Systematic review of the patient burden of generalised myasthenia gravis in Europe, the Middle East, and Africa.

BACKGROUND: Myasthenia gravis (MG) is a rare autoimmune disease characterised by muscle weakness, and progression from ocular (oMG) to generalised (gMG) symptoms results in a substantial negative impact on quality of life (QoL). This systematic review aimed to provide an overview of the patient burden experienced by people living with gMG. METHODS: Electronic database searches (conducted March 2022), supplemented by interrogation of grey literature, were conducted to identify studies reporting patient burden outcomes in patients with gMG in Europe, the Middle East and Africa. Results were synthesised narratively due to the heterogeneity across trials. RESULTS: In total, 39 patient burden publications (representing 38 unique studies) were identified as relevant for inclusion in the systematic review, consisting of 37 publications reporting formal patient-reported outcome measures (PROMs), and two publications describing alternative qualitative assessments of patient experience. The studies included a variety of measures including generic and disease-specific PROMs, as well as symptom-specific PROMs focusing on key comorbidities including depression, anxiety, fatigue and sleep disturbance. The findings showed some variation across studies and PROMs; however, in general there was evidence for worse QoL in patients with gMG than in healthy controls or in patients with oMG, and a trend for worsening QoL with increasing MG severity. CONCLUSIONS: This review highlights the importance of considering patient QoL when developing and assessing treatment and management plans for patients with gMG. However, the heterogeneity identified across studies illustrates the need for further representative and well-powered studies in large cohorts administering consistent, validated questionnaires. TRIAL REGISTRATION: The protocol for this systematic review was registered in PROSPERO: CRD42022328444.

Reliability and validity of PRO-CTCAE® daily reporting with a 24-hour recall period.

PURPOSE: The standard recall period for the patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE®) is the past 7 days, but there are contexts where a 24-hour recall may be desirable. The purpose of this analysis was to investigate the reliability and validity of a subset of PRO-CTCAE items captured using a 24-hour recall. METHODS: 27 PRO-CTCAE items representing 14 symptomatic adverse events (AEs) were collected using both a 24-hour recall (24 h) and the standard 7 day recall (7d) in a sample of patients receiving active cancer treatment (n = 113). Using data captured with a PRO-CTCAE-24h on days 6 and 7, and 20 and 21, we computed intra-class correlation coefficients (ICC); an ICC ≥ 0.70 was interpreted as demonstrating high test-retest reliability. Correlations between PRO-CTCAE-24h items on day 7 and conceptually relevant EORTC QLQ-C30 domains were examined. In responsiveness analysis, patients were deemed changed if they had a one-point or greater change in the corresponding PRO-CTCAE-7d item (from week 0 to week 1). RESULTS: PRO-CTCAE-24h captured on two consecutive days demonstrated that 21 of 27 items (78%) had ICCs ≥ 0.70 (day 6/7 median ICC 0.76), (day 20/21 median ICC 0.84). Median correlation between attributes within a common AE was 0.75, and the median correlation between conceptually relevant EORTC QLQ-C30 domains and PRO-CTCAE-24 h items captured on day 7 was 0.44. In the analysis of responsiveness to change, the median standardized response mean (SRM) for patients with improvement was - 0.52 and that for patients with worsening was 0.71. CONCLUSION: A 24-hour recall period for PRO-CTCAE items has acceptable measurement properties and can inform day-to-day variations in symptomatic AEs when daily PRO-CTCAE administration is implemented in a clinical trial.

Linguistic validation of the simplified Chinese version of the US National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

BACKGROUND: The aim of this study was to translate and linguistically validate the U.S. National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) into Simplified Chinese for use in Singapore. METHODS: All 124 items of the English source PRO-CTCAE item library were translated into Simplified Chinese using internationally established translation procedures. Two rounds of cognitive interviews were conducted with 96 cancer patients undergoing adjuvant treatment to determine if the translations adequately captured the PRO-CTCAE source concepts, and to evaluate comprehension, clarity and ease of judgement. Interview probes addressed the 78 PRO-CTCAE symptom terms (e.g. fatigue), as well as the attributes (e.g. severity), response choices, and phrasing of 'at its worst'. Items that met the a priori threshold of ≥20% of participants with comprehension difficulties were considered for rephrasing and retesting. Items where < 20% of the sample experienced comprehension difficulties were also considered for rephrasing if better phrasing options were available. RESULTS: A majority of PRO-CTCAE-Simplified Chinese items were well comprehended by participants in Round 1. One item posed difficulties in ≥20% and was revised. Two items presented difficulties in < 20% but were revised as there were preferred alternative phrasings. Twenty-four items presented difficulties in < 10% of respondents. Of these, eleven items were revised to an alternative preferred phrasing, four items were revised to include synonyms. Revised items were tested in Round 2 and demonstrated satisfactory comprehension. CONCLUSIONS: PRO-CTCAE-Simplified Chinese has been successfully developed and linguistically validated in a sample of cancer patients residing in Singapore.

Non-pharmacological interventions for chronic cough: The past, present and future.

Non-pharmacological interventions have been explored in people with refractory chronic cough. Normally delivered by Physiotherapists and or Speech and Language Therapists, these interventions aim to educate patients about their cough, provide them with cough suppression techniques and breathing exercises, improve vocal/laryngeal hydration and psychoeducational counselling to help them gain greater control of their cough. Six key studies have been completed over the past 12 years that have consistently found non-pharmacological interventions help to improve quality of life and reduce cough frequency. Some studies also found improvements in cough reflex sensitivity and severity. Despite promising results there now needs to be further work to optimise these interventions. There is a need to standardise terminology used such as relabelling the intervention as cough control therapy and move away from uni-disciplinary terms. Standardised patient selection, including screening protocols, optimal timing and delivery of the interventions as well as the outcome measures used to evaluate interventions need further exploration.

Cancer survivor perspectives on sharing patient-generated health data with central cancer registries.

PURPOSE: Central cancer registries collect data and provide population-level statistics that can be tracked over time; yet registries may not capture the full range of clinically relevant outcomes. Patient-generated health data (PGHD) include health/treatment history, biometrics, and patient-reported outcomes (PROs). Collection of PGHD would broaden registry outcomes to better inform research, policy, and care. However, this is dependent on the willingness of patients to share such data. This study examines cancer survivors' perspectives about sharing PGHD with central cancer registries. METHODS: Three U.S. central registries sampled colorectal, non-Hodgkin lymphoma, and metastatic breast cancer survivors 1-4 years after diagnosis, recruiting them via mail to participate in one of seven focus groups (n = 52). Group discussions were recorded, transcribed, and thematically analyzed. RESULTS: Most survivor-participants were unaware of the existence of registries. After having registries explained, all participants expressed their willingness to share PGHD with them if treated confidentially. Participants were willing to provide information on a variety of topics (e.g., medical history, medications, symptoms, financial difficulties, quality of life, biometrics, nutrition, exercise, and mental health), with a focus on long-term effects of cancer and its treatment. Participants' preferred mode for providing data varied. Participants were also interested in receiving information from registries. CONCLUSIONS: Our results suggest that registry-based collection of PGHD is acceptable to most cancer survivors and could facilitate registry-based efforts to collect PGHD/PROs. Central cancer registry-based collection of PGHD/PROs, especially on long-term effects, could enhance registry support of cancer control efforts including research and population health management.

Validation of the German patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™).

BACKGROUND: Integrating the patient's perspective has become an increasingly important component of adverse event reporting. The National Cancer Institute has developed a Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™). This instrument has been translated into German and linguistically validated; however, its quantitative measurement properties have not been evaluated. PATIENTS AND METHODS: A German language survey that included 31 PRO-CTCAE items, as well as the EORTC QLQ-C30 and the Oral Mucositis Daily Questionnaire (OMDQ), was distributed at 10 cancer treatment settings in Germany and Austria. Item quality was assessed by analysis of acceptability and comprehensibility. Reliability was evaluated by using Cronbach's' alpha and validity by principal components analysis (PCA), multitrait-multimethod matrix (MTMM) and known groups validity techniques. RESULTS: Of 660 surveys distributed to the study centres, 271 were returned (return rate 41%), and data from 262 were available for analysis. Participants' median age was 59.7 years, and 69.5% of the patients were female. Analysis of item quality supported the comprehensibility of the 31 PRO-CTCAE items. Reliability was very good; Cronbach's' alpha correlation coefficients were >0.9 for almost all item clusters. Construct validity of the PRO-CTCAE core item set was shown by identifying 10 conceptually meaningful item clusters via PCA. Moreover, construct validity was confirmed by the MTMM: monotrait-heteromethod comparison showed 100% high correlation, whereas heterotrait-monomethod comparison indicated 0% high correlation. Known groups validity was supported; PRO-CTCAE scores were significantly lower for those with impaired versus preserved health-related quality of life. CONCLUSION: A set of 31 items drawn from the German PRO-CTCAE item library demonstrated favourable measurement properties. These findings add to the body of evidence that PRO-CTCAE provides a rigorous method to capture patient self-reports of symptomatic toxicity for use in cancer clinical trials.

System dynamic modelling to assess economic viability and risk trade-offs for ecological restoration in South Africa.

Can markets assist by providing support for ecological restoration, and if so, under what conditions? The first step in addressing this question is to develop a consistent methodology for economic evaluation of ecological restoration projects. A risk analysis process was followed in which a system dynamics model was constructed for eight diverse case study sites where ecological restoration is currently being pursued. Restoration costs vary across each of these sites, as do the benefits associated with restored ecosystem functioning. The system dynamics model simulates the ecological, hydrological and economic benefits of ecological restoration and informs a portfolio mapping exercise where payoffs are matched against the likelihood of success of a project, as well as a number of other factors (such as project costs and risk measures). This is the first known application that couples ecological restoration with system dynamics and portfolio mapping. The results suggest an approach that is able to move beyond traditional indicators of project success, since the effect of discounting is virtually eliminated. We conclude that systems dynamic modelling with portfolio mapping can guide decisions on when markets for restoration activities may be feasible.

Comparison of ionisation chamber and semiconductor detector devices for measurement of the dose-width product for panoramic dental units.

Doses for panoramic dental radiography are assessed in terms of the dose-width product (DWP) or dose-area product, which gives a measure of the radiation through a whole exposure. The DWP can be measured using a pencil ionisation chamber (IC) similar to that used for computed tomography dose assessment. However, ICs are sensitive to radiation incident from all directions and so backscatter from the image receptor may increase the recorded dose. This study compares measurements performed using four options: a pencil IC mounted straight on the image receptor, the IC mounted with a steel plate to the rear to standardise scatter conditions, the IC mounted with a steel plate and lead collimators in front to minimise the effect of extra-focal radiation, and a Quart Dido employing a one square centimetre semiconductor detector (SD) designed for panoramic measurements. The results indicate that modification of the current method by incorporating a steel plate reduced the measurement dose by 7% on average, but the reduction was greater for units with semiconductor imaging plates. The measurements with the SD agree more closely with the IC with the steel plate to the rear. An IC with a backing plate to standardise scatter or a suitable SD is recommended for measurement on panoramic dental units.

Reliability of the School Food Checklist for in-school audits and photograph analysis of children's packed lunches.

BACKGROUND: Assessment of children's diets is problematic, typically relying on error-prone parent or child recall or reporting, or resource intensive direct observation. The School Food Checklist (SFC) is an objective instrument comprising of 20 food and beverage categories designed to measure the foods contained in children's packed lunches. The present study aimed to assess intra-rater and inter-rater reliability of each of the food and beverage categories of the SFC for both in-school audits and photograph analysis of children's school lunches. METHODS: Participants comprised 176 children aged 5-8 years from five primary schools in Northern Metropolitan Melbourne. The SFC was used to measure the foods contained in children's packed lunches in the school setting and using photographs. Photograph analysis was conducted by the auditors 2-3 months after completion of in-school audits. RESULTS: Both intra-rater [intra-class correlation coefficient (ICC) = 0.78-1] and inter-rater (ICC = 0.50-0.95) reliability analysis indicated strong agreement for in-school auditing. With the exception of the food category titled 'leftovers', there was strong intra-rater reliability for auditors' live audits and their analysis of photographs [ICC = 0.57-0.98 (Auditor 1); ICC = 0.72-0.90 (Auditor 2)], and strong inter-rater reliability for photograph analysis (ICC = 0.68-0.92). CONCLUSIONS: The SFC is a reliable method of measuring the foods and beverages contained in children's packed lunches when used in the school setting or for photograph analysis. This finding has broad implications, particularly for the use of photograph analysis, because this approach offers a convenient and cost effective method of measuring what food and beverages children bring to school in home packed lunches.

Indole adsorption to a lipid monolayer studied by optical second harmonic generation.

Adsorption of indole from an aqueous subphase to a lipid (DPPC) monolayer at the air/water interface is studied by nonresonant second harmonic generation (SHG) with lambda = 800 nm and by observation of compression isotherms with a Langmuir trough. The nonlinear susceptibilities of the monolayers have been carefully measured, including corrections for the contributions of the lipid monolayer and subphase, calibration of absolute values by comparison with a quartz reference, and measurement of absolute phase by comparison with a clean air/water interface. Details of the calibrations involving z-cut quartz and the clean air/water interface are presented. The number density of adsorbed indole molecules has been estimated by comparison of nonlinear susceptibilities with a reference monolayer of hexadecyl 3-indoleacetate. The extent of adsorption of indole to the lipid monolayer is maximum at low surface pressure, decreasing from an indole/DPPC ratio near 2:1 as the monolayer is compressed. The free energy change for adsorption of indole to the monolayer is estimated as -8.1 kcal/mol, which is similar to a result reported previously for a lipid bilayer. Information on the orientation of adsorbed indole is derived by comparison of observed ratios of nonlinear susceptibilities with calculated ratios for model indole monolayers with assumed orientational distributions. Measurement and analysis procedures are described in detail for effective nonlinear susceptibilities in a s/p polarization basis. The calculations use as input the molecular hyperpolarizability tensor of indole, which is obtained by using several computational approaches including sum-over-states calculations and time-dependent Hartree-Fock and density functional methods. The analysis shows that the pyrrole ring of indole points toward the water subphase, and the tilt angle of the long axis of indole increases from near 50 degrees to near 60 degrees as the monolayer is compressed. The analysis also suggests that the plane of indole lies more nearly parallel than perpendicular to the plane of the interface.

Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer's disease: systematic review of the 'real-world' evidence.

BACKGROUND/AIMS: The purpose of this systematic review was to compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer's disease (AD) patients in routine clinical practice. METHODS: Electronic databases (Cochrane Library, Medline, EMBASE; accessed October 2008) and manual bibliographic searches were conducted to identify head-to-head non-randomised studies examining ChEIs for the treatment of AD. Data were extracted by 2 independent reviewers. RESULTS: Twelve head-to-head studies comparing ChEIs met the pre-specified inclusion criteria; 6 retrospective analyses and 6 prospective cohort studies. Donepezil was the most widely studied treatment and galantamine the least widely prescribed therapy. Fewer donepezil-treated subjects withdrew due to adverse events (AEs) compared with rivastigmine and galantamine-treated subjects. The incidence of gastrointestinal (GI) AEs was lower following treatment with donepezil compared with rivastigmine and galantamine. Non-GI (CNS and cardiovascular) AEs occurred at a low frequency, and had a similar incidence in subjects treated with the different ChEIs. CONCLUSIONS: Subjects with mild to moderate AD treated in routine clinical practice with donepezil were more adherent to pharmacotherapy, and had a lower risk of GI AEs compared with rivastigmine or galantamine. This finding accords with results reported in the randomised clinical trial literature.

Protein factor requirements of the Apaf-1 internal ribosome entry segment: roles of polypyrimidine tract binding protein and upstream of N-ras.

It has been reported previously that the 5' untranslated region of the mRNA encoding Apaf-1 (apoptotic protease-activating factor 1) has an internal ribosome entry site (IRES), whose activity varies widely among different cell types. Here it is shown that the Apaf-1 IRES is active in rabbit reticulocyte lysates, provided that the system is supplemented with polypyrimidine tract binding protein (PTB) and upstream of N-ras (unr), two cellular RNA binding proteins previously identified to be required for rhinovirus IRES activity. In UV cross-linking assays and electrophoretic mobility shift assays with individual recombinant proteins, the Apaf-1 IRES binds unr but not PTB; however, PTB binding occurs if unr is present. Over a range of different cell types there is a broad correlation between the activity of the Apaf-1 IRES and their content of PTB and unr. In cell lines deficient in these proteins, overexpression of PTB and unr stimulated Apaf-1 IRES function. This is the first example where an IRES in a cellular mRNA has been shown to be functionally dependent, both in vitro and in vivo, on specific cellular RNA binding proteins. Given the critical role of Apaf-1 in apoptosis, these results have important implications for the control of the apoptotic cascade.

Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries.

BACKGROUND: Surgical site infections (SSIs) are associated with increased morbidity and mortality. Furthermore, SSIs constitute a financial burden and negatively impact on patient quality of life (QoL). AIM: To assess, and evaluate the evidence for, the cost and health-related QoL (HRQoL) burden of SSIs across various surgical specialties in six European countries. METHODS: Electronic databases and conference proceedings were systematically searched to identify studies reporting the cost and HRQoL burden of SSIs. Studies published post 2005 in France, Germany, the Netherlands, Italy, Spain, and the UK were eligible for data extraction. Studies were categorized by surgical specialty, and the primary outcomes were the cost of infection, economic evaluations, and HRQoL. FINDINGS: Twenty-six studies met the eligibility criteria and were included for analysis. There was a paucity of evidence in the countries of interest; however, SSIs were consistently associated with elevated costs, relative to uninfected patients. Several studies reported that SSI patients required prolonged hospitalization, reoperation, readmission, and that SSIs increased mortality rates. Only one study reported QoL evidence, the results of which demonstrated that SSIs reduced HRQoL scores (EQ-5D). Hospitalization reportedly constituted a substantial cost burden, with additional costs arising from medical staff, investigation, and treatment costs. CONCLUSION: Disparate reporting of SSIs makes direct cost comparisons difficult, but this review indicated that SSIs are extremely costly. Thus, rigorous procedures must be implemented to minimize SSIs. More economic and QoL studies are required to make accurate cost estimates and to understand the true burden of SSIs.

Internal ribosome entry segment-mediated translation during apoptosis: the role of IRES-trans-acting factors.

During apoptosis, there is a reduction in translation initiation caused by caspase cleavage of several of the factors required for the cap-dependent scanning mechanism. Under these circumstances, many proteins that are required for apoptosis are instead translated by the alternative method of internal ribosome entry. This mechanism requires the formation of a complex RNA structural element and in the presence of internal ribosome entry segment (IRES)-trans-acting factors (ITAFs), the ribosome is recruited to the RNA. The interactions of several ITAFs with IRESs have been investigated in detail, and several mechanisms of action have been noted, including acting as chaperones, stabilising and remodelling the RNA structure. Structural remodelling by PTB in particular will be discussed, and how this protein is able to facilitate recruitment of the ribosome to several IRESs by causing previously occluded sites to become more accessible.

Nonlinear susceptibility of a cyanobiphenyl derivative at the air/water interface: improved measurement of molecular orientation by optical second harmonic generation.

The nonlinear susceptibility tensor, chi(2), for second harmonic generation (SHG) by a monolayer of the cyanobiphenyl derivative 4-n-octyl-4'-cyanobiphenyl (8CB) at the air/water interface has been measured with the fundamental frequency variant Planck's over 2piomega=1.55 eV (lambda=800 nm). The contribution of the water subphase was estimated by measuring the magnitudes and relative phases of the nonlinear susceptibilities of the bare and monolayer-covered water surfaces. All nonzero elements of chi(2) are placed on an absolute scale by comparison with SHG in reflection from a z-cut quartz crystal. The experimental measurements for the 8CB monolayer are compared with computed susceptibilities derived by using standard time-dependent perturbation theory in conjunction with a semiempirical electronic structure model. Good agreement has been found between experimental and computational results when the average tilt angle of the cyanobiphenyl chromophore of 8CB is in the range 60-70 degrees relative to the surface normal. A critique is given of an alternative, simplified measurement procedure of the tilt angle in which only the dominant element of the molecular hyperpolarizability tensor is considered. It is shown that the simplified procedure is invalid for 8CB monolayers when the tilt angle is greater than approximately 70 degrees.

A review of medicinal plant research at the University of the West Indies, Jamaica, 1948-2001.

This review summarizes research carried out on Jamaican medicinal plants at the Faculty of Pure and Applied Science, The University of the West Indies (UWI), Mona, Jamaica, between 1948 and 2001. The plants identified as being medicinal are listed along with their folk use and a summary of the scientific research done at UWI leading to the identification of natural products (NPs) and determination of their bioactivity. Natural product research on Jamaican medicinal plants began with the inception of UWI in 1948, leading to many postgraduate degrees being awarded (22 MPhil and 31 PhD). At least 334 plant species growing in Jamaica have been identified as having medicinal qualities, 193 of these have been tested for their bioactivity. Crude extracts from 80 of these plants have reasonable bioactivity and natural products (NP) have been identified from 44 plants. At least 29 of these NPs were found to be bioactive. Only 31 of the plants tested at UWI are endemic to Jamaica. Of these 23% were bioactive, as compared to 11% of the non-endemics. Based on these results, patents have been obtained and drugs have been developed. This review represents the first attempt to gather this information together in one place.