The outsourcing of research and development (R&D) activities has frequently been characterized as an important instrument to acquire external technological knowledge that is subsequently integrated ...into a firm's own knowledge base. However, in this paper we argue that these ‘gains’ from R&D outsourcing need to be balanced against the ‘pains’ that stem from a dilution of firm‐specific resources, the deterioration of integrative capabilities and the high demands on management attention. Based on a panel dataset of innovating firms in Germany, we find evidence for an inverse U‐shaped relationship between R&D outsourcing and innovation performance. This relationship is positively moderated by the extent to which firms engage in internal R&D and by the breadth of formal R&D collaborations: both serve as an instrument to increase the effectiveness of R&D outsourcing.
Summary Background Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent ...lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas. Methods We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m2 on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m2 , doxorubicin 50 mg/m2 , and vincristine 1·4 mg/m2 on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m2 on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov , number NCT00991211 , and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335. Findings 274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25–57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69·5 months 26·1 to not yet reached vs 31·2 months 15·2–65·7; hazard ratio 0·58, 95% CI 0·44–0·74; p<0·0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p<0·0001), haematological toxicity (77 30% vs 173 68%; p<0·0001), infections (96 37% vs 127 50%); p=0·0025), peripheral neuropathy (18 7% vs 73 29%; p<0·0001), and stomatitis (16 6% vs 47 19%; p<0·0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 16% vs 23 9%; p=0·024). Interpretation In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects. Funding Roche Pharma AG, Ribosepharm/Mundipharma GmbH.
Introduction Five months after COVID-19 first occurred and protective regulations were introduced, patients at three outpatient hematological/oncological centers in Bavaria who had received ...antiproliferative tumor therapy (n = 30) were questioned about the pandemic's impact. Patients, materials and methods In recorded semi-structured telephone interviews, the patients answered questions about their quality of life, treatment procedures, their relationship with medical care staff and modern communication technologies. Each interview consisted of 28 questions. The average length of an interview was 30 minutes. The interviews were transcribed and analyzed by means of a qualitative content analysis according to Mayring. Results The COVID-19 pandemic adds to the burden of patients by decreasing their social contacts. They perceived the new isolation and protective measures in outpatient clinics as mostly positive and said its impact had been only slightly adverse. With the implemented safety measures, they feel adequately protected and looked after and want their antiproliferative therapy to be performed as scheduled. Talking to medical staff provides additional reassurance. Conclusion Although the COVID-19 pandemic has exacerbated the social isolation of tumor patients, it has had only a minor effect on tumor therapy in the surveyed patient population. The benefits of modern communication options to tumor patients remains uncertain and should be investigated further in future studies.
This paper examines how the ability of traditional media firms to engage in targeted advertising has changed with the advent of the Internet. We find that the premium for reaching a homogeneous ...audience increases for magazines that have a companion website, as well as for those whose readers are more likely to be online. This indicates a complementarity between offline and online channels with respect to targeted advertising. We hypothesize that this result is driven by multihoming consumers who enhance the value of targeted advertising, in contrast to the usual assumption that multiple advertising messages are redundant.
This paper was accepted by Pradeep Chintagunta, marketing.
Summary Background Fludarabine-based chemoimmunotherapy with rituximab is frequently used in patients with indolent and mantle-cell lymphomas who relapse after alkylating chemotherapy. We aimed to ...compare the efficacy and safety of rituximab with bendamustine or fludarabine in patients with relapsed, indolent, non-Hodgkin lymphoma and mantle-cell lymphoma. Methods For this randomised, non-inferiority, open-label, phase 3 trial, we recruited patients from 55 centres in Germany, who were subsequently randomised centrally according to prespecified randomisation lists with permuted blocks of randomly variable block size to rituximab (375 mg/m2 , day 1) plus either bendamustine (90 mg/m2 , days 1 and 2) or fludarabine (25 mg/m2 , days 1–3) every 28 days for a maximum of six 28-day cycles. Patients were aged 18 years or older with a WHO performance status of 0–2 and had relapsed or refractory indolent or mantle-cell lymphoma; patients refractory to regimens that included rituximab, bendamustine, or purine analogue drugs were excluded. Patients were stratified by histological subtypes of lymphoma and by their latest previous therapies. Treatment allocation was not masked. The primary endpoint was progression-free survival and the final analysis was completed per protocol. Non-inferiority of bendamustine plus rituximab versus fludarabine plus rituximab was defined as a difference of less than 15% in 1-year progression-free survival. The protocol was amended in July, 2006, after approval of rituximab maintenance (375 mg/m2 every 3 months for up to 2 years), which was then given to patients achieving a response to either trial treatment. This study is registered with ClinicalTrials.gov , number NCT01456351 (closed to enrolment, follow-up is ongoing). Findings Between Oct 8, 2003, and Aug 5, 2010, we randomly assigned 230 patients to treatment groups (116 bendamustine plus rituximab, 114 fludarabine plus rituximab). 11 patients were excluded for protocol violations and were not followed up further (two in the bendamustine plus rituximab group and nine in the fludarabine plus rituximab group). Thus, 219 patients were included in the per-protocol analysis (114 bendamustine plus rituximab, 105 fludarabine plus rituximab). 1-year progression-free survival with bendamustine plus rituximab was 0·76 (95% CI 0·68–0·84) and 0·48 (0·39–0·58) with fludarabine plus rituximab (non-inferiority p<0·0001). At a median follow-up of 96 months (IQR 73·2–112·9), median progression-free survival with bendamustine plus rituximab was 34·2 months (95% CI 23·5–52·7) and 11·7 months (8·0–16·1) with fludarabine plus rituximab (hazard ratio HR 0·54 95% CI 0·38–0·72, log-rank test p<0·0001). Safety outcomes were similar in both groups, with 46 serious adverse events recorded (23 in the bendamustine plus rituximab group and 23 in the fludarabine plus rituximab group), most commonly myelosuppression and infections. Interpretation In combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. Funding Roche Pharma AG, Ribosepharm GmbH, Mundipharma GmbH, Studiengruppe indolente Lymphome (StiL).
Rapid evolution of ultrasound technology has allowed widespread use of handheld ultrasound devices (HHUDs) for many possible applications. Along with the adult population, the use of HHUDs for Point ...of Care Ultrasound (POCUS) in pediatric medicine has been increasing over the last few years. However, pediatric-specific literature is still scarce on mobile vascular ultrasound.
To evaluate diagnostic capabilities of Vscan Air™ in comparison with high-end ultrasound for the assessment of the internal jugular vein in children and adolescents.
42 Internal Jugular Veins (IJVs) of 21 pediatric patients were scanned by an experienced examiner using a WLAN-supported handheld ultrasound device (Vscan Air™) and high-end cart-based ultrasound (LOGIQ E9) as reference. B-Mode and Color-coded Doppler (CCDS) were performed and compared. Image quality was assessed using a score of 0 to 5 and statistically analyzed. Results were interpreted independently by two readers in consensus.
21 patients (2-17 years; mean 11,00±4,5 years; female n = 11, male n = 10) were examined. The rating score never dropped below 3 for both devices. The median score evaluation of B-Mode and CCDS for the high-end device was 5.00, of Vscan Air™ 5.00 for B-Mode and 4.00 for CCDS. A significant difference was shown between the two devices in the evaluation of CCDS.
Vscan Air™ ultrasound device allows sufficient assessability of the IJV in pediatric patients, opening up new possibilities for fast and mobile POCUS of cervical veins and potential guidance of central venous catheter placement.
In this paper it is tested which of the various alternative approaches for constructing knowledge spillover pools suggested in existing literature measures the extent to which a firm can costlessly ...receive external knowledge best. Since knowledge spillovers are unmeasurable, a ‘goodness of fit’ measure is constructed using innovation survey data. It turns out that measures of the uncentered correlation of firm characteristics seem to fit actual knowledge spillovers best. Direct measures constructed from innovation survey data appear to work reasonably well while measures of the Euclidean technological distance and of the geographical distance lead to counterintuitive results. Empirical evidence is provided for both the German service sector and the manufacturing sector.
Currently, a conclusive experience on the uniform implementation and benefits of day hospice structures and interventions is lacking in Germany. The following questions should be clarified: (1) Which ...structural conditions and interventional measures should be established in day hospices from the point of view of patients, relatives, and specialist staff?; (2) Are the planned structures or interventions feasible and implementable under real conditions and accepted by patients, relatives, and staff?; (3) How can a final implementation and intervention catalog for day hospices be designed?; (4) Is this final catalog of services feasible, reasonable, economical, and effective under everyday conditions in day hospices?
We planned to perform a multistage investigation, guided by the Medical Research Council Framework for the development and evaluation of complex interventions. In Stage 1, an initial theoretical construct on structures and interventions will be established through an extensive literature and guideline review on day hospices and through qualitative interviews. In a nominal group process, we will create a catalog of offers. In Stage 2, feasibility testing is conducted in a single-day hospice under real-life conditions using quantitative quality indicators and qualitative interviews. Structures and interventions can be adapted here if necessary. In a second nominal group process, a final structure and offer catalog is created, which is then implemented in Stage 3 in the day hospice under investigation and evaluated under real daily conditions through a process and effectiveness test. For this purpose, qualitative and quantitative quality indicators will be used and a comparative cohort of patients who are not cared for in the day hospice - but in the same network structure (oncology-palliative care network Lower Bavaria) - is examined.
Finally, the initial statements on the reasonable and realizable structures or interventions in day hospices and their benefits in daily real-life conditions as well as possible optimization processes shall be made.
The study was retrospectively registered in the German Clinical Trials Register (DRKS-ID DRKS00031613, registration date April 04, 2023) and the display portal of the Center for Clinical Trials of the University Hospital Regensburg (Z-2022-1734-6, registration date July 01, 2023).
Background:
More than 80% of the residents in German hospices suffer from tumor disease. But the administration of supportive-oncological therapies in hospices for symptom control is controversially ...discussed.
Objectives:
This study aims to investigate the care situation of tumor patients in German hospices with regard to medical care and the use of supportive-oncological therapies.
Methods:
In February 2019, all hospices in Germany were offered the opportunity to participate in an anonymous online survey on medical and drug care for their tumor patients. The survey was conducted using the online platform SoSci Survey and ended in April 2019. The analysis was descriptive.
Results:
Of 202 hospices, 112 responded to the questionnaire. The hospices were distributed nationwide. Most have 8 to 10 places. More than 80% of hospice residents are tumor patients, and the length of stay is usually three to four weeks. Medical care is primarily provided by primary care physicians. While specialized outpatient palliative care is increasingly involved in care, hematologists/oncologists are rarely represented. Supportive-oncological therapies are rarely prescribed, whereas medication for other chronic conditions is often continued. The percentage of supportive-oncological therapies prescribed is higher in hospices with oncology co-care.
Conclusions:
Although most hospice residents suffer from malignant disease, co-care by a hematologist/oncologist is rare. Supportive-oncology therapies, particularly for symptom relief, may therefore be rarely used. However, since a small select group of hospice residents may benefit from these therapies, further investigation in this direction should be undertaken.
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