• Allergen immunotherapy for allergic asthma: A systematic review and meta-analysis

      Dhami, S.; Kakourou, A.; Asamoah, F.; Agache, I.; Lau, S.; Jutel, M.; Muraro, A.; Roberts, G.; Akdis, C.A.; Bonini, M.; et al. (2017-11)
      Background:To inform the development of the European Academy of Allergy and Clinical Immunology’s (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on the effectiveness, cost-effectiveness and safety of AIT. Methods:We performed a systematic review, which involved searching nine data-bases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random-effects meta-analyses.Results:98 studies satisfied the inclusion criteria. Short-term symptom scores were reduced with a standardized mean difference (SMD) of 1.11 (95% CI 1.66, 0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short-term medication scores were reduced SMD 1.21 (95% CI 1.87, 0.54), again with evidence of potential publication bias. There was no reduction in short-term combined medication and symptom scores SMD 0.17 (95% CI 0.23, 0.58), but one study showed a beneficial long-term effect. For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen-specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR. AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported. The limited evidence on cost-effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost-effective. Conclusions: AIT can achieve substantial reductions in short-term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer-term effectiveness and cost-effectiveness.
    • Allergen immunotherapy for allergic rhinoconjunctivitis: A systematic review and meta‐analysis

      Dhami, S.; Nurmatov, U.; Arasi, S.; Khan, T.; Asaria, M.; Zaman, Hadar; Agarwal, A.; Netuveli, G.; Roberts, G.; Pfaar, O.; et al. (2017-11)
      Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. Methods: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication,and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. Results: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD -0.53, 95% CI -0.63,-0.42), medication (SMD -0.37, 95% CI -0.49, -0.26), and combined symptom and medication (SMD -0.49, 95% CI -0.69, -0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores.Conclusions: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy.
    • Allergen immunotherapy for insect venom allergy: a systematic review and meta-analysis

      Dhami, S.; Zaman, Hadar; Varga, E.M.; Sturm, G.J.; Muraro, A.; Akdis, C.A.; Antolın-Amerigo, D.; Bilo, M.B.; Bokanovic, D.; Calderon, M.A.; et al. (2017-02-17)
      Background The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines on Allergen Immunotherapy (AIT) for the management of insect venom allergy. To inform this process, we sought to assess the effectiveness, cost‐effectiveness and safety of AIT in the management of insect venom allergy. Methods We undertook a systematic review, which involved searching 15 international biomedical databases for published and unpublished evidence. Studies were independently screened and critically appraised using established instruments. Data were descriptively summarized and, where possible, meta‐analysed. Results Our searches identified a total of 16 950 potentially eligible studies; of which, 17 satisfied our inclusion criteria. The available evidence was limited both in volume and in quality, but suggested that venom immunotherapy (VIT) could substantially reduce the risk of subsequent severe systemic sting reactions (OR = 0.08, 95% CI 0.03–0.26); meta‐analysis showed that it also improved disease‐specific quality of life (risk difference = 1.41, 95% CI 1.04–1.79). Adverse effects were experienced in both the build‐up and maintenance phases, but most were mild with no fatalities being reported. The very limited evidence found on modelling cost‐effectiveness suggested that VIT was likely to be cost‐effective in those at high risk of repeated systemic sting reactions and/or impaired quality of life. Conclusions The limited available evidence suggested that VIT is effective in reducing severe subsequent systemic sting reactions and in improving disease‐specific quality of life. VIT proved to be safe and no fatalities were recorded in the studies included in this review. The cost‐effectiveness of VIT needs to be established.
    • Benzodiazepines for psychosis-induced aggression or agitation

      Zaman, Hadar; Sampson, S.; Beck, A.; Sharma, T.; Clay, F.; Spyridi, S.; Zhao, S.; Gillies, D. (2018-08)
    • Benzodiazepines for psychosis-induced aggression or agitation

      Zaman, Hadar; Sampson, S.J.; Beck, A.L.S.; Sharma, T.; Clay, F.J.; Spyridi, S.; Zhao, S.; Gillies, D. (2017)
    • Challenges in the implementation of the EAACI AIT guidelines: A situational analysis of current provision of allergen immunotherapy

      Ryan, D.; van Wijk, R.G.; Angier, E.; Kristiansen, M.; Zaman, Hadar; Sheikh, A.; Cardona, V.; Vidal, C.; Warner, A.; Agache, I.; et al. (2018-04)
      Purpose: The European Academy of Allergy and Clinical Immunology (EAACI) has produced Guidelines on Allergen Immunotherapy (AIT). We sought to gauge the preparedness of primary care to participate in the delivery of AIT in Europe. Methods: We undertook a mixed‐methods, situational analysis. This involved a purposeful literature search and two surveys: one to primary care clinicians and the other to a wider group of stakeholders across Europe. Results: The 10 papers identified all pointed out gaps or deficiencies in allergy care provision in primary care. The surveys also highlighted similar concerns, particularly in relation to concerns about lack of knowledge, skills, infrastructural weaknesses, reimbursement policies and communication with specialists as barriers to evidence‐based care. Almost all countries (92%) reported the availability of AIT. In spite of that, only 28% and 44% of the countries reported the availability of guidelines for primary care physicians and specialists, respectively. Agreed pathways between specialists and primary care physicians were reported as existing in 32%‐48% of countries. Reimbursement appeared to be an important barrier as AIT was only fully reimbursed in 32% of countries. Additionally, 44% of respondents considered accessibility to AIT and 36% stating patient costs were barriers. Conclusions: Successful working with primary care providers is essential to scaling‐up AIT provision in Europe, but to achieve this, the identified barriers must be overcome. Development of primary care interpretation of guidelines to aid patient selection, establishment of disease management pathways and collaboration with specialist groups are required as a matter of urgency.
    • Characterisation of aggregates of cyclodextrin-drug complexes using Taylor Dispersion Analysis

      Zaman, Hadar; Bright, A.G.; Adams, Kevin; Goodall, D.M.; Forbes, Robert T. (2017-04-30)
      There is a need to understand the nature of aggregation of cyclodextrins (CDs) with guest molecules in increasingly complex formulation systems. To this end an innovative application of Taylor dispersion analysis (TDA) and comparison with dynamic light scattering (DLS) have been carried out to probe the nature of ICT01-2588 (ICT-2588), a novel tumor-targeted vascular disrupting agent, in solvents including a potential buffered formulation containing 10% hydroxypropyl-β-cyclodextrin. The two hydrodynamic sizing techniques give measurement responses are that fundamentally different for aggregated solutions containing the target molecule, and the benefits of using TDA in conjunction with DLS are that systems are characterised through measurement of both mass- and z-average hydrodynamic radii. Whereas DLS measurements primarily resolve the large aggregates of ICT01-2588 in its formulation medium, methodology for TDA is described to determine the size and notably to quantify the proportion of monomers in the presence of large aggregates, and at the same time measure the formulation viscosity. Interestingly TDA and DLS have also distinguished between aggregate profiles formed using HP-β-CD samples from different suppliers. The approach is expected to be widely applicable to this important class of drug formulations where drug solubility is enhanced by cyclodextrin and other excipients.
    • Clinical pharmacists in primary care: a safe solution to the workforce crisis?

      Komwong, D.; Greenfield, G.; Zaman, Hadar; Majeed, A.; Hayhoe, B. (2018-04)
    • DOOP Kit, Domestic Bin Or Watery Grave? A Study Investigating Disposal Practices Of Transdermal Drug Delivery Products In Care Homes

      Breen, Liz; Zaman, Hadar; McCulloch, Elizabeth; Isaq, Sabah (2018)
      Background The issue of opioid use and misuse is current and topical at present with reports of opioid epidemics in the USA and the increasing use of opioids in other parts of the world. The New Scientist asserted that America was in the throes of an opioid epidemic with reports of fatalities linked to physical contact with fentanyl. Discussions have progressed from an American focus to speculating on the spread of this issue to UK cities, Glasgow in particular. Safety issues have more recently come to light regarding the physical application and management of specific drug forms e.g. opioid transdermal patches (OTPs). The prescribing, application and safe disposal of OTPs within both healthcare settings and personal dwellings is critical to the effective use of these products. Healthcare professionals have a duty of care and responsibility to ensure the safe application and disposal of OTPs. Aims The aims of this study were to 1) gain insight into current practices of healthcare professionals regarding OTPs (fentanyl and buprenorphine) disposal practices and 2) identify Abstract knowledge and system awareness surrounding the disposal of these products in care home settings. Methods We decided to focus on care homes due to the estimated high prevalence of prescribing of OTPs in these care settings. The study was undertaken by the University of Bradford School of Pharmacy in 2015 and the participant sample focussed on the North of England (UK). Results The findings (based on 56 survey responses) displayed a significant variation in current disposal practices and a lack of specific working policies. We unearthed anomalies in the participants’ knowledge of the active ingredient volume held in depleted patches which, if not disposed of correctly, can lead to harm. This has highlighted the need for more thorough training and education on the safe and effective management of OTPs. Conclusions Further education and training is needed regarding safe disposal practices of OTPs, with the suggestion of pharmacist-led interventions. This will minimise confusion and reinforce safe disposal practices (denaturing products) and support the reduction of unsafe disposal practices (domestic waste or flushing).
    • EAACI guidelines on allergen immunotherapy: Hymenoptera venom allergy

      Sturm, G.J.; Varga, E.M.; Roberts, G.; Mosbech, H.; Bilo, M.B.; Akdis, C.A.; Antolın-Amerigo, D.; Cichocka-Jarosz, E.; Gawlik, R.; Jakob, T.; et al. (2018-04-16)
      Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.
    • Klüver-Bucy Syndrome following traumatic brain injury: a systematic synthesis and review of pharmacological treatment from cases in adolescents and adults

      Clay, F.J.; Kuriakose, A.; Lesche, D.; Hicks, A.J.; Zaman, Hadar; Azizi, E.; Ponsford, J.L.; Jayaram, M.; Hopwood, M. (2018)
      Klüver-Bucy syndrome (KBS) is a rare clinical presentation following traumatic brain injury (TBI). Symptoms include visual agnosia, placidity, hyperorality, sexual hyperactivity, changes in dietary behavior, and hypermetamorphosis. The purpose of this article was to identify and synthesize the available evidence from case reports and case series on the treatment profile of KBS among adolescents and adults after TBI. Four bibliographic databases (MEDLINE OVID, EMBASE, PsycINFO, and SCOPUS) were searched for relevant literature. No date or language restrictions were applied. All case reports containing original data on KBS following TBI among adolescents and adults were included. Articles were evaluated, and data were extracted according to predefined criteria. The literature search identified 24 case reports of KBS post-TBI published between 1968 and 2017. Most case subjects were male (70.1%), and the mean age at injury was 25.1 years (range, 13–67 years). Injury to one or both temporal lobes occurred in most cases. Inappropriate sexual hyperactivity was the most common KBS symptom, followed by a change in dietary behavior and hyperorality. Visual agnosia was the least reported. In 50% of cases, the patient fully recovered from KBS. One-half of all participants described pharmacological management; the most common medication prescribed was carbamazepine. Overall, there was a lack of data available on pharmacotherapy initiation and duration. The complex presentation of KBS presents challenges in terms of treatment options. Although overall individuals who were prescribed carbamazepine had positive outcomes, given the reliance on case reports, it is difficult to make a definitive recommendation to guide clinical practice.
    • Prophylaxis pharmacotherapy to prevent the onset of post traumatic brain injury depression: a systematic review

      Clay, F.; Hicks, A.; Zaman, Hadar; Ponsford, J.; Batty, R.; Perry, L.; Hopwood, M.J. (2019)
      Background: Depression is a common psychiatric problem following traumatic brain injury (TBI) with reported prevalence rates of 30-77% in the first year post-TBI. Given the negative influence of post-TBI depression on cognition, interpersonal, social, physical and occupational functioning; early initiation of pharmacotherapy to prevent post-TBI depression has been considered. This systematic review will synthesize the available evidence from published studies on the effectiveness and harms of pharmacotherapy for the secondary prevention of post-TBI depression. Method: Studies published before November 2017 were reviewed. Six databases were searched, with additional searching of key additional documents. Studies meeting inclusion criteria were evaluated for methodological quality. Results: Six articles addressing five studies met inclusion criteria. Study designs included three randomised controlled trials (RCT), two retrospective cohorts and one case-control. Prophylactic pharmacotherapy included antidepressants, beta-blockers and statins. In one RCT, the number-needed-to-treat with sertraline to prevent one case of depression post-TBI at 24 weeks was 5.9 (95%CI: 3.1-71.1). Prescribing beta-blockers prior to TBI reduced the depression risk regardless of the specific brain trauma. TBI patients with pre-existing hyperlipidemia not treated with statins had an increased depression risk compared to those without hyperlipidemia. Conclusion: Early initiation of sertraline prophylaxis in nondepressed TBI patients shows promise to reduce the odds of post-TBI depression developing. However, in the absence of rigorous study of tolerability, existing data are insufficient to recommend sertraline prophylaxis. Optimal timing and treatment duration with identification of patients most likely to benefit from prophylaxis require further consideration. Dedicated prospective studies assessing the effects of beta-blockers and statins on post-TBI depression are required.
    • United Kingdom: Brief overview of the health supply chain in the country

      Breen, Liz; Urban, Rachel L.; Zaman, Hadar (2018)
      The health supply chain within the United Kingdom follows a traditional model adopted by many countries globally. This is typically the sourcing of products from manufacturer to pharmacy (hospital and community) via wholesaler or direct. New models of delivery are being piloted and evaluated to improve supply chain efficiency and effectiveness