ABSTRACT
BACKGROUND: Patients with multimorbidity, having two or more chronic diseases, suffer frequently from undiagnosed common mental health problems and are an increasing challenge in primary care. There is a call to improve care delivery to address all these patients' needs at the same time. The aim of this study was to identify general practitioners' experiences of managing patients with multimorbidity and common mental health problems in primary care. METHODS: We conducted five focus group interviews with 28 physicians (3-8 participants in each group) in 5 primary care practices in and outside of Stockholm, Sweden. We used a semi-structured interview guide, and we analysed the data using reflexive thematic analysis. The methodological orientation of the study was inductive, latent constructivism. RESULTS: We generated two themes from the data: Unmet patient needs and fragmented care send patients and physicians off balance and Dancing with the patient individually and together with others leads to confident and satisfied patients and physicians. The two themes are related as general practitioners expressed a need to shift from disease-specific fragmentation to relational continuity, teamwork, and flexibility to meet the needs of patients with multimorbidity and common mental health problems. CONCLUSIONS: These findings can provide guidance in developing future interventions for patients with multimorbidity and common mental health problems in primary care in general, and in Sweden in particular.
Subject(s)
General Practitioners , Humans , Multimorbidity , Mental Health , Attitude of Health Personnel , Qualitative ResearchABSTRACT
The in vivo preclinical pharmacodynamic profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity, was compared to that of the clinically studied gastrointestinal pro-kinetic agents, tegaserod, cisapride and mosapride. The activity of TD-5108 was evaluated in guinea pig colonic transit, rat oesophageal relaxation and dog gastrointestinal smooth muscle contractility models. Subcutaneous administration of TD-5108, tegaserod, cisapride and mosapride increased guinea pig colonic transit (rank order of potencies: TD-5108 > tegaserod > cisapride > mosapride). Following intravenous and intraduodenal dosing, TD-5108, tegaserod, cisapride and mosapride produced dose-dependent relaxation of the rat oesophagus. On a molar basis, TD-5108 was approximately twofold less potent than tegaserod following intravenous dosing but 6- or 86-fold more potent than cisapride or mosapride, respectively, and 9- or 18-fold more potent than tegaserod or cisapride, respectively, after intraduodenal administration. Orally dosed TD-5108 increased the contractility of the canine antrum, duodenum and jejunum with higher potency than tegaserod. The selective 5-HT(4) receptor agonist, TD-5108, demonstrates robust in vivo activity in the guinea pig, rat and dog gastrointestinal tracts.
Subject(s)
Azabicyclo Compounds/pharmacology , Gastrointestinal Transit/drug effects , Serotonin 5-HT4 Receptor Agonists , Serotonin Receptor Agonists/pharmacology , Administration, Oral , Animals , Azabicyclo Compounds/administration & dosage , Benzamides/administration & dosage , Benzamides/pharmacology , Cisapride/administration & dosage , Cisapride/pharmacology , Colon/drug effects , Colon/metabolism , Dogs , Dose-Response Relationship, Drug , Esophagus/drug effects , Esophagus/metabolism , Female , Guinea Pigs , Indoles/administration & dosage , Indoles/pharmacology , Male , Morpholines/administration & dosage , Morpholines/pharmacology , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Muscle, Smooth/metabolism , Rats , Rats, Sprague-Dawley , Serotonin Receptor Agonists/administration & dosageABSTRACT
1 Tegaserod (Zelnorm) is a potent 5-hydroxytryptamine4 (5-HT4) receptor agonist with clinical efficacy in disorders associated with reduced gastrointestinal motility and transit. The present study investigated the interaction of tegaserod with 5-HT2 receptors, and compared its potency in this respect to its 5-HT4 receptor agonist activity. 2 Tegaserod had significant binding affinity for human recombinant 5-HT2A, 5-HT2B and 5-HT2C receptors (pKi=7.5, 8.4 and 7.0, respectively). The 5-HT2B receptor-binding affinity of tegaserod was identical to that at human recombinant 5-HT4(c) receptors (mean pKi=8.4) in human embryonic kidney-293 (HEK-293) cells stably transfected with the human 5-HT4(c) receptor. 3 Tegaserod (0.1-3 microm) inhibited 5-HT-mediated contraction of the rat isolated stomach fundus potently (pA2=8.3), consistent with 5-HT(2B) receptor antagonist activity. Tegaserod produced, with similar potency, an elevation of adenosine 3',5' cyclic monophosphate in HEK-293 cells stably transfected with the human 5-HT4(c) receptor (mean pEC50=8.6), as well as 5-HT4) receptor-mediated relaxation of the rat isolated oesophagus (mean pEC50=8.2) and contraction of the guinea-pig isolated colon (mean pEC50=8.3). 4 Following subcutaneous administration, tegaserod (0.3 or 1 mg kg(-1)) inhibited contractions of the stomach fundus in anaesthetized rats in response to intravenous dosing of alpha-methyl 5-HT (0.03 mg kg(-1)) and BW 723C86 (0.3 mg kg(-1)), selective 5-HT2B receptor agonists. At similar doses, tegaserod (1 and 3 mg kg(-1) subcutaneously) evoked a 5-HT4 receptor-mediated increase in colonic transit in conscious guinea-pigs. 5 The data from this study indicate that tegaserod antagonizes 5-HT2B receptors at concentrations similar to those that activate 5-HT4 receptors. It remains to be determined whether this 5-HT2B receptor antagonist activity of tegaserod contributes to its clinical profile.