Prescribing Cascade Research Articles

Identifying and quantifying potentially problematic prescribing cascades in clinical practice: A mixed‐methods study

AbstractBackgroundA prescribing cascade occurs when medication causes an adverse drug reaction (ADR) that leads to the prescription of additional medication. Prescribing cascades can cause excess medication burden, which is of particular concern in older adults. This study aims to identify and quantify potentially problematic prescribing cascades relevant for clinical practice.MethodsA mixed‐methods study was conducted. First, prescribing cascades were identified through literature search. An expert panel (n = 16) of pharmacists and physicians assessed whether these prescribing cascades were potentially problematic. Next, a cohort study quantified potentially problematic prescribing cascades in adults using Dutch community pharmacy data for the period 2015–2020. Additionally, the influence of multiple medications potentially causing the same ADR was evaluated. Prescription sequence symmetry analysis was used to calculate adjusted sequence ratios (aSRs), adjusting for temporal prescribing trends. An aSR >1.0 indicates the occurrence of a prescribing cascade. In a subgroup analysis, aSRs were calculated for older adults.ResultsSeventy‐six prescribing cascades were identified in literature and three were provided by experts. Of these, 66 (83.5%) were considered potentially problematic. A significant positive aSR for the medication sequence was found for 41 (62.1%) of these prescribing cascades. The highest aSR was found for amiodarone potentially causing hypothyroidism treated with thyroid hormones (4.63 [95% confidence interval 4.40–4.85]), based on 565 incident users. The biggest population (n = 34,645) was found for angiotensin converting enzyme‐inhibitors potentially causing urinary tract infections treated with antibiotics. Regarding four potential ADRs, the aSRs were higher for people using multiple medications that cause the same ADR as compared to people using only one of those medications. Among older adults the aSRs remained significant for 37 prescribing cascades.ConclusionAn overview was generated of potentially problematic prescribing cascades relevant for clinical practice. These results can support healthcare providers to intervene and reduce medication burden for older adults.

Community pharmacists’ awareness, identification, and management of prescribing cascades: A cross-sectional survey

BackgroundPrescribing cascades can lead to unnecessary medication use, healthcare costs, and patient harm. Pharmacists oversee prescriptions from multiple prescribers and are well positioned to identify such cascades, making pharmacists key stakeholders to address them. ObjectivesTo evaluate community pharmacists’ awareness, identification, and management of prescribing cascades and to assess behavioural determinants that may be targeted in future strategies to minimise inappropriate prescribing cascades. MethodsAn online survey was developed using the Theoretical Domains Framework (TDF) and emailed to all registered community pharmacists in Ireland (n = 3775) in November 2021. Quantitative data were analysed using descriptive and inferential statistics. Free-text sections were given to capture reasons for non-resolution of identified prescribing cascades and suggestions to aid prescribing cascade identification and management; this text underwent content analysis. ResultsOf the 220 respondents, 51% were aware of the term ‘prescribing cascade’ before the survey, whilst 69% had identified a potentially inappropriate prescribing cascade in practice. Over one third were either slightly confident (26.4%) or not confident at all (10%) in their ability to identify potentially inappropriate prescribing cascades in patients' prescriptions before the survey, whilst 55.2% were concerned that patients were receiving prescribing cascades they had not identified. Most respondents wanted further information/training to help prescribing cascade identification (88.3%) and management (86.1%). Four predominant TDF domains identified were common to both i) influencing non-resolution of identified prescribing cascades and ii) in the suggestions to help identify and manage prescribing cascades: ‘Environmental Context and Resources’, ‘Social/Professional Role and Identity’, ‘Social Influences’ and ‘Memory, Attention and Decision Processes’. ConclusionsThere is a clear need to provide additional resources to help community pharmacists identify and manage prescribing cascades. These findings will support the development of theory-informed behaviour change strategies to aid the minimisation of inappropriate prescribing cascades and decrease the risk of medication-related harm for patients.

Which older adults are at highest risk of prescribing cascades? A national study of the gabapentinoid-loop diuretic cascade.

Prescribing cascades are important contributors to polypharmacy. Little is known about which older adults are at highest risk of experiencing prescribing cascades. We explored which older veterans are at highest risk of the gabapentinoid (including gabapentin and pregabalin)-loop diuretic (LD) cascade, given the dramatic increase in gabapentinoid prescribing in recent years. Using Veterans Affairs and Medicare claims data (2010-2019), we performed a prescription sequence symmetry analysis (PSSA) to assess loop diuretic initiation before and after gabapentinoid initiation among older veterans (≥66 years). To identify the cascade, we calculated the adjusted sequence ratio (aSR), which assesses the temporality of LD relative to gabapentinoid initiation. To explore high-risk groups, we used multivariable logistic regression with prescribing order modeled as a binary dependent variable. We calculated adjusted odds ratios (aORs), measuring the extent to which factors are associated with one prescribing order versus another. Of 151,442 veterans who initiated a gabapentinoid, there were 1,981 patients who initiated a LD within 6 months after initiating a gabapentinoid compared to 1,599 patients who initiated a LD within 6 months before initiating a gabapentinoid. In the gabapentinoid-LD group, the mean age was 73 years, 98% were male, 13% were Black, 5% were Hispanic, and 80% were White. Patients in each group were similar across patient and health utilization factors (standardized mean difference <0.10 for all comparisons). The aSR was 1.23 (95% CI: 1.13, 1.34), strongly suggesting the cascade's presence. People age ≥85 years were less likely to have the cascade (compared to 66-74 years; aOR 0.74, 95% CI: 0.56-0.96), and people taking ≥10 medications were more likely to have the cascade (compared to 0-4 drugs; aOR 1.39, 95% CI: 1.07-1.82). Among older adults, those who are younger and taking many medications may be at higher risk of the gabapentinoid-LD cascade, contributing to worsening polypharmacy and potential drug-related harms. We did not identify strong predictors of this cascade, suggesting that prescribing cascade prevention efforts should be widespread rather than focused on specific subgroups.

Prescribing cascades of antigout medications from thiazide diuretics in gout-naïve hypertensive adults receiving first-line pharmacological management

Prescribing cascade is a significant clinical problem but is often overlooked. We explore the incidence of the prescribing cascades of antigout medications related to thiazide treatment in gout-naïve hypertensive adults newly exposed to the pharmacological treatment. This population-based, retrospective cohort study used the Taiwan National Health Insurance Registry Database. Gout-naïve hypertensive adults who were newly dispensed first-line antihypertensive drugs between January 1, 2000, and December 31, 2016, were enrolled. Patients were divided into the thiazide group (n = 4192) and the non-thiazide group (n = 81,083). The non-thiazide group included patients who received an angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, calcium channel blocker, or beta-blocker. The study utilized propensity score matching and multivariable Cox regression models to investigate the prescribing cascade of antigout agents following antihypertensive treatment, adjusting for factors like age, sex, comorbidities, and concurrent medications. After propensity score matching, each group consisted of 4045 patients, with the thiazide group exhibiting a higher risk of being prescribed antigout medications across different time intervals post-treatment initiation. Specifically, adjusted hazard ratios (aHRs) for the thiazide group were 2.23, 2.07, and 2.41 for < 30 days, 31–180 days, and > 180 days, respectively, indicating a sustained and significant risk over time. Comparative analyses revealed thiazide diuretics were associated with a higher risk of antigout medication prescriptions compared to other antihypertensive classes, particularly evident after 180 days. Subgroup analyses across various demographics and comorbidities consistently showed an increased risk in the thiazide cohort. Gout-naïve hypertensive adults newly dispensed thiazide had a higher risk of subsequently adding antigout agents than those taking other first-line antihypertensive medications. The awareness and interruption of these prescribing cascades are critical to improving patient safety.

Dopaminergic Drugs and Valproate-associated Refractory Hyponatremia Over Levosulpiride-induced Parkinsonism in an Elderly Female Patient When Deprescribing was the Only Therapy

Prescribing cascade is a condition in which a drug administered to a patient causes an adverse reaction that is misinterpreted as a new condition, resulting in the addition of a new drug. Here, we report the case of an elderly female patient who suffered from metabolic, neurologic, and urinary consequences of a prescribing cascade of antiemetic, antiepileptic, and dopaminergic drugs. While levosulpiride caused Parkinsonian symptoms, the dopaminergic drugs and valproate caused refractory hyponatremia followed by altered sensorium, and clidinium contributed to urinary retention. The case highlights the need to be vigilant for adverse consequences of the prescribing cascade, especially for antiemetic drugs, such as levosulpiride, because of its propensity to induce extrapyramidal reactions in older patients. In cases of refractory hyponatremia, a trial of de-challenge of valproate and dopaminergic drugs should be considered. The identification and removal of the culprit drugs can rescue the patient from a disabling cycle of adverse drug reactions.

Evaluating Provider and Pharmacy Discordance in Potential Calcium Channel Blocker-Loop Diuretic Prescribing Cascade.

Prescribing cascades occur when a drug-induced adverse event is treated with a new medication. Identifying clinical scenarios in which prescribing cascades are more likely to occur may help determine ways to prevent prescribing cascades. To understand the extent to which discordant providers and discordant pharmacies contribute to the dihydropyridine calcium channel blocker (DH CCB)-loop diuretic prescribing cascade. A retrospective cohort study using Medicare Fee-For-Service data (2011-2018) of adults aged ≥ 66 years. Patients who initiated DH CCB with subsequent initiation of loop diuretic (DH CCB-loop diuretic dyad) within 90 days or patients who initiated angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) with subsequent initiation of a loop diuretic (ACEI/ARB-loop diuretic dyad; control). The primary outcomes were provider and pharmacy discordance for prescribing cascades and control drug pairs. Baseline clinical and socio-demographic characteristics were balanced using inverse probability of treatment weighting with propensity scores. Overall, we identified 1987 DH CCB-loop diuretic dyads and 3148 ACEI/ARB-loop diuretic dyads. Discordant providers occurred in 64% of DH CCB-loop diuretic dyads and 55% of ACEI/ARB-loop diuretic dyads, while discordant pharmacies occurred in 19% of DH CCB-loop diuretic dyads and 16% of ACEI/ARB-loop diuretic dyads. After adjustment, the risk of having discordant providers was 20% {Relative Risk (RR) 1.20 [95% confidence interval (CI), 1.14-1.26]} higher in the DH CCB-loop diuretic dyad compared with the ACEI/ARB-loop diuretic dyad. Moreover, pharmacy discordance was 17% (RR 1.17 [95% CI 1.02-1.33]) higher. Our findings suggest that discordant providers and discordant pharmacies were more commonly involved in the potentialprescribing cascade when compared with a similar control dyad of medications. Opportunities for enhanced care coordination and medication reconciliation should be explored to prevent unnecessary polypharmacy.

Investigation of geriatric syndromes associated with medication in Japan using insurance claims data.

Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible prescribing cascade rate among older outpatients eligible for Late-stage Elderly Health Insurance and elucidated the differences between GS and GS associated with medication (GSAM) trends. This retrospective study enrolled patients from health insurance claims data in Japan between October 2018 and March 2019; hospitalized patients were excluded. Two groups were identified among the participants with GS: GS (no use of GS-causing medications) and possible-GSAM (p-GSAM; use of GS-causing medications). The collected data were analyzed using the Bell Curve for Excel, and statistical significance was set at P < 0.05. In total, 137 781 outpatients were enrolled. Of the 32 259 outpatients who did not use GS-causing medications, 7342 were classified into the GS group. Among 105 522 outpatients who used GS-causing medications, 8347 were classified as having p-GSAM. The mean number of prescriptions was significantly higher in the p-GSAM group than in the GS group (P < 0.01). Furthermore, all GS symptoms showed significant differences, with impaired appetite being the most prevalent in the p-GSAM group than in the GS group (P < 0.01). A possible prescribing cascade was suspected in 2826 (33.9%) of 8347 outpatients in the p-GSAM group. Impaired appetite in patients taking GS-causing medications might lead to prescribing cascades. Further studies are needed to prevent such prescribing cascades. Geriatr Gerontol Int 2024; 24: 61-67.

Association of a calcium channel blocker and diuretic prescribing cascade with adverse events: A population-based cohort study.

Prescribing cascades occur when a drug adverse event is misinterpreted as a new medical condition and a second, potentially unnecessary drug, is prescribed to treat the adverse event. The population-level consequences of prescribing cascades remain unknown. This population-based cohort study used linked health administrative databases in Ontario, Canada. The study included community-dwelling adults, 66 years of age or older with hypertension and no history of heart failure (HF) or diuretic use in the prior year, newly dispensed a calcium channel blocker (CCB). Individuals subsequently dispensed a diuretic within 90 days of incident CCB dispensing were classified as the prescribing cascade group, and compared to those not dispensed a diuretic, classified as the non-prescribing cascade group. Those with and without a prescribing cascade were matched one-to-one on the propensity score and sex. The primary outcome was a serious adverse event (SAE), which was the composite of emergency room visits and hospitalizations in the 90-day follow-up period. We estimated hazard ratios (HRs) with 95% confidence intervals (CI) for SAE using an Andersen-Gill recurrent events regression model. Among 39,347 older adults with hypertension and no history of HF who were newly dispensed a CCB, 1881 (4.8%) had a new diuretic dispensed within 90 days after CCB initiation. Compared to the non-prescribing cascade group, those in the prescribing cascade group had higher rates of SAEs (HR: 1.21, 95% CI: 1.02-1.43). The CCB-diuretic prescribing cascade was associated with an increased rate of SAEs, suggesting harm beyond prescribing a second drug therapy. Our study raises awareness of the downstream impact of the CCB-diuretic prescribing cascade at a population level and provides an opportunity for clinicians who identify this prescribing cascade to review their patients' medications to determine if they can be optimized.

Modifiable Statin Characteristics Associated with Potential Statin-Related Prescribing Cascades.

Clinicians may prescribe new medications (marker drug) to treat statin-related (index drug) adverse events, constituting a prescribing cascade. We aimed to identify modifiable statin characteristics (intensity and individual statin agents) associated with lower risk of prescribing cascades to inform clinical decisions in the presence of statin-related adverse events. We conducted a secondary analysis based on our previous work, a high-throughput sequence symmetry analysis screening for potential statin-related prescribing cascades using MarketScan Commercial and Medicare Supplemental Insurance claims databases between 2005 and 2019. Among the previously identified 57 potential prescribing cascades, 42 statin-marker class dyad with a sample size of ≥ 500 were assessed in this study. Herein, we measured patients' baseline characteristics within -360 days of statin initiation and reported by modifiable statin characteristics. We also performed logistic regression and reported the adjusted odds ratios (aOR) with 95% confidence intervals (CIs) of modifiable statin characteristics after adjusting for baseline characteristics. We identified 1,307,867 statin initiators who met the study criteria (21% elderly, 52% female). Compared with patients initiating low-intensity statins, those initiating moderate- or high-intensity statins had significantly greater odds to develop 29 (69%) prescribing cascades, including antidiabetic drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors (aOR 1.22; 95% CI, 1.11-1.35) and glucagon-like peptide-1 (GLP-1) analogues (aOR 1.31; 95% CI, 1.16-1.47), and opioids (aOR 1.18; 95% CI, 1.13-1.23). Individual statin agent selection also had a differential effect on 34 (81%) of the prescribing cascades. For example, compared with simvastatin initiators, the probability of initiating osmotically-acting laxatives was significantly higher for lovastatin initiators (aOR 1.09; 95% CI, 1.03-1.15) and significantly lower in atorvastatin initiators (aOR 0.92; 95% CI, 0.89-0.94). Compared with low-intensity statins, high-intensity statins are associated with increased risk in many potential prescribing cascades, while the choice of individual statin agents affects the risk of prescribing cascades bidirectionally.

Abstract P106: High-throughput Sequence Symmetry Analysis To Detect Angiotensin-receptor Blockers (arb) Induced Prescribing Cascades.

Introduction: ARBs are considered first-line antiHTN therapy, but side effects may prompt additional therapy resulting in prescribing cascades. We sought to screen for potential ARB-induced prescribing cascades during real-world use via high-throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-for-service beneficiaries we identified new ARB users aged ≥66 years who had continuous enrollment for ≥360 days pre- and ≥180 days post-ARB initiation. We screened for initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of ARB initiation, generating sequence ratios (SRs) representing proportions of ARB initiators starting the marker class after, compared to before, the ARB. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs &gt;1 considered statistically significant. Results: We identified 278,586 ARB initiators (mean ± SD age, 76.3 ± 7.3 years; 63% women, 92% hypertension). Of 446 ‘marker’ classes studied, and excluding other antihypertensive classes, we discovered 49 statistically significant signals indicative of potential prescribing cascades. The 30 strongest prescribing cascade signals by aSR are summarized (Figure), and included iron trivalent medications and H. pylori treatments. Conclusion: We identified potential prescribing cascade signals reflecting known as well as potentially underrecognized ARB adverse events in this Medicare cohort. Future work is needed to assess biologic plausibility and determine impact of these cascades on patient outcomes.

Abstract P105: High-throughput Sequence Symmetry Analysis To Detect Angiotensin-converting Enzyme Inhibitors (acei) Induced Prescribing Cascades.

Introduction: ACEIs are the most commonly prescribed antiHTN drugs, but side effects may prompt additional therapy resulting in a prescribing cascade. We aimed to identify potential ACEI-induced prescribing cascades using high throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) national samples of Medicare FFS beneficiaries, we identified new ACEI users aged ≥66 y with continuous enrollment for ≥360 days pre- and ≥180 days post-ACEI initiation. We screened for initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of ACE initiation, generating sequence ratios (SRs) representing the proportions of ACEI initiators starting the marker class after, vs before, the ACEI. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs &gt;1 considered statistically significant. Results: We identified 297,410 ACEI initiators (mean ± SD age, 76.1 ± 7.5 y; 59% women, 88% HTN). Of 446 ‘marker’ classes studied, and excluding other antiHTN classes, we identified 110 statistically significant signals indicative of potential prescribing cascades. The 30 strongest prescribing cascade signals (by aSR) are summarized (Figure) and included decongestant nasal preparations and monoamine oxidase B inhibitors. Conclusion: We identified potential prescribing cascade signals reflecting known and possibly underrecognized ACEI adverse events in this Medicare cohort. Additional research is needed to determine impact of these cascades on patient outcomes.

Abstract P107: High-throughput Screening Detects Thiazide-induced Prescribing Cascades.

Introduction: Thiazide diuretics are effective but can cause adverse effects that prompt the use of additional therapy, i.e., a prescribing cascade. We aimed to identify potential thiazide-induced prescribing cascades using high throughput sequence symmetry analysis. Methods: Using claims from 5% (2011-15) and 15% (2016-20) samples of Medicare fee-for-service beneficiaries we identified new thiazide users aged ≥66 years who had continuous enrollment for ≥360 days pre- and ≥180 days post-thiazide initiation. We screened for the initiation of 446 other ‘marker’ drug classes (based on WHO Anatomical Therapeutic Classification level 4 codes) within ±90 days of thiazide initiation, generating sequence ratios (SRs) representing the proportion of thiazide initiators starting the marker class after, compared to before, the thiazide. Adjusted SRs (aSRs), accounting for prescribing trends over time, were calculated with 95% CIs &gt;1 suggesting a prescribing cascade signal. Results: We identified unique 189,971 thiazide initiators (mean ± SD age 76.2 ± 7.4 years, 66% women, 90% with hypertension). Among 446 ‘marker’ classes analyzed, we identified 21 statistically significant prescribing cascade signals (Figure). The 2 strongest prescribing cascade signals were carbohydrates and electrolyte solutions. Conclusion: Among 446 classes, we identified 21 possible prescribing cascades in our Medicare population, which may impact patient care outcomes. Further investigation is required to determine the biological plausibility of these signals.

EPH2 Using Drug Package Insert Data to Identify Statin-Related Prescribing Cascades - an Evaluation of Findings from Side Effect Resource (SIDER) and Commercial Claims Data

Statin-induced adverse events may prompt additional pharmacotherapy resulting in prescribing cascades. We previously performed untargeted prescribing cascade signal detection using high throughput sequence symmetry analysis (HTSSA), identifying 57 plausible prescribing cascades. However, this endeavor requires access to big data sources and significant computational efforts; false positives are common. We evaluated whether a targeted approach – using Side Effect Resource (SIDER), a public database containing pharmaceutical package inserts data – captures similar findings more efficiently.

High-throughput screening for prescribing cascades among real world statin initiators.

Statins are among the most prevalent medications prescribed and associated with adverse events that may prompt additional treatment (i.e., a prescribing cascade). No comprehensive assessment of statin-related prescribing cascades has been performed to our knowledge. We utilized sequence symmetry analysis to iteratively screen prescribing sequences of all therapeutic classes ("marker" classes) based on Level 4 Anatomical Therapeutic Chemical codes among adult statin initiators, using IBM Marketscan commercial and Medicare supplemental claims databases (2005-2019). Order of initiation and secular trend-adjusted sequence ratios were calculated for each statin-marker class dyad, among marker class initiators ±90 days of statin initiation. Among signals classified as prescribing cascades, we calculated naturalistic number needed to harm (NNTH) within 1 year as the inverse of the excess risk among exposed. We identified 2 265 519 statin initiators (mean ± SD age, 56.4 ± 12.0 years; 48.7% women; 7.5% with cardiovascular disease). Simvastatin (34.4% of statin initiators) and atorvastatin (33.9%) were the most commonly initiated statins. We identified 160 significant statin-marker class dyad signals, of which 35.6% (n=57) were classified as potential prescribing cascades. Of the top 25 strongest signals (lowest NNTH), 12 were classified as potential prescribing cascades, including osmotically acting laxatives (NNTH, 44, 95% CI 43-46), opioids + non-opioid combination analgesics (81, 95% CI 74-91), and first-generation cephalosporins (204, 95% CI 175-246). Using high-throughput sequence symmetry analysis screening, we identified previously known prescribing cascades as well as potentially new prescribing cascades based on known and unknown statin-related adverse events.

Understanding Prescribing Cascades: Evaluating Risks and its Management

Prescribing cascade occurs when an adverse drug event is misinterpreted as a new medical condition resulting in a new medication being prescribed to treat the adverse drug event. A simple example is prescription of a proton pump inhibitor(PPIs) to counteract the acid reflux caused by non-steroidal anti-inflammatory drugs(NSAIDs). An interconnection between polypharmacy and prescribing cascade is established where both have a direct influence on each other. Prescribing cascade can affect people of any age but has shown to frequently affect the elderly patients. Assessment tools include both simpler ways like effective communication, clinical process mapping, NO TEARS checklist and complex algorithms like the Screening Tool for Potentially Inappropriate Prescriptions (STOPP), Beers criteria, Medication Appropriateness Index. Identifying and disrupting the prescribing cascade is an important, feasible, and undervalued opportunity to improve patient drug safety.

ThinkCascades: A Tool for Identifying Clinically Important Prescribing Cascades Affecting Older People.

Background and ObjectivePrescribing cascades occur when a drug is prescribed to manage side effects of another drug, typically when a side effect is misinterpreted as a new condition. A consensus list of clinically important prescribing cascades that adversely affect older persons’ health (i.e., where risks of the prescribing cascade usually exceed benefits) was developed to help identify, prevent, and manage prescribing cascades.MethodsThree rounds of a modified Delphi process were conducted with a multidisciplinary panel of 38 clinicians from six countries with expertise in geriatric pharmacotherapy. The clinical importance of 139 prescribing cascades was assessed in Round 1. Cascades highly rated by ≥ 70% of panelists were included in subsequent rounds. Factors influencing ratings in Rounds 1 and 3 were categorized. After three Delphi rounds, highly rated prescribing cascades were reviewed by the study team to determine the final list of clinically important cascades consistent with potentially inappropriate prescribing.ResultsAfter three rounds, 13 prescribing cascades were highly rated by panelists. Following a study team review, the final tool includes nine clinically important prescribing cascades consistent with potentially inappropriate prescribing. Panelists reported that their ratings were influenced by many factors (e.g., how commonly they encountered the medications involved and the cascade itself, the severity of side effects, availability of alternatives). The relative importance of these factors in determining clinical importance varied by panelist.ConclusionsA nine-item consensus-based list of clinically important prescribing cascades, representing potentially inappropriate prescribing, was developed. Panelists’ decisions about what constituted a clinically important prescribing cascade were multi-factorial. This tool not only raises awareness about these cascades but will also help clinicians recognize these and other important prescribing cascades. This list contributes to the prevention and management of polypharmacy and medication-related harm in older people.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40266-022-00964-9.

"Kind of blurry": Deciphering clues to prevent, investigate and manage prescribing cascades.

BackgroundPrescribing cascades, where a medication is used to treat the side effect of another medication, contribute to polypharmacy and related morbidity. Little is known about clinicians’ and patients’ experiences with prescribing cascades. In this study, we explored why and how prescribing cascades occur across a variety of care settings and how they are managed.Methods and findingsThis descriptive qualitative study employed semi-structured interviews with older adults who may have experienced a prescribing cascade(s), their caregivers, and healthcare providers. Interviewees were recruited through physician referral from a Geriatric Day Hospital, two long-term care homes in Ottawa, Ontario, and through self-referral across Ontario, Canada. An inductive approach was used to code data and determine themes. Thirty-one interviews were conducted for ten unique patient cases. Some interviewees were involved in more than one case, resulting in 22 unique interviewees. Three themes were identified. First, recognition of prescribing cascades is linked to awareness of medication side effects. Second, investigation and management of prescribing cascades is simultaneous and iterative (rather than linear and sequential). Third, prevention of prescribing cascades requires intentional strategies to help people anticipate and recognize medication side effects. Difficulty with recruitment from both long-term care homes and through self-referral was the central limitation. This exemplifies challenges associated with studying a poorly recognized and underexplored phenomenon.ConclusionsIn order to better recognize, investigate and manage prescribing cascades, clinicians and patients need to know more about medication side effects; they need to ask ‘can this be caused by a drug?’ when signs and symptoms arise or worsen; and they need access to information about medication experiences to have benefit-risk discussions and make decisions about deprescribing. Approaches for raising public awareness of prescribing cascades should be trialed to raise the profile of this issue and facilitate continued exploration of the phenomenon.

Prescribing cascades: we see only what we look for, we look for only what we know.

Prescribing cascades are increasingly recognized since they were described in the mid-1990s. Cascades are more likely in older people with multimorbidity and associated polypharmacy where multiple medications can induce a variety of side effects that manifest with various non-specific symptoms that may be misidentified as new geriatric syndromes such as falls, dizziness and new-onset incontinence. Geriatricians encounter medication side effects frequently and will usually consider if an older patient presenting with new symptoms could be experiencing an adverse drug reaction or event. However, most medications prescribed to multimorbid older patients are initiated and continued by prescribers without specialist geriatric training who may not detect medication-induced morbidity. Therefore, novel approaches to the detection and management of prescribing cascades in older people are needed. Currently, the knowledge base surrounding prescribing cascades in older people is evolving towards better methods for cascade detection and secondary prevention. However, the large number of cascades described in the literature, the wide-ranging symptomatology of cascades and the rapidly increasing number of multimorbid older people at risk of cascades represent major challenges for prescribers. Furthermore, prospective prevalence studies of prescribing cascades in older people are lacking. To detect and correct prescribing cascades during routine medication review in multimorbid older people, awareness of cascades is essential. Prescribing cascade awareness in turn requires novel explicit ways of defining cascades to facilitate their rapid detection and correction during medication review. Given that prescribing cascades represent another aspect of inappropriate prescribing (IP), explicit cascades criteria should be integrated with other explicit IP criteria.

Evaluation of a Beta-Blocker-Edema-Loop Diuretic Prescribing Cascade: A Prescription Sequence Symmetry Analysis.

Drug-related adverse events associated with antihypertensive therapy may result in subsequent prescribing of other potentially harmful medications, known as prescribing cascades. The aim of this study was to assess the magnitude and characteristics of a beta-blocker-edema-loop diuretic prescribing cascade. A prescription sequence symmetry analysis was used to assess loop diuretic initiation before and after initiation of beta-blockers among patients 20 years or older without heart failure, atrial fibrillation, other arrythmias, or use of calcium channel blocker within a U.S. private insurance claims database (2005-2018). The temporality of loop diuretic initiation relative to a beta-blocker or negative control (renin-angiotensin system blocker) initiation was tabulated. Secular trend-adjusted sequence ratios (aSRs) with 95% confidence intervals (CIs) compared the initiation of loop diuretic 90 days before and after initiation of beta-blockers. Among 988,675 beta-blocker initiators, 9,489 patients initiated a new loop diuretic prescription 90 days after and 5,245 patients before beta-blocker initiation, resulting in an aSR of 1.78 (95% CI, 1.72-1.84). An estimated 1.72 beta-blocker initiators per 100 patient-years experienced the prescribing cascade in the first 90 days. The aSR was disproportionately higher among older adults (aSR 1.97), men (aSR 2.25), and patients who initiated metoprolol tartrate (aSR 2.48), labetalol (aSR 2.18), or metoprolol succinate (aSR 2.11). Negative control results (aSR 1.09, 95% CI, 1.05-1.13) generally corroborated our findings, but suggested modest within-person time-varying confounding. We observed excess use of loop diuretics following beta-blocker initiation that was only partially explained by secular trends or hypertension progression.

POSB399 Systematic Identification of Pharmacological Inefficiencies By a Value-Based Patient Drug Safety Program

To describe the results of the systematic identification of pharmacological inefficiencies through a value-based patient drug safety program. Descriptive observational study, conducted between August 2020 - May 2021, in patients diagnosed with high-cost chronic pathologies. The pharmacists systematically identified and resolved the potential inefficiencies associated with drugs. A univariate analysis was performed, with summary measures of central tendency and relative and cumulative frequencies. R Core Team statistical package (2019) was used. Further, the potential savings of wasteful spending health was calculated. 13768 patients were evaluated with a mean age of 59 years (SD:4), 65.0% were women. In 1.9% of the patients evaluated, 16503 inefficiencies associated with inappropriate medication use were identified and intervened. 51.7% corresponded to therapeutic duplications, 12.9% unneeded medication, 10.3% drug interactions, 8.1% overdosage, 8.0% incorrect medication, 4.6% chronification of treatment, 1.4% incorrect use frequency, 1.1% underdosing, 1.1% prescribing cascade, 0.5% contraindications and, 0.3% dose adjustment due to renal or hepatic failure. The acceptance rate of pharmaceutical management was 18%. The potential savings from pharmacist interventions was 452002.44 USD (50222 USD an average month). The value-based patient drug safety program allows the systematic identification and management of pharmacological inefficiencies, generating impact on clinical and economic Results: However, articulation between pharmacist-physician-insurer health is required to improve the effectiveness of the pharmacist intervention.