Hospital physicians' and older patients' agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting

OBJECTIVE: To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. METHODS: This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. RESULTS: 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9-14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30-50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients' reluctance to discontinue or initiate medication. CONCLUSION: Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations. CLINICAL TRIAL REGISTRATION: Trial Registration Number NCT02986425

Fibrinogen and fibrin are novel substrates for Fasciola hepatica cathepsin L peptidases

Cathepsin peptidases form a major component of the secreted proteins of the blood-feeding trematodes Fasciola hepatica and Schistosoma mansoni. These peptidases fulfill many functions, from facilitating infection to feeding and immune evasion. In this study, we examined the Fasciola cathepsin L peptidases FhCL1, FhCL2, and FhCL3 and the schistosomal cathepsin peptidases SmCB1 and SmCL3 for their anticoagulant properties. Although no direct anticoagulant effect of these peptidases was observed, we discovered that cathepsin peptidases from Fasciola, but not from Schistosoma, were able to degrade purified fibrinogen, with FhCL1 having the highest fibrinogenolytic activity. Additionally, FhCL1 and FhCL2 both efficiently degraded fibrin. The lack of a direct anticoagulant or fibrinolytic effect of these peptidases is explained by their inhibition by plasma components. However, within the parasite gut, high concentrations of these peptidases could induce an anticoagulant environment, facilitating blood-feeding for extended periods

Fibrinogen and fibrin are novel substrates for Fasciola hepatica cathepsin L peptidases

Cathepsin peptidases form a major component of the secreted proteins of the blood-feeding trematodes Fasciola hepatica and Schistosoma mansoni. These peptidases fulfill many functions, from facilitating infection to feeding and immune evasion. In this study, we examined the Fasciola cathepsin L peptidases FhCL1, FhCL2, and FhCL3 and the schistosomal cathepsin peptidases SmCB1 and SmCL3 for their anticoagulant properties. Although no direct anticoagulant effect of these peptidases was observed, we discovered that cathepsin peptidases from Fasciola, but not from Schistosoma, were able to degrade purified fibrinogen, with FhCL1 having the highest fibrinogenolytic activity. Additionally, FhCL1 and FhCL2 both efficiently degraded fibrin. The lack of a direct anticoagulant or fibrinolytic effect of these peptidases is explained by their inhibition by plasma components. However, within the parasite gut, high concentrations of these peptidases could induce an anticoagulant environment, facilitating blood-feeding for extended periods

Hospital physicians’ and older patients’ agreement with individualised STOPP/START-based medication optimisation recommendations in a clinical trial setting

Objective To evaluate the agreement of hospital physicians and older patients with individualised STOPP/START-based medication optimisation recommendations from a pharmacotherapy team. Methods This study was embedded within a large European, multicentre, cluster randomised controlled trial examining the effect of a structured medication review on drug-related hospital admissions in multimorbid (≥ 3 chronic conditions) older people (≥ 70 years) with polypharmacy (≥ 5 chronic medications), called OPERAM. Data from the Dutch intervention arm of this trial were used for this study. Medication review was performed jointly by a physician and pharmacist (i.e. pharmacotherapy team) supported by a Clinical Decision Support System with integrated STOPP/START criteria. Individualised STOPP/START-based medication optimisation recommendations were discussed with patients and attending hospital physicians. Results 139 patients were included, mean (SD) age 78.3 (5.1) years, 47% male and median (IQR) number of medications at admission 11 (9–14). In total, 371 recommendations were discussed with patients and physicians, overall agreement was 61.6% for STOPP and 60.7% for START recommendations. Highest agreement was found for initiation of osteoporosis agents and discontinuation of proton pump inhibitors (both 74%). Factors associated with higher agreement in multivariate analysis were: female gender (+ 17.1% [3.7; 30.4]), ≥ 1 falls in the past year (+ 15.0% [1.5; 28.5]) and renal impairment i.e. eGFR 30–50 ml/min/1.73 m2; (+ 18.0% [2.0; 34.0]). The main reason for disagreement (40%) was patients’ reluctance to discontinue or initiate medication. Conclusion Better patient and physician education regarding the benefit/risk balance of pharmacotherapy, in addition to more precise and up-to-date medical records to avoid irrelevant recommendations, will likely result in higher adherence with future pharmacotherapy optimisation recommendations

Frequency and Acceptance of Clinical Decision Support System-Generated STOPP/START Signals for Hospitalised Older Patients with Polypharmacy and Multimorbidity

BACKGROUND: The Screening Tool of Older Persons' Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) instrument is used to evaluate the appropriateness of medication in older people. STOPP/START criteria have been converted into software algorithms and implemented in a clinical decision support system (CDSS) to facilitate their use in clinical practice. OBJECTIVE: Our objective was to determine the frequency of CDSS-generated STOPP/START signals and their subsequent acceptance by a pharmacotherapy team in a hospital setting. DESIGN AND METHODS: Hospitalised older patients with polypharmacy and multimorbidity allocated to the intervention arm of the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial underwent a CDSS-assisted structured medication review in four European hospitals. We evaluated the frequency of CDSS-generated STOPP/START signals and the subsequent acceptance of these signals by a trained pharmacotherapy team consisting of a physician and pharmacist after evaluation of clinical applicability to the individual patient, prior to discussing pharmacotherapy optimisation recommendations with the patient and attending physicians. Multivariate linear regression analysis was used to investigate potential patient-related (e.g. age, number of co-morbidities and medications) and setting-related (e.g. ward type, country of inclusion) determinants for acceptance of STOPP and START signals. RESULTS: In 819/826 (99%) of the patients, at least one STOPP/START signal was generated using a set of 110 algorithms based on STOPP/START v2 criteria. Overall, 39% of the 5080 signals were accepted by the pharmacotherapy team. There was a high variability in the frequency and the subsequent acceptance of the individual STOPP/START criteria. The acceptance ranged from 2.5 to 75.8% for the top ten most frequently generated STOPP and START signals. The signal to stop a drug without a clinical indication was most frequently generated (28%), with more than half of the signals accepted (54%). No difference in mean acceptance of STOPP versus START signals was found. In multivariate analysis, most patient-related determinants did not predict acceptance, although the acceptance of START signals increased in patients with one or more hospital admissions (+ 7.9; 95% confidence interval [CI] 1.6-14.1) or one or more falls in the previous year (+ 7.1; 95% CI 0.7-13.4). A higher number of co-morbidities was associated with lower acceptance of STOPP (- 11.8%; 95% CI - 19.2 to - 4.5) and START (- 11.0%; 95% CI - 19.4 to - 2.6) signals for patients with more than nine and between seven and nine co-morbidities, respectively. For setting-related determinants, the acceptance differed significantly between the participating trial sites. Compared with Switzerland, the acceptance was higher in Ireland (STOPP: + 26.8%; 95% CI 16.8-36.7; START: + 31.1%; 95% CI 18.2-44.0) and in the Netherlands (STOPP: + 14.7%; 95% CI 7.8-21.7). Admission to a surgical ward was positively associated with acceptance of STOPP signals (+ 10.3%; 95% CI 3.8-16.8). CONCLUSION: The involvement of an expert team in translating population-based CDSS signals to individual patients is essential, as more than half of the signals for potential overuse, underuse, and misuse were not deemed clinically appropriate in a hospital setting. Patient-related potential determinants were poor predictors of acceptance. Future research investigating factors that affect patients' and physicians' agreement with medication changes recommended by expert teams may provide further insight for implementation in clinical practice. REGISTRATION: ClinicalTrials.gov Identifier: NCT02986425

Frequency and Acceptance of Clinical Decision Support System-Generated STOPP/START Signals for Hospitalised Older Patients with Polypharmacy and Multimorbidity

Background The Screening Tool of Older Persons’ Prescriptions (STOPP)/Screening Tool to Alert to Right Treatment (START) instrument is used to evaluate the appropriateness of medication in older people. STOPP/START criteria have been converted into software algorithms and implemented in a clinical decision support system (CDSS) to facilitate their use in clinical practice. Objective Our objective was to determine the frequency of CDSS-generated STOPP/START signals and their subsequent acceptance by a pharmacotherapy team in a hospital setting. Design and Methods Hospitalised older patients with polypharmacy and multimorbidity allocated to the intervention arm of the OPERAM (OPtimising thERapy to prevent Avoidable hospital admissions in the Multimorbid elderly) trial underwent a CDSS-assisted structured medication review in four European hospitals. We evaluated the frequency of CDSS-generated STOPP/START signals and the subsequent acceptance of these signals by a trained pharmacotherapy team consisting of a physician and pharmacist after evaluation of clinical applicability to the individual patient, prior to discussing pharmacotherapy optimisation recommendations with the patient and attending physicians. Multivariate linear regression analysis was used to investigate potential patient-related (e.g. age, number of co-morbidities and medications) and setting-related (e.g. ward type, country of inclusion) determinants for acceptance of STOPP and START signals

Efeitos do AEB conjugado e do Bionator no tratamento da Classe II, 1ª divisão Treatment effects of maxillary splint and Bionator appliances in the treatment of Class II division 1 malocclusion

Este estudo cefalométrico objetivou avaliar as alterações dentárias e esqueléticas, em jovens com má oclusão de Classe II, 1ª divisão, tratados com o aparelho extrabucal conjugado (splint maxilar) e com o Bionator. Estes dois grupos experimentais foram comparados a um grupo de jovens portadores da mesma má oclusão que não receberam tratamento, pareados pelo gênero, idade, tempo de observação e grandezas cefalométricas iniciais. A amostra constou de 180 telerradiografias em norma lateral de 90 jovens, divididos em três grupos de 30, sendo 15 do gênero masculino e 15 do feminino. Os jovens do grupo 1 foram mantidos como controle e apresentaram uma idade inicial média de 10,02 anos e foram observados pelo período médio de 1,49 anos. O grupo 2 foi submetido ao tratamento utilizando o aparelho extrabucal conjugado (splint maxilar), com idade inicial média de 10,02 anos e tempo de observação de 1,78 anos. O grupo 3 foi tratado com o Bionator por um tempo médio de 1,52 anos e os jovens apresentavam idade inicial média de 10,35 anos. A análise dos resultados mostrou que o tratamento da má oclusão de Classe II, 1ª divisão com o AEB conjugado e com o Bionator resultou de efeitos específicos e inerentes a cada aparelho. Os resultados patentearam que o deslocamento anterior da maxila foi restringido significantemente pelo tratamento com o AEB conjugado. O Bionator promoveu um aumento significante na protrusão mandibular, enquanto que o AEB conjugado mostrou efeitos esqueléticos menos evidentes. No entanto, ambos aparelhos estudados produziram um aumento nos comprimentos efetivo e do corpo da mandíbula, com valores maiores para o grupo 2. A relação maxilo-mandibular melhorou significantemente nos grupos tratados em comparação ao grupo controle. A análise do padrão de crescimento craniofacial e das alturas faciais não revelou alteração significante entre os grupos. Em relação às alterações dentoalveolares ambos aparelhos provocaram inclinação para lingual e retrusão dos incisivos superiores, porém os efeitos do AEB conjugado foram significantemente mais intensos. Os incisivos inferiores foram afetados de maneira distinta pelos aparelhos. No grupo tratado com o AEB conjugado, os incisivos lingualizaram e retruíram enquanto que o grupo tratado com o Bionator apresentou inclinação para vestibular e protrusão destes dentes. Os molares inferiores apresentaram um maior desenvolvimento vertical e horizontal nos grupos 2 e 3. Os primeiros molares superiores distalizaram no grupo tratado com o AEB conjugado, enquanto nos grupos 3 (Bionator) e controle houve mesialização. Deste modo, verificou-se que ambos os protocolos de tratamento propiciaram alterações esqueléticas, dentárias e tegumentares, distintas e clinicamente relevantes para a correção da má oclusão de Classe II, 1ª divisão.<br>The purpose of this investigation was to evaluate and compare the cephalometric changes of maxillary splint and bionator appliances on individuals with Class II, division 1 malocclusion. Lateral cephalograms were available for 90 patients of both sex, divided in three groups of 30 each one. The first group served as a control group, with initial mean age of 10.02 years. The second group was treated with maxillary splint appliance with initial mean age of 10.02 years. The group 3 was treated with Bionator appliance with initial mean age of 10.35 years. The lateral cephalometric headfilms were taken of each patient at the beginning and the end of treatment, in a total of 180 headfilms. The cephalometric variables were analyzed with statistical tests. The results showed that only maxillary splint influenced changes in forward growth of the maxilla and Bionator appliances provides a statistically significant increase in mandibular protrusion. However, it was observed that both appliances provides an increase in total mandibular and body length, with greater values in group 2, but these results do not showed statistically differences. This study indicated that both appliances provide an improvement in the maxillomandibular relationship, compared to the control group. In addition, there were no statistically significant differences in the craniofacial growth pattern among the three groups nor in the facial heights. It was observed that both appliances produced lingual inclination and retrusion of the upper incisors. Maxillary splint provided lingual tipping of the lower incisors while Bionator produced labial tipping and protrusion of these teeth. The lower molars showed a greater vertical development and extrusion in experimental groups. The maxillary splint produced distal movement of the first upper molars and bionator showed mesial inclination