Changes in work tasks and organization of general practice in Norway during the COVID-19 pandemic: results from a comparative international study.

BACKGROUND: The COVID-19 pandemic led to huge and rapid changes in general practice in Norway as in the rest of Europe. This paper aims to explore to what extent the COVID-19 pandemic changed the work tasks and organization of Norwegian general practice. MATERIAL AND METHOD: We analysed data from the Norwegian part of the international, cross-sectional PRICOV-19 study, collecting data from general practice via an online self-reported questionnaire. We included 130 Norwegian general practices, representing an estimated 520 Norwegian general practitioners (GPs). All Norwegian GPs were invited to participate. In the analyses, we focused on items related to the use of alternatives to face-to-face consultations, changes in the workload, tasks and delegated responsibilities of both the GPs and other personnel in the GP offices, adaptations in routines related to hygiene measures, triage of patients, and how the official rules and recommendations affected the practices. RESULTS: There was a large and significant increase in the use of all forms of alternative consultation forms (digital text-based, video- and telephone consultations). The use of several different infection prevention measures were significantly increased, and the provision of hand sanitizer to patients increased from 29.6% pre-pandemic to 95.1% since the pandemic. More than half of the GPs (59.5%) reported that their responsibilities in the practice had increased, and 41% were happy with the task shift. 27% felt that they received adequate support from the government; however, 20% reported that guidelines from the government posed a threat to the well-being of the practice staff. We found no associations with the rurality of the practice location or size of the municipalities. CONCLUSION: Norwegian GPs adapted well to the need for increased use of alternatives to face-to-face consultations, and reported a high acceptance of their increased responsibilities. However, only one in four received adequate support from the government, which is an important learning point for similar situations in the future.

Decisions regarding antibiotic prescribing for acute sinusitis in Norwegian general practice. A qualitative focus group study.

BACKGROUND: Acute sinusitis is a frequent reason for primary care visits. Most patients recover within two weeks without antibiotic treatment. Despite this, about 50% of patients with acute sinusitis in Norwegian general practice are still prescribed antibiotics. We do not know the reason behind this discrepancy. AIM: To explore the clinical decision-making process and reasons for treatment with antibiotics for acute sinusitis among Norwegian general practitioners (GPs). METHODS: Five focus group interviews were conducted (N = 25) in different parts of Norway, including GPs of various age, gender, and experience. The interviews were analysed using Systematic Text Condensation. RESULTS: The results showed a very diverse management of acute sinusitis among GPs, with decisions regarding antibiotics not always aligning with guideline recommendations. Many of the GPs did not agree with the Norwegian guidelines for antibiotics and chose something other than phenoxymethylpenicillin as their first choice. Clinical predictors emphasized in decision-making were pain complaints and patient exhaustion. Pragmatic factors such as weekday, travel plans, or a full waiting room could also influence the decision. CONCLUSION: GPs found it difficult to identify when patients would benefit from antibiotic treatment for acute sinusitis, and different strategies were used to make prescribing decisions. For several GPs the degree of pain was one of the decisive reasons for antibiotic prescribing, however the guidelines for antibiotics do not give sufficient advice regarding pain treatment. These results suggest a need for revaluation of guideline contents and the way they are communicated to GPs.

We know that antibiotics are often overused in the treatment of acute sinusitis, but there is lack of knowledge about the reasons behind GPs decision to prescribe them.There were considerable variations in clinical decision-making regarding the treatment of acute sinusitis among Norwegian GPs.The patients' pain level, as well as pragmatic factors, were important deciding factors in the prescription of antibiotics.Guidelines for treatment regarding acute sinusitis may include more emphasis on pain management.

Feedback reports to the general practitioner (GP) on the patients' experiences: are GPs interested, and is this interest associated with GP factors and patient experience scores?

BACKGROUND: Patient experience feedback is key in patient centred health systems, but empirical evidence of general practitioner (GP) interest in it is sparse. We aimed to: (i) quantitatively estimate the level of GP interest for feedback reports on patient experience; (ii) explore determinants of such interest; and (iii) examine potential association between a priori interest and patient experience. METHODS: The patient experience survey included maximum 300 randomly selected patients for each of 50 randomly selected GPs (response rate 41.4%, n = 5,623). GPs were sent a postal letter offering feedback reports and were grouped according to their replies: (i) interested in the report; (ii) not interested. Associations between interest and GP variables were assessed with Chi-square tests and multivariate logistic regression, while associations between interest and scores for 5 patient experiences scales were assessed with multilevel regression models. RESULTS: About half (n = 21; 45.7%) of the GPs showed interest in the report by asking to receive the report. The only GP variable associated with a priori interest was being a specialist in general practice (58.6% vs. 23.5% for those without) (P = 0.021). Interest was significantly associated with the practice patient experience scale (4.1 higher score compared with those not interested, P = 0.048). Interest in the report had small and nonsignificant associations with the remaining patient experience scales. CONCLUSIONS: Almost half of the GPs, and almost 3 in 5 of specialists in general practice, were interested in receiving a GP-specific feedback report on patient experiences. Interest in the report was generally not related to patient experience scores.

Promoters and inhibitors for quality improvement work in general practice: a qualitative analysis of 2715 free-text replies.

BACKGROUND: Continuous quality improvement (QI) is necessary to develop and maintain high quality general practice services. General Practitioners (GPs') motivation is an important factor in the success of QI initiatives. We aimed to identify factors that impair or promote GPs' motivation for and participation in QI projects. MATERIAL AND METHODS: We analysed 2715 free-text survey replies from 2208 GPs participating in the QI intervention 'Correct Antibiotic Use in the Municipalities'. GPs received reports detailing their individual antibiotic prescriptions for a defined period, including a comparison with a corresponding previous period. The content was discussed in peer group meetings. Each GP individually answered work-sheets on three separate time-points, including free-text questions regarding their experiences with the intervention. Data were analysed using inductive thematic analysis. RESULTS: We identified three overarching themes in the GPs' thoughts on inhibitors and promoters of QI work: (1) the desire to be a better doctor, (2) structural and organisational factors as both promoters and inhibitors and (3) properties related to different QI measures. The provision of individual prescription data was generally very well received. The participants stressed the importance of a safe peer group, like the Continuous Medical Education group, for discussions, and also underlined the motivating effect of working together with their practice as a whole. Lack of time was essential in GPs' motivation for QI work. QI tools should be easily available and directly relevant in clinical work. CONCLUSION: The desire to be good doctor is a strong motivator for improvement, but the framework for general practice must allow for QI initiatives. QI tools must be easily obtainable and relevant for practice. Better tools for obtaining clinical data for individual GPs are needed.

Practice and System Factors Impact on Infection Prevention and Control in General Practice during COVID-19 across 33 Countries: Results of the PRICOV Cross-Sectional Survey.

Infection prevention and control (IPC) is an evidence-based approach used to reduce the risk of infection transmission within the healthcare environment. Effective IPC practices ensure safe and quality healthcare. The COVID-19 pandemic highlighted the need for enhanced IPC measures and the World Health Organization (WHO) emphasized the need for strict adherence to the basic principles of IPC. This paper aims to describe the IPC strategies implemented in general practice during the COVID-19 pandemic and to identify the factors that impact their adoption. Data were collected by means of an online self-reported questionnaire among general practices. Data from 4466 practices in 33 countries were included in the analysis. Our results showed a notable improvement in IPC during COVID-19 with more practices reporting that staff members never wore nail polish (increased from 34% to 46.2%); more practices reporting that staff never wear a ring/bracelet (increased from 16.1% to 32.3%); and more practices using a cleaning protocol (increased from 54.9% to 72.7%). Practice population size and the practice payment system were key factors related to adoption of a) range of IPC measures including patient flow arrangements and infrastructural elements. An understanding of the interplay between policy, culture, systemic supports, and behavior are necessary to obtain sustained improvement in IPC measures.

How to Realize the Benefits of Point-of-Care Testing at the General Practice: A Comparison of Four High-Income Countries.

BACKGROUND: In some countries, such as the Netherlands and Norway, point-of-care testing (POCT) is more widely implemented in general practice compared to countries such as England and Australia. To comprehend what is necessary to realize the benefits of POCT, regarding its integration in primary care, it would be beneficial to have an overview of the structure of healthcare operations and the transactions between stakeholders (also referred to as value networks). The aim of this paper is to identify the current value networks in place applying to POCT implementation at general practices in England, Australia, Norway and the Netherlands and to compare these networks in terms of seven previously published factors that support the successful implementation, sustainability and scale-up of innovations. METHODS: The value networks were described based on formal guidelines and standards published by the respective governments, organizational bodies and affiliates. The value network of each country was validated by at least two relevant stakeholders from the respective country. RESULTS: The analysis revealed that the biggest challenge for countries with low POCT uptake was the lack of effective communication between the several organizations involved with POCT as well as the high workload for general practitioners (GPs) aiming to implement POCT. It is observed that countries with a single national authority responsible for POCT have a better uptake as they can govern the task of POCT roll-out and management and reduce the workload for GPs by assisting with set-up, quality control, training and support. CONCLUSION: Setting up a single national authority may be an effective step towards realizing the full benefits of POCT. Although it is possible for day-to-day operations to fall under the responsibility of the GP, this is only feasible if support and guidance are readily available to ensure that the workload associated with POCT is limited and as low as possible.

Daytime contacts and general practitioner consultations, and pain as a reason for encounter in children with cerebral palsy; a Norwegian national registry linkage study.

AIM: The aim of this study was to compare the prevalence of daytime contacts and consultations, and pain as a reason for encounter (RFE) with a general practitioner (GP), in children with cerebral palsy (CP) (cases) to that of the general paediatric population (controls). METHODS: The study linked the Norwegian Directorate of Health's database for the control and reimbursement of health expenses, and the Norwegian Quality and Surveillance Registry for Cerebral Palsy, including children born from 1996 to 2012 in the period 2006 to 2018. All daytime contacts were included. International Classification for Primary Care was applied for RFE. RESULTS: Cases accounted for 0.46% of all daytime contacts and 0.27% of all daytime consultations, the latter corresponding with the estimated national prevalence of CP. GPs registered more administrative contact and coded pain as an RFE less frequently in consultations with cases (6%) than with controls (12%). INTERPRETATION: Children with CP did not consult GPs more than the general paediatric population did. In consultations, GPs should ask for pain even if the child with CP or parent does not address pain. The local multidisciplinary team should encourage the family to consider consulting a GP if the child is in pain.KEY MESSAGESPrevalence of GP consultations in children with CP is similar to that of children in the general population.GPs perform more administrative work for children with CP than for their other paediatric patients.GPs code pain as an RFE less frequently in consultations with children with CP than in consultations with children in the general population.

Good communication was valued as more important than accessibility according to 707 Nordic primary care patients: a report from the QUALICOPC study.

OBJECTIVE: To explore Nordic patients' ranking of the importance of different aspects of general practice. DESIGN: Patients ranked the importance of 47 statements reflecting five quality domains: communication, involvement, accessibility, continuity, and comprehensiveness. SETTING: Nordic general practice. SUBJECTS: Patients ≥18 years in general practitioners waiting rooms. MAIN OUTCOME MEASURES: Items rated as important or very important by ≥ 90% in all countries were identified. Associations with patient characteristics were analysed by logistic regression. RESULTS: 209 Danish, 175 Norwegian, 129 Finnish, 112 Swedish and 82 Icelandic patients responded. Ten statements were ranked as important or very important by ≥90% in each country. Six pertained to communication, three to patient involvement and one to the comprehensiveness of care. No items regarding accessibility or continuity exceeded the 90% limit. The item most frequently rated as very important was 'I understand what the GP explains''. Female patients were more likely to value personal treatment (OR = 2.9; 95%CI 1.5-5.5) and receiving instructions if things went wrong (1.7; 1.2-2.2). Older patients >65 years put less emphasis than those <35 on whether the GP takes them seriously (0.4; 0.3-0.5) and on the importance of instructions (0.5; 0.4-0.7). Patients with chronic diseases were less concerned (0.6; 0.4-0.8) with receiving instructions, but valued strongly that a GP knows when to refer (2.2; 1.5-3.3). CONCLUSION: Patients in all countries assigned high value to good communication. Availability was deemed important but came secondary to good communication. IMPLICATIONS: Organisational framework for general practice must allow for acceptable communication quality as well as availability.Key pointsIn order to identify relevant service areas for quality improvement in primary care, we aimed to increase knowledge of patient ranked importance of different dimensions of care.Nordic primary care patients valued good communication and involvement in decisions higher than accessibility to care.A singular focus on the access of care when developing services may not be in accordance with patient preferences.

Patient enablement after a consultation with a general practitioner-Explaining variation between countries, practices and patients.

BACKGROUND: Patient enablement is a concept developed to measure quality in primary health care. The comparative analysis of patient enablement in an international context is lacking. OBJECTIVE: To explain variation in patient enablement between patients, general practitioners (GPs) and countries. To find independent variables associated with enablement. DESIGN: We constructed multi-level logistic regression models encompassing variables from patient, GP and country levels. The proportions of explained variances at each level and odds ratios for independent variables were calculated. SETTING AND PARTICIPANTS: A total of 7210 GPs and 58 930 patients in 31 countries were recruited through the Quality and Costs of Primary Care in Europe (QUALICOPC) study framework. In addition, data from the Primary Health Care Activity Monitor for Europe (PHAMEU) study and Hofstede's national cultural dimensions were combined with QUALICOPC data. RESULTS: In the final model, 50.6% of the country variance and 18.4% of the practice variance could be explained. Cultural dimensions explained a major part of the variation between countries. Several patient-level and only a few practice-level variables showed statistically significant associations with patient enablement. Structural elements of the relevant health-care system showed no associations. From the 20 study hypotheses, eight were supported and four were partly supported. DISCUSSION AND CONCLUSIONS: There are large differences in patient enablement between GPs and countries. Patient characteristics and patients' perceptions of consultation seem to have the strongest associations with patient enablement. When comparing patient-reported measures as an indicator of health-care system performance, researchers should be aware of the influence of cultural elements.

Nitric oxide in exhaled gas and tetrahydrobiopterin in plasma after exposure to hyperoxia.

The fraction of nitric oxide in exhaled gas (FENO) is decreased after exposure to hyperoxia in vivo, although the mechanisms for this decrease is not clear. A key co-factor for nitric oxide synthase (NOS), tetrahydrobiopterin (BH4), has been shown to be oxidized in vitro when exposed to hyperoxia. We hypothesized that the decrease of FENO is due to decreased enzymatic generation of NO due to oxidation of BH4. The present study was performed to investigate the relationship between levels of FENO and plasma BH4 following hyperoxic exposure in humans. Two groups of healthy subjects were exposed to 100% oxygen for 90 minutes. FENO was measured before and 10 minutes (n = 13) or 60 minutes (n = 14) after the exposure. Blood samples were collected at the same time points for quantification of biopterin levels (BH4, BH2 and B) using LC-MS/MS. Each subject was his or her own control, breathing air for 90 minutes on a separate day. Hyperoxia resulted in a 28.6 % decrease in FENO 10 minutes after exposure (p < 0.001), confirming previous findings. Moreover, hyperoxia also caused a 14.2% decrease in plasma BH4 (p = 0.012). No significant differences were observed in the group measured 60 minutes after exposure. No significant correlation was found between the changes in FENO and BH4 after the hyperoxic exposure (r = 0.052, p = 0.795), this might be due to the recovery of BH4 being faster than the recovery of FENO.

Hyperoxia and lack of ascorbic acid deplete tetrahydrobiopterin without affecting NO generation in endothelial cells.

Nitric oxide (NO) may protect against gas bubble formation and risk of decompression sickness. We have previously shown that the crucial co-factor tetrahydrobiopterin (BH4) is oxidized in a dose-dependent manner when exposed to hyperoxia similar to diving conditions but with minor effects on the NO production by nitric oxide synthase. By manipulating the intracellular redox state, we further investigated the relationship between BH4 levels and production of NO in human endothelial cells (HUVECs). HUVECs were cultured with and without ascorbic acid (AA) and the glutathione (GSH) synthesis inhibitor buthionine sulfoximine, prior to hyperoxic exposure. The levels of biopterins and GSH were determined in cell lysates while the production of NO was determined in intact cells. Omitting AA resulted in a 91% decrease in BH4 levels (0.49 ± 0.08 to 0.04 ± 0.01 pmol/106 cells, p⟨0.001) at 20 kPa oxygen (O2), and 88% decrease (0.24 ± 0.03 to 0.03 ± 0.01 pmol/106 cells, p=0.01) after exposure to 60 kPa O2. The NO generation was decreased by 23% (74.5 ± 2.2 to 57.3 ± 5.6 pmol/min/mg protein, p⟨0.001) at 20 kPa O2, but no significant change was observed at 60 kPa O2. GSH depletion had no effects on the NO generation. No correlation was found between NO generation and the corresponding intracellular BH4 concentration (p=0.675, r=-0.055) or the BH4 to BH2 ratio (p=0.983, r=0.003), determined across 18 in vitro experiments. Decreased BH4 in HUVECs, due to hyperoxia or lack of ascorbic acid, does not imply corresponding decreases in NO generation.

Decrease of tetrahydrobiopterin and NO generation in endothelial cells exposed to simulated diving.

Purpose: Nitric oxide (NO) has been shown to protect against bubble formation and the risk of decompression sickness. We hypothesize that oxidation of tetrahydrobiopterin (BH4) leads to a decreased production of NO during simulated diving. Methods: Human umbilical vein endothelial cells (HUVEC) were exposed to hyperoxia or simulated diving for 24 hours. The levels of biopterins (BH4, BH2 and B) were determined by LC-MS/MS, and the production of NO by monitoring the conversion of L-arginine to L-citrulline. Results: Exposure to hyperoxia decreased BH4 in a dose-dependent manner; by 48 ± 15% following exposure to 40 kPa O2 (P⟨0.001 vs. control at 20 kPa O2), and 70 ± 16% following exposure to 60 kPa O2. Exposure to 40 kPa O2 decreased NO production by 25 ± 9%, but there was no further decrease when increasing oxygen exposure to 60 kPa (25 ± 10%). No additional effects of simulated diving were observed, indicating no additive or synergistic effects of hyperbaria and hyperoxia on the BH4 level or NO generation. Conclusion: NO generation in intact human endothelial cells was decreased by simulated diving, as well as by hyperoxic exposure, while BH4 levels seem to be affected only by hyperoxia. Hence, the results suggest that BH4 is not the sole determinant of NO generation in HUVEC.

Patients' and GPs' expectations regarding healthcare-seeking behaviour: a Norwegian comparative study.

BACKGROUND: GPs are Norwegian patients' first contact point with the healthcare system for most medical problems. However, little is known regarding GPs' expectations towards their patients' healthcare-seeking behaviour, or whether doctors and patients have coinciding expectations of what GPs can do for their patients. AIM: To investigate patients' and GPs' expectations regarding patients' healthcare-seeking behaviour in primary care, and to make comparisons between the two. DESIGN & SETTING: Norwegian data from the Quality and Costs of Primary Care in Europe (QUALICOPC) questionnaire study, with information from GPs and their patients. METHOD: Binary logistic regression was used to investigate associations between expectations, sex and age of GPs and patients, list size, and geographical location of practice. Results are presented as odds ratios (ORs) with 95% confidence intervals (CIs). Expectation differences between GPs and patients were analysed using generalised estimating equations (GEEs). Due to multiple testing, Bonferroni correction was used to define significance level at P≤0.002. RESULTS: In total, 198 GPs (39.1% female) and 1529 patients (61.9% female) responded. No associations with sex or age were found for the GPs' expectations regarding patients' healthcare-seeking behaviour. Among patients, fewer males than females expected that most people would see their GP for sprained ankle (OR 0.7, 95% CI = 0.5 to 0.9), finger cut (OR 0.6, 95% CI = 0.4 to 0.7), smoking cessation (OR 0.6, 95% CI = 0.5 to 0.8), or anxiety (OR 0.4, 95% CI = 0.3 to 0.6). Older patients (aged >65 years) found it more important than younger patients to see a doctor in the presence of medical symptoms. GPs had higher expectations than their patients that people in general would see them for deteriorated vision (OR 4.2, 95% CI = 2.5 to 6.9), sexual problems (OR 1.8, 95% CI =1.3 to 2.6), and anxiety (OR 3.0, 95% CI =1.5 to 6.0). CONCLUSION: For several common health problems, males are less likely than females to believe that people will see their GP. GPs may overestimate to what degree their patients will see them for a number of common medical problems.

Differences in medical services in Nordic general practice: a comparative survey from the QUALICOPC study.

OBJECTIVE: We aim to describe medical services provided by Nordic general practitioners (GPs), and to explore possible differences between the countries. DESIGN AND SETTING: We did a comparative analysis of selected data from the Nordic part of the study Quality and Costs of Primary Care in Europe. SUBJECTS: 875 Nordic GPs (198 Norwegian, 80 Icelandic, 97 Swedish, 212 Danish and 288 Finnish) answered identical questionnaires regarding their practices. MAIN OUTCOME MEASURES: The GPs indicated which equipment they used in practice, which procedures that were carried out, and to what extent they were involved in treatment/follow-up of a selection of diagnoses. RESULTS: The Danish GPs performed minor surgical procedures significantly less frequent than GPs in all other countries, although they inserted intrauterine devices significantly more often than GPs in Iceland, Sweden and Finland. Finnish GPs performed a majority of the medical procedures more frequently than GPs in the other countries. The GPs in Iceland reported involvement in a more narrow selection of conditions than the GPs in the other countries. The Finnish GPs had more advanced technical equipment than GPs in all other Nordic countries. CONCLUSION: GPs in all Nordic countries are well equipped and offer a wide range of medical services, yet with a substantial variation between countries. There was no clear pattern of GPs in one country doing consistently more procedures, having consistently more equipment and treating a larger diversity of medical conditions than GPs in the other countries. However, structural factors seemed to affect the services offered.

Differences in medical services in Nordic general practice: a comparative survey from the QUALICOPC study.

OBJECTIVE: We aim to describe medical services provided by Nordic general practitioners (GPs), and to explore possible differences between the countries. DESIGN AND SETTING: We did a comparative analysis of selected data from the Nordic part of the study Quality and Costs of Primary Care in Europe (QUALICOPC). SUBJECTS: A total of 875 Nordic GPs (198 Norwegian, 80 Icelandic, 97 Swedish, 212 Danish and 288 Finnish) answered identical questionnaires regarding their practices. MAIN OUTCOME MEASURES: The GPs indicated which equipment they used in practice, which procedures that were carried out, and to what extent they were involved in treatment/follow-up of a selection of diagnoses. RESULTS: The Danish GPs performed minor surgical procedures significantly less frequent than GPs in all other countries, although they inserted IUDs significantly more often than GPs in Iceland, Sweden and Finland. Finnish GPs performed a majority of the medical procedures more frequently than GPs in the other countries. The GPs in Iceland reported involvement in a more narrow selection of conditions than the GPs in the other countries. The Finnish GPs had more advanced technical equipment than GPs in all other Nordic countries. CONCLUSIONS: GPs in all Nordic countries are well equipped and offer a wide range of medical services, yet with a substantial variation between countries. There was no clear pattern of GPs in one country doing consistently more procedures, having consistently more equipment and treating a larger diversity of medical conditions than GPs in the other countries. However, structural factors seemed to affect the services offered.

Patient experiences and the association with organizational factors in general practice: results from the Norwegian part of the international, multi-centre, cross-sectional QUALICOPC study.

BACKGROUND: General practitioners (GPs) constitute a vital part of a strong primary health care system. We need further knowledge concerning factors that may affect the patients' experiences in their meetings with the GPs. We investigated to what degree organizational factors and GP characteristics are associated with patients' communicative experiences in a consultation. METHODS: We used data from the Norwegian part of the international, multi-center study Quality and Costs of Primary Care in Europe (QUALICOPC). We included 198 Norwegian GPs and 1529 patients. The patients completed a survey concerning experiences in a consultation with a GP on the inclusion day. The GPs completed a survey regarding organizational aspects of their own practice. Main outcome measures were seven statements concerning how the patients experienced the communication with the GP during the consultation. A generalized estimating equation logistic regression model was used to identify variations in patient experiences associated with characteristics of the GPs and their practices. RESULTS: The patients reported overall positive experiences with their GP consultations. Patients who consulted a GP with a short patient list were less likely than patients who consulted a GP with a medium sized list to regard the GP as polite (Odds Ratio (OR) 0.2; 95 % CI 0.1-0.7), to report that the GP asked questions about their health problems (OR 0.6; 0.4-1.0) or that the GP used sufficient time (OR 0.5; CI 0.3-0.9). Patients who consulted a GP with a long patient list compared to patients who consulted a GP with a medium sized list were less likely to feel that they could cope better after the GP visit (OR 0.5; 0.3-0.9) and more likely to feel that the GP hardly looked at them while talking (OR 1.8; 1.0-3.0). No associations with patient experiences were found with the average duration of the consultations, whether the GP worked in a fee-for-service model or whether the GP was the patient's regular doctor. CONCLUSIONS: Norwegian patients report predominantly positive experiences when consulting a GP. Positive communication experiences are most likely to be reported when the GP has a medium sized patient list.

Preanalytical Stability of Gemcitabine and its Metabolite 2', 2'-Difluoro-2'-Deoxyuridine in Whole Blood-Assessed by Liquid Chromatography Tandem Mass Spectrometry.

Gemcitabine (2',2'-difluoro-2'-deoxycytidine, dFdC) and metabolite (2',2'-difluoro-2'-deoxyuridine, dFdU) quantification is warranted for individualized treatment strategies. Analyte stability is crucial for the validity of such quantification. We therefore studied the impact of the time interval from blood sampling to separation of plasma on gemcitabine stability. Blood from gemcitabine-treated patients was drawn into tetrahydrouridine (THU)-spiked heparin and ethylenediaminetetraacetic acid tubes and kept on ice until separation. Plasma was separated sequentially up to 24 h after sampling and dFdC and dFdU were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS). The change in plasma concentrations over time was compared with the highest imprecision for concentrations above the lower limit of quantification of the LC-MS/MS method. Analyte concentrations decreased slightly over time, but for samples stored for 4 h on ice, the decline was smaller than the expected analytical imprecision. After 24 h, the maximum decline was 14.0%, which exceeded the expected analytical imprecision. dFdC and dFdU stabilities were acceptable for at least 4 h when THU-spiked whole blood samples were kept on ice. This is within the scope of routine sampling procedures. Further, variations in separation time intervals within this time frame are negligible when interpreting drug concentrations.

Liquid chromatography/tandem mass spectrometry method for simultaneous quantification of eight endogenous nucleotides and the intracellular gemcitabine metabolite dFdCTP in human peripheral blood mononuclear cells.

Quantification of endogenous nucleotides is of interest for investigation of numerous cellular biochemical processes, such as energy metabolism and signal transduction, and may also be applied in cancer and antiretroviral therapies in which nucleoside analogues are used. For these purposes we developed and validated a sensitive and high accuracy ion-pair liquid chromatography tandem mass spectrometry (IP LC-MS/MS) method for simultaneous quantification of eight endogenous nucleotides (ATP, CTP, GTP, UTP, dATP, dCTP, dGTP, dTTP) and 2',2'-difluoro-2'-deoxycytidine triphosphate (dFdCTP), an intracellular metabolite of the nucleoside analogue gemcitabine. The assay was validated using 200µL aliquots of peripheral blood mononuclear cell (20×10(6)cells/ml, 4×10(6)cells) extracts, pretreated with activated charcoal and spiked with unlabeled nucleotides, deoxynucleotides and dFdCTP. Analytes were extracted by simple precipitation with cold 60% methanol containing isotope labeled internal standards and separated on a porous graphitic carbon column. For method validation, the concentration ranges were: 0.125-20.8pmol injected for deoxynucleotides, 0.25-312.5pmol injected for dFdCTP and 5-3200pmol injected for nucleotides. The highest coefficients of variation (CV) were 12.1% for within run assay and 11.4% for between run assay, both representing the precision at the lowest analyte concentrations. The method was applied to monitor dFdCTP and changes in endogenous nucleotides in patients who were receiving gemcitabine infusions.

Hyperoxia but not ambient pressure decreases tetrahydrobiopterin level without affecting the enzymatic capability of nitric oxide synthase in human endothelial cells.

Nitric oxide (NO) seems to be related to bubble formation and endothelial dysfunction resulting in decompression sickness. Bubble formation can be affected by aerobic exercise or manipulating NO. A prior heat stress (HS) has been shown to confer protection against decompression sickness in rats. An important question was if the oxidative environment experienced during diving limits the availability of the nitric oxide synthase (NOS) cofactor tetrahydrobiopterin (BH4). Human endothelial cells were used to investigate how HS and simulated diving affected NO synthesis and defense systems such as heat shock protein 70 (HSP70) and glutathione (GSH). BH4 was measured using a novel LC-MS/MS method and NOS by monitoring the conversion of radiolabeled L-arginine to L-citrulline. Increased pO2 reduced BH4 levels in cells in a dose-dependent manner independently of high pressure. This effect may result in decreased generation of NO by NOS. The BH4 decrease seemed to be abolished when cells were exposed to HS prior to hyperoxia. NOS enzyme was unaffected by increased pO2 but substantially reduced after HS. The BH4 level seemed to a minor extent to be dependent upon GSH and probably to a higher degree dependent on other antioxidants such as ascorbic acid. A simulated dive at 60 kPa O2 had a potentiating effect on the heat-induced HSP70 expression, whereas GSH levels were unaffected by hyperoxic exposure. HS, hyperoxia, and dive affected several biochemical parameters that may play important roles in the mechanisms protecting against the adverse effects of saturation diving.

Simultaneous quantification of tetrahydrobiopterin, dihydrobiopterin, and biopterin by liquid chromatography coupled electrospray tandem mass spectrometry.

A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based method was developed for the quantification of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), and biopterin (B) in human umbilical vein endothelial cells (HUVECs). Freshly prepared cell samples were treated with a mixture consisting of 0.2M trichloroacetic acid (TCA) and a cocktail of various antioxidants in order to precipitate proteins and other cellular components and to stabilize red/ox conditions in the lysates. Chromatography of the cell lysates was performed on a Poroshell 120 SB-C18 column (2.7µm, 150×2.1mm) using a stepwise gradient elution made from two mobile phases. Quantification was performed on a triple quadrupole mass spectrometer employing electrospray ionization with the operating conditions as multiple reaction monitoring (MRM) at positive ion mode. Total chromatographic run time was 23min. The method was validated for analysis in HUVECs, and the limits of quantification were 1nM for BH4 and BH2 and 2.5nM for B. Standard curves were linear in the concentration ranges of 1 to 100nM for BH4 and BH2 and 2.5 to 100nM for B. The current study reports a novel method for the simultaneous and direct quantification of BH4, BH2, and B in a single injection.