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1.
BackgroundDrug shortages affect health systems worldwide. Research in community pharmacy has focused on the nature, extent and impact of these shortages on patients and pharmacists. However, pharmacists’ moral reasoning in situations of drug shortages has not been addressed.ObjectiveTo explore the moral reasoning perspectives of Dutch community pharmacists in situations of drug shortages.MethodAn electronic survey was developed around three drug shortage scenarios with a varying impact on patient outcomes: a Contraceptive, a Parkinson's and an Osteoporosis scenario. Pharmacists rated the likelihood of nine handling options and rated and ranked 13 considerations that may have played a role therein. The considerations represented three moral reasoning perspectives (MRPs): a business orientation (BO), a rules and regulations (RR), and a professional ethics (PE) MRP. Principle component analysis (PCA) was used to investigate construct validity of the MRPs. MRP rating and MRP ranking scores measured the relative importance of the different MRPs of pharmacists in the three shortages.ResultsResults from 267 Pharmacists were obtained. They reported mostly similar handling in the three shortages, except for the likelihood to make agreements with prescribers or other pharmacists and regarding the decision to import a product. The PCA analysis confirmed the three MRPs that accounted for 29% of variance in the data. Both the MRP rating and especially the MRP ranking scores indicated that PE-MRP considerations were most influential on pharmacists' intended handling of the shortages. In the Contraceptive and the Osteoporosis scenarios, the relative importance of a BO-MRP was higher than in the Parkinson's scenario.ConclusionPharmacists predominantly reason with a PE-MRP when handling drug shortages. However, this perspective can be compromised when the drug shortage is perceived to have a lower impact on patient outcomes and when alternative drugs or therapy are expensive.  相似文献   
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BackgroundThe aim of this population-based study was to determine the prognostic value of the histologic subtypes mucinous (MAC), non-mucinous (AC) and signet ring cell (SRCC) adenocarcinoma among patients with appendiceal cancer.Methods and materialsData from the Netherlands Cancer Registry (NCR) of patients with primary appendiceal adenocarcinomas with MAC, AC and SRCC histologic subtype, diagnosed between 2001 and 2015 were used (n = 675). To categorize patients according to the recent histopathological classification, the NCR was linked with the Dutch Pathology Registry (PALGA). Log-rank tests and Kaplan-Meier analyses were performed to estimate overall survival (OS), and the cox proportional hazards model was run to identify prognostic factors.ResultsAC was the most frequently encountered histologic subtype (50.9%), followed by MAC (35.8%) and SRCC (13.3%). In locoregional disease, histologic subtype was not a prognostic factor for OS with 5-year survival rates for patients with AC, MAC and SRCC of 60.0%, 60.5% and 69.6% respectively (p = 0.68). Metastatic disease was more common in SRCC (53.8%) than in MAC (38.8%) and AC (23.4%) (p < 0.0001). Median OS for patients with metastatic disease was 12.6, 27.7 and 18.2 months in AC, MAC and SRCC respectively (p < 0.005). MAC was associated with higher survival compared to AC (HR 0.48, 95%CI 0.34–0.69). In subanalyses, MAC was only a positive prognostic factor compared to AC in patients with peritoneal metastases (HR 0.42, 95%CI 0.28–0.62).ConclusionHistologic subtype had no prognostic relevance in locoregional or systemic metastatic disease in appendiceal adenocarcinoma. In peritoneal metastases, mucinous histologic subtype was a favorable prognostic factor, compared to non-mucinous and signet ring cell subtype.  相似文献   
3.

Purpose

Many authors suggest that extremity soft tissue sarcomas (ESTS) do not change significantly in size during preoperative radiation therapy (RT). This cone beam computed tomography study investigates the justification to deliver the entire course with 1 initial RT plan by observing anatomic changes during RT.

Methods and Materials

Between 2015 and 2017, 99 patients with ESTS were treated with either curative (n = 80) or palliative intent (n = 19) with a regimen of at least 6 fractions. The clinical target volume to planning target volume margin was 1 cm. Action levels were assigned by radiation technicians. An extremity contour change of >1 cm and/or tumor size change >0.5 cm required a physician's action before the next fraction.

Results

A total of 982 cone beam computed tomography logfiles were studied. In 41 of 99 patients, the dose coverage of the initial treatment plan was fully satisfactory throughout the RT course. However, action levels were observed in 58 patients (59%). In 41 of these 58 patients, a contour increase of 5 to 23 mm was noted (29 tumor size increase only, 3 extremity contour increase, and 9 both). In 21 of 58 patients, a decrease of 5 to 33 mm was observed (20 tumor size decrease only and 1 tumor size decrease and extremity contour decrease). In 4 cases, contours initially increased and subsequently decreased. In 33 of 41 patients with increasing contours, the dose distribution adequately covered gross tumor volume because of the 1 cm planning target volume margin applied. For the remaining 8 patients (8%), the plan needed to be adapted.

Conclusions

ESTS volumes may change substantially during RT in 59% of all patients, leading to plan adaptations resulting from increased volumes in 8%. Daily critical observation of these patients is mandatory to avoid geographic misses because of increases in size and overdosing of normal tissues when masses shrink.  相似文献   
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ObjectiveTo support decision-making in aortic valve replacement (AVR) in elderly patients, we provide a comprehensive overview of outcome after AVR with bioprostheses.MethodsA systematic review was conducted of studies reporting clinical outcome after AVR with bioprostheses in elderly patients (mean age ≥70 years; minimum age ≥65 years) published between January 1, 2000, to September 1, 2016. Reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risks.ResultsForty-two studies reporting on 34 patient cohorts were included, encompassing a total of 12,842 patients with 55,437 patient-years of follow-up (pooled mean follow-up 5.0 ± 3.3 years). Pooled mean age was 76.5 ± 5.5 years. Pooled early mortality risk was 5.42% (95% confidence interval [CI], 4.49-6.55), thromboembolism rate was 1.83%/year (95% CI, 1.28-3.61), and bleeding rate was 0.75%/year (95% CI, 0.50-1.11). Structural valve deterioration (SVD) was based on pooled time to SVD data (Gompertz; shape: 0.124, rate: 0.003). For a 75-year-old patient, this translated to an estimated life expectancy of 9.8 years (general population: 10.2 years) and lifetime risks of bleeding of 7%, thromboembolism of 17%, and reintervention of 9%.ConclusionsThe low risks of SVD and reintervention support the use of bioprostheses in elderly patients in need of AVR. The estimated life expectancy after AVR was comparable with the general population. The results of this study inform patients and clinicians about the expected outcomes after bioprosthetic AVR and thereby support treatment decision-making. Furthermore, our results can be used as a benchmark for long-term outcomes after transcatheter aortic valve implantation in patients who were eligible for surgery and other (future) alternative treatments (eg, tissue-engineered heart valves).  相似文献   
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Implantable motor cortex stimulation (iMCS) has been performed for >25 years to treat various intractable pain syndromes. Its effectiveness is highly variable and, although various studies revealed predictive variables, none of these were found repeatedly. This study uses neural network analysis (NNA) to identify predictive factors of iMCS treatment for intractable pain. A systematic review provided a database of patient data on an individual level of patients who underwent iMCS to treat refractory pain between 1991 and 2017. Responders were defined as patients with a pain relief of >40% as measured by a numerical rating scale (NRS) score. NNA was carried out to predict the outcome of iMCS and to identify predictive factors that impacted the outcome of iMCS. The outcome prediction value of the NNA was expressed as the mean accuracy, sensitivity, and specificity. The NNA furthermore provided the mean weight of predictive variables, which shows the impact of the predictive variable on the prediction. The mean weight was converted into the mean relative influence (M), a value that varies between 0 and 100%. A total of 358 patients were included (202 males [56.4%]; mean age, 54.2 ±13.3 years), 201 of whom were responders to iMCS. NNA had a mean accuracy of 66.3% and a sensitivity and specificity of 69.8% and 69.4%, respectively. NNA further identified 6 predictive variables that had a relatively high M: 1) the sex of the patient (M = 19.7%); 2) the origin of the lesion (M = 15.1%); 3) the preoperative numerical rating scale score (M = 9.2%); 4) preoperative use of repetitive transcranial magnetic stimulation (M = 7.3%); 5) preoperative intake of opioids (M = 7.1%); and 6) the follow-up period (M = 13.1%). The results from the present study show that these 6 predictive variables influence the outcome of iMCS and that, based on these variables, a fair prediction model can be built to predict outcome after iMCS surgery.PerspectiveThe presented NNA analyzed the functioning of computational models and modeled nonlinear statistical data. Based on this NNA, 6 predictive variables were identified that are suggested to be of importance in the improvement of future iMCS to treat chronic pain.  相似文献   
9.
AimsTo compare microvascular and macrovascular complication rates among Ghanaians with type 2 diabetes (T2D) living in Ghana and in three European cities (Amsterdam, London and Berlin).MethodsData from the multicenter Research on Obesity and Diabetes among African Migrants (RODAM) study were analyzed. 650 Ghanaian participants with T2D (206 non-migrant and 444 migrants) were included. Logistic regression analyses were used to determine the association between migrant status and microvascular (nephropathy and retinopathy) and macrovascular (coronary artery disease (CAD), peripheral artery disease (PAD) and stroke) complications with adjustment for age, gender, socioeconomic status, alcohol, smoking, physical activity, hypertension, BMI, total-cholesterol, and HbA1c.ResultsMicrovascular and macrovascular complications rates were higher in non-migrant Ghanaians than in migrant Ghanaians (nephropathy 32.0% vs. 19.8%; PAD 11.2% vs. 3.4%; CAD 18.4% vs. 8.3%; and stroke 14.5% vs. 5.6%), except for self-reported retinopathy (11.0% vs. 21.6%). Except nephropathy and stroke, the differences persisted after adjustment for the above-mentioned covariates: PAD (OR 7.48; 95% CI, 2.16–25.90); CAD (2.32; 1.09–4.93); and retinopathy (0.23; 0.07–0.75).ConclusionsExcept retinopathy, the rates of microvascular and macrovascular complications were higher in non-migrant than in migrant Ghanaians with T2D. Conventional cardiovascular risk factors did not explain the differences except for nephropathy and stroke.  相似文献   
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