The Role of Chief Medical officers in making Public Health Overview Documents in Norwegian Municipalities. A qualitative Study.

Aims: To investigate how Chief Medical Officers experience their role in the municipalities´ work with making the public health overview documents, demanded by the Norwegian Public Health Act from 2012.

Methods: A qualitative study with semi-structured focus group interviews with 21 Chief Medical Officers from 20 different municipalities in Norway. The interviews were conducted in 2017.

General practitioners' experiences of being involved in local public health work in Norway. A qualitative study.

Aim: The aim was to explore how general practitioners experienced being involved in local public health work and how they worked with prevention and health promotion clinically after the introduction of the Public Health Act in 2012.

Design, Setting And Subjects: Qualitative study with focus groups interviews with 18 GPs from different municipalities in Norway.

Results: The GPs said that they either had not at all or only to a limited extent been involved in local public health work in their municipalities.

A cross-industry survey on photosafety evaluation of pharmaceuticals after implementation of ICH S10.

A cross-industry survey was conducted by EFPIA/IQ DruSafe in 2018 to provide information on photosafety evaluation of pharmaceuticals after implementation of ICH S10. This survey focused on the strategy utilized for photosafety risk assessment, the design of nonclinical (in vitro and in vivo) and clinical evaluations, the use of exposure margins in risk assessment, and regulatory interactions. The survey results indicated that a staged approach for phototoxicity assessment has been widely accepted by regulatory authorities globally.

GDF-15 Neutralization Alleviates Platinum-Based Chemotherapy-Induced Emesis, Anorexia, and Weight Loss in Mice and Nonhuman Primates.

Platinum-based cancer therapy is restricted by dose-limiting side effects and is associated with elevation of growth differentiation factor 15 (GDF-15). But whether this elevation contributes to such side effects has been unclear. Here, we explored the effects of GDF-15 blockade on platinum-based chemotherapy-induced emesis, anorexia, and weight loss in mice and/or nonhuman primate models.

Design and Synthesis of γ- and δ-Lactam M Positive Allosteric Modulators (PAMs): Convulsion and Cholinergic Toxicity of an M-Selective PAM with Weak Agonist Activity.

Recent data demonstrated that activation of the muscarinic M receptor by a subtype-selective positive allosteric modulator (PAM) contributes to the gastrointestinal (GI) and cardiovascular (CV) cholinergic adverse events (AEs) previously attributed to M and M activation. These studies were conducted using PAMs that also exhibited allosteric agonist activity, leaving open the possibility that direct activation by allosteric agonism, rather than allosteric modulation, could be responsible for the adverse effects. This article describes the design and synthesis of lactam-derived M PAMs that address this hypothesis.

Discovery of cyclopropyl chromane-derived pyridopyrazine-1,6-dione γ-secretase modulators with robust central efficacy.

Herein we describe the discovery of a novel series of cyclopropyl chromane-derived pyridopyrazine-1,6-dione γ-secretase modulators for the treatment of Alzheimer's disease (AD). Using ligand-based design tactics such as conformational analysis and molecular modeling, a cyclopropyl chromane unit was identified as a suitable heterocyclic replacement for a naphthyl moiety that was present in the preliminary lead . The optimized lead molecule achieved good central exposure resulting in robust and sustained reduction of brain amyloid-β42 (Aβ42) when dosed orally at 10 mg kg in a rat time-course study.

Discovery of the Potent and Selective M1 PAM-Agonist N-[(3R,4S)-3-Hydroxytetrahydro-2H-pyran-4-yl]-5-methyl-4-[4-(1,3-thiazol-4-yl)benzyl]pyridine-2-carboxamide (PF-06767832): Evaluation of Efficacy and Cholinergic Side Effects.

It is hypothesized that selective muscarinic M1 subtype activation could be a strategy to provide cognitive benefits to schizophrenia and Alzheimer's disease patients while minimizing the cholinergic side effects observed with nonselective muscarinic orthosteric agonists. Selective activation of M1 with a positive allosteric modulator (PAM) has emerged as a new approach to achieve selective M1 activation. This manuscript describes the development of a series of M1-selective pyridone and pyridine amides and their key pharmacophores.

Standardized UV-vis spectra as the foundation for a threshold-based, integrated photosafety evaluation.

Phototoxicity is a relatively common phenomenon and is an adverse effect of some systemic drugs. The fundamental initial step of photochemical reactivity is absorption of a photon; however, little guidance has been provided thus far regarding how ultraviolet-visible (UV-vis) light absorption spectra may be used to inform testing strategies for investigational drugs. Here we report the results of an inter-laboratory study comparing the data from harmonized UV-vis light absorption spectra obtained in methanol with data from the in vitro 3T3 Neutral Red Uptake Phototoxicity Test.

GlyT1 inhibitor reduces oscillatory potentials of the electroretinogram in rats.

Context: Selective inhibitors of glycine transporter type 1 (GlyT1) increase synaptic glycine concentrations and are being developed to treat cognitive and negative symptoms of schizophrenia. However, increases in systemic glycine levels have been associated with visual disturbances and electroretinogram (ERG) alternations.

Objective: To determine whether the selective GlyT1 inhibitor PF-03463275 causes changes in ERG responses in albino rats.

Identification of multiple 5-HT₄ partial agonist clinical candidates for the treatment of Alzheimer's disease.

The cognitive impairments observed in Alzheimer's disease (AD) are in part a consequence of reduced acetylcholine (ACh) levels resulting from a loss of cholinergic neurons. Preclinically, serotonin 4 receptor (5-HT(4)) agonists are reported to modulate cholinergic function and therefore may provide a new mechanistic approach for treating cognitive deficits associated with AD. Herein we communicate the design and synthesis of potent, selective, and brain penetrant 5-HT(4) agonists.

Vegetarian diets and blood pressure among white subjects: results from the Adventist Health Study-2 (AHS-2).

Objective: Previous work studying vegetarians has often found that they have lower blood pressure (BP). Reasons may include their lower BMI and higher intake levels of fruit and vegetables. Here we seek to extend this evidence in a geographically diverse population containing vegans, lacto-ovo vegetarians and omnivores.

Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764).

The discovery of two histamine H(3) antagonist clinical candidates is disclosed. The pathway to identification of the two clinical candidates, 6 (PF-03654746) and 7 (PF-03654764) required five hypothesis driven design cycles. The key to success in identifying these clinical candidates was the development of a compound design strategy that leveraged medicinal chemistry knowledge and traditional assays in conjunction with computational and in vitro safety tools.

Are public health physicians fading out of management?

Background: Recent developments in health services in the local arena in Norway have challenged the theoretical and applied scientific basis for both public health medicine and management. During the 1990s although public health physicians in Norway increased in number, they worked less with public health, as well as public health management. The effects of these developments on public health management are largely unknown.

[Physicians' experience with and attitudes to interaction between health care levels].

Background: We have studied physicians' experience with and attitudes to interaction between health care levels, and their opinions on how this can be improved.

Material And Methods: Three focus groups were established. They consisted of 15 male and 2 female physicians with 3 months to 28 years of experience.

More physicians in public health: less public health work?

Aim: The object was to assess changes in work priorities in local public health medicine in Norway over the period from 1994 to 1999.

Methods: Two cross-sectional studies were undertaken of physicians working in local public health medicine in all Norwegian municipalities, using a postal questionnaire.

Results: Half of the physicians working in public health in 1999 were recruited after 1994.