In the Wnt signalin

In the treatment arm, paramedics will undertake immediate cooling on arrival and during cardiac arrest, using a large volume (20 mL/kg up to 2 litres) intravenous bolus of ice-cold saline. The saline infusion will be continued after return of circulation and en-route to hospital. In the control arm, patients will receive standard paramedic care, which includes the administration of normal saline at ambient temperature and will be cooled after arrival at the hospital (the current standard of care in ambulances in Australasia). Inhibitors,research,lifescience,medical Study sites This is a three-centre selleck products funded study administered centrally

through the Monash University Department of Epidemiology and Preventive Medicine with study sites in Victoria (Victoria Ambulance and Monash University); South Australia (South Australia Ambulance Service and Flinders University) and Western Australia (St John Ambulance and Inhibitors,research,lifescience,medical University of Western Australia). In Victoria, only MICA paramedics will enroll Inhibitors,research,lifescience,medical patients whereas in WA and SA all paramedics (but not transport officers) will recruit patients. Inclusion/Exclusion Criteria Paramedics will screen patients during cardiac arrest and determine eligibility for

enrolment. Adults 18 years and over, in cardiac arrest on arrival of paramedics are eligible for inclusion. Patients who are in cardiac arrest Inhibitors,research,lifescience,medical following trauma, or who are obviously pregnant or who are already hypothermic (tympanic temperature < 34.5°C) will be excluded. Randomisation The ambulances will be provided with a set of randomisation envelopes. Block randomization will be used with instructions for immediate cooling therapy during CPR or instructions for standard treatment. Standard treatment includes Inhibitors,research,lifescience,medical cooling commenced at hospital as per ILCOR recommendations [7,8]. The envelopes will be randomised

by computer-generated code into blocks of ten, numbered externally, and then sealed within an opaque envelope that conceals the treatment designation. All vehicles will carry two envelopes and as each Idoxuridine is used, it will be replaced at the earliest convenient time from the remaining envelopes held at the ambulance station. Randomisation will be stratified by state to control for possible differences in paramedics skills and hospital treatment. Study Treatments For patients randomised to paramedic cooling: – Standard advanced cardiac life support – Advanced Airway (Endotracheal Tube/Laryngeal Mask Airway) and ventilation with 100% oxygen – Infuse 20 mL/kg cold fluid via IV stat during CPR – Measure temperature using tympanic probe – If temperature > 34.

The extremely high absorption of MM could be due to the easy pene

The extremely high NSC 683864 supplier absorption of MM could be due to the easy penetration of the small structures into fabrics. However, the increase in the size of these structures (see Table 3) did not prevent their exit from the fibres, and desorption was notable. This finding could be due to the higher permeability of textiles compared with human skin, which may explain why this effect was not observed [25, 26]. To study the penetration of active principles through the skin, an in vitro methodology based on percutaneous absorption

is performed to demonstrate the delivery of an encapsulated principle from a textile to the different layers of the skin (stratum corneum, epidermis, or dermis). The percutaneous Inhibitors,research,lifescience,medical absorption of the two formulations, Lip (2% GA, 4% PC) and MM (2% GA, 4% PC, and 30% Oramix CG 110), was evaluated, as were the CO and PA textiles impregnated

with the same Lip or MM. The two formulations and Inhibitors,research,lifescience,medical the CO and PA textiles previously treated with the Inhibitors,research,lifescience,medical formulations were placed in contact with the skin discs as described in Section 2. The aim of this assay was to demonstrate tracer delivery into the different layers of the skin. GAs encapsulated in MMs and Lips, which were either embedded or not embedded in cosmetotextiles, were applied to the skin to study the percutaneous absorption profiles of the agents. The GA extracted from a washing sample, the fabric, the stratum corneum, the rest of the epidermis, the dermis, and the receptor Inhibitors,research,lifescience,medical fluid was analysed. The results are listed in Table 4 and graphically represented in Figure 2. Figure 2 In vitro percutaneous absorption of gallic acid (GA) in Lip and MM formulations and the PA and CO cosmetotextiles Inhibitors,research,lifescience,medical (SC: stratum corneum, R. Fluid: receptor fluid) (significant level accepted *P < 0.01). Table 4 In vitro percutaneous absorption

of GA (gallic acid) in Lip and MM formulations and the PA and CO cosmetotextiles. Comparison of percutaneous absorption in percentage indicates that it is higher when GA was applied as a formulation (Lip or MM) than when it is applied through cosmetotextile. Besides, CO delivers to the skin GA in a greater extent than PA. As shown in Figure 2, the penetration of GA formulated in Lip much was much higher than that of GA formulated in MM. All skin compartments showed a higher amount of GA when vehiculised with Lip than when vehiculised with MM. This result could be due to the bilayer structure of the Lip, which is similar to the lipid bilayer structures present in the SC and in the cellular membranes of the skin [28]. Evidence that Lips do not penetrate deeper than the stratum corneum layer has been published [29]. However, Lips enhance the penetration of both hydrophilic and lipophilic drugs [30, 31].

Higher scores represent higher positive/negative affect Cronbach

Higher scores represent higher positive/negative affect. Cronbach’s α is 0.85 for both scales (Krohne et al. 1996). The current sample achieved a Cronbach’s α of 0.79 for the PA subscale and 0.88 for the NA subscale. In addition, the PD group completed the Panik und Agoraphobie

Skala (PAS, Bandelow 1997), which measures severity of PD on four scales Inhibitors,research,lifescience,medical comprising two items (panic attacks, agoraphobic avoidance, constraints in daily life and worry on healthiness), one scale with three items (anticipatory anxiety), plus one additional item to assess whether panic attacks are mostly unexpected or related to feared situations. The PAS overall score ranges from 0 to 52 with a cutoff of 9 indicating slight PD. Psychometric properties are overall sound with a test–retest reliability of 0.73, Inhibitors,research,lifescience,medical Cronbach’s α of 0.86 and high convergent validity ranging from 0.58 to 0.76 (Bandelow 1997). Cronbach’s α for the individual subscales ranged

between 0.70 and 0.94 in the current sample. There are reports on associations between performance in the mental heartbeat-tracking task and participant’s gender (Ludwick-Rosenthal and Neufeld 1985) and body mass index Inhibitors,research,lifescience,medical (BMI, Montgomery et al. 1984; Jones et al. 1987), as well as between educational level and IGT performance (Davis et al. 2008). We assessed gender and educational level as control variables Inhibitors,research,lifescience,medical via self-report questionnaires. BMI was assessed at a medical examination during admission. Procedure The study was carried out in compliance with the Code of Ethics of the World Medical Association (Declaration of Helsinki) and was approved by the ethics committee of the Schön Klinik Roseneck. Participants participated voluntarily and received no compensation for taking part in the study. Signed informed consent was obtained Inhibitors,research,lifescience,medical for subjects after the nature of the procedures was explained. Next, participants completed the questionnaires and

subsequently performed the Epacadostat mental-tracking task. After assessment of cardiocepetive accuracy, the participants performed the IGT. Data reduction First, interbeat intervals were extracted from the raw ECG using ARTiiFACT (Kaufmann et al. 2011). Next, for each time interval of Thalidomide 25-, 35-, and 45-sec cardioceptive accuracy was calculated with the formula presented in Figure ​Figure1.1. The result is an index that ranges from 0 to 1, with 1 indicating perfect accuracy of heartbeat detection. Figure 1 Formula for computing the cardioceptive accuracy index across three time intervals (Werner et al. 2009). Statistical analysis All data were checked for normal distribution with Kolmogorov–Smirnov tests and Lilliefors Significance Correction. The various group characteristics were compared using independent sample t-tests. To assess associations of cardioception with IGT parameters and other variables, Pearson’s correlations were computed.

Meaning is embedded in the person’s lifeworld and must be underst

Meaning is embedded in the person’s lifeworld and must be understood

in the context of “a before” and “a next” (Galvin & Todres, 2013). To understand next of kin’s vulnerability, attention to how the changes affect everyday life is demanded. Furthermore, attention must be paid to how the changes influence previous expectations and plans, and what is possible now and in the future. Policy documents (Report No. 47 [2008–2009] to the Storting, Report No. 29 [2012–2013], and Report No. 10 [2012–2013]) address the need to humanize care. However, an increasing focus on efficiency and cost containment in the prevailing caring practices seems to be a serious threat to this ambition (Bauer et al., 2009; Hvalvik & Dale, 2013; Vabø, 2012). A humanized

practice means to see the patient (or the next of kin) in both their agency and vulnerability (Galvin & Todres, 2013). This is in accordance with the next of kin’s wishes in our study. They strongly wanted to Selleckchem AG 14699 be involved and share information in the transition process, and although their vulnerability was less obvious, their desire to be seen as human beings was inherent in their stories. It is crucial that health care professionals acknowledge the humanizing dimension when they consider the complexity of next of kin’s lived situation. Strengths and limitations of the study A phenomenological hermeneutic approach was considered relevant as the aim of this study was to illuminate and gain insight in next of kin’s experiences. Narrative interviews were conducted. This is an appropriate method for disclosing the meaning of lived experience (Lindseth first & Norberg, 2004). find more Those who chose to participate in the study were resourceful and had strong meanings about the transition process; they were mainly daughters. Overall, this may be considered a limitation of the present study. However, their ability to express and describe their experiences resulted in rich amounts of data, which may be regarded as

a strength. During the whole research process, the two researchers tried to be conscious of and challenge their pre-understanding. In order to arrive at possible interpretations, rigour was endeavoured throughout the process. A text has never only one meaning (Ricoeur, 1976). The comprehensive understanding of the present study is therefore only one of many possible interpretations. It is, however, the one that the two researchers found most probable and meaningful. Conclusion Our findings suggest that lack of involvement in the transition process strongly influenced next of kin’s lived experiences and made them vulnerable. Incomplete communication among health care providers and across the health care sectors during the transition made the next of kin uncertain and worried. However, in striving to maintain continuity and safety in the older person’s life, they demonstrated strength and were significant agents in the transition process.

Regarding PDGFRA-mutated

GISTs, PDGFRA exon 18 mutations

Regarding PDGFRA-mutated

GISTs, PDGFRA exon 18 mutations have better response to imatinib therapy but not with PDFGRA exon 18 D842V-mutation (71). According to the NCCN guidelines, patients with progressive disease after imatinib treatment are allowed to be re-assessed for surgery. Surgical resection has been achieved in those cases (166-168). ALK assay However, the timing of the surgical intervention is very important and was recommended as the time at which patients reached maximum benefit from imatinib Inhibitors,research,lifescience,medical but before tumor progression occurs (139,169). In addition, neoadjuvant therapy with TKI should be considered to facilitate complete resection and allow for a less morbid operation, especially in duodenal GIST which can be sometimes hardly resected completely (170,171). With a short neoadjuvant imatinib therapy, tumor blood flow was decreased and apoptosis was increased Inhibitors,research,lifescience,medical within 3-7 days of starting therapy compared with pre-imatinib tumor tissue, although minimal size reduction

was observed (171). Assessment of treatment response According to the NCCN guidelines, imaging study of contrast-enhanced CT scan is the technique of choice to detect recurrence or progression of GISTs (138,139,172). In rectal GIST, MRI should be used or additional PET or PET-CT/MRI Inhibitors,research,lifescience,medical may be useful for early detection of tumor response to neoadjuvant therapy (172). Inhibitors,research,lifescience,medical Choi and colleagues (173) proposed modified response evaluation criteria which is considered to predict response more accurately than previously proposed Response Evaluation Criteria in Solid Tumor (RECIST) (174) and has a better correlation with time to progression (175). Resistant disease and alterative treatments Although TKIs, especially imatinib, have resulted in disease-free survival Inhibitors,research,lifescience,medical for patients following surgical resection of their primary tumors and increased response rates and survival for patients with metastatic disease, some patients will eventually develop resistance to imatinib (176). Several potential

mechanisms of resistance were proposed and include specific types of mutations (KIT exon 9, KIT wild-type or PDGFRA exon 18) (31,135), acquisition of secondary mutations within the KIT gene, KIT gene amplification, loss of the wild-type allele, or inadequate to imatinib plasma levels (176-179). Sunitinib is the only second-line TKI approved for use after imatinib failure due to its inhibitory function on multi-kinases receptors (136). It has also been shown to be effective against secondary mutations in vitro and in vivo studies (136,161). However, as with imatinib, resistance has recently been documented in patients with prolonged exposure to sunitinib (180,181). In addition, it has been shown that sunitinib can cause serious, life-threatening adverse effects, including hypertension, cardiotoxicity, and hypothyroidism (30,182,183).

80 These older

80 These older agents appear as effective as more recent antidepressant agents.83 However, the widespread use of these agents is limited by their relatively unfavorable side-effect profile, including problematic anticholinergic and PF2341066 antiadrenergic effects,84 and they are not recommended as first-line agents.8-11 Similarly, while classic monoamine oxidase inhibitors (MAOIs) may be

effective for panic disorder, they are not commonly prescribed for this indication. These agents exert their antidepressant effect by inhibiting the MAO enzyme, so decreasing the breakdown Inhibitors,research,lifescience,medical of serotonin and noradrenaline and increasing the net level of these neurotransmitters in the CNS.15 However, Inhibitors,research,lifescience,medical as is the case with TCAs, the widespread use of MAOIs is generally limited by their associated adverse effects (including the risk of hypertensive crisis when taken with tyramine-containing foods) and their numerous potential drug interactions. Alprazolam, a short-acting agent, is the best studied benzodiazepine in panic disorder.80 It has shown efficacy compared with placebo in short and longer-term studies, and it has been found comparable in effect to the tricyclics

and to the Inhibitors,research,lifescience,medical SSRIs.85 Alprazolam as well as a number of other benzodiazepines (clonazepam, diazepam, and lorazepam) are FDA-approved for PD.15 Nevertheless, once again, given their relatively unfavorable Inhibitors,research,lifescience,medical side-effect profile, most treatment guidelines do not list these agents as a first-line option.8-11 Fluoxetine, paroxetine, and sertraline have all been rigorously investigated in clinical trials and have received

FDA approval for use in PD.15 They are as effective, but better tolerated, than the older TCAs.83 There seems to be little difference in efficacy within this group of agents.80 Current guidelines recommend that active medication be continued for at least a year, in order to prevent relapse and optimize outcome.8-11 There is partial evidence that SNRIs Inhibitors,research,lifescience,medical and other newer antidepressants are effective in PD.80 On the one hand, relatively few of these agents have been well studied in PD, not all findings have been consistently positive, and concerns have also been raised about the safety profile of certain agents (eg, venlafaxine) in comparison with the SSRIs.85 Org 27569 On the other hand, there is some evidence that more noradrenergic antidepressants may be of benefit in PD patients who have failed to respond to serotonergic antidepressants.86 Thus SNRIs and some other newer antidepressants (for example, mirtazapine and reboxetine) can be considered as a treatment option in the pharmacotherapy of PD:87 There is also some evidence of the efficacy of other classes of agent in panic disorder. In particular, anticonvulsant agents have been investigated for use.

Model 1 where; Yijkl = Phenolic acid content, µ = Overall mean of

Model 1 where; Yijkl = Phenolic acid content, µ = Overall mean of phenolic acid content, Treati = fixed effect of Treatment (i = IN, LG, IS, MCoA and control),

Timej = fixed effect of harvesting time in hours (j = 2, 24, 48, 96, 144, 192, 240 and 280), FWk = fixed effect of fresh weight (k = sample), Treati*Timej = interaction between treatment and time of harvest (i = treatment, j = time) eijkl = residual error. 4. Conclusions Inhibitors,research,lifescience,medical This study showed and confirmed many phenolic metabolites in a grape suspension culture such as stilbenes, phenolic acid and anthocyanins, to name just a few. Treatment with IN, LG, MCoA or IS did not provide any significant inhibitory effect on the cell growth. The stimulation with biological substances such as IN, saliva and MCoA improved the biosynthesis of phenolic compounds and promising higher yields

of bioactive metabolites. The rapid effect of these biological stimulants on the amounts of phenolic substances may be of high pharmaceutical importance as well as economic value because of the high exploitation rate of secondary metabolites Inhibitors,research,lifescience,medical within a very short time lapse. Although all treatments positively Sotrastaurin in vitro influenced the synthesis of phenolic acid and biomass, it is advisable to use them for phenolic acid extraction rather than biomass. The major reason is the inhibitory effect of the stimulants on cell propagation after some time, whereas indefinite growth is achieved with untreated grape cells. Inhibitors,research,lifescience,medical Nevertheless, MCoA was the preferred stimulant with the highest yield in phenolic acid within just 2 h of treatment. Furthermore, MCoA is an important natural regulator and metabolite Inhibitors,research,lifescience,medical in the biosynthesis of phenolic compounds. It remains of interest to evaluate in future studies whether the effect of MCoA is by its regulatory

role or as a direct substrate. Naturally, plants have to activate their defense mechanisms by producing signaling molecules within a short time for survival. This explains why different biological elicitors used in this study serve as excellent stimulants to plant Inhibitors,research,lifescience,medical in vitro cultures of V. vinifera. Although MCoA directly may be too expensive for use in a production process, our results may provide ideas for genetic modifications or metabolic treatments only to obtain a similar effect, also with cheaper compounds. Acknowledgments The authors are very grateful to Knorr for providing the grape cell culture and also to Irene Hemmerich for technical and scientific assistance. This special experiment was supported by Boland (MPI Jena) and his working group as well as Steppuhn from the Free University Berlin who provided us with the substances without complications. Conflict of Interest Conflict of Interest All authors have read and approve this version of the manuscript and due care has been taken to ensure the integrity of the work. No part of this paper has been published elsewhere and no conflict of interest exists in the submission of this manuscript.

10 Furthermore, these proteases can contribute to the sustained g

10 Furthermore, these find more proteases can contribute to the sustained growth of established tumor foci by cleavage of the ectodomain of membrane-bound proforms of growth factors, releasing peptides that are mitogens for tumor cells and/or vascular endothelial cells.10 The other chief components of the ECM are glycosaminoglycan polysaccharides, of which heparan sulfate Inhibitors,research,lifescience,medical (HS) is the most abundant in

the subepithelial and subendothelial basement membranes. Heparan sulfate proteoglycans (HSPGs) are composed of a protein core covalently linked to heparan sulfate (HS) glycosaminoglycan chains that interact closely with other ECM components.11,12 These linear saccharide chains are cleaved by an endoglycosidase activity, heparanase, that degrades the HS side chains of HSPGs.13–15 Normally, the enzyme Inhibitors,research,lifescience,medical is found mainly in platelets, mast cells, placental trophoblasts, keratinocytes,

and leukocytes. Heparanase released from activated platelets and cells of the immune system facilitates extravasation of inflammatory cells. It also stimulates endothelial mitogenesis, primarily through release of HS-bound growth factors (i.e. fibroblast growth factor (FGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF)) Inhibitors,research,lifescience,medical residing in the ECM.16,17 Tumor cells appear to use the same molecular machinery during metastasis and neoangiogenesis (Figure 1). Thus, the normal physiological functions of proteases and heparanases in embryonic morphogenesis, wound-healing, tissue repair, and inflammation have been effectively “hijacked” Inhibitors,research,lifescience,medical by tumor cells. Figure 1 Heparanase-mediated extravasation of blood-borne cells. Heparanase expressed by tumor cells (left) and neutrophils (right) promotes cell invasion in between adjacent vascular endothelial cells (EC) and through their underlying basal lamina (BL) into the … Evidence indicates that heparanase not only assists in the break-down of ECM but also is involved in regulating the bioavailability and activity of growth factors Inhibitors,research,lifescience,medical and cytokines. Briefly, various heparin-binding growth factors are sequestered

by HS in the ECM, providing a localized, readily accessible depot, protected from proteolytic degradation,18,19 yet available to activate cells after being released by heparanase. It is conceivable that release of tissue-specific growth factors may be involved in the organ selectivity of metastasis. Although these well documented phenomena were investigated not by us and other groups, it has taken nearly 15 years to isolate and clone the heparanase gene, mainly because of instability of the enzyme(s) and the difficulty in designing specific, quantitative assays. The cDNA sequences of the first and apparently only mammalian heparanase, isolated from human placenta14 and platelets,15 have been reported in 1999, and putative precursor and active recombinant enzymes have been expressed.

Successful management of side effects enhances adherence, permits

Successful management of side effects enhances adherence, permits adequate dosing, improves patient comfort and function, and prevents premature discontinuation of therapy. Appropriate management, includes thoughtful drug selection, the anticipation of common and rare but serious side effects with patients, and striving for the lowest effective dose and simplest, drug regimens consistent with appropriately vigorous treatment. It also includes the addition of appropriate adjunctive therapies to manage emergent complaints. Inhibitors,research,lifescience,medical Fatigue and somnolence Fatigue or drowsiness is a common side effect experienced by 10% to 38% of antidepressant-treated outpatients.1-13 In one study of 401

outpatients,1 70% of people who experienced fatigue had Inhibitors,research,lifescience,medical it by 2 weeks, and 63% continued to experience it at 3 months. In comparative studies, SSRIs had a higher rate of sleepiness than bupropion14 and the noradrenergic reuptake inhibitor, reboxetine,15 and equivalent rates as nefazodonc,16-18 venlafaxine,19-21 and duloxetine22-23 and the reversible Inhibitors,research,lifescience,medical monoamine oxidase inhibitor moclobemide.24 Mirtazapine25 and trazodone26 are associated with greater rates of somnolence

and fatigue than SSRIs. The differential of drowsiness should include residual symptoms of depression, a primary sleep disorder such as obstructive sleep apnea or restless leg syndrome or altered sleep cycle, and substance-use disorders. Management of drowsiness Inhibitors,research,lifescience,medical includes careful evaluation of sleep patterns and counseling on sleep hygiene measures (such as avoidance of daytime napping), changes

in antidepressant dosing schedule such as a shift from morning to nighttime administration, divided dosing or use of a slower release preparation, as well as pharmacological management, with psychostimulants, Inhibitors,research,lifescience,medical modafinil, bupropion, rcboxetine, or protriptylinc, or consideration of alternative remedies such as methylfolate or S-adenosylmethionine. For some patients, a graduated increase in exercise may also help reduce fatigue. Sexual Dorsomorphin purchase dysfunction Sexual dysfunction is a common long-term problem on antidepressants. Medication side effects typically affect libido, arousal, orgasm, and ejaculation,27 and may affect lubrication and erection. These side Isotretinoin effects have traditionally been greatly underreported, largely related to patients’ and clinicians’ reticence to address this topic. In a study of 344 patients by Montejo-Gonzalez et al,28 58% of patients reported sexual dysfunction when physicians directly inquired, compared with only 14% of those who spontaneously reported sexual dysfunction. In a naturalistic study that directly inquired about, side effects through closed-ended questions,1 34% of patients reported sexual dysfunction, with half of these patients (17% of the overall group) deeming it bothersome. Seventy percent of patients who experienced sexual dysfunction did so by 2 weeks, with 80% experiencing it at 3 months.

The inhibiting factors most frequently spontaneously reported by

The inhibiting factors most frequently spontaneously reported by the GPs were only very few palliative care patients in their practice during the

course (11x) and not enough time available for the AT13387 mw Training programme (10x). Inhibiting factors reported by the GPTs were that medical elements were lacking in the programme (5x) and Inhibitors,research,lifescience,medical that not all steps in the programme had been addressed (3x). During the 6months duration of the programme the GPTs provided palliative care for an average of two patients (range 0–5). Discussion Main findings We developed the ACA training programme to improve communication between GPs and their palliative care patients, consisting of eight consecutive steps, and based on three key areas of attention in communication: availability of the GP for the patient, current issues that should be raised by the GP, and anticipating various scenarios. The results of this study show that the programme appears to be applicable to practising GPs Inhibitors,research,lifescience,medical who attended a 2-year Palliative Care Peer Group Training Inhibitors,research,lifescience,medical Course and to (inexperienced) GPTs from five vocational training groups. The ACA checklist was appreciated by GPs as useful both in practice and as a learning tool, whereas GPTs mainly appreciated the list for use in practice. A quarter of the GPs

and a third of the Inhibitors,research,lifescience,medical GPTs spontaneously reported the ACA checklist to be a useful guide for communication with palliative care patients. Strengths and limitations of this study Both content and educational approach of the ACA training programme are evidence-based. The content of the ACA training programme is based on the results of recent studies among palliative

care patients, their relatives, GPs, and end-of-life consultants. The educational approach was derived from two systematic Inhibitors,research,lifescience,medical reviews of methods in training programmes for communication in palliative and cancer care. Attendance and appreciation of the training programme were evaluated for each step of the programme. The newly developed training programme was assessed among practising GPs and inexperienced GPTs. The GPs participated found in a two-year Palliative Care Peer Group Training Course, and probably had a more than average commitment to palliative care, unlike the GPTs, who participated as part of their vocational training, with no special commitment. This might explain the moderate GPT response rate (67%) and their lower scores for appreciation. The appreciation scores of the two groups can only be compared with caution, because the GPs scored their appreciation on a 10-point scale and the GPTs on a 5-point scale. Non-responding GP(T)s might have had lower attendance rates and lower appreciation scores.