Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.
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SUBMITTER: Hendrix MRS
PROVIDER: S-EPMC10782776 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Prescription Sequence Symmetry Analysis (PSSA) to assess prescribing cascades: a step-by-step guide.
Hendrix Mandy R S MRS Yasar Mustafa M Mohammad Atiya K AK Hugtenburg Jacqueline G JG Vanhommerig Joost W JW Gündoğan-Yilmaz Ruveyda R van den Bemt Patricia M L A PMLA Denig Petra P Karapinar-Carkıt Fatma F
BMC medical research methodology 20240111 1
Prescribing cascades occur when patients are prescribed medication to treat the adverse drug reaction of previously prescribed medication. Prescription sequence symmetry analysis (PSSA) can be used to assess the association between two medications in prescription or dispensing databases and thus the potential occurrence of prescribing cascades. In this article, a step-by-step guide is presented for conducting PSSA to assess prescribing cascades. We describe considerations for medication data col ...[more]
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Project description:Prescription sequence symmetry analysis (PSSA), a case-only design introduced in 1996, has been increasingly used to identify unintentional drug effects, and has potential applications as a hypothesis-testing and a hypothesis-generating method, due to its easy application and effective control of time-invariant confounders. The aim of this study is to systematically compare effect estimates from the PSSA to effect estimates from conventional observational parallel group study designs, to assess the validity and constraints of the PSSA study design. We reviewed the MEDLINE, EMBASE, and Web of Science databases until February 2016 to identify studies that compared PSSA to a parallel group design. Data from the eligible articles was extracted and analyzed, including making a Bland-Altman plot and calculating the number of discrepancies between the designs. 63 comparisons (from two studies) were included in the review. There was a significant correlation (p < 0.001) between the effect estimates of the PSSA and the parallel group designs, but the bias indicated by the Bland-Altman plot (0.20) and the percentage of discrepancies (70-80%) showed that this correlation was not accompanied by a considerable similarity of the effect estimates. Overall, the effect estimates of the parallel group designs were higher than those of the PSSA, not necessarily further away from 1, and the parallel group designs also generated more significant signals. However, these results should be approached with caution, as the effect estimates were only retrieved from two separate studies. This review indicates that, even though PSSA has a lot of potential, the effect estimates generated by the PSSA are usually lower than the effect estimates generated by parallel group designs, and PSSA mostly has a lower power than the conventional study designs, but this is based on limited comparisons, and more comparisons are needed to make a proper conclusion.
| S-EPMC6283622 | biostudies-literature
Project description:BackgroundGabapentinoids (GBP) and benzodiazepines (BZ) are commonly prescribed in older adults and their package inserts list edema and vertigo as adverse drug reactions. These adverse drug reactions may be treated with symptomatic drug therapies without discontinuing the culprit drugs or decreasing their dose, thereby initiating a prescribing cascade and often resulting in polypharmacy. Whether prescribing cascades occur in the treatment of edema and dizziness among Japanese patients treated with GBP and BZ has not been investigated, including treatment with mirogabalin, a class drug of GBP marketed in Japan.ObjectiveWe aimed to investigate prescribing cascades with GBP-induced and BZ-induced edema and dizziness treated with loop diuretics (LD) and anti-vertigo drugs (AVD), respectively, among older adults.MethodsA prescription sequence symmetry analysis design was used to detect signals of prescribing cascades associated with edema and dizziness induced by GBP and BZ (exposure drugs). Loop diuretics and AVD were the outcome drugs used to identify prescribing cascades following the initiation of exposure drugs. The study population consisted of enrollees of a large-scale health claims database provided by DeSC Healthcare, Inc., between April 2014 and March 2021. Subjects eligible for a prescription sequence symmetry analysis were patients aged ≥ 65 years prescribed an outcome drug within 90 days before and after exposure drug initiation. A signal of a prescribing cascade was detected if secular trend-adjusted sequence ratios were statistically significant on comparison of the frequencies of outcome drug initiation before and after exposure drug initiation.ResultsWe identified 2671 patients with prescriptions of a GBP-LD combination, 4009 with a GBP-AVD combination, 8675 with a BZ-LD combination, and 9462 with a BZ-AVD combination. The adjusted sequence ratios for GBP-LD and BZ-LD cascades were significantly larger than one (adjusted sequence ratio [95% confidence interval], 1.69 [1.56-1.83]; 1.35 [1.29-1.41], respectively), indicating positive signals of prescribing cascades. No signal was detected for the GBP-AVD or BZ-AVD cascade (0.89 [0.83-0.94]; 0.90 [0.87-0.94], respectively). The adjusted sequence ratio for the mirogabalin cascade was higher than that for pregabalin (2.23 [1.84-2.71] vs 1.59 [1.46-1.73]).ConclusionsOur study provides good evidence that LD-prescribing cascades associated with edema would be a class effect of GBP and BZ. Edema emerging around 1 month after GBP initiation should be carefully differentiated from pathological edema, and undue LD prescription as a prescribing cascade should be avoided.
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Project description:BackgroundSequence symmetry analysis (SSA) is a signal detection method that can be used to assist with adverse drug event detection. It provides both a risk estimate and a data visualisation. Published methods provide results in the form of an adjusted sequence ratio, which adjusts for underlying market trends of medicine use, however no method for adjusting the visualisation is available. We aimed to develop and evaluate another method of adjustment for prescribing trends and apply it to the SSA visualisation.MethodsThe SSA method relies on incident prescriptions for pairs of medicines of interest. Smoothing curves were fitted to the frequency distributions of incident medicine use. When divided and normalised, these curves yielded a set of proportions related to differences in prescribing trends over follow-up. These were then used to adjust the unit counts for incident prescriptions in the SAA visualisation and to calculate the sequence ratio. Curve fitting was also used to identify the proportional relationship between sequences over time for SSA and is presented as a supplementary visualisation to the SSA. We compared the sensitivity and specificity of our method with that from the SSA method of Tsiropolous et al. RESULTS: Curve-fit adjusted SSA visualisations yielded adjusted sequence ratios very close to those of Tsiropolous, with a p-value of 0.999 for the two sample Kolmogorov-Smirnov test. Results for sensitivity and specificity derived from adjusted sequence ratios were also practically the same. The curve-fit method graphically indicates the proportionality of the sequence and provides a useful supplement of net differences between the two sides of the SSA visualisation. Additionally, we found that incident prescriptions for patients common to both distributions are best precluded from adjustment calculations, leaving only incident prescriptions for patients unique to one or other distribution. This improved the accuracy of SSA in some atypical instances with negligible affect on accuracy elsewhere.ConclusionsOur curve-fit method is equivalent to current methods in the literature for adjusting prescribing trends in SAA, with the advantage of providing adjustment incorporated in the SAA visualisation.
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Project description:This paper provides a step-by-step guide for the morphological analysis of corolla and the decomposition of corolla shape variation into its symmetric and asymmetric components. The shape and symmetric organisation of corolla are key traits in the developmental and evolutionary biology of flowering plants. The various spatial layout of petals can exhibit bilateral symmetry, rotational symmetry or more complex combination of symmetry types. Here, I describe a general landmark-based geometric morphometric framework for the full statistical shape analysis of corolla and exemplify its use with four fully worked out case studies including tissue treatment, imaging, landmark data collection, file formatting, and statistical analyses: (i) bilateral symmetry (Fedia graciliflora), (ii) two perpendicular axes of bilateral symmetry (Erysimum mediohispanicum), (iii) rotational symmetry (Vinca minor), and (iv) combined bilateral and rotational symmetry (Trillium undulatum). The necessary tools for such analyses are not implemented in standard morphometric software and they are therefore provided here as functions running in the R environment. Principal Component Analysis is used to separate symmetric and asymmetric components of variation, respectively, quantifying variation among and within individuals. For bilaterally symmetric flowers, only one component of left-right asymmetric variation is extracted, while flowers with more complex symmetric layout have components of asymmetric variation associated with each symmetry operator implied (e.g., left-right asymmetry and adaxial-abaxial asymmetry). Fundamental information on the genetic, developmental, and environmental determinants of shape variation can be inferred from this decomposition (e.g., directional asymmetry, fluctuating asymmetry) and further exploited to document patterns of canalization, developmental stability, developmental modularity and morphological integration. Even if symmetry and asymmetry are not the primary interest of a study on corolla shape variation, statistical and anatomical arguments support the use of the framework advocated. This didactic protocol will help both morphometricians and non-morphometricians to further understand the role of symmetry in the development, variation and adaptive evolution of flowers.
| S-EPMC6191499 | biostudies-literature
Project description:PurposePrevious studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects.Materials and methodsPatients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias.ResultsA total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46-2.06) and hyperprolactinemia (12.04; 1.59-91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment.ConclusionsWe found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological, dermatological, and musculoskeletal or joint side effects, constipation, and pneumonia.
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Project description: Not available
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Project description:The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. A systematic review was reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline [Ovid], EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: community-dwelling adults; risk-prescription medication; outcomes-initiation of new medicine to "treat" or reduce ADR risk; study type-cohort, cross-sectional, case-control, and case-series studies. Title/abstract screening, full-text screening, data extraction, and methodological quality assessment were conducted independently in duplicate. A narrative synthesis was conducted. A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11 593 989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n = 5), amiodarone to levothyroxine (n = 5), inhaled corticosteroid to topical antifungal (n = 4), antipsychotic to anti-Parkinson drug (n = 4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n = 4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months.
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Project description:Among the variety of correlated states exhibited by twisted bilayer graphene, cascades in the spectroscopic properties and in the electronic compressibility occur over larger ranges of energy, twist angle and temperature compared to other effects. This suggests a hierarchy of phenomena. Using a combined dynamical mean-field theory and Hartree calculation, we show that the spectral weight reorganisation associated with the formation of local moments and heavy quasiparticles can explain the cascade of electronic resets without invoking symmetry breaking orders. The phenomena reproduced here include the cascade flow of spectral weight, the oscillations of remote band energies, and the asymmetric jumps of the inverse compressibility. We also predict a strong momentum differentiation in the incoherent spectral weight associated with the fragile topology of twisted bilayer graphene.
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Project description:BackgroundIncrements of 1000 steps/d predict cardiovascular disease (CVD) event reductions. In adults with type 2 diabetes and/or hypertension, our Step Monitoring to Improve Arterial Health (SMARTER) trial demonstrated a physician-delivered step-count prescription strategy to increase steps by more than this amount over 1 year, compared to usual care. In the present analysis, we aimed to determine the costs of the intervention compared to usual care, incorporating 1-year intervention costs and projected savings from lower CVD hospitalizations over the subsequent 5 years.MethodsWe considered Canadians aged 55 to 74 years with type 2 diabetes and/or hypertension. Using time estimates from our trial, we computed nursing costs corresponding to patient support time over 1 year, and pedometer costs for an anticipated 50% of patients without a smartphone. We estimated the number of CVD hospitalizations, the reduction expected with a mean 1000 steps/d increase, and the associated savings. We calculated the net cost (savings), the proportion of patients with their own device required for cost neutrality, and costs (savings) if all patients needed to be provided with a device.ResultsAt an average intervention cost of $51.28/patient, the total cost would be $168 million. With an estimated 8875 CVD events prevented, $208 million would be saved. This savings would result in ~$40 million in net savings with 50% device ownership, cost neutrality with 25% device ownership, and ~$42 million in net costs if all patients required the healthcare system to provide a device.ConclusionsAt current levels of smartphone ownership, adoption of the SMARTER strategy is cost-saving to cost-neutral from the healthcare system perspective.
| S-EPMC8413227 | biostudies-literature