Does the Duration of Perioperative Antibiotic Prophylaxis Influence the Incidence of Postoperative Surgical-Site Infections in Implant-Based Breast Reconstruction in Women with Breast Cancer? A Retrospective Study.

BACKGROUND: Perioperative antibiotic prophylaxis is an established concept to reduce the risk of surgical-site infections; however, the optimal treatment duration in prosthetic breast reconstruction is still controversial. This study evaluated a potential association between the perioperative antibiotic prophylaxis duration (≤24 hours versus >24 hours) and incidence of postoperative surgical-site infections in immediate implant-based breast reconstruction in breast cancer patients. METHODS: A descriptive, retrospective analysis of surgical-site infections after immediate implant-based breast reconstruction in breast cancer patients between January of 2011 and December of 2018 was performed. The incidence of postoperative surgical-site infections in patients with more than 24 hours of perioperative antibiotic prophylaxis was compared to patients treated for 24 hours or less. RESULTS: A total of 240 patients who met criteria were included. There were no relevant epidemiologic, clinical, or histopathologic differences between groups. Surgical-site infections as defined by the Centers for Disease Control and Prevention criteria occurred in 25.8 percent. A risk factor-adjusted analysis by a prespecified multiple logistic regression model showed that 24 hours or less of perioperative antibiotic prophylaxis was not inferior to treatment for more than 24 hours. The upper limit of the one-sided 95 percent confidence interval of the risk difference was 9.4 percent (below the prespecified noninferiority margin of 10 percent leading to statistical significance). Risk factors for a surgical-site infection included obesity and postoperative wound complications. CONCLUSIONS: The study found no association between short-course perioperative antibiotic prophylaxis (≤24 hours) and an increased rate of postoperative surgical-site infection. This is of high clinical relevance because short-course treatment can help reduce side effects and the emergence of antimicrobial resistance and prevent surgical-site infections as effectively as a prolonged perioperative antibiotic prophylaxis course. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Clinical pharmacists' interventions across German hospitals: results from a repetitive cross-sectional study.

Background Pharmacists' interventions (PI) are suitable to improve medication safety and optimise patient outcome. However, in Germany, clinical pharmacy services are not yet available nationwide. Aim To gain prospective data on the extent and the composition of routine PI with special focus on intervention rates among German hospital pharmacists during two intervention weeks. Methods Within a repetitive cross-sectional study, clinical pharmacists documented all PIs on five days during a one-month period (intervention week) in 2017 and 2019 using the validated online-database ADKA-DokuPIK. Additionally, data regarding the supply structure/level of medical care, the extent of clinical pharmacy services and their professional experience were collected. All data were anonymised before analysis. Results In total, 2,282 PI from 62 pharmacists (2017) and 2578 PI from 52 pharmacists (2019) were entered. Intervention rate increased from 27.5 PI/100 patient days in 2017 to 38.5 PI/100 patient days in 2019 (p = 0.0097). Frequency of clinical pharmacy services on a daily basis significantly increased from 60% (2017) to 83% (2019). Reasons for PIs from the categories "drugs" (e.g. indication, choice, documentation/transcription) and "dose" were most common in both intervention weeks. The vast majority of underlying medication errors in both intervention weeks were categorised as "error, no harm" (80.3 vs. 78.6%), while the proportion of errors which did not reach the patient, doubled to 39.8% in IW-2019. Conclusion Regular and daily clinical pharmacy services become more established in Germany and clinical pharmacists are increasingly involved in solving drug related problems proactively and early during the medication management process.

Prospective survey-based study on the categorization quality of hospital pharmacists' interventions using DokuPIK.

Background There is a growing need to categorize pharmacists' interventions (PIs) in Germany to document their impact on solving or avoiding drug-related problems. Objective To validate the categorization of drug-related problems-one aspect of the categorical internet database DokuPIK, designed for recording routinely PIs. To identify case-specific predictive values. Setting German hospitals. Methods Within a prospective, nationwide survey-based study, 37 of 498 registered database users volunteered to evaluate 24 standardized case reports independently. Case evaluation was restricted to classify problems, based on 26 given categories with no limit on the number of item choices. Ratings were conducted electronically and anonymously. A gold standard of one or more problems per case was developed by majority consensus of five senior clinical pharmacists. Agreement of raters' case classification with the gold standard was assessed by calculating sensitivity, specificity and positive and negative predictive value and was reported as median and range. Main outcome Level of agreement. Results Independent assessment yielded a median agreement of 90% [79-94%]. Sensitivity and specificity were 37% [21-57%] and 99% [97-100%], respectively. Median positive and negative predicted value were both 90% [60-100%] and 90% [78-95%]. Mean case-specific agreement was robust (≥ 79%) with respect to a majority and maximum consensus (three and five out of five raters). Conclusion DokuPIK seems to have a high level of agreement and a good specificity according to the majority of clinical pharmacists in a panel of assessors. Despite the allowance of multiple choices, predictive values were high and indicated a well-constructed classification by pharmacists.

Nationwide evaluation of day-to-day clinical pharmacists' interventions in German hospitals.

STUDY OBJECTIVE: To describe and evaluate the extent and diversity of nationwide data from clinical pharmacists' interventions (PIs) in German hospitals. DESIGN: Retrospective analysis. DATA SOURCE: The ADKA-DokuPIK German database, a national anonymous self-reported Internet-based documentation system for routine PIs as well as for medication errors reported by German hospital pharmacists. MEASUREMENTS AND MAIN RESULTS: Data sets from ADKA-DokuPIK entered between January 2009 and December 2012 were analyzed descriptively. A total of 27,610 PIs were entered, mainly by ward-based clinical pharmacists (82.5%). Most of the PIs were performed on surgical wards (37.8%), followed by anesthesiology/intensive care unit/intermediate care unit and internal medicine. The most prevalent therapeutic subgroup that was the trigger for the PIs was antibacterials for systemic use (13.9%), followed by antithrombotic agents, analgesics, drugs for acid-related disorders, and agents acting on the renin-angiotensin system. About a quarter of interventions (23.4%) were performed due to inappropriate use of drugs, followed by use of a wrong dose or administration interval (22.1%), resulting in the most frequently taken actions of change of dose, change of drug, and drug stopped/paused (withheld). Altogether, the implementation rate of the PIs was 85.5%. Underlying medication errors were predominantly classified as "error, no harm" according to the National Coordinating Council for Medication Error Reporting and Prevention. CONCLUSION: For the first time in a European country, our findings show the scope of clinical pharmacist involvement in patient care in daily clinical practice and demonstrate the usefulness and importance of their proactive interventions in the prevention of hazards and risks for hospital inpatients.

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care--an observational analysis on non-small-cell lung cancer patients.

PURPOSE: To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective. RESULTS: A total of 120 consecutive NSCLC patients (mean age, 63.0 ± 8.4 (SD) years; men, 64.2%; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3%; tumour stage III/IV, 85%; history of comorbidity, 93.3%) receiving 130 CT lines were evaluated. 80% of CT lines were associated with grade 3 or 4 ADRs, 22.3% developed potential life-threatening complications, 77.7% were associated with at least one hospital stay (inpatient, 63.9%; outpatient/day clinic 39.2%, ICU 6.9%), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25% of total expenses (€109,861 out of €437,580). CONCLUSIONS: In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.

Blood component use and associated costs after standard dose chemotherapy--a prospective analysis of routine hospital care in lymphoproliferative disorders and NSCLC in Germany.

PURPOSE: The purpose of this study was to describe blood component (BC) use and respective cost after standard dose chemotherapy (CT) in routine hospital care. METHODS: Analysis of data from a prospective, multicenter, longitudinal, observational study on lymphoproliferative disorder (LPD) and non-small cell lung cancer (NSCLC) patients undergoing first or second line standard dose (immuno-)CT. Data were collected from patient interviews and pre-planned chart reviews. Costs of BC are presented from provider perspective. RESULTS: One hundred eighty patients (n = 85 NSCLC, n = 95 LPD) receiving 189 CT lines/633 CT cycles) were evaluable (mean ± SD age, 59 ± 13.2 years, 68% stage III/IV, 14% Eastern Cooperative Oncology Group ≥ 2). During 11% of cycles, BC were transfused to 27% of patients (n = 49; n = 22 NSCLC, n = 27 LPD). Of 310 transfused units (TU), 68% were red blood cells (RBC). Mean number of TU per cycle with transfusion was 3.3 ± 2.9 (median = 2, range = 2-17) for RBC, 4.8 ± 6.8 (median = 2, range = 1-23) for platelets (PLT) and 12.8 ± 14.6 (median = 8, range = 2-33) for fresh frozen plasma (FFP). Fifteen per cent of RBC units, 60% of PLT units and 92% of FFP in this study were transfused in cycles with sepsis. Mean BC cost per CT line were euro 602 ± 1,458 (median = 135, range = 135-9,385; NSCLC: euro 292 ± 376, median = 135, range = 135-2,124; LPD: euro 1,010 ± 2,137, median = 212, range = 135-9,385, p = 0.2137). For 55% of transfused RBC units, haemoglobin levels on the day of transfusion were 8.0-8.9 g/dl, for 38% <8 g/dl and for 7% ≥ 9 g/dl. Seventy-five per cent of PLT units were transfused at a PLT count <11,000/µl and 21% at 20,000-11,000/µl. CONCLUSIONS: The results reflect the diversity of BC use after standard dose CT. High transfusion need is associated with infectious complications, i.e. sepsis emphasising the need for adequate prophylaxis and further knowledge of baseline risk factors.

Comparison of actual hospital costs versus DRG revenues for in-patient treatment of febrile neutropenia during adjuvant anthracycline plus/minus taxane-based chemotherapy for primary breast cancer.

BACKGROUND: In flat-rate reimbursement systems, the hospital's own costs should not exceed its revenues. In a cohort of primary breast cancer (pBC) patients, costs and reimbursement for febrile neutropenia (FN) were compared to verify cost coverage. METHODS: A prospective, observational study in pBC patients receiving adjuvant anthracycline ± taxane-based chemotherapy calculated the costs per in-patient FN episode. The correlating revenues were retrospectively analyzed from diagnosis-related group (DRG) invoices. The actual costs of the therapies were compared to the individual DRG revenues, and the results are presented from the provider's perspective. RESULTS: In 50 patients, n = 11 patients were treated for FN as in-patients. The hospital's overall treatment costs were € 18,288, on average (Ø) € 1663 per case (range € 1139-2344); the overall DRG revenues were € 23,593, Ø € 2145 per case (range € 1266-2660). In n = 8 cases, the DRGs were cost covering, and in n = 3 cases, a loss was observed, but overall resulting in a gain of Ø € 482 per case and thus being cost covering for the provider. Inadequate DRG coding (n = 4/11; 36.4%) resulted in a preventable loss of Ø € 1069/case. CONCLUSIONS: The costs of FN treatment vary substantially and DRG reimbursements do not necessarily reflect the provider's costs. Surprisingly, the in-patient treatment of FN here is overall more than cost covering if adequately coded. The main reasons are asymmetrical costs for this FN low-risk pBC group. These results emphasize the importance of correct medical coding to avoid potential losses.

Management of febrile neutropenia--a German prospective hospital cost analysis in lymphoproliferative disorders, non-small cell lung cancer, and primary breast cancer.

BACKGROUND: Febrile neutropenia/leukopenia (FN/FL) is the most frequent dose-limiting toxicity of myelosuppressive chemotherapy, but German data on economic consequences are limited. PATIENTS AND METHODS: A prospective, multicentre, longitudinal, observational study was carried out to evaluate the occurrence of FN/FL and its impact on health resource utilization and costs in non-small cell lung cancer (NSCLC), lymphoproliferative disorder (LPD), and primary breast cancer (PBC) patients. Costs are presented from a hospital perspective. RESULTS: A total of 325 consecutive patients (47% LPD, 37% NSCLC, 16% PBC; 46% women; 38% age = 65 years) with 68 FN/FL episodes were evaluated. FN/FL occurred in 22% of the LPD patients, 8% of the NSCLC patients, and 27% of the PBC patients. 55 FN/FL episodes were associated with at least 1 hospital stay (LPD n = 34, NSCLC n = 10, PBC n = 11). Mean (median) cost per FN/FL episode requiring hospital care amounted to € 3,950 (€ 2,355) and varied between € 4,808 (€ 3,056) for LPD, € 3,627 (€ 2,255) for NSCLC, and € 1,827 (€ 1,969) for PBC patients. 12 FN/FL episodes (LPD n = 9, NSCLC n = 3) accounted for 60% of the total expenses. Main cost drivers were hospitalization and drugs (60 and 19% of the total costs). CONCLUSIONS: FN/FL treatment has economic relevance for hospitals. Costs vary between tumour types, being significantly higher for LPD compared to PBC patients. The impact of clinical characteristics on asymmetrically distributed costs needs further evaluation.

Cost analysis comparing an anthracycline/docetaxel regimen to CMF in patients with early stage breast cancer.

BACKGROUND: Taxane-based adjuvant chemotherapy is the current standard for node-positive breast cancer patients. Recent data identified relevant patient subgroups with questionable benefit. To estimate the incremental burden on health care resources and costs, we compared a modern sequential regimen (4x epirubicin/cyclophosphamide; 4x docetaxel: EC-->DOC) to CMF. PATIENTS AND METHODS: Data were obtained alongside the phase III WSG-AGO Intergroup trial (2000-2005). A cohort of 110 patients receiving 1,047 chemotherapy cycle days at 38 study sites was analyzed from a hospital perspective. RESULTS: Mean age was 52.4 years. Mean costs for the EC-->DOC group (n = 54) totaled euro8,459 per patient (95% confidence interval (CI): euro7,785-9,132) with cytostatic drug costs being the largest burden (euro5,673; 67%). CMF was significantly (-41.2%) less expensive (euro4,973; 95% CI: euro4,706-5,240), and toxicity-associated rehospitalization was reduced by half (CMF: n = 4, EC-->DOC:n =8). CONCLUSIONS: Our results demonstrate a substantial budget increase attributable to introduction of taxanes to adjuvant chemotherapy of breast cancer. Data will allow estimating cost-effectiveness of individualized chemotherapy strategies.

Chemotherapy-induced nausea and vomiting in the treatment of gastrointestinal tumors and secondary prophylaxis with aprepitant.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) belongs to the most feared side-effects of cancer treatment. Its incidence during chemotherapy of gastrointestinal tumors (GITs) with highly and moderately emetogenic regimens is not well documented. It is also unknown whether aprepitant, a neurokinin-1 receptor antagonist, can be used as secondary antiemetic prophylaxis in case of CINV during cycle 1. PATIENTS AND METHODS: Patients with GITs who were treated with highly and moderately emetogenic chemotherapy received standard antiemetic prophylaxis including a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. In case of CINV > grade 1 (National Cancer Institute classification) during the first chemotherapy course, aprepitant was additionally administered with further cycles. RESULTS: We screened 109 patients. 16 patients (15%) experienced acute and/or delayed CINV. Features associated with CINV were low-dose cisplatin-containing chemotherapy (15/16 patients), female gender (11/16 patients), abstinence to alcohol (11/16 patients) and former emesis gravidarum (11/16 patients). 11 patients who got further courses of the same chemotherapy received aprepitant. 7 are fully assessable for response. 5 of 7 patients had a complete protection from CINV (71%) and 1 patient had improved symptoms. CONCLUSIONS: In the majority of cases, primary standard antiemetic prophylaxis provided adequate protection against CINV. In case of failure to primary prophylaxis, secondary prophylaxis with aprepitant showed a high efficacy against CINV.

Health outcomes and cost-effectiveness of aprepitant in outpatients receiving antiemetic prophylaxis for highly emetogenic chemotherapy in Germany.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer therapy. We aimed to determine outcomes associated with use of aprepitant in outpatients undergoing highly emetogenic chemotherapy in Germany from a patient's and payer's perspective. METHODS: A decision-analytic model compared an aprepitant regimen (aprepitant/ondansetron/dexamethasone) to a control regimen (ondansetron/dexamethasone) over a five days period. Clinical results and resource utilisation observed in aprepitant phase III clinical trials were assigned German unit cost data. RESULTS: Complete response over one chemotherapy cycle was observed in 68% of patients in the aprepitant group (N=514) compared to 48% of patients in the control group (N=518). Patients were estimated to have gained an equivalent of 15 additional hours of perfect health per cycle (0.63 quality-adjusted life days) with aprepitant-based regimen compared to control regimen. Cost per quality-adjusted life year gained with aprepitant was estimated at euro28,891. CONCLUSIONS: Aprepitant substantially improved CINV-related health outcomes in patients undergoing highly emetogenic chemotherapy. Incremental benefits materialised in a cost-effective fashion.

Acupuncture and acupressure for the prevention of chemotherapy-induced nausea--a randomised cross-over pilot study.

OBJECTIVE: To investigate whether a combination of acupuncture and acupressure is effective for reducing chemotherapy-induced nausea and vomiting. PATIENTS AND METHODS: In a randomised cross-over trial, 28 patients receiving moderately or highly emetogenic chemotherapy and conventional standard antiemesis were treated for one chemotherapy cycle with a combination of acupuncture and acupressure at point P6 and for one cycle at a close sham point. The main outcome measure was a nausea score derived from daily intensity rating. RESULTS: There was no difference between combined acupuncture and acupressure treatment at P6 and at the sham point for the nausea score, but the level of nausea was very low in both phases. The mean nausea score was 6.2 (standard deviation 9.0) for treatment at P6 and 6.3 (9.1) for treatment at the sham point (mean difference -0.1, 95% confidence interval -3.9 to 3.7; p=0.96). Seventeen of 21 participants completing the study would desire acupuncture and acupressure for future chemotherapy cycles, but there was no clear preference for either point. CONCLUSION: In this small pilot study a significant difference between treatment at P6 and a close sham point could not be detected. However, it cannot be ruled out that an existing difference was missed due to the small sample size.