Purpose
Research into causality assessment tools enabling patients to assess suspected adverse drug reactions (ADRs) is limited. Supporting patients with tools could improve their confidence in ...discussions with health professionals and encourage reporting of suspected ADRs to regulators. This study describes development and preliminary validation of an instrument: Side Effect Patient ASsessment Tool (SE‐PAST).
Methods
SE‐PAST was developed from survey and interview data involving patients experiencing suspected ADRs. It included 10 statements enabling causality assessment, covering timing, additional information sources, and experiences, with four options: yes/no/don't know/not applicable. Scoring and weighting resulted in four categories of causal association: highly probable, probable, possible, unlikely.
Validation involved obtaining feedback from 31 individuals experiencing an ADR. Further validation involved online distribution through patient support groups and comparison of reported symptoms to known ADRs.
Results
Validators found SE‐PAST easy to read (31), to understand (27), and to complete (29). A total of 294 respondents completed SE‐PAST online, with 98% completing eight or more causality assessment statements. Symptoms were categorised as highly probable (46; 16%), probable (80; 62%), possible (44; 15%), and unlikely (21; 7%). A total of 221 respondents identified one suspected medicine, with 95% of these reporting at least one symptom known to be an ADR.
Of 227 providing feedback, 139 (61%) found SE‐PAST useful, 160 (71%) felt motivated to discuss their experience with a health professional, and 136 (60%) were encouraged to report to the regulator.
Conclusion
SE‐PAST was easily completed and understood by people experiencing suspected ADRs and could be useful in encouraging patient reporting to health professionals and agencies.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Fixed high-energy selective laser trabeculoplasty (SLT) is associated with a greater reduction in intraocular pressure (IOP) compared with the standard titrated approach at up to 36 months ...postprocedure.
There is no consensus on ideal SLT procedural laser energy settings. This study aims to compare fixed high-energy SLT to the standard titrated-energy approach within the setting of a residency training program.
Patients over the age of 18 years received SLT between 2011 and 2017, a total of 354 eyes. Patients with a prior history of SLT were excluded.
Retrospective review of clinical data from 354 eyes that underwent SLT. Eyes that underwent SLT using fixed high energy (1.2 mJ/spot) were compared with those with the standard titrated approach starting at 0.8 mJ/spot and titrating to "champagne" bubbles. The entirety of the angle was treated using a Lumenis laser set to the SLT setting (532 nm). No repeat treatments were included.
IOP and glaucoma medications.
In our residency training program, fixed high-energy SLT was associated with a reduction in IOP compared with a baseline of -4.65 (±4.49, n = 120), -3.79 (±4.49, n = 109), and -4.40 (±5.01, n =119) while standard titrated-energy was associated with IOP reduction of -2.07 (±5.06, n = 133), -2.67 (±5.28, n = 107), and -1.88 (±4.96, n = 115) at each respective postprocedural time point (12, 24, and 36 months). The fixed high-energy SLT group had significantly greater IOP reduction at 12 months and 36 months. The same comparison was performed for medication naïve individuals. For these individuals, fixed high-energy SLT resulted in IOP reductions of -6.88 (±3.72, n = 47), -6.01 (±3.80, n = 41), and -6.52 (±4.10, n = 46) while standard titrated-energy had IOP reductions of -3.82 (±4.51, n = 25), -1.85 (±4.88, n = 20), and -0.65 (±4.64, n = 27). For medication naïve individuals, fixed high-energy SLT resulted in a significantly greater reduction in IOP at each respective time point. Complication rates (IOP spike, iritis, and macular edema) were similar between the two groups. The study is limited by overall poor response to standard-energy treatments, whereas high-energy treatments showed similar efficacy to those in literature.
This study demonstrates that fixed-energy SLT produces at least equivalent results compared with the standard-energy approach, without an increase in adverse outcomes. Particularly in the medication naïve subpopulation, fixed-energy SLT was associated with a significantly greater IOP reduction at each respective time point. The study is limited by overall poor response to standard-energy treatments, with our results showing decreased IOP reduction compared with those of previous studies. These poor outcomes of the standard SLT group may be responsible for our conclusion that fixed high-energy SLT results in a greater reduction in IOP. These results may be useful when considering optimal SLT procedural energy in future studies for validation.
Exercise capacity is a strong predictor of all-cause mortality. Skeletal muscle mitochondrial respiratory capacity, its biggest contributor, adapts robustly to changes in energy demands induced by ...contractile activity. While transcriptional regulation of mitochondrial enzymes has been extensively studied, there is limited information on how mitochondrial membrane lipids are regulated. Here, we show that exercise training or muscle disuse alters mitochondrial membrane phospholipids including phosphatidylethanolamine (PE). Addition of PE promoted, whereas removal of PE diminished, mitochondrial respiratory capacity. Unexpectedly, skeletal muscle-specific inhibition of mitochondria-autonomous synthesis of PE caused respiratory failure because of metabolic insults in the diaphragm muscle. While mitochondrial PE deficiency coincided with increased oxidative stress, neutralization of the latter did not rescue lethality. These findings highlight the previously underappreciated role of mitochondrial membrane phospholipids in dynamically controlling skeletal muscle energetics and function.
Abstract
Background
Opioid deaths have increased in England and Wales. Coroners’ Prevention of Future Deaths reports (PFDs) provide important insights that may enable safer use and avert harms, yet ...reports implicating opioids have not been synthesized. We aimed to identify opioid-related PFDs and explore coroners’ concerns to prevent future deaths.
Methods
In this systematic case series, we screened 3897 coronial PFDs dated between 01 July 2013 and 23 February 2022, obtained by web scraping the UK’s Courts and Tribunals Judiciary website. PFDs were included when an opioid was implicated in the death. Included PFDs were descriptively analysed, and content analysis was used to assess concerns reported by coroners.
Results
Opioids were involved in 219 deaths reported in PFDs (5·6% of PFDs), equating to 4418 years of life lost (median 33 years/person). Morphine (29%), methadone (23%) and diamorphine (16%) were the most common implicated opioids. Coroners most frequently raised concerns regarding systems and protocols (52%) or safety issues (15%). These concerns were most often addressed to National Health Service (NHS) organizations (51%), but response rates were low overall (47%).
Conclusions
Opioids could be used more safely if coroners’ concerns in PFDs were addressed by national organizations such as NHS bodies, government agencies and policymakers, as well as individual prescribing clinicians.
Deliberate injection of aerosol particles into the stratosphere is a potential climate engineering scheme. Particles injected into the stratosphere would scatter solar radiation back to space, ...thereby reducing the temperature at the Earth's surface and hence the impacts of global warming. Minerals such as TiO2 or SiO2 are among the potentially suitable aerosol materials for stratospheric particle injection due to their greater light-scattering ability than stratospheric sulfuric acid particles. However, the heterogeneous reactivity of mineral particles towards trace gases important for stratospheric chemistry largely remains unknown, precluding reliable assessment of their impacts on stratospheric ozone, which is of key environmental significance. In this work we have investigated for the first time the heterogeneous hydrolysis of ClONO2 on TiO2 and SiO2 aerosol particles at room temperature and at different relative humidities (RHs), using an aerosol flow tube. The uptake coefficient,γ(ClONO2), on TiO2 was ∼ 1.2 × 10-3 at 7 % RH and remained unchanged at 33 % RH, and increased for SiO2 from ∼ 2 × 10-4 at 7 % RH to∼ 5 × 10-4 at 35 % RH, reaching a value of∼ 6 × 10-4 at 59 % RH. We have also examined the impacts of a hypothetical TiO2 injection on stratospheric chemistry using the UKCA (United Kingdom Chemistry and Aerosol) chemistry–climate model, in which heterogeneous hydrolysis of N2O5 and ClONO2 on TiO2 particles is considered. A TiO2 injection scenario with a solar-radiation scattering effect very similar to the eruption of Mt Pinatubo was constructed. It is found that, compared to the eruption of Mt Pinatubo, TiO2 injection causes less ClOx activation and less ozone destruction in the lowermost stratosphere, while reduced depletion of N2O5 and NOx in the middle stratosphere results in decreased ozone levels. Overall, no significant difference in the vertically integrated ozone abundances is found between TiO2 injection and the eruption of Mt Pinatubo. Future work required to further assess the impacts of TiO2 injection on stratospheric chemistry is also discussed.
TiO2, a component of atmospheric mineral aerosol, catalyses the reduction of NO2 to nitrous acid (HONO) when present as an aerosol and illuminated with near UV light under conditions pertinent to the ...troposphere.
Objectives: No studies describing UK patient Yellow Card reports have been published since the evaluation of the first two years of direct patient reporting (2005-7), when 5,180 reports were ...analyzed.
Methods: Patient Yellow Card reports submitted July-December 2015 for vaccines and other drugs were analyzed. Comparisons to the initial evaluation were made of: reporting method, number of suspect drugs, proportion classed as serious. Factors affecting seriousness of reports were examined.
Results: There were 3,060 patient Yellow Card reports analyzed. Vaccine reports have increased from very few in 2005-7 to 25% of reports. The proportion of reports citing one drug (94.3%) and the proportion considered serious (70.3%) increased from the 84% and 58% respectively found in 2005-7. The main method of reporting had changed from paper (61%) to internet (88.5%). Serious reports were more common in females, for vaccines in young persons, but in adults for other drugs, and included more reaction terms than non-serious reports.
Conclusion: Patient reporting, in particular to vaccines, has increased dramatically since 2005-7. Increases in the proportion of reports concerning one drug and the proportion considered serious could indicate that the usability of patient reports may have improved in comparison to early reporting.
To determine the use and perceived value of different information sources that patients may use to support identification of medicine side effects; to explore associations between coping styles and ...use of information sources.
Side effects from medicines can have considerable negative impact on peoples' daily lives. As a result of an ageing UK population and attendant multi-morbidity, an increasing number of medicines are being prescribed for patients, leading to increased risk of unintended side effects.
A cross-sectional survey of patients who use medicine, recruited from community pharmacies. The survey sought views on attributes of various information sources, their predicted and actual use, incorporating a shortened Side Effects Coping Questionnaire (SECope) scale and the abbreviated Miller Behavioural Style Scale (MBSS).
Of 935 questionnaires distributed, 230 (25.0%) were returned, 61.3% from females; 44.7% were retired and 84.6% used at least one medicine regularly. 69.6% had experienced a side effect, resulting in 57.5% of these stopping the medicine. Patient information leaflets (PILs) and GPs were both predicted and actually most widely used sources, despite GPs being judged as relatively less accessible and PILs less trustworthy, particularly by regular medicine users. Pharmacists, considered both easy to access and trustworthy, were used by few in practice, while the internet was considered easy to access, but less trustworthy and was also little used. SECope sub-scales for non-adherence and information seeking showed positive associations with stopping a medicine and seeking information from a health professional. More high monitors than low monitors stopped a medicine themselves, but there were no differences in use of information sources. Information seeking following a side effect is a common strategy, potentially predicted by the SECope, but not the MBSS. Limited GP accessibility could contribute to high internet use. Further research could determine how the trustworthiness of PILs can be improved.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Objective
To explore amateur endurance athletes’ use and views about non‐steroidal anti‐inflammatory drugs (NSAIDs).
Methods
An online cross‐sectional survey of amateur athletes at four athletic ...clubs.
Key findings
Of a sample of 129 of amateur athletes, 68% (n = 88) reported using NSAIDs in the previous 12 months (84.4% in triathletes, 70.9% in runners and 52.5% in cyclists). Overall, ibuprofen was the most popular drug (n = 48). There was a lack of knowledge of adverse drug reactions, with only 26% of use advised by a doctor or pharmacist.
Conclusions
There is high usage of NSAIDs in amateur athletes, including before and during events, largely without professional health advice. Informational needs of amateur athletes are not being met.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK, VSZLJ
The photoenhanced uptake of nitrogen dioxide (NO
2) to the surface of commercially available self-cleaning window glass has been studied under controlled laboratory conditions. This material is one ...of an array of modern building products which incorporate titanium dioxide (TiO
2) nanoparticles and are finding increasing use in populated urban areas. Amongst the principal drivers for the use of these materials is that they are thought to facilitate the irreversible removal of pollutants such as NO
2 and organic molecules from the atmosphere and thus act to remediate air quality. While it appears that TiO
2 materials do indeed remove organic molecules from built environments, in this study we show that the photoenhanced uptake of NO
2 to one example material, self-cleaning window glass, is in fact accompanied by the substantial formation (50–70%) of gaseous nitrous acid (HONO). This finding has direct and serious implications for the use of these materials in urban areas. Not only is HONO a harmful respiratory irritant, it is also readily photolysed by solar radiation leading to the formation of hydroxyl radicals (OH) together with the re-release of NO
x as NO. The net effect of subsequent OH initiated chemistry can then be the further degradation of air quality through the formation of secondary pollutants such as ozone and VOC oxidation products. In summary, we suggest that a scientifically conceived technical strategy for air quality remediation based on this technology, while widely perceived as universally beneficial, could in fact have effects precisely opposite to those intended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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