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Exposure to seed treatment neonicotinoids during corn planting has clear short-term detrimental effects on honey bee colonies and may affect the viability of beekeeping operations that are dependent on maximizing colony size in the springtime. Environ Toxicol Chem 2021;401212-1221. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

In preclinical Ewing sarcoma (ES) models, poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors were identified as a potential therapeutic strategy with synergy in combination with cytotoxic agents. This study evaluated the safety and dosing of the PARP1/2 inhibitor niraparib (NIR) with temozolomide (TMZ; arm 1) or irinotecan (IRN; arm 2) in patients with pretreated ES.

Eligible patients in arm 1 received continuous NIR daily and escalating TMZ (days 2-6 [D2-6]) in cohort A. Subsequent patients received intermittent NIR dosing (cohort B), with TMZ re-escalation in cohort C. In arm 2, patients were assigned to NIR (days 1-7 [D1-7]) and escalating doses of IRN (D2-6).

From July 2014 to May 2018, 29 eligible patients (23 males and 6 females) were enrolled in arms 1 and 2, which had 7 dose levels combined. Five patients experienced at least 1 dose-limiting toxicity (DLT) in arm 1 (grade 4 [G4] neutropenia for >7 days or G4 thrombocytopenia), and 3 patients experienced at least 1 DLT in arm 2 (grade 3 [G3] colitis, G3 anorexia, or G3 alanine aminotransferase elevation). The maximum tolerated dose was NIR at 200 mg every day on D1-7 plus TMZ at 30 mg/m

every day on D2-6 (arm 1) or NIR at 100 mg every day on D1-7 plus IRN at 20 mg/m

every day on D2-6 (arm 2). One confirmed partial response was observed in arm 2; the median progression-free survival was 9.0 weeks (95% CI, 7.0-10.1 weeks) and 16.3 weeks (95% CI, 5.1-69.7 weeks) in arms 1 and 2, respectively. The median decrease in tumor poly(ADP-ribose) activity was 89% (range, 83%-98%).

The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced.

The combination of NIR and TMZ or IRN was tolerable, but at lower doses in comparison with conventional cytotoxic combinations. A triple-combination study of NIR, IRN, and TMZ has commenced.

Treatment and diagnostic recommendations are often made in clinical guidelines, reports from advisory committee meetings, opinion pieces such as editorials, and narrative reviews. Quite often, the authors or members of advisory committees have industry ties or particular specialty interests which may impact on which interventions are recommended. Similarly, clinical guidelines and narrative reviews may be funded by industry sources resulting in conflicts of interest.

To investigate to what degree financial and non-financial conflicts of interest are associated with favourable recommendations in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews.

We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to February 2020. We also searched reference lists of included studies, Web of Science for studies citing the included studies, and grey literature sources.

We included studies comparing the association between conflicts of interest anto indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.

We interpret our findings to indicate that financial conflicts of interest are associated with favourable recommendations of drugs and devices in clinical guidelines, advisory committee reports, opinion pieces, and narrative reviews. However, we also stress risk of confounding in the included studies and the statistical imprecision of individual analyses of each document type. It is not certain whether non-financial conflicts of interest impact on recommendations.

Biliary tract cancer (BTC) has a poor prognosis despite treatment with first-line gemcitabine and cisplatin. In BTC, PI3K/AKT pathway activation has been shown to increase resistance to chemotherapy, which may be overcome with PI3K inhibition. This phase 2 study evaluated the safety and efficacy of copanlisib, a PI3K inhibitor, with gemcitabine and cisplatin in advanced BTCs. The role of PTEN expression in outcomes was also explored.

Patients with advanced/unresectable BTC received gemcitabine, cisplatin, and copanlisib as their first-line treatment. The primary endpoint was progression-free survival (PFS) at 6 months. Secondary endpoints were the response rate (RR), median overall survival (OS)/PFS, and safety profile. An assessment of PTEN expression by immunohistochemistry was also performed along with molecular profiling.

Twenty-four patients received at least 1 dose of the study drug. The PFS rate at 6 months was 51%; the median OS was 13.7 months (95% CI, 6.8-18.0 months), and the median PFS was 6th the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.

The addition of copanlisib, a PI3K inhibitor, to standard chemotherapy for advanced biliary tract cancers was assessed for efficacy and safety. Twenty-four patients with advanced biliary tract cancer received treatment in this study. There was no difference in survival with the addition of copanlisib in comparison with standard chemotherapy. Copanlisib may be more effective and increase survival in patients with low PTEN expression levels. Further studies are needed to confirm this. No unexpected adverse events occurred.THE EXPERIENCE OF PALLIATIVE WORK IN A PALLIATIVE CONSULTANCY SERVICE IN WESTFALEN-LIPPE Background In Westfalen-Lippe there has been a care concept for 8 years which does not insitutionalize general and specialized outpatient palliative care (AAPV and SAPV), which integrates the family doctor in a prominent position and orientates the service density to the changing needs of patients and their relatives (palliative medical consultancy service Iserlohn-Letmathe network, PKD NIL). The new Federal Framework Agreement (SAPV) emphasizes a nationwide, basically uniform structure in Germany. Existing regional structures are being put to the test.

Exploratory qualitative research was carried out. Using semi-structured, guided expert interviews, PKD NIL employees were asked how they experience their everyday work. Data from 17 people were evaluated.

Teamwork and cooperation in the network are experienced positively by everyone working in the PKD NIL. The concept is based on the family doctor, holistic care is carried out. Cooperation with individual professional groups who are critical of the cooperation with the PKD NIL, cooperation with other PKDs, communication with relatives and those affected, the shortage of skilled workers, as well as the concern of upheaval due to the framework agreement on the SAPV in Germany are challenging.

The research gives an insight into the experience of working in the PKD NIL. However, further studies are necessary in order to be able to make comparisons and to be able to assess whether improved palliative care can really be achieved in Germany.

The research gives an insight into the experience of working in the PKD NIL. However, further studies are necessary in order to be able to make comparisons and to be able to assess whether improved palliative care can really be achieved in Germany.

A 58-year-old woman presented with a symptomatic, hypertensive crisis, acute kidney failure AKIN2 and a severe hypercalcemia. The parathyroid hormone levels were in the lower normal range with highly elevated Vitamin D levels. For more than half a year she was taking 100'000 IU Vitamin D daily. Under volume loading, calcium-low-diet, Denosumab for blocking calcium resorption from bone and Ketoconazol to inhibit activation of Vitamin D a normalization of the calcium levels as well as an improvement of renal function could be observed. Loss-of-function mutations in the genes CYP24A1 and SLC34A1, involved in vitamin D metabolism leading to hypercalcemia could not be found in this patient.

A 58-year-old woman presented with a symptomatic, hypertensive crisis, acute kidney failure AKIN2 and a severe hypercalcemia. The parathyroid hormone levels were in the lower normal range with highly elevated Vitamin D levels. For more than half a year she was taking 100'000 IU Vitamin D daily. Under volume loading, calcium-low-diet, Denosumab for blocking calcium resorption from bone and Ketoconazol to inhibit activation of Vitamin D a normalization of the calcium levels as well as an improvement of renal function could be observed. Loss-of-function mutations in the genes CYP24A1 and SLC34A1, involved in vitamin D metabolism leading to hypercalcemia could not be found in this patient.

This paper deals with biomechanics of the cervical spine when using a smartphone. The forces acting on the vertebral bodies, vertebral joints, intervertebral discs, muscles and ligaments increase as the angle of flexion of the cervical spine increases. The disorders caused by smartphone neck, on the other hand, are mostly acute and can be treated well with regular exercise and strengthening the neck muscles. Therapy is therefore also suitable for prevention. However, the long-term effects should not be disregarded, because the increasing possibilities for using smartphones also mean that the average daily use increases more. Especially the daily screen time for young people is getting longer and longer. The currently still acute clinical picture of the smartphone neck, which rarely takes a chronic course and causes long-term damage, could develop into a larger chronic clinical picture due to missing or too late measures.

This paper deals with biomechanics of the cervical spine when using a smartphone. The forces acting on the vertebral bodies, vertebral joints, intervertebral discs, muscles and ligaments increase as the angle of flexion of the cervical spine increases. The disorders caused by smartphone neck, on the other hand, are mostly acute and can be treated well with regular exercise and strengthening the neck muscles. Therapy is therefore also suitable for prevention. However, the long-term effects should not be disregarded, because the increasing possibilities for using smartphones also mean that the average daily use increases more. Especially the daily screen time for young people is getting longer and longer. selleck The currently still acute clinical picture of the smartphone neck, which rarely takes a chronic course and causes long-term damage, could develop into a larger chronic clinical picture due to missing or too late measures.CARE OF PATIENTS WITH MENTAL ILLNESS AND SARS-COV-2 INFECTION AT THE DEPARTMENT OF PSYCHIATRY AND PSYCHOTHERAPY LMU MUNICH, GERMANY People with mental illness are particularly at risk in the event of a SARS-CoV-2 infection. In order to ensure their care, a 5-stage pandemic plan has been drawn up in the Clinic for Psychiatry and Psychotherapy at LMU Munich. This includes, among other things, which patients can be treated in the clinic, how registration is carried out, how the diagnosis is carried out and which treatment strategies are available. Predictors for severe disease progression are mentioned, as well as criteria for a transfer to intensive care unit. It is discussed when coercive measures are permitted in the treatment of patients with mental illness and SARS-CoV-2 infection.

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