Key components of anaphylaxis management plans: consensus findings from a national electronic Delphi study

OBJECTIVES: There is no international consensus on the components of anaphylaxis management plans and responsibility for their design and delivery is contested. We set out to establish consensus among relevant specialist and generalist clinicians on this issue to inform future randomized controlled trials. DESIGN: A two-round electronic Delphi study completed by a 25-person, multidisciplinary expert panel. Participants scored the importance of a range of statements on anaphylaxis management, identified from a systematic review of the literature, on a five-point scale ranging from 'very important' to 'irrelevant'. Consensus was defined a priori as being achieved if 80% or more of panel members rated a statement as 'important' or 'very important' after Round 2. SETTING: Primary and secondary care and academic settings in the UK and Ireland. PARTICIPANTS: Twenty-five medical, nursing and allied health professionals. MAIN OUTCOME MEASURES: Consensus on the key components of anaphylaxis management plans. RESULTS: The response rate was 84% (n = 21) for Round 1 and 96% (n = 24) for Round 2. The key components of emergency care on which consensus was achieved included: awareness of trigger factors (100%); recognition and emergency management of reactions of different severity (100%); and clear information on adrenaline (epinephrine) use (100%). Consensus on longer-term management issues included: clear written guidelines on anaphylaxis management (96%); annual review of plans (87%); and plans that were tailored to individual needs (82%). CONCLUSIONS: This national consensus-building exercise generated widespread agreement that emergency plans need to be simple, clear and generic, making them easy to implement in a crisis. In contrast, long-term plans need to be negotiated between patient/carers and professionals, and tailored to individual needs. The effectiveness of this expert-agreed long-term plan now needs to be evaluated rigorously

Adherence with tobramycin inhaled solution and health care utilization

<p>Abstract</p> <p>Background</p> <p>Adherence with tobramycin inhalation solution (TIS) during routine cystic fibrosis (CF) care may differ from recommended guidelines and affect health care utilization.</p> <p>Methods</p> <p>We analyzed 2001-2006 healthcare claims data from 45 large employers. Study subjects had diagnoses of CF and at least 1 prescription for TIS. We measured adherence as the number of TIS therapy cycles completed during the year and categorized overall adherence as: low ≤ 2 cycles, medium >2 to <4 cycles, and high ≥ 4 cycles per year. Interquartile ranges (IQR) were created for health care utilization and logistic regression analysis of hospitalization risk was conducted by TIS adherence categories.</p> <p>Results</p> <p>Among 804 individuals identified with CF and a prescription for TIS, only 7% (n = 54) received ≥ 4 cycles of TIS per year. High adherence with TIS was associated with a decreased risk of hospitalization when compared to individuals receiving ≤ 2 cycles (adjusted odds ratio 0.40; 95% confidence interval 0.19-0.84). High adherence with TIS was also associated with lower outpatient service costs (IQR: $2,159-$8444 vs. $2,410-$14,423) and higher outpatient prescription drug costs (IQR: $35,125-$60,969 vs. $10,353-$46,768).</p> <p>Conclusions</p> <p>Use of TIS did not reflect recommended guidelines and may impact other health care utilization.</p

All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions – an observational study

BACKGROUND: Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. METHODS: 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. RESULTS: There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. CONCLUSION: While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance

Synapsis and Meiotic Recombination in Male Chinese Muntjac (Muntiacus reevesi)

The muntjacs (Muntiacus, Cervidae) have been extensively studied in terms of chromosomal and karyotypic evolution. However, little is known about their meiotic chromosomes particularly the recombination patterns of homologous chromosomes. We used immunostained surface spreads to visualise synaptonemal complexes (SCs), recombination foci and kinetochores with antibodies against marker proteins. As in other mammals pachytene was the longest stage of meiotic prophase. 39.4% of XY bivalents lacked MLH1 foci compared to less than 0.5% of autosomes. The average number of MLH1 foci per pachytene cell in M. reevesi was 29.8. The distribution of MLH1 foci differed from other mammals. On SCs with one focus, the distribution was more even in M. reevesi than in other mammals; for SCs that have two or more MLH1 foci, usually there was a larger peak in the sub-centromere region than other regions on SC in M. reevesi. Additionally, there was a lower level of interference between foci in M. reevesi than in mouse or human. These observations may suggest that the regulation of homologous recombination in M. reevesi is slightly different from other mammals and will improve our understanding of the regulation of meiotic recombination, with respect to recombination frequency and position

Impact of herpes zoster and post-herpetic neuralgia on patients’ quality of life: a patient-reported outcomes survey

Background: The impact of herpes zoster (HZ) and post-herpetic neuralgia (PHN) on patients’ quality of life (QoL) is currently poorly documented. Subjects and methods: Telephone interviews in Germany identified patients ≥50 years old with painful HZ diagnosed during the previous 5 years. Bespoke questions evaluated previous HZ episodes. Results: Of 11,009 respondents, 280 met the screening criteria, and 32 (11%) developed PHN. PHN was associated with significantly worse outcomes than HZ (all P < 0.05). Mean pain scores associated with PHN and HZ, respectively, were 7.1 and 6.2 (average) and 8.2 and 7.0 (worst). Many patients with PHN (91%) and HZ (73%) experienced problems with daily activities, including work, studies, housework, family and leisure activities. Mean pain interference scores in patients with PHN versus HZ were highest for sleep (6.5 versus 4.9), normal work (6.1 versus 4.4) and mood (5.9 versus 4.4). Most employed interviewees with PHN (70%) and HZ (64%) stopped work during the disease. Pain and QoL outcomes were not significantly different between all patients versus those diagnosed during the previous 12 months or between patients aged 50–59 years versus ≥60 years. Conclusions: HZ causes substantial pain, which seriously interferes with many aspects of daily life, particularly in patients with PHN

“The Good into the Pot, the Bad into the Crop!”—A New Technology to Free Stem Cells from Feeder Cells

A variety of embryonic and adult stem cell lines require an intial co-culturing with feeder cells for non-differentiated growth, self renewal and maintenance of pluripotency. However for many downstream ES cell applications the feeder cells have to be considered contaminations that might interfere not just with the analysis of experimental data but also with clinical application and tissue engineering approaches. Here we introduce a novel technique that allows for the selection of pure feeder-freed stem cells, following stem cell proliferation on feeder cell layers. Complete and reproducible separation of feeder and embryonic stem cells was accomplished by adaptation of an automated cell selection system that resulted in the aspiration of distinct cell colonies or fraction of colonies according to predefined physical parameters. Analyzing neuronal differentiation we demonstrated feeder-freed stem cells to exhibit differentiation potentials comparable to embryonic stem cells differentiated under standard conditions. However, embryoid body growth as well as differentiation of stem cells into cardiomyocytes was significantly enhanced in feeder-freed cells, indicating a feeder cell dependent modulation of lineage differentiation during early embryoid body development. These findings underline the necessity to separate stem and feeder cells before the initiation of in vitro differentiation. The complete separation of stem and feeder cells by this new technology results in pure stem cell populations for translational approaches. Furthermore, a more detailed analysis of the effect of feeder cells on stem cell differentiation is now possible, that might facilitate the identification and development of new optimized human or genetically modified feeder cell lines

Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals

<p>Abstract</p> <p>Background</p> <p>Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed.</p> <p>Methods</p> <p>We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel.</p> <p>Results</p> <p>Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports.</p> <p>Conclusions</p> <p>Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic <it>in silico </it>simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.</p

Epidemiology and economic burden of herpes zoster and post-herpetic neuralgia in Italy: A retrospective, population-based study

<p>Abstract</p> <p>Background</p> <p>Data on the epidemiology and cost of herpes zoster (HZ) and post-herpetic neuralgia (PHN) in Italy are limited. This retrospective, population-based study was designed to determine the incidence of HZ and the proportion developing PHN in Italy and the associated medical resource utilisation and costs. It focused primarily on immunocompetent patients aged ≥50 years who would be eligible for preventive vaccination.</p> <p>Method</p> <p>Data were extracted from a primary-care database and national hospital-discharge records covering four major regions in Italy for 2003-2005. Cases of HZ and PHN (1 and 3 months' duration; PHN1 and PHN3) were identified by ICD9-CM codes and, additionally for PHN, prescription of neuropathic pain medication.</p> <p>Results</p> <p>Over 3 years, 5675 incident cases of HZ were documented in adults, of which 3620 occurred in immunocompetent patients aged ≥50 years (incidence of 6.31 per 1000 person-years [95% CI: 6.01-6.62]). Of the immunocompetent patients aged ≥50 years with HZ, 9.4% (95% CI: 8.2-10.7) and 7.2% (95% CI: 6.2-8.2) developed PHN1 and PHN3, respectively. Increasing age, female sex, and being immunologically compromised conferred increased risk for both HZ and PHN. Overall, about 1.3% of HZ and almost 2% of PHN cases required inpatient care, with 16.9% of all HZ-related hospitalisations due specifically to PHN. In patients aged ≥50 years, mean stay was 7.8 ± 5.4 days for HZ and 10.2 ± 8.6 days for PHN, and direct costs associated with inpatient care were more than 20 times outpatient costs per HZ case (mean ± SD: €2592 ± €1313 vs. €122.68 ± €97.51) and over 5 times more per episode of PHN (mean ± SD: €2806 ± €2641 vs. €446.10 ± €442.97). Total annual costs were €41.2 million, of which €28.2 million were direct costs and €13.0 million indirect costs.</p> <p>Conclusions</p> <p>This study, the largest to date on the epidemiology and economic impact of HZ and PHN in Italy, confirms the considerable disease and economic burden posed by HZ. As HZ and PHN disproportionately affect the elderly, without intervention this problem is likely to grow as the proportion of elderly in the Italian population continues to increase.</p

Functional cyclophilin D moderates platelet adhesion, but enhances the lytic resistance of fibrin

In the course of thrombosis, platelets are exposed to a variety of activating stimuli classified as ‘strong’ (e.g. thrombin and collagen) or ‘mild’ (e.g. ADP). In response, activated platelets adhere to injured vasculature, aggregate, and stabilise the three-dimensional fibrin scaffold of the expanding thrombus. Since ‘strong’ stimuli also induce opening of the mitochondrial permeability transition pore (MPTP) in platelets, the MPTP-enhancer Cyclophilin D (CypD) has been suggested as a critical pharmacological target to influence thrombosis. However, it is poorly understood what role CypD plays in the platelet response to ‘mild’ stimuli which act independently of MPTP. Furthermore, it is unknown how CypD influences platelet-driven clot stabilisation against enzymatic breakdown (fibrinolysis). Here we show that treatment of human platelets with Cyclosporine A (a cyclophilin-inhibitor) boosts ADP-induced adhesion and aggregation, while genetic ablation of CypD in murine platelets enhances adhesion but not aggregation. We also report that platelets lacking CypD preserve their integrity in a fibrin environment, and lose their ability to render clots resistant against fibrinolysis. Our results indicate that CypD has opposing haemostatic roles depending on the stimulus and stage of platelet activation, warranting a careful design of any antithrombotic strategy targeting CypD