], the patients in the intervention group received IVMP 1000 mg/day and intravenous (IV) EPO 20000 U/day for five days. IVMP 1000 mg/day and normal saline (NS) were administered in the control group. Staged eye score and motor forces were evaluated in the patients with ON and myelitis, respectively, at the time of the attack and three months later. Primary patient allocation and clinical assessments were blinded to the physicians. Results: Mean age of participants was 53.87 ± 11.53 years. At follow-up, in the ON arm, the median improvement in staged eye score was 2 in the control and 5 in the intervention group. The difference was significant (P < 0.001). In the myelitis group, none of the patients in the control group had improvement in motor forces. All the patients in the intervention group showed substantial improvement with minimal or no remaining weakness. The difference was statistically significant (P = 0.029). Conclusion: The results show the possible benefit of adding EPO to the classic IVMP in attacks of NMOSD in both visual and motor aspects.

Survey the effect of drug treatment on modulation of cytokines gene expression in allergic rhinitis.

Allergic rhinitis as common airway disease has high prevalence in all peoples worldwide. In allergic diseases, Th2 cells release type 2 cytokines that support the inflammation in airways. All the drugs used for allergic rhinitis do not cure completely, and the choice of drugs according to cost and efficacy is very important in all groups of atopic patients. Therefore, in this study, the effect of commercial drugs on cytokine gene expression has been studied. Male Balb/c mice were divided into six groups. Allergic rhinitis was induced in five of the six groups with ovalbumin, and four of these five groups were treated with salbutamol, budesonide, theophylline, and montelukast. The fifth group was used as positive control group and the sixth group as negative control group. For the survey, RNA was extracted, cDNA was synthesized, and quantitative real-time PCR was done for 21 genes. The four drugs had different effects on mRNA expression of cytokines (IL-1b, 2, 4, 5, 7, 8, 9, 11, 12, 13, 17, 18, 22, 25, 31, 33, 37, IFN-γ, TNF-α, TGF-β1, and eotaxin) in the allergic rhinitis groups. Salbutamol can be used during pregnancy and breastfeeding, but it has some side effects. Budesonide in the inhaled form is generally safe in pregnancy. Theophylline cannot control allergic attack in the long run. Montelukast is not useful in the treatment of acute allergic attacks. Immunomodulatory and anti-inflammatory effects of drugs in control of allergic rhinitis via Th2 cytokines can be new approaches in molecular medicine.

PHARMACOKINETICS OF PHVS719, EXTENDED-RELEASE TABLET FORMULATION OF PHA121, A FIRST-IN-CLASS ORAL HUMAN BRADYKININ B2-RECEPTOR ANTAGONIST

<h3>Introduction</h3> PHA121 is an orally bioavailable potent, competitive and selective antagonist of the human bradykinin B2 receptor (B2R) being developed in two formulations for treatment of hereditary angioedema (HAE): PHVS416 soft capsule for treatment of acute attacks and PHVS719 extended-release tablet for prophylaxis. <h3>Methods</h3> Bioavailability of the extended-release formulation PHVS719 in comparison with PHVS416 was evaluated in an open-label, crossover single-dose study. Eight healthy volunteers received treatment with PHVS416 (2x soft capsules each containing 10 mg-of PHA121) and PHVS719 (1x extended-release tablet containing 40 mg of PHA121) in randomized order and in variable experimental conditions. <h3>Results</h3> Administration of PHVS416 resulted in rapid clinically relevant exposure of PHA121 active ingredient above EC₈₅ determined from the bradykinin challenge (13.8 ng/mL) within 15 minutes. A single dose of PHVS719 yielded exposure of PHA121 above EC₈₅ by the 3-hour timepoint and maintained it for at least 28 hours with or without food. The 24-hour area under the curve exposure of PHA121 using PHVS719 was similar to that observed in studies with PHVS416 soft capsules dosed 20 mg twice a day with food (being investigated in the ongoing CHAPTER-1 prophylactic trial). PHVS416 and PHVS719 were well tolerated. <h3>Conclusions</h3> Findings from this study confirmed rapid achievement of clinically relevant exposure of PHA121 after administration of PHVS416. The observed pharmacokinetic of PHVS719 is consistent with the extended-release formulation designed to provide long-term exposure to PHA121. PHVS719 appears to be suitable for once-daily prophylactic dosing in HAE.

DEVELOPMENT OF PHVS719: AN ORAL EXTENDED-RELEASE BRADYKININ B2 RECEPTOR ANTAGONIST TO PREVENT HEREDITARY ANGIOEDEMA ATTACKS

<h3>Introduction</h3> Hereditary angioedema (HAE) is managed by either of two treatment paradigms: on demand or prophylaxis. PHA121, an orally active bradykinin B2 receptor antagonist, is being developed as two drug products to optimize patient choice. PHVS416, the softgel capsule providing quick absorption for fast onset of symptom relief, is currently in clinical trials for treatment of acute attacks; PHVS719, an extended-release tablet, is being developed for use in prophylaxis. <h3>Methods</h3> To develop a daily oral pill for the prevention of attacks, we developed a PHA121 formulation (PHVS719) providing 24 h plasma exposure. Our strategy relied upon a combination of an optimally designed extended-release formulation and the ability of PHA121 to be absorbed throughout the full gastrointestinal tract. <h3>Results</h3> PHA121 is absorbed following intracolonic administration in rats. A human mass balance study showed only 3% PHA121 excreted in feces and oral bioavailability of 57%. An in vitro dissolution experiment conducted with PHVS719 in conditions mimicking fasted and fed gastrointestinal environments showed a linear dissolution of PHA121 over time. Using PHVS719, a PK study in healthy volunteers demonstrated that a single 40 mg dose provides 24 h plasma exposure above the anticipated therapeutic level. Together these data provide evidence that PHVS719 is optimally suited to serve as a once-daily oral pill. <h3>Conclusion</h3> The active ingredient PHA121 is under clinical investigation in the form of two therapeutic treatment modalities: PHVS416 softgel capsule providing quick absorption for fast symptom relief and PHVS719 once-daily extended-release tablet providing 24 hours coverage to prevent attacks from occurring.

52 Use of corticosteroids in childhood systemic lupus erythematosus: experience from a pediatric rheumatology center

BackgroundChildhood-onset Systemic Lupus Erythematosus (cSLE) is a rare but severe multisystem autoimmune/inflammatory disease that can affect any organ system and cause significant damage, disability and/or death. Corticosteroids are one of the important therapeutic weapons for childhood Systemic Lupus Erythematosus (SLE). Prednisone doses are increased during flare-ups of lupus disease, and then progressively reduced to reach a threshold dose in order to avoid the harmful effects of this treatment in growing children. The oral route is by far the most used over prolonged periods, however corticosteroid boluses are recommended in the treatment of severe acute attacks of the disease.ObjectiveAssess the use of corticosteroids in childhood systemic lupus erythematosus (SLE) and the risk of steroid-related damage.MethodsPatients with childhood -onset SLE (n = 83) treated at paediatric rheumatology centre were followed for 36 months. Information on medication use, disease activity as measured by SLEDAI was collected.ResultsEighty-three (83) patients were studied. Female: male ratio was 1:49. Mean ages at lupus onset and diagnosis were respectively: 10, 12 (±3,88_ and 11, 3 (±3,62) years. Corticosteroids were used in 92% of cases in oral form and on 37% of cases as a bolus of high dose intravenous methylprednisolone. The indication of corticoids bolus was significantly related to severe forms (p = 0,001), high disease activity (p = 0, 00008), and macrophage activation Syndrome (p = 0, 0006). The doses varied between 0.5–1 g/1.73m2. The mean initial disease activity in these patients was 30 ± 10, while that found after taking the treatment was 12.9 ± 15. The decrease was statistically significant (p = 0, 000001). More than half of our patients were on high dose oral corticosteroids (2 mg/kg/d) and only 1/5 of the patients benefited from a dose of (1 mg/kg/day). The use of corticosteroids has been associated with significant side effects, including growth delay (22%), cushingoid obesity (58%), stretch marks (49%), osteoporosis (33%), femoral head osteonecrosis (1%), infections (54%). The association of certain side effects with a high dose of oral corticosteroids (2 mg/kg/day) was significant in this case cushingoid obesity (p = 0, 0003), stretch marks (p = 0.014).ConclusionCorticosteroids are the mainstay of therapy for prompt control of acute disease related inflammation in patients with SLE; they remain the first-line treatment for significant lupus manifestations, especially severe forms and life-threatening situations Higher dosage and longer duration of therapy, which are common in SLE, result in greater risk of adverse effects. Their use wisely is the guarantee of a better response and the reduction of deleterious effect.

Factors and Treatment of Acute Gout Attack Induced by Upper Gastrointestinal Bleeding

Factors and Treatment of Acute Gout Attack Induced by Upper Gastrointestinal Bleeding

Development of an ethanol-free salbutamol sulfate metered-dose inhaler: Application of molecular dynamic simulation-based prediction of intermolecular interaction

IntroductionMore than fifty years after the commercialization of the Ventolin metered-dose inhaler (MDI), its constituent active ingredient, salbutamol sulfate (SS), remains the most prescribed short-acting beta agonist for the first-line treatment of acute asthma attacks and the metered-dose inhaler remains its primary dosage form. The first generation of Ventolin MDI was developed at a time when environmental and regulatory concerns were less stringent than today. The MDI industry is now on the verge of a second major reformulation effort in response to environmental concerns. This paper serves to illustrate how modern computational modeling of molecular interactions can aid the reformulation process. By way of a case study, computational modeling was performed to compare poly(ethylene glycol) 400 (PEG400) and, separately, isopropyl myristate (IPM) as substitutes for the ethanol used in some generic salbutamol sulfate suspension-based hydrofluoroalkane MDIs. MethodsPEG400 and IPM were investigated as potential alternative cosolvents to ethanol in HFA134a-based SS suspension MDI formulations. Density functional theory (DFT) molecular dynamics simulations were used to evaluate the compatibility of the candidate cosolvents with the formulation's components. Corresponding physical formulations were filled into polyethylene terephthalate (PET) and, separately, aluminium canisters. In-vitro pharmaceutical product performance and macroscopic visual appearance were assessed and compared to the results of the simulation studies. ResultsThe simulation studies indicated that PEG400 would be a good candidate as a replacement for ethanol whereas IPM would not. The in-vitro and visual assessments support the predicted outcome of the simulation studies. ConclusionThis work suggests that molecular dynamics simulations may provide a useful tool to aid the selection of compatible excipients when reformulating MDI suspension-based products, thereby reducing the time and cost associated with manufacturing and testing of physical samples.

Efficacy of inhaled salbutamol therapy through nebulizer versus mdi with spacer in children with acute asthmatic attack and short-term course

Introduction: Asthma is a common chronic disease in childhood and has been subject of studies for at least two decades, due to its increasing prevalence. The symptoms are persistent, recurrent, and entirely related to bronchial hyper-responsiveness to many environmental triggers. Nebulization and metered dose inhaler (MDI) are two available modalities of salbutamol administration in patients with acute asthmatic attack. Aim: The aim of the study was to compare the relative efficacy of nebulizer and MDI with spacer for the administration of salbutamol in the treatment of acute asthmatic attack. Materials and Methods: A randomized, prospective, and interventional study was conducted on 100 children aged 1–12 years with acute asthmatic attack at a tertiary care. The subjects were randomized into two groups for salbutamol administration. Group I was given salbutamol by nebulizer and Group II by MDI with spacer. Demographic data and detailed history was collected. Children were categorized into mild, moderate, and severe grade according to peak expiratory flow rate (PEFR) and pulmonary index (PI) score. Oxygen saturation, PEFR, and PI were monitored at 0, 20, 40, and 60 min of therapy. Other details such as duration of hospital stay and oxygen requirement were also noted. Results: One hundred children with male female ratio of 1.12:1 were included in the study. Highest incidence was seen in age group of 1–3 years (38%). Statistically significant change in PI and PEFR was noted with treatment in both the groups (p&lt;0.05). On comparison between MDI and nebulizer group, no statistically significant difference was found (p&gt;0.05). Conclusion: MDI with spacer is an effective alternative to nebulizer for the administration of salbutamol drug in acute asthmatic attack in pediatric patients.

Pharmacological treatment of acute Gout attacks

Gout is an inflammatory condition of the joints caused by deposition of crystallized monosodium urate (MSU) in the joint which leads to Arthritis. there are many debates about the suitable pharmacological therapy for the acute inflammatory gout attacks. The Pharmacological treatment included colchicine, non steroidal anti- inflammatory (NASIDS) and corticosteroid injection. The aim of this study is to review the evidences which studied the effect of Colchicine, NASID and corticosteroid injections and discuss their effectiveness in treating the acute flares of Gout. After evaluation the validity of the latest best evidences presented in the database by using the AMSTAR tool. There was no best drug and no optimal dose identified in treating acute Gout attacks. Doctors should be careful in selecting the treatment considering the side effect of each medication and deal with each patient individually to provide the best health care.

National audit of a hereditary and acquired angioedema cohort in New Zealand.

Hereditary angioedema (HAE) leads to significant morbidity and mortality from unpredictable intermittent peripheral, abdominal and laryngeal swelling. Access to appropriate healthcare and effective therapies, which can prevent and treat attacks, reduce the suffering and greatly improve quality of life. Although treatments such as C1 inhibitor (Berinert), and Icatibant are available in New Zealand (Aotearoa), there are no published data available on their use. To present a national audit of HAE and acquired angioedema (AAE) in 2019. Patients were identfied and demographical and clinical data on HAE were collected retrospectively by interview and notes review. The total number of known adult (48) and children (3) HAE and AAE (3) patients is 54. Of these, 41/54 (75%) of HAE and AAE patients were recruited to the audit. Icatibant has been available for the treatment of acute HAE attacks since 2016, and is now used in 73% of HAE patients. Icatibant is also used by patients for laryngeal attacks in the community, who may not then present to hospital. Androgens are used in half of the patients as prophylaxis, but 33% of the latter were identified as not having regular liver ultrasound screening. Tranexamic acid is used as prophylaxis in one-fifth of patients. Participants have had 40 children, half of whom may be affected. Three have been diagnosed with HAE, suggesting that the majority have not yet been tested. Corrective actions arising from this audit will improve our capacity to provide long-term care for HAE patients and their families.

Applications of transcranial magnetic stimulation in migraine: evidence from a scoping review.

Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation method, is trying to emerge as a migraine management strategy for both attack treatment and prevention. This scoping review presents 16 among single-pulse (to manage episodic and chronic migraine) and repetitive TMS randomized clinical trials (to manage chronic migraine). The works we reviewed suggest that TMS may be adopted as add-on therapy in those patients who are refractory to pharmacological therapy only with special arrangements for individualized treatment strategies or research. There are still limited clinical research programs and metaanalysis to promote routinely TMS employment, as TMS has been shown either to have no significant effects for any outcome or to be effective for migraine. These diverging conclusions depend on several biasing factors, including the lack of reliable, large, sham-controlled clinical trials, the dyshomogeneity in study designs (including the area of stimulation, the frequency of stimulation, the number of pulses, pulse intensity, and the number of sessions), patient selection criteria (migraine w/o aura, episodic and chronic migraine; TMS contraindication), and the lack of outcomes homogeneity and long-term real-world efficacy data. Therefore, in the future, it will be important to conduct larger randomized trials to confirm TMS usefulness in migraine management (acute attack and prophylactic treatment), identify those patients who may benefit from TMS, maybe independently of pharmacological treatments (i.e., using TMS as an alternative and not only as an add-on treatment). Otherwise, TMS will play a role in treating migraine only with special arrangements for individualized management strategies or research.

Benefits and Harms of Treatment and Preventive Interventions for Hereditary Angioedema: Protocol for a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Background: Hereditary angioedema (HAE) is a rare genetic disease that can lead to potentially life-threatening airway attacks. Although novel therapies for HAE treatment have become available over the past decades, a comparison of all available treatments has not yet been conducted. As such, we will perform a systematic review and network meta-analysis to identify the best evidence-based treatments for the management of acute attacks and prophylaxis of HAE. Methods: This study will include both parallel and crossover randomized controlled trials that have investigated prevention or treatment strategies for HAE attacks. We will search electronic databases, including Medline, Embase, PubMed, Cochrane Library, Scopus, and CINAHL, from inception with no language restrictions. Potential trials will be supplemented through a gray literature search. The process of study screening, selection, data extraction, risk-of-bias assessment, certainty assessment and classification of treatments will be performed independently by a pair of reviewers. Any discrepancy will be addressed through team discussion. A two-step approach of pairwise and network meta-analysis will be performed. The summarized effect estimates of direct and indirect treatment comparisons will be pooled using DerSimonion–Laird random-effects models. The incoherence assumption, in terms of the consistency of direct and indirect effects, will be assessed. An evidence-based synthesis will be performed, based on the magnitudes of effect size, evidence certainty, and ranking of treatment effects, with respect to treatment benefits and harms. Discussion: This systematic review and network meta-analysis will summarize evidence-based conclusions with respect to the ratio of benefits and harms arising from interventions for the treatment of acute attacks and prophylaxis of HAE. Evidence from this network estimate could promote the rational use of interventions among people living with HAE in clinical practice settings. PROSPERO registration number: CRD42021251367.