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1.  Evaluation of a Single Dose of Ferric Carboxymaltose in Fatigued, Iron-Deficient Women – PREFER a Randomized, Placebo-Controlled Study 
PLoS ONE  2014;9(4):e94217.
Background
Unexplained fatigue is often left untreated or treated with antidepressants. This randomized, placebo-controlled, single-blinded study evaluated the efficacy and tolerability of single-dose intravenous ferric carboxymaltose (FCM) in iron-deficient, premenopausal women with symptomatic, unexplained fatigue.
Methods
Fatigued women (Piper Fatigue Scale [PFS] score ≥5) with iron deficiency (ferritin <50 µg/L and transferrin saturation <20%, or ferritin <15 µg/L) and normal or borderline hemoglobin (≥115 g/L) were enrolled in 21 sites in Austria, Germany, Sweden and Switzerland, blinded to the study drug and randomized (computer-generated randomization sequence) to a single FCM (1000 mg iron) or saline (placebo) infusion. Primary endpoint was the proportion of patients with reduced fatigue (≥1 point decrease in PFS score from baseline to Day 56).
Results
The full analysis included 290 women (FCM 144, placebo 146). Fatigue was reduced in 65.3% (FCM) and 52.7% (placebo) of patients (OR 1.68, 95%CI 1.05–2.70; p = 0.03). A 50% reduction of PFS score was achieved in 33.3% FCM- vs. 16.4% placebo-treated patients (p<0.001). At Day 56, all FCM-treated patients had hemoglobin levels ≥120 g/L (vs. 87% at baseline); with placebo, the proportion decreased from 86% to 81%. Mental quality-of-life (SF-12) and the cognitive function scores improved better with FCM. ‘Power of attention’ improved better in FCM-treated patients with ferritin <15 µg/L. Treatment-emergent adverse events (placebo 114, FCM 209; most frequently headache, nasopharyngitis, pyrexia and nausea) were mainly mild or moderate.
Conclusion
A single infusion of FCM improved fatigue, mental quality-of-life, cognitive function and erythropoiesis in iron-deficient women with normal or borderline hemoglobin. Although more side effects were reported compared to placebo, FCM can be an effective alternative in patients who cannot tolerate or use oral iron, the common treatment of iron deficiency. Overall, the results support the hypothesis that iron deficiency can affect women’s health, and a normal iron status should be maintained independent of hemoglobin levels.
Trial Registration
ClinicalTrials.gov NCT01110356
doi:10.1371/journal.pone.0094217
PMCID: PMC3994001  PMID: 24751822
2.  Screening Primary-Care Patients Forgoing Health Care for Economic Reasons 
PLoS ONE  2014;9(4):e94006.
Background
Growing social inequities have made it important for general practitioners to verify if patients can afford treatment and procedures. Incorporating social conditions into clinical decision-making allows general practitioners to address mismatches between patients' health-care needs and financial resources.
Objectives
Identify a screening question to, indirectly, rule out patients' social risk of forgoing health care for economic reasons, and estimate prevalence of forgoing health care and the influence of physicians' attitudes toward deprivation.
Design
Multicenter cross-sectional survey.
Participants
Forty-seven general practitioners working in the French–speaking part of Switzerland enrolled a random sample of patients attending their private practices.
Main Measures
Patients who had forgone health care were defined as those reporting a household member (including themselves) having forgone treatment for economic reasons during the previous 12 months, through a self-administered questionnaire. Patients were also asked about education and income levels, self-perceived social position, and deprivation levels.
Key Results
Overall, 2,026 patients were included in the analysis; 10.7% (CI95% 9.4–12.1) reported a member of their household to have forgone health care during the 12 previous months. The question “Did you have difficulties paying your household bills during the last 12 months” performed better in identifying patients at risk of forgoing health care than a combination of four objective measures of socio-economic status (gender, age, education level, and income) (R2 = 0.184 vs. 0.083). This question effectively ruled out that patients had forgone health care, with a negative predictive value of 96%. Furthermore, for physicians who felt powerless in the face of deprivation, we observed an increase in the odds of patients forgoing health care of 1.5 times.
Conclusion
General practitioners should systematically evaluate the socio-economic status of their patients. Asking patients whether they experience any difficulties in paying their bills is an effective means of identifying patients who might forgo health care.
doi:10.1371/journal.pone.0094006
PMCID: PMC3974836  PMID: 24699726
3.  Rendu-Osler disease: treatment with oestrogen/progestagen versus octreotide 
BMJ Case Reports  2011;2011:bcr1120103534.
In Rendu-Osler disease, haemorrhages due to gastrointestinal vascular malformations are common. Surgical and endoscopic treatments for haemorrhage due to gastrointestinal vascular malformations are compromised when lesions are diffuse, escape identification or are inaccessible to treatment. Hormonal treatment with oestrogen and progestagens is still controversial based on contradictory results from two randomised clinical trials. Although somatostatin and its long-acting analogue, octreotide, have been reported to be beneficial in preventing rebleeding, there is no consensus on this type of treatment. This case report shows how the combination of ethinyloestradiol and norethisterone markedly reduced the need for blood transfusions with few side effects in one patient; in comparison, octreotide seems less effective but this could be related to a worsening of the disease.
doi:10.1136/bcr.11.2010.3534
PMCID: PMC3062877  PMID: 22707551
4.  Weed or Wheel! fMRI, Behavioural, and Toxicological Investigations of How Cannabis Smoking Affects Skills Necessary for Driving 
PLoS ONE  2013;8(1):e52545.
Marijuana is the most widely used illicit drug, however its effects on cognitive functions underling safe driving remain mostly unexplored. Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ9-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions. Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. We show that cannabis smoking, even at low Δ9-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection. In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity. Subjects are more attracted by intrapersonal stimuli (“self”) and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ9-Tetrahydrocannabinol. These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving.
doi:10.1371/journal.pone.0052545
PMCID: PMC3534702  PMID: 23300977
5.  Development of mental disorders one year after exposure to psychosocial stressors; a cohort study in primary care patients with a physical complaint 
BMC Psychiatry  2012;12:120.
Background
Mental disorders, common in primary care, are often associated with physical complaints. While exposure to psychosocial stressors and development or presence of principal mental disorders (i.e. depression, anxiety and somatoform disorders defined as multisomatoforme disorders) is commonly correlated, temporal association remains unproven. The study explores the onset of such disorders after exposure to psychosocial stressors in a cohort of primary care patients with at least one physical symptom.
Method
The cohort study SODA (SOmatization, Depression and Anxiety) was conducted by 21 private-practice GPs and three fellow physicians in a Swiss academic primary care centre. GPs included patients via randomized daily identifiers. Depression, anxiety or somatoform disorders were identified by the full Patient Health Questionnaire (PHQ), a validated procedure to identify mental disorders based on DSM-IV criteria. The PHQ was also used to investigate exposure to psychosocial stressors (before the index consultation and during follow up) and the onset of principal mental disorders after one year of follow up.
Results
From November 2004 to July 2005, 1020 patients were screened for inclusion. 627 were eligible and 482 completed the PHQ one year later and were included in the analysis (77%). At one year, prevalence of principal mental disorders was 30/153 (19.6% CI95% 13.6; 26.8) for those initially exposed to a major psychosocial stressor and 26/329 (7.9% CI95% 5.2; 11.4) for those not. Stronger association exists between psychosocial stressors and depression (RR = 2.4) or anxiety (RR = 3.5) than multisomatoforme disorders (RR = 1.8). Patients who are “bothered a lot” (subjective distress) by a stressor are therefore 2.5 times (CI95% 1.5; 4.0) more likely to experience a mental disorder at one year. A history of psychiatric comorbidities or psychological treatment was not a confounding factor for developing a principal mental disorder after exposure to psychosocial stressors.
Conclusion
This primary care study shows that patients with physical complaints exposed to psychosocial stressors had a higher risk for developing mental disorders one year later. This temporal association opens the field for further research in preventive care for mental diseases in primary care patients.
doi:10.1186/1471-244X-12-120
PMCID: PMC3549739  PMID: 22906197
Primary health care; Longitudinal studies; Mental disorder; Psychosocial deprivation; Stress
6.  Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial 
Background:
The true benefit of iron supplementation for nonanemic menstruating women with fatigue is unknown. We studied the effect of oral iron therapy on fatigue and quality of life, as well as on hemoglobin, ferritin and soluble transferrin receptor levels, in nonanemic iron-deficient women with unexplained fatigue.
Methods:
We performed a multicentre, parallel, randomized controlled, closed-label, observer-blinded trial. We recruited from the practices of 44 primary care physicians in France from March to July 2006. We randomly assigned 198 women aged 18–53 years who complained of fatigue and who had a ferritin level of less than 50 ug/L and hemoglobin greater than 12.0 g/dL to receive either oral ferrous sulfate (80 mg of elemental iron daily; n = 102) or placebo (n = 96) for 12 weeks. The primary outcome was fatigue as measured on the Current and Past Psychological Scale. Biological markers were measured at 6 and 12 weeks.
Results:
The mean score on the Current and Past Psychological Scale for fatigue decreased by 47.7% in the iron group and by 28.8% in the placebo group (difference –18.9%, 95% CI −34.5 to −3.2; p = 0.02), but there were no significant effects on quality of life (p = 0.2), depression (p = 0.97) or anxiety (p = 0.5). Compared with placebo, iron supplementation increased hemoglobin (0.32 g/dL; p = 0.002) and ferritin (11.4 μg/L; p < 0.001) and decreased soluble transferrin receptor (−0.54 mg/L; p < 0.001) at 12 weeks.
Interpretation:
Iron supplementation should be considered for women with unexplained fatigue who have ferritin levels below 50 μg/L. We suggest assessing the efficiency using blood markers after six weeks of treatment. Trial registration no. EudraCT 2006–000478–56.
doi:10.1503/cmaj.110950
PMCID: PMC3414597  PMID: 22777991
7.  Development and validation of a clinical prediction rule for chest wall syndrome in primary care 
BMC Family Practice  2012;13:74.
Background
Chest wall syndrome (CWS), the main cause of chest pain in primary care practice, is most often an exclusion diagnosis. We developed and evaluated a clinical prediction rule for CWS.
Methods
Data from a multicenter clinical cohort of consecutive primary care patients with chest pain were used (59 general practitioners, 672 patients). A final diagnosis was determined after 12 months of follow-up. We used the literature and bivariate analyses to identify candidate predictors, and multivariate logistic regression was used to develop a clinical prediction rule for CWS. We used data from a German cohort (n = 1212) for external validation.
Results
From bivariate analyses, we identified six variables characterizing CWS: thoracic pain (neither retrosternal nor oppressive), stabbing, well localized pain, no history of coronary heart disease, absence of general practitioner’s concern, and pain reproducible by palpation. This last variable accounted for 2 points in the clinical prediction rule, the others for 1 point each; the total score ranged from 0 to 7 points. The area under the receiver operating characteristic (ROC) curve was 0.80 (95% confidence interval 0.76-0.83) in the derivation cohort (specificity: 89%; sensitivity: 45%; cut-off set at 6 points). Among all patients presenting CWS (n = 284), 71% (n = 201) had a pain reproducible by palpation and 45% (n = 127) were correctly diagnosed. For a subset (n = 43) of these correctly classified CWS patients, 65 additional investigations (30 electrocardiograms, 16 thoracic radiographies, 10 laboratory tests, eight specialist referrals, one thoracic computed tomography) had been performed to achieve diagnosis. False positives (n = 41) included three patients with stable angina (1.8% of all positives). External validation revealed the ROC curve to be 0.76 (95% confidence interval 0.73-0.79) with a sensitivity of 22% and a specificity of 93%.
Conclusions
This CWS score offers a useful complement to the usual CWS exclusion diagnosing process. Indeed, for the 127 patients presenting CWS and correctly classified by our clinical prediction rule, 65 additional tests and exams could have been avoided. However, the reproduction of chest pain by palpation, the most important characteristic to diagnose CWS, is not pathognomonic.
doi:10.1186/1471-2296-13-74
PMCID: PMC3444903  PMID: 22866824
Chest pain; Primary care; Thoracic wall; Musculoskeletal system; Decision support techniques; Diagnosis
8.  Detecting and measuring deprivation in primary care: development, reliability and validity of a self-reported questionnaire: the DiPCare-Q 
BMJ Open  2012;2(1):e000692.
Objectives
Advances in biopsychosocial science have underlined the importance of taking social history and life course perspective into consideration in primary care. For both clinical and research purposes, this study aims to develop and validate a standardised instrument measuring both material and social deprivation at an individual level.
Methods
We identified relevant potential questions regarding deprivation using a systematic review, structured interviews, focus group interviews and a think-aloud approach. Item response theory analysis was then used to reduce the length of the 38-item questionnaire and derive the deprivation in primary care questionnaire (DiPCare-Q) index using data obtained from a random sample of 200 patients during their planned visits to an ambulatory general internal medicine clinic. Patients completed the questionnaire a second time over the phone 3 days later to enable us to assess reliability. Content validity of the DiPCare-Q was then assessed by 17 general practitioners. Psychometric properties and validity of the final instrument were investigated in a second set of patients. The DiPCare-Q was administered to a random sample of 1898 patients attending one of 47 different private primary care practices in western Switzerland along with questions on subjective social status, education, source of income, welfare status and subjective poverty.
Results
Deprivation was defined in three distinct dimensions: material (eight items), social (five items) and health deprivation (three items). Item consistency was high in both the derivation (Kuder-Richardson Formula 20 (KR20) =0.827) and the validation set (KR20 =0.778). The DiPCare-Q index was reliable (interclass correlation coefficients=0.847) and was correlated to subjective social status (rs=−0.539).
Conclusion
The DiPCare-Q is a rapid, reliable and validated instrument that may prove useful for measuring both material and social deprivation in primary care.
Article summary
Article focus
This study aims to identify and test the relevance of existing indicators of deprivation to help clinicians investigate social status.
We constructed and validated an individual-level measurement of deprivation for patients attending their general practitioner: the deprivation in primary care questionnaire (DiPCare-Q).
Key messages
The DiPCare-Q proposes a reliable, validated instrument for screening and measuring deprivation among patients in developed countries.
Compared with usual indicators of socioeconomical status, the DipCare-Q index gives important additional information on subjective social status and state of deprivation.
Social deprivation is an important aspect of deprivation in general and needs to be distinguished from material deprivation.
Strengths and limitations of this study
Compared with socioeconomical status, self-reported perceived signs of deprivation are more relevant in identifying potential underlying social distress. However, the DiPCare-Q only identifies signs of deprivation without highlighting their reasons.
To improve public health and limit effects of health disparities, detecting deprivation also requires physicians to know how this is to affect their relation with their patient's in a beneficial way.
doi:10.1136/bmjopen-2011-000692
PMCID: PMC3274718  PMID: 22307103
9.  Clinical evaluation of iron treatment efficiency among non-anemic but iron-deficient female blood donors: a randomized controlled trial 
BMC Medicine  2012;10:8.
Background
Iron deficiency without anemia is related to adverse symptoms that can be relieved by supplementation. Since a blood donation can induce such an iron deficiency, we investigated the clinical impact of iron treatment after a blood donation.
Methods
One week after donation, we randomly assigned 154 female donors with iron deficiency without anemia, aged below 50 years, to a four-week oral treatment of ferrous sulfate versus a placebo. The main outcome was the change in the level of fatigue before and after the intervention. Aerobic capacity, mood disorder, quality of life, compliance and adverse events were also evaluated. Hemoglobin and ferritin were used as biological markers.
Results
The effect of the treatment from baseline to four weeks of iron treatment was an increase in hemoglobin and ferritin levels to 5.2 g/L (P < 0.01) and 14.8 ng/mL (P < 0.01), respectively. No significant clinical effect was observed for fatigue (-0.15 points, 95% confidence interval -0.9 points to 0.6 points, P = 0.697) or for other outcomes. Compliance and interruption for side effects was similar in both groups. Additionally, blood donation did not induce overt symptoms of fatigue in spite of the significant biological changes it produces.
Conclusions
These data are valuable as they enable us to conclude that donors with iron deficiency without anemia after a blood donation would not clinically benefit from iron supplementation.
Trial Registration
ClinicalTrials.gov: NCT00981877
doi:10.1186/1741-7015-10-8
PMCID: PMC3292842  PMID: 22272750
10.  The 'help' question doesn't help when screening for major depression: external validation of the three-question screening test for primary care patients managed for physical complaints 
BMC Medicine  2011;9:114.
Background
Major depression, although frequent in primary care, is commonly hidden behind multiple physical complaints that are often the first and only reason for patient consultation. Major depression can be screened by two validated questions that are easier to use in primary care than the full Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. A third question, called the 'help' question, improves the specificity without apparently decreasing the sensitivity of this screening procedure. We validated the abbreviated screening procedure for major depression with and without the 'help' question in primary care patients managed for a physical complaint.
Methods
This diagnostic accuracy study used data from the SODA (for 'SOmatisation Depression Anxiety') cohort study conducted by 24 general practitioners (GPs) in western Switzerland that included patients over 18 years of age with at least a single physical complaint at index consultation. Major depression was identified with the full Patient Health Questionnaire. GPs were asked to screen patients for major depression with the three screening questions 1 year after inclusion.
Results
Of 937 patients with at least a single physical complaint, 751 were eligible 1 year after index consultation. Major depression was diagnosed in 69/724 (9.5%) patients. The sensitivity and specificity of the two-question method alone were 91.3% (95% CI 81.4 to 96.4) and 65.0% (95% CI 61.2 to 68.6), respectively. Adding the 'help' question decreased the sensitivity (59.4%; 95% CI 47.0 to 70.9) but improved the specificity (88.2%; 95% CI 85.4 to 90.5) of the three-question method.
Conclusions
The use of two screening questions for major depression was associated with high sensitivity and low specificity in primary care patients presenting a physical complaint. Adding the 'help' question improved the specificity but clearly decreased the sensitivity; when using the 'help' question, four out of ten patients with depression will be missed, compared to only one out of ten with the two-question method. Therefore, the 'help' question is not useful as a screening question, but may help discussing management strategies.
doi:10.1186/1741-7015-9-114
PMCID: PMC3213092  PMID: 22005130
11.  Oral vitamin B12 for patients suspected of subtle cobalamin deficiency: a multicentre pragmatic randomised controlled trial 
BMC Family Practice  2011;12:2.
Background
Evidence regarding the effectiveness of oral vitamin B12 in patients with serum vitamin B12 levels between 125-200 pM/l is lacking. We compared the effectiveness of one-month oral vitamin B12 supplementation in patients with a subtle vitamin B12 deficiency to that of a placebo.
Methods
This multicentre (13 general practices, two nursing homes, and one primary care center in western Switzerland), parallel, randomised, controlled, closed-label, observer-blind trial included 50 patients with serum vitamin B12 levels between 125-200 pM/l who were randomized to receive either oral vitamin B12 (1000 μg daily, N = 26) or placebo (N = 24) for four weeks. The institution's pharmacist used simple randomisation to generate a table and allocate treatments. The primary outcome was the change in serum methylmalonic acid (MMA) levels after one month of treatment. Secondary outcomes were changes in total homocysteine and serum vitamin B12 levels. Blood samples were centralised for analysis and adherence to treatment was verified by an electronic device (MEMS; Aardex Europe, Switzerland). Trial registration: ISRCTN 22063938.
Results
Baseline characteristics and adherence to treatment were similar in both groups. After one month, one patient in the placebo group was lost to follow-up. Data were evaluated by intention-to-treat analysis. One month of vitamin B12 treatment (N = 26) lowered serum MMA levels by 0.13 μmol/l (95%CI 0.06-0.19) more than the change observed in the placebo group (N = 23). The number of patients needed to treat to detect a metabolic response in MMA after one month was 2.6 (95% CI 1.7-6.4). A significant change was observed for the B12 serum level, but not for the homocysteine level, hematocrit, or mean corpuscular volume. After three months without active treatment (at four months), significant differences in MMA levels were no longer detected.
Conclusions
Oral vitamin B12 treatment normalised the metabolic markers of vitamin B12 deficiency. However, a one-month daily treatment with1000 μg oral vitamin B12 was not sufficient to normalise the deficiency markers for four months, and treatment had no effect on haematological signs of B12 deficiency.
doi:10.1186/1471-2296-12-2
PMCID: PMC3033340  PMID: 21232119
12.  Patients presenting with somatic complaints in general practice: depression, anxiety and somatoform disorders are frequent and associated with psychosocial stressors 
BMC Family Practice  2010;11:67.
Background
Mental disorders in primary care patients are frequently associated with physical complaints that can mask the disorder. There is insufficient knowledge concerning the role of anxiety, depression, and somatoform disorders in patients presenting with physical symptoms. Our primary objective was to determine the prevalence of depression, anxiety, and somatoform disorders among primary care patients with a physical complaint. We also investigated the relationship between cumulated psychosocial stressors and mental disorders.
Methods
We conducted a multicentre cross-sectional study in twenty-one private practices and in one academic primary care centre in Western Switzerland. Randomly selected patients presenting with a spontaneous physical complaint were asked to complete the self-administered Patient Health Questionnaire (PHQ) between November 2004 and July 2005. The validated French version of the PHQ allowed the diagnosis of mental disorders (DSM-IV criteria) and the analyses of exposure to psychosocial stressors.
Results
There were 917 patients exhibiting at least one physical symptom included. The rate of depression, anxiety, and somatoform disorders was 20.0% (95% confidence interval [CI] = 17.4% to 22.7%), 15.5% (95% CI = 13.2% to 18.0%), and 15.1% (95% CI = 12.8% to 17.5%), respectively. Psychosocial stressors were significantly associated with mental disorders. Patients with an accumulation of psychosocial stressors were more likely to present anxiety, depression, or somatoform disorders, with an increase of 2.2 fold (95% CI = 2.0 to 2.5) for each additional stressor.
Conclusions
The investigation of mental disorders and psychosocial stressors among patients with physical complaints is relevant in primary care. Psychosocial stressors should be explored as potential epidemiological causes of mental disorders.
doi:10.1186/1471-2296-11-67
PMCID: PMC2945969  PMID: 20843358
13.  Predictive ability of an early diagnostic guess in patients presenting with chest pain; a longitudinal descriptive study 
BMC Family Practice  2010;11:14.
Background
The intuitive early diagnostic guess could play an important role in reaching a final diagnosis. However, no study to date has attempted to quantify the importance of general practitioners' (GPs) ability to correctly appraise the origin of chest pain within the first minutes of an encounter.
Methods
The validation study was nested in a multicentre cohort study with a one year follow-up and included 626 successive patients who presented with chest pain and were attended by 58 GPs in Western Switzerland. The early diagnostic guess was assessed prior to a patient's history being taken by a GP and was then compared to a diagnosis of chest pain observed over the next year.
Results
Using summary measures clustered at the GP's level, the early diagnostic guess was confirmed by further investigation in 51.0% (CI 95%; 49.4% to 52.5%) of patients presenting with chest pain. The early diagnostic guess was more accurate in patients with a life threatening illness (65.4%; CI 95% 64.5% to 66.3%) and in patients who did not feel anxious (62.9%; CI 95% 62.5% to 63.3%). The predictive abilities of an early diagnostic guess were consistent among GPs.
Conclusions
The GPs early diagnostic guess was correct in one out of two patients presenting with chest pain. The probability of a correct guess was higher in patients with a life-threatening illness and in patients not feeling anxious about their pain.
doi:10.1186/1471-2296-11-14
PMCID: PMC2836993  PMID: 20170544
14.  Ruling out coronary heart disease in primary care patients with chest pain: a clinical prediction score 
BMC Medicine  2010;8:9.
Background
Chest pain raises concern for the possibility of coronary heart disease. Scoring methods have been developed to identify coronary heart disease in emergency settings, but not in primary care.
Methods
Data were collected from a multicenter Swiss clinical cohort study including 672 consecutive patients with chest pain, who had visited one of 59 family practitioners' offices. Using delayed diagnosis we derived a prediction rule to rule out coronary heart disease by means of a logistic regression model. Known cardiovascular risk factors, pain characteristics, and physical signs associated with coronary heart disease were explored to develop a clinical score. Patients diagnosed with angina or acute myocardial infarction within the year following their initial visit comprised the coronary heart disease group.
Results
The coronary heart disease score was derived from eight variables: age, gender, duration of chest pain from 1 to 60 minutes, substernal chest pain location, pain increasing with exertion, absence of tenderness point at palpation, cardiovascular risks factors, and personal history of cardiovascular disease. Area under the receiver operating characteristics curve was of 0.95 with a 95% confidence interval of 0.92; 0.97. From this score, 413 patients were considered as low risk for values of percentile 5 of the coronary heart disease patients. Internal validity was confirmed by bootstrapping. External validation using data from a German cohort (Marburg, n = 774) revealed a receiver operating characteristics curve of 0.75 (95% confidence interval, 0.72; 0.81) with a sensitivity of 85.6% and a specificity of 47.2%.
Conclusions
This score, based only on history and physical examination, is a complementary tool for ruling out coronary heart disease in primary care patients complaining of chest pain.
doi:10.1186/1741-7015-8-9
PMCID: PMC2832616  PMID: 20092615
15.  Cobalamin deficiency resulting in a rare haematological disorder: a case report 
Introduction
We present the case of a patient with a cobalamin deficiency resulting in pancytopaenia, emphasizing the importance to define, diagnose and treat cobalamin deficiency.
Case presentation
A 52-year-old man from the Democratic Republic of Congo presented to the emergency department with shortness of breath and a sore tongue. Physical examination was unremarkable. His haemoglobin was low and the peripheral blood smear revealed pancytopaenia with a thrombotic microangiopathy. The findings were low cobalamin and folate levels, and high homocysteine and methylmalonate levels. Pernicious anaemia with chronic atrophic gastritis was confirmed by gastric biopsy and positive antiparietal cell and anti-intrinsic factor antibodies. Cobalamin with added folate was given. Six months later, the patient was asymptomatic.
Conclusion
Cobalamin deficiency should always be ruled out in a patient with pancytopaenia. Our case report highlights a life-threatening cobalamin deficiency completely reversible after treatment.
doi:10.1186/1752-1947-3-80
PMCID: PMC2783079  PMID: 19946556
16.  Management options for accidental injection of epinephrine from an autoinjector: a case report 
Introduction
Epinephrine autoinjector devices are used with increasing frequency to treat severe anaphylactic reactions. Accidental injection, usually involving a finger, is a potential complication.
Case presentation
A physician in a Family Practice training program accidentally injected epinephrine into his left thumb while reading the operating instructions of an autoinjector (Epipen®). He developed swelling, pallor, and pain in the thumb. Treatment included topical nitroglycerin, oral vasodilators and warming of the thumb. As expected, none caused an immediate response; however, after 8 hours, the thumb was pink and warm. There was full recovery 2 months after the accident. We reviewed the treatment of accidental epinephrine injection, and found that the use of parenteral adrenergic alpha blocker phentolamine would have produced immediate recovery.
Conclusions
All health professionals concerned with the use of epinephrine autoinjectors should receive adequate instruction on their use. A regimen for management of accidental epinephrine injection, in particular the use of phentolamine, should be emphasized.
doi:10.4076/1752-1947-3-7268
PMCID: PMC2726472  PMID: 19830160
17.  Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study 
Background
Migration is one of the major causes of tuberculosis in developed countries. Undocumented patients are usually not screened at the border and are not covered by a health insurance increasing their risk of developing the disease unnoticed. Urban health centres could help identify this population at risk. The objective of this study is to assess the prevalence of latent tuberculosis infection (LTBI) and adherence to preventive treatment in a population of undocumented immigrant patients.
Methods
All consecutive undocumented patients that visited two urban healthcare centres for vulnerable populations in Lausanne, Switzerland for the first time were offered tuberculosis screening with an interferon-γ assay. Preventive treatment was offered if indicated. Adherence to treatment was evaluated monthly over a nine month period.
Results
Of the 161 participants, 131 (81.4%) agreed to screening and 125 had complete examinations. Twenty-four of the 125 patients (19.2%; CI95% 12.7;27.2) had positive interferon-γ assay results, two of which had active tuberculosis. Only five patients with LTBI completed full preventive treatments. Five others initiated the treatment but did not follow through.
Conclusion
Screening for tuberculosis infection in this hard-to-reach population is feasible in dedicated urban clinics, and the prevalence of LTBI is high in this vulnerable population. However, the low adherence to treatment is an important public health concern, and new strategies are needed to address this problem.
doi:10.1186/1471-2334-9-34
PMCID: PMC2667187  PMID: 19317899
18.  The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol 
Trials  2009;10:4.
Background
There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin ≤ 30 ng/ml.
Methods/Design
In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level ≤ 30 ng/ml and haemoglobin level ≥ 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention.
Discussion
Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation.
Trial registration
NCT00689793
doi:10.1186/1745-6215-10-4
PMCID: PMC2637271  PMID: 19149890
19.  Chest wall syndrome among primary care patients: a cohort study 
BMC Family Practice  2007;8:51.
Background
The epidemiology of chest pain differs strongly between outpatient and emergency settings. In general practice, the most frequent cause is the chest wall pain. However, there is a lack of information about the characteristics of this syndrome. The aims of the study are to describe the clinical aspects of chest wall syndrome (CWS).
Methods
Prospective, observational, cohort study of patients attending 58 private practices over a five-week period from March to May 2001 with undifferentiated chest pain. During a one-year follow-up, questionnaires including detailed history and physical exam, were filled out at initial consultation, 3 and 12 months. The outcomes were: clinical characteristics associated with the CWS diagnosis and clinical evolution of the syndrome.
Results
Among 24 620 consultations, we observed 672 cases of chest pain and 300 (44.6%) patients had a diagnosis of chest wall syndrome. It affected all ages with a sex ratio of 1:1. History and sensibility to palpation were the keys for diagnosis. Pain was generally moderate, well localised, continuous or intermittent over a number of hours to days or weeks, and amplified by position or movement. The pain however, may be acute. Eighty-eight patients were affected at several painful sites, and 210 patients at a single site, most frequently in the midline or a left-sided site. Pain was a cause of anxiety and cardiac concern, especially when acute. CWS coexisted with coronary disease in 19 and neoplasm in 6. Outcome at one year was favourable even though CWS recurred in half of patients.
Conclusion
CWS is common and benign, but leads to anxiety and recurred frequently. Because the majority of chest wall pain is left-sided, the possibility of coexistence with coronary disease needs careful consideration.
doi:10.1186/1471-2296-8-51
PMCID: PMC2072948  PMID: 17850647
20.  Chronic fatigue 
doi:10.1503/cmaj.1060137
PMCID: PMC1534098
22.  Violence in primary care: Prevalence and follow-up of victims 
BMC Family Practice  2006;7:15.
Background
Primary care physicians underestimate the prevalence of domestic violence and community violence. Victims are therefore at risk of further episodes of violence, with psychological and physical consequences. We used an interview to assess the prevalence of domestic and community violence among Swiss natives and foreigners. In a follow-up study, we evaluated the consequences of the interview for the positive patients.
Methods
We evaluated the prevalence of violence by use of a questionnaire in an interview, in an academic general internal medicine clinic in Switzerland. In a follow-up, we evaluated the consequences of the interview for positive patients. The participants were 38 residents and 446 consecutive patients. Questionnaires were presented in the principal language spoken by our patients. They addressed sociodemographics, present and past violence, the security or lack of security felt by victims of violence, and the patients' own violence. Between 3 and 6 months after the first interview, we did a follow-up of all patients who had reported domestic violence in the last year.
Results
Of the 366 patients included in the study, 36 (9.8%) reported being victims of physical violence during the last year (physicians identified only 4 patients out of the 36), and 34/366 (9.3%) reported being victims of psychological violence. Domestic violence was responsible for 67.3% of the cases, and community violence for 21.8%. In 10.9% of the cases, both forms of violence were found.
Of 29 patients who reported being victims of domestic violence, 22 were found in the follow-up. The frequency of violence had diminished (4/22) or the violence had ceased (17/22).
Conclusion
The prevalence of violence is high; domestic violence is more frequent than community violence. There was no statistically significant difference between the Swiss and foreign patients' responses related to the rates of violence. Patients in a currently violent relationship stated that participating in the study helped them and that the violence decreased or ceased a few months later.
doi:10.1186/1471-2296-7-15
PMCID: PMC1421406  PMID: 16526962
23.  Difficulties associated with outpatient management of drug abusers by general practitioners. A cross-sectional survey of general practitioners with and without methadone patients in Switzerland 
BMC Family Practice  2005;6:51.
Background
In Switzerland, general practitioners (GPs) manage most of the patients receiving methadone maintenance treatment (MMT).
Methods
Using a cross-sectional postal survey of GPs who treat MMT patients and GPs who do not, we studied the difficulties encountered in the out-patient management of drug-addicted patients. We sent a questionnaire to every GP with MMT patients (556) in the French-speaking part of Switzerland (1,757,000 inhabitants). We sent another shorter questionnaire to primary care physicians without MMT patients living in the Swiss Canton of Vaud.
Results
The response rate was 63.3%. The highest methadone dose given by GPs to MMT patients averaged 120.4 mg/day. When asked about help they would like to be given, GPs with MMT patients primarily mentioned the importance of receiving adequate fees for the care they provide. Secondly, they mentioned the importance of better training, better knowledge of psychiatric pathologies, and discussion groups on practical cases. GPs without MMT patients refuse to treat these patients mostly for emotional and relational reasons.
Conclusion
GPs encounter financial, relational and emotional difficulties with MMT patients. They desire better fees for services and better training.
doi:10.1186/1471-2296-6-51
PMCID: PMC1351183  PMID: 16364176
24.  Two cases of "cannabis acute psychosis" following the administration of oral cannabis 
BMC Psychiatry  2005;5:17.
Background
Cannabis is the most commonly used illegal drug and its therapeutic aspects have a growing interest. Short-term psychotic reactions have been described but not clearly with synthetic oral THC, especially in occasional users.
Case presentations
We report two cases of healthy subjects who were occasional but regular cannabis users without psychiatric history who developed transient psychotic symptoms (depersonalization, paranoid feelings and derealisation) following oral administration of cannabis. In contrast to most other case reports where circumstances and blood concentrations are unknown, the two cases reported here happened under experimental conditions with all subjects negative for cannabis, opiates, amphetamines, cocaine, benzodiazepines and alcohol, and therefore the ingested dose, the time-events of effects on behavior and performance as well as the cannabinoid blood levels were documented.
Conclusion
While the oral route of administration achieves only limited blood concentrations, significant psychotic reactions may occur.
doi:10.1186/1471-244X-5-17
PMCID: PMC1079888  PMID: 15804348

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