Systematic review of the impact of appropriate versus inappropriate initial antibiotic therapy on outcomes of patients with severe bacterial infections.

We investigated the impact of appropriate versus inappropriate initial antimicrobial therapy on the clinical outcomes of patients with severe bacterial infections as part of a systematic review and meta-analyses assessing the impact of delay in appropriate antimicrobial therapy. Literature searches of MEDLINE and Embase, conducted on 24 July 2018, identified studies published after 2007 reporting the impact of delay in appropriate antibiotic therapy for hospitalised adult patients with bacterial infections. Results were statistically pooled for outcomes including mortality, hospital length of stay (LOS) and treatment failure. Subgroup analyses were explored by site of infection where data permitted. Inclusion criteria were met by 145 studies, of which 114 reported data on the impact of appropriate versus inappropriate initial therapy. In the pooled analysis, rates of mortality were significantly in favour of appropriate therapy [odds ratio (OR) = 0.44, 95% CI 0.38-0.50]. Across eight studies, LOS was shorter with appropriate therapy compared with inappropriate therapy [mean difference (MD) -2.54 days (95% CI -5.30 to 0.23)], but not significantly so. The incidence of treatment failure was significantly lower in patients who received appropriate therapy compared with patients who received inappropriate therapy (six studies: OR = 0.33, 95% CI 0.16-0.66) as was mean hospital costs (four studies: MD -7.38 thousand US$ or Euros, 95% CI -14.14 to -0.62). Initiation of appropriate versus inappropriate antibiotics can reduce mortality, reduce treatment failure and decrease LOS, highlighting the importance of broad­spectrum empirical therapy and rapid diagnostics for early identification of the causative pathogen. [Study registration: PROSPERO: CRD42018104669].

Does potentially inappropriate prescribing predict an increased risk of admission to hospital and mortality? A longitudinal study of the 'oldest old'.

BACKGROUND: Potentially inappropriate prescribing (PIP) is associated with negative health outcomes, including hospitalisation and mortality. Life and Living in Advanced Age: a Cohort Study in New Zealand (LiLACS NZ) is a longitudinal study of Maori (the indigenous population of New Zealand) and non-Maori octogenarians. Health disparities between indigenous and non-indigenous populations are prevalent internationally and engagement of indigenous populations in health research is necessary to understand and address these disparities. Using LiLACS NZ data, this study reports the association of PIP with hospitalisations and mortality prospectively over 36-months follow-up. METHODS: PIP, from pharmacist applied criteria, was reported as potentially inappropriate medicines (PIMs) and potential prescribing omissions (PPOs). The association between PIP and hospitalisations (all-cause, cardiovascular disease-specific and ambulatory-sensitive) and mortality was determined throughout a series of 12-month follow-ups using binary logistic (hospitalisations) and Cox (mortality) regression analysis, reported as odds ratios (ORs) and hazard ratios (HRs), respectively, and the corresponding confidence intervals (CIs). RESULTS: Full demographic data were obtained for 267 Maori and 404 non-Maori at baseline, 178 Maori and 332 non-Maori at 12-months, and 122 Maori and 281 non-Maori at 24-months. The prevalence of any PIP (i.e. ≥1 PIM and/or PPO) was 66, 75 and 72% for Maori at baseline, 12-months and 24-months, respectively. In non-Maori, the prevalence of any PIP was 62, 71 and 73% at baseline, 12-months and 24-months, respectively. At each time-point, there were more PPOs than PIMs; at baseline Maori were exposed to a significantly greater proportion of PPOs compared to non-Maori (p = 0.02). In Maori: PPOs were associated with a 1.5-fold increase in hospitalisations and mortality. In non-Maori, PIMs were associated with a double risk of mortality. CONCLUSIONS: PIP was associated with an increased risk of hospitalisation and mortality in this cohort. Omissions appear more important for Maori in predicting hospitalisations, and PIMs were more important in non-Maori in predicting mortality. These results suggest understanding prescribing outcomes across and between population groups is needed and emphasises prescribing quality assessment is useful.

Deaths among opioid users: impact of potential inappropriate prescribing practices.

OBJECTIVES: To examine the association between potential inappropriate prescribing practices of opioids and deaths among opioid users in the Georgia Medicaid population. STUDY DESIGN: A retrospective analysis of individual pharmacy claims data from Georgia Medicaid from 2009 through 2014. METHODS: The sample was restricted to patients without cancer aged 18 to 64 years with an opioid prescription and included 3,562,227 observations representing 401,488 individuals. A descriptive analysis and a multivariate logistic regression analysis were conducted. RESULTS: Results indicate a total of 14,516 deaths among opioid users in the study sample, of whom approximately 42% experienced at least 1 incidence of potential inappropriate prescribing practices. Regression results indicate that the odds of opioid users experiencing death were 1.76 times higher for those who experienced at least 1 incidence of potential inappropriate prescribing practices of opioids compared with those who did not experience any incidence, even after controlling for other covariates (P <.001). Moreover, opioid users in managed care Medicaid were less likely to experience death compared with fee-for-service (FFS) enrollees. CONCLUSIONS: The results indicate a positive and statistically significant association between potential inappropriate opioid prescribing practices and deaths among opioid users in Georgia Medicaid, with FFS enrollees experiencing higher rates of death compared with managed care enrollees. Appropriate policies and interventions targeted at reducing potential inappropriate prescribing practices may help reduce the risk factors associated with mortality among opioid users in this population.

Opioid overdose deaths and potentially inappropriate opioid prescribing practices (PIP): A spatial epidemiological study.

INTRODUCTION: Opioid overdose deaths quintupled in Massachusetts between 2000 and 2016. Potentially inappropriate opioid prescribing practices (PIP) are associated with increases in overdoses. The purpose of this study was to conduct spatial epidemiological analyses of novel comprehensively linked data to identify overdose and PIP hotspots. METHODS: Sixteen administrative datasets, including prescription monitoring, medical claims, vital statistics, and medical examiner data, covering >98% of Massachusetts residents between 2011-2015, were linked in 2017 to better investigate the opioid epidemic. PIP was defined by six measures: ≥100 morphine milligram equivalents (MMEs), co-prescription of benzodiazepines and opioids, cash purchases of opioid prescriptions, opioid prescriptions without a recorded pain diagnosis, and opioid prescriptions through multiple prescribers or pharmacies. Using spatial autocorrelation and cluster analyses, overdose and PIP hotspots were identified among 538 ZIP codes. RESULTS: More than half of the adult population (n = 3,143,817, ages 18 and older) were prescribed opioids. Nearly all ZIP codes showed increasing rates of overdose over time. Overdose clusters were identified in Worcester, Northampton, Lee/Tyringham, Wareham/Bourne, Lynn, and Revere/Chelsea (Getis-Ord Gi*; p < 0.05). Large PIP clusters for ≥100 MMEs and prescription without pain diagnosis were identified in Western Massachusetts; and smaller clusters for multiple prescribers in Nantucket, Berkshire, and Hampden Counties (p < 0.05). Co-prescriptions and cash payment clusters were localized and nearly identical (p < 0.05). Overlap in PIP and overdose clusters was identified in Cape Cod and Berkshire County. However, we also found contradictory patterns in overdose and PIP hotspots. CONCLUSIONS: Overdose and PIP hotspots were identified, as well as regions where the two overlapped, and where they diverged. Results indicate that PIP clustering alone does not explain overdose clustering patterns. Our findings can inform public health policy decisions at the local level, which include a focus on PIP and misuse of heroin and fentanyl that aim to curb opioid overdoses.

Electronic assessment of cardiovascular potentially inappropriate medications in an administrative population database.

AIM: To explore the feasibility of the electronic assessment of potentially inappropriate medication (PIM) criteria in a large administrative database and to explore the validity of the cardiovascular subset of PIM criteria, by studying the association with relevant outcome. METHOD: A cohort study using administrative data from Stockholm County, Sweden (VAL database). Eligible for inclusion were community-dwelling older people (≥65 years), alive in Stockholm County on 31 December 2015. We applied PIM criteria pertaining to the cardiovascular medication group (first-level ATC C group), and we assessed the association between PIM use and mortality and hospitalisation. RESULTS: Patients' (n = 315 120) mean age was 74.0 years (range 65-114), and 54.7% were women. There were 111 cardiovascular PIM criteria in the repository, from which 44 were not registered or prescribed in our population. We excluded another 43 requiring information not available in the database, or duplicates, resulting in 24 applicable criteria. The prevalence of polypharmacy (≥ five medications) was 25.5% and the prevalence of at least one PIM use was 8.3%, including 2.8% underuse and 5.3% misuse. Patients with intake of ≥10 medications had 38% increased mortality risk compared to those with 0-4 medications. Unplanned hospitalisation and emergency department visits were positively associated with underuse (12% and 25%, respectively) and misuse (13% and 12%, respectively). CONCLUSION: It was feasible to select a subset of cardiovascular PIM criteria originating from different PIM lists and to apply this subset in an administrative database. Additionally, by applying this subset, we showed significant associations with clinical outcome.

Retrospective Observational Study from a Chinese Network of the Impact of Combination Therapy versus Monotherapy on Mortality from Carbapenem-Resistant Enterobacteriaceae Bacteremia.

Data for a total of 164 bloodstream infection cases due to carbapenem-resistant Enterobacteriaceae (CRE) from 2013 to 2017 were retrospectively collected from 36 tertiary hospitals in 19 provinces in China to evaluate the outcomes and risk factors for mortality by univariable and multivariable analysis. The most frequent infecting species was Klebsiella pneumoniae (69.5%, 114/164). The overall in-hospital and 14-day mortality rates were 32.9% (54/164) and 31.1% (42/135), respectively. Multivariable analysis revealed that septic shock (adjusted odds ratio [aOR], 6.339; 95% confidence interval [CI], 1.586 to 25.332; P = 0.009), the Pitt bacteremia score (aOR, 1.300; 95% CI, 1.009 to 1.676; P = 0.042), and the Charlson comorbidity index (aOR, 1.392; 95% CI, 1.104 to 1.755; P = 0.005) were independently associated with a hazard effect on mortality. Combination therapy, especially tigecycline-based combination therapy, resulted in relatively low rates of in-hospital mortality and failure in clearance of CRE infection. Survival analysis revealed that appropriate therapy was associated with a lower 14-day mortality rate than inappropriate therapy (including nonactive therapy; P = 0.022), that combination therapy was superior to monotherapy (P = 0.036), that metallo-ß-lactamase producers were associated with a lower 14-day mortality than strains without carbapenemases or KPC-2 producers (P = 0.009), and that strains with MICs of >8 mg/liter for meropenem were associated with a higher 14-day mortality rate than those with MICs of ≤8 mg/liter (P = 0.037). Collectively, the severity of illness, meropenem MICs of >8 mg/liter, and carbapenemase-producing types were associated with the clinical outcome. Early detection of the carbapenemase type and initiation of appropriate combination therapy within 96 h might be helpful for improving survival.

Methadone: Maximizing Safety and Efficacy for Pain Control in Patients with Cancer.

Methadone is a valuable opioid in the management of patients who have cancer with pain. Methadone is a mu-, kappa-, and delta-opioid agonist, and an N-methyl-D-aspartate receptor antagonist. These mechanisms of action make methadone an attractive option for complex pain syndromes. It is critically important that providers consider a patient's risk status before beginning methadone. Careful consideration must be given to dosing methadone in both opioid-naïve and opioid-tolerant patients, with vigilant monitoring for therapeutic effectiveness and potential toxicity until the patient achieves steady state.

Systematic Review of the Prevalence of Medication Errors Resulting in Hospitalization and Death of Nursing Home Residents.

Medication errors (MEs) result in preventable harm to nursing home (NH) residents and pose a significant financial burden. Institutionalized older people are particularly vulnerable because of various organizational and individual factors. This systematic review reports the prevalence of MEs leading to hospitalization and death in NH residents and the factors associated with risk of death and hospitalization. A systematic search was conducted of the relevant peer-reviewed research published between January 1, 2000, and October 1, 2015, in English, French, German, or Spanish examining serious outcomes of MEs in NHs residents. Eleven studies met the inclusion criteria and examined three types of MEs: all MEs (n = 5), transfer-related MEs (n = 5), and potentially inappropriate medications (PIMs) (n = 1). MEs were common, involving 16-27% of residents in studies examining all types of MEs and 13-31% of residents in studies examining transfer-related MEs, and 75% of residents were prescribed at least one PIM. That said, serious effects of MEs were surprisingly low and were reported in only a small proportion of errors (0-1% of MEs), with death being rare. Whether MEs resulting in serious outcomes are truly infrequent, or are underreported because of the difficulty in ascertaining them, remains to be elucidated to assist in designing safer systems.

State-level and system-level opioid prescribing policies: The impact on provider practices and overdose deaths, a systematic review.

OBJECTIVE: In response to persistent public health concerns regarding prescription opioids, many states and healthcare systems have implemented legislation and policies intended to regulate or guide opioid prescribing. The overall impact of these policies is still uncertain. The aim of this systematic review was to examine the existing evidence of provider-level and patient-level outcomes preimplementation and postimplementation of policies and legislation constructed to impact provider prescribing practices around opioid analgesics. DESIGN: A systematic search of MEDLINE, EMBASE, the Web of Science, and the Cochrane Database of Systematic Reviews was conducted to identify studies evaluating the impact of opioid prescribing policies on provider-level and patient-level outcomes. The systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Eleven studies were included in the review. A meta-analysis was not possible due to between-study heterogeneity. Six of the studies assessed state-level policies, and five were at the level of the healthcare system or hospital. Studies showed temporal associations between policy implementation and reductions in opioid prescribing, as well as opioid-related overdoses. Results were mixed regarding the impact of policies on misuse. The majority of the studies were judged to be of low quality based on the GRADE criteria. CONCLUSIONS: There is low to moderate quality evidence suggesting that the presence of opioid prescribing policy will reduce the amount and strength of opioid prescribed. The presence of these policies may impact the number of overdoses, but there is no clear evidence to suggest that it reduces opioid misuse.

The feasibility and effect of deprescribing in older adults on mortality and health: a systematic review and meta-analysis.

AIMS: Deprescribing is a suggested intervention to reverse the potential iatrogenic harms of inappropriate polypharmacy. The review aimed to determine whether or not deprescribing is a safe, effective and feasible intervention to modify mortality and health outcomes in older adults. METHODS: Specified databases were searched from inception to February 2015. Two researchers independently screened all retrieved articles for inclusion, assessed study quality and extracted data. Data were pooled using RevMan v5.3. Eligible studies included those where older adults had at least one medication deprescribed. The primary outcome was mortality. Secondary outcomes were adverse drug withdrawal events, psychological and physical health outcomes, quality of life, and medication usage (e.g. successful deprescribing, number of medications prescribed, potentially inappropriate medication use). RESULTS: A total of 132 papers met the inclusion criteria, which included 34 143 participants aged 73.8 ± 5.4 years. In nonrandomized studies, deprescribing polypharmacy was shown to significantly decrease mortality (OR 0.32, 95% CI: 0.17-0.60). However, this was not statistically significant in the randomized studies (OR 0.82, 95% CI 0.61-1.11). Subgroup analysis revealed patient-specific interventions to deprescribe demonstrated a significant reduction in mortality (OR 0.62, 95% CI 0.43-0.88). However, generalized educational programmes did not change mortality (OR 1.21, 95% CI 0.86-1.69). CONCLUSIONS: Although nonrandomized data suggested that deprescribing reduces mortality, deprescribing was not shown to alter mortality in randomized studies. Mortality was significantly reduced when applying patient-specific interventions to deprescribe in randomized studies.

Prescripción inapropiada de fármacos en personas mayores atendidas en un centro de Atención Primaria según los criterios STOPP-START / Inappropriate prescribing of drugs in older people attending primary care health centres: Detection using STOPP-START criteria

Objetivo. Conocer la prevalencia y características de prescripción inapropiada (PI) de los fármacos en los pacientes mayores de 65 años atendidos por un Equipo de Atención Primaria (EAP), utilizando los criterios STOPP-START. Material y método. Estudio transversal de muestra representativa de pacientes mayores de 65 años con historia activa en 2010, atendidos en 13 consultorios urbanos (muestreo sistemático aleatorizado; prevalencia esperada de PI del 40%; precisión: 5%; nivel de confianza: 95%). Se revisó la prescripción en las historias durante 2010, valorando los criterios STOPP-START. Resultados. Se seleccionaron 363 pacientes (56,7% mujeres); con una edad media de 75,2 años (DE: 7,02). Las enfermedades más frecuentes fueron cardiovascular (76,9%) y osteoarticular (57,6%), y el promedio de fármacos en prescripción crónica fue de 4,9 (DE: 3,32). Se detectó PI en 170 pacientes (46,8%, IC 95%: 41,7-52,0%), 42% en varones (IC 95%: 34,3-49,8%) y 46,6% en mujeres (IC 95%: 39,8-53,4%), sin diferencias entre sexos (p = 0,386) y con una mayor prevalencia si hay polimedicación o comorbilidad (p < 0,001). En cuanto al tipo de PI se cumplían criterios STOPP en 131 pacientes (36,1%, IC 95%: 31,1-41,0%) y START en 73 (20,1%, IC 95%: 16-24,2%), sin diferencias entre sexos (p = 0,623 para STOPP; p = 0,678 para START). Las PI STOPP más frecuentes se observan en indicadores del sistema musculoesquelético (50 pacientes: 38,2%, IC 95%: 29,8-46,5%) y las START en indicadores de endocrinología (38 pacientes: 52,1%, IC 95%: 40,0-63,9%). Conclusiones. La herramienta STOPP-START permite detectar y sistematizar la aplicación de criterios de PI en un porcentaje elevado de pacientes mayores atendidos por un EAP, pudiendo promover estrategias de mejora de la prescripción (AU)

ObjectiveTo determine the prevalence and characteristics of inappropriate prescribing of drugs (IP) in patients >65 years-old evaluated by a primary care team (PCT), using the STOPP-START criteria.Material and methodCross-sectional sample of patients older than 65 years-old with active clinical history in 2010, and who were attended in 13 urban clinics (systematic random sampling, expected IP prevalence of 40%, precision: 5% confidence level: 95%). Requirement was reviewed clinical histories in 2010, using the STOPP-START criteria.ResultsA total of 363 patients were selected (56.7% women), mean age 75.2 years (SD: 7.02). The most frequent diseases were cardiovascular (76.9%) and osteoarticular (57.6%) diseases, and the average number of prescription drugs was 4.9 (SD: 3.32). IP was detected in 170 patients (46.8%; 95% CI: 41.7-52.0%), 42% in men (95% CI: 34.3-49.8%) and 46.6% in women (95% CI: 39.8-53.4%), with no differences between sexes (P=.386), with a higher prevalence if polypharmacy or comorbidity were present (P<.001). The STOPP criteria were met in 131 patients (36.1%; 95% CI: 31.1-41.0%), and START criteria in 73 (20.1%; 95% CI: 16-24.2%), with no difference between sexes (P=.623 for STOPP, and P=.678 for START). The most frequent STOPP criteria were observed in the musculoskeletal system (50 patients, 38.2%; 95% CI: 29.8-46.5%) and START endocrinology indicators (38 patients, 52.1%; 95% CI: 40.0-63.9%).ConclusionsThe STOPP-START tool detected and systematised IP in a high percentage of elderly patients treated by a PCT, and can promote improvement in prescribing strategies (AU)

Impact of inappropriate empirical antibiotic therapy on outcome of bacteremic adults visiting the ED.

OBJECTIVES: To investigate the clinical impact of inappropriate empirical antibiotics on patient outcome and determine the risk factors for mortality in bacteremic adults who visited the emergency department (ED). METHODS: Bacteremic adults visiting the ED from January 2007 to June 2008 were identified retrospectively. Demographic characteristics, clinical conditions, bacteremic pathogens, antimicrobial agents, and outcomes were determined from chart records. RESULTS: The total of 454 eligible bacteremic adults were included in the analysis; excluded from the study were another 261 patients with contaminated blood cultures and 64 patients with ED stays of less than 24 hours. Among the included individuals, the mean age was 64.6 years, with a small predominance of males (230 patients, 50.7%). Of a total 494 bacteremic isolates, Escherichia coli (206, 41.7%) and Klebsiella species (81, 16.4%) were the most frequently encountered microorganisms. A lower 28-day mortality rate was demonstrated in bacteremic patients treated with appropriate antibiotics than that in those with inappropriate antibiotics or that in those with no antibiotic therapy, as judged by Kaplan-Meier survival curves (P = .01). Moreover, the differences among these three groups achieved higher significance (P = .002) in critically ill patients (Pittsburgh bacteremia scores of ≥ 4 points). In multivariate analyses, inappropriate antibiotic therapy in the ED was associated independently with mortality at 28 days (odds ratio, 2.26; 95% confidence interval, 1.01-5.13; P = .04). CONCLUSIONS: For bacteremic adults visiting the ED, their outcomes were favorable following appropriate antibiotics, compared to treatment with inappropriate antibiotics or no antibiotics.