Fecal calprotectin as a biomarker of intestinal inflammation in ICU patients with diarrhea - testing the pipette method against the collection pin and weighing methods.

Fecal calprotectin is an established biomarker in inflammatory bowel disease, but its role in assessment of intestinal inflammation in ICU patients is yet to be explored. ICU patients tend to acquire diarrhea, which complicates the extraction of fecal calprotectin using a collection pin for stool sampling. Pipetting is an alternative sampling method. The aim of the study was to compare the collection pin method with the pipette method for measurement of fecal calprotectin in ICU patients with diarrhea. Stool samples were collected from fecal bags used in the patients and then analyzed for calprotectin using an extraction device and a piston pipette, respectively. In addition, a validation test for the pipette method of extraction was conducted on liquid stool samples. Eleven stool samples were collected from five randomly selected ICU patients. Calprotectin was detectable in all fecal samples. On average the collection pin measured 45% lower than the pipette method with a 95% confidence interval (30 - 59%). The coefficient of variation when using the pipette method was 13% in low calprotectin concentrations and 39% in high concentrations. In conclusion, the pipette method seems to be appropriate for measuring calprotectin in liquid feces, due to practicalities and a greater precision.

Correction to: Mathematical arterialisation of peripheral venous blood gas for obtainment of arterial blood gas values: a methodological validation study in the clinical setting.

The corresponding author has identified a calculation mistake in the original publication of the article. The corrected value is given in this Correction. Under the Results section, the median (range) age of the patients in the methodological study should read 76 (26-86) years instead of 56 (26-86) years.

Mathematical arterialisation of peripheral venous blood gas for obtainment of arterial blood gas values: a methodological validation study in the clinical setting.

Arterial blood gas (ABG) analysis is an essential tool in the clinical assessment of acutely ill patients. Venous to arterial conversion (v-TAC), a mathematical method, has been developed recently to convert peripheral venous blood gas (VBG) values to arterialized VBG (aVBG) values. The aim of this study was to test the validity of aVBG compared to ABG in an emergency department (ED) setting. Twenty ED patients were included in this study. ABG and three aVBG samples were collected from each patient. The aVBG samples were processed in three different ways to investigate appropriate sample handling. All VBG samples were arterialized using the v-TAC method. ABG and aVBG samples were compared using Lin's concordance correlation coefficient (CCC), Bland-Altman plots and misclassification analysis. Clinical acceptable threshold of aVBG value deviance from ABG values were ± 0.05 pH units, ± 0.88 kPa pCO2 and ± 0.88 kPa pO2. CCC revealed an agreement in pH and pCO2 parameters for both aVBG in comparison to ABG. In all aVBG samples, an overestimation of pO2 compared to ABG was observed. Bland-Altman plot revealed clinically acceptable mean difference and limits-of-agreement intervals between ABG and aVBG pH and pCO2, but not between ABG and aVBG pO2. Arterialization of VBG using v-TAC is a valid method for measuring pH and pCO2, but not for pO2. Larger clinical studies are required to evaluate the applicability of v-TAC in different patient subpopulations.

Immunogenicity of twenty peptides representing epitopes of the hepatitis B core and surface antigens by IFN-γ response in chronic and resolved HBV.

BACKGROUND: Patients with chronic hepatitis B virus infection (CHB) usually mount a modest T cell response against HBV epitopes. In order to determine immunogenic epitopes of HBV recognized by HBV-specific T cells, previous studies focused on previously confirmed HBV epitopes and assessed the T cell response by the number of HBV-specific T cells by IFN-γ ELISPOT. METHODS: We studied T cell functionality by combined in silico methods predicting HBV-specific epitopes and experimental investigations on the recognition of these epitopes. 30 chronic CHB patients and 10 patients with resolved HBV (RHB) were included in the study. We identified epitopes from the literature and by in silico analysis. These were evaluated for immunogenicity by use of synthetic peptides representing the epitopes through exposure to PBMCs from patients with CHB or RHB by IFN-γ ELISPOT. The number of IFN-γ producing cells (SFC), mean spot size (MSS) and stimulation index (SI) were recorded. RESULTS: The frequency of HBV-specific T cells producing IFN-γ after stimulation with HBV epitopes was similar in CHB and RHB patients. CHB patients had a higher MSS SI than RHB patients. Patients not carrying the HLA-A2 genotype had higher SFC SI and MSS SI. Patients with HLA-A11 had higher MSS SI compared to non- HLA-A11 allele patients. HBeAg-positive patients had a lower MSS SI, and none of the HBeAg positive patients had the HLA-A11 genotype. We found 3 immunogenic epitopes not described previously. CONCLUSION: IFN-γ ELISPOT-determined MSS is an efficient marker for T cell recognition of epitopes. This experimental measure showed the in silico analysis for epitope prediction to be a valuable tool in future studies on HLA genotypes and HBV epitopes. This way our study now points to previously unappreciated consequences of carrying the HLA-A11 allele in terms of stronger immunity to HBV.

Need for improvements in the surveillance and management of chronic viral hepatitis in HIV patients followed in a Danish outpatient clinic.

OBJECTIVES: The aim of this study was to assess hepatitis B virus (HBV) and hepatitis C virus (HCV) surveillance and management in HIV patients currently followed in an outpatient clinic at a Danish University Hospital. METHODS: Patient data, including demographic characteristics, clinical findings, and hepatitis serology, were reviewed at baseline. Patients with incomplete or non-updated serology within the last 2 y were retested in the next 6 months, and the results were reviewed again at follow-up. RESULTS: At baseline, 84% and 74% of the 574 HIV patients were found to have incomplete and/or non-updated HBV and HCV serology, respectively. At follow-up, updated HBV serology was achieved in 535 (93%) patients; 15 (3%) patients were found to have a chronic active infection and 156 (27%) had a resolved infection, whereas 65 (11%) were vaccinated against HBV and 299 (52%) were non-immune. No patients were found to have developed chronic HBV infection following HIV diagnosis (equal to 3649 patient-y). Updated HCV serology revealed that 25 (4%) had a chronic active HCV infection and 15 (3%) had a resolved HCV infection. The anti-HCV incidence rate was 0.27/100 patient-y. A liver pathology assessment had not been performed within the last 2 y in 80% of the HBV and 32% of the HCV co-infected patients. CONCLUSIONS: Hepatitis screening and assessment had been inadequately performed. New cases of chronic hepatitis seem to occur infrequently. However, a more proactive hepatitis surveillance and management strategy integrated into the overall HIV health care program is warranted.

Cannabis medicine for chronic pain.

In the last decade, patients with chronic pain have expressed increasing interest in cannabis-derived products for adjuvant therapy when treatment is deemed refractory to conventional analgesics. At present, clinical evidence to support this treatment approach appears to be sparse. Not because clinical studies as such are lacking, but rather as a result of methodological bias in relation to study design, patient populations, and treatment protocols. In this review, research in cannabis medicine for relief of chronic pain is reviewed, mainly with reference to published meta-analytic studies.

Health literacy and cognitive function in people with diabetic foot ulcer with focus on knowledge, attitude, and practice in relation to foot self-care.

Introduction: Preventative foot self-care is vital for avoiding diabetic foot ulcer episodes and lowering the risk of amputations. Yet, it demands high levels of health literacy and cognitive function. Objective: To investigate health literacy and cognitive function in persons presenting with a diabetic foot ulcer. Methods: Participants with type 2 diabetes were recruited from the tertiary foot clinic at Steno Diabetes Center North Denmark. The European Health Literacy Survey Questionnaire and Addenbrooke's Cognitive Examination were applied. A semi-structured interview guide was developed to evaluate foot self-care knowledge, attitude, and practice. The qualitative data were analyzed with a deductive approach based on a qualitative thematic analysis model. Subsequently, an integrated analysis of the quantitative and qualitative results was conducted. Results: The participants (n = 12) had a mean age of 62.6 ± 8.4 years, and 11 were males. The mean diabetes duration was 15.9 ± 8.9 years. Eight participants had a recurrent diabetic foot ulcer. The health literacy level was sufficient in nine participants, and cognitive function was normal in five participants. Three different profiles related to foot self-care (proactive, active, or passive, respectively) were constructed by the final integrated analysis: a proactive profile refers to taking preventative action in concordance with knowledge and attitude, an active profile to taking action in response to a situation, but challenged by conflicting levels of knowledge and attitude, and a passive profile to not taking action. Conclusion: The study suggests that people presenting with a diabetic foot ulcer have different foot self-care profiles based on person-specific health literacy, cognitive function, and knowledge, attitude, and practice element characteristics, highlighting the need for individualized education and intervention strategy instead of a one-size-fits-all approach.

Naïve Inflammatory Proteome Profiles of Glucocorticoid Responsive Polymyalgia Rheumatica and Rheumatic Arthritis Patients-Links to Triggers and Proteomic Manifestations.

Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown etiology, sharing symptoms with giant cell arthritis (GCA) and rheumatoid arthritis (RA). The pathogenic inflammatory roots are still not well understood, and there is a lack of extensive biomarker studies to explain the disease debut and post-acute phase. This study aimed to deeply analyze the serum proteome and inflammatory response of PMR patients before and after glucocorticoid treatment. We included treatment-naïve PMR patients, collecting samples before and after 3 months of treatment. For comparison, disease-modifying antirheumatic drug (DMARD)-naïve RA patients were included and matched to healthy controls (CTL). The serum proteome was examined using label-free quantitative mass spectrometry, while inflammation levels were assessed using multiplex inflammatory cytokine and cell-free DNA assays. The serum proteomes of the four groups comprised acute phase reactants, coagulation factors, complement proteins, immunoglobulins, and apolipoproteins. Serum amyloid A (SAA1) was significantly reduced by active PMR treatment. Cell-free DNA levels in PMR and RA groups were significantly higher than in healthy controls due to acute inflammation. Complement factors had minimal changes post-treatment. The individual serum proteome in PMR patients showed over 100 abundantly variable proteins, emphasizing the systemic impact of PMR disease debut and the effect of treatment. Interleukin (IL)-6 and interferon-gamma (IFN-γ) were significantly impacted by glucocorticoid treatment. Our study defines the PMR serum proteome during glucocorticoid treatment and highlights the role of SAA1, IL-6, and IFN-γ in treatment responses. An involvement of PGLYRP2 in acute PMR could indicate a response to bacterial infection, highlighting its role in the acute phase of the immune response. The results suggest that PMR may be an aberrant response to a bacterial infection with an exacerbated IL-6 and acute phase inflammatory response and molecular attempts to limit the inflammation.

Discontinuation of efavirenz therapy in HIV patients due to neuropsychiatric adverse effects.

BACKGROUND: Efavirenz (EFV) is associated with neuropsychiatric manifestations that may compromise the course of HIV treatment. METHODS: Adverse effects leading to drug discontinuation among naïve HIV-1 patients starting on a first-line antiretroviral therapy (ART) regimen were investigated by a review of patient medical files. RESULTS: Among 276 patients, 168 (61%) were given EFV as part of the initial ART regimen. Female gender and past mental disorders were identified as predictors for selecting a non-EFV based regimen. EFV was later discontinued during the course of treatment for 90 (54%) patients. The EFV discontinuation rate due to neuropsychiatric disturbances, such as dizziness, abnormal dreams, mood changes, and anxiety, was 60%, versus 3% among patients on a third non-EFV agent based regimen (p < 0.0001). Half of the patients discontinued EFV later than 12 months after initiation of treatment, and in most cases at the discretion of the physician. Improvement in neuropsychiatric symptoms was reported by more than 90% of the patients for whom EFV discontinuation and follow-up outcome had been reported in the medical charts. CONCLUSIONS: Discontinuation of EFV occurs in more than half the treated patients. Neuropsychiatric adverse effects are by far the most common reasons for discontinuation. Discontinuation occurs late in the course of treatment suggesting persistence of central nervous system toxicity, which may impact quality of life negatively on a long-term basis. The role of EFV as a first-line ART agent should be reconsidered in the current guidelines, in particular due to the availability of other equally effective, but less toxic, ART agents.

Safety and effectiveness of cannabinoids to Danish patients with treatment refractory chronic pain-A retrospective observational real-world study.

BACKGROUND: Cannabinoids are considered a therapeutic option to patients suffering from treatment refractory chronic pain (TRCP) insufficiently relieved by conventional analgesics or experiencing intolerable adverse events (AEs) from those. This study aimed to explore safety and effectiveness of oral cannabinoids among patients with TRCP. METHODS: A retrospective study was conducted among Danish patients with TRCP being prescribed oral cannabinoids. Data on AEs and changes in pain intensity by numeric rating scale (NRS) before and after initiation of oral cannabinoid therapy were analysed. RESULTS: Among 826 eligible patients ≥18 years old, 529 (64%) were included for data analysis at first follow-up (F/U1) (median 56 days from baseline) and 214 (26%) for second follow-up (F/U2) (median 126 days from F/U1). Mean age was 60 ± 15.9 years and 70% were females. AEs were in general reported mild to moderate by 42% of patients at F/U1 and 34% at F/U2. AEs were mainly related to gastrointestinal (F/U1: 17% and F/U2: 13%) and nervous system disorders (F/U1: 14% and F/U2: 11%). Reduction in NRS was significantly different at both follow-up consultations compared with baseline (<0.0001). Clinically relevant pain reduction (NRS ≥30%) was reported by 17% at F/U1 and 10% of patients at F/U2 in intention-to-treat analysis whereas the figures were 32% and 45% respectively, in per-protocol analysis. CONCLUSION: Oral cannabinoid therapy seems to be safe and mildly effective in patients with TRCP. Randomized controlled trials with focus on comparable pain characteristics in diagnostical homogenous patient subgroups are needed for further improvement of evidence level for relief of chronic pain using oral cannabinoids. SIGNIFICANCE: The findings in this retrospective study conducted in a real-world clinical setting suggest a favourable safety profile of cannabinoids. Moreover, one-sixth (intention-to-treat) and one-third (per-protocol) of patients with chronic pain refractory to conventional analgesics, or experiencing intolerable adverse effects, benefited significantly from therapy with oral cannabinoid regimens. Combination of THC and CBD seems overall more effective than cannabinoid monotherapy. Conduction of randomized controlled trials investigating safety and efficacy of cannabinoid therapy to diagnosis specific patient subgroups with comparable clinical and pathophysiological chronic pain characteristics is warranted, hence contributing further to the process of clinical evidence clarification currently in progress.

Assessment of neuropsychiatric manifestations in a cohort of intensive care unit survivors: A proof of concept study.

The aim of this study was to assess the feasibility and outcome of a neuropsychiatric evaluation protocol intended for adult intensive care unit survivors in a Danish regional hospital, in which a follow-up consultation was conducted 2 months after hospital discharge. Twenty-three participants were able to finalize the neuropsychiatric evaluation, and 20 (87%) among those were detected with neuropsychiatric manifestations, including cognitive impairment (n = 17; 74%) and fatigue (n = 17, 74%). This study finds a high prevalence of neuropsychiatric manifestations and fatigue, and evaluates a follow-up protocol for the ICU patient population.

Increasing use of computed tomography scans in the North Denmark Region raises patient safety concern.

PURPOSE: Use of computed tomography (CT) scans raises safety concern as lifetime cumulative ionising radiation exposure is associated with risk of developing malignancies. This study aimed to investigate use of abdominal CT scans in the Danish health care sector. METHODS: Data on abdominal CT scans performed annually in the North Denmark Region between 2005 and 2018 were extracted from the regional registry with emphasis on patients with a medical history of a repeated abdominal CT scan within 28 days. An audit of the medical files was subsequently conducted in 100 randomly selected patient cases to evaluate clinical information being provided, in addition to justification for a repeated abdominal CT scan, and finally if other radiology modalities could have been applied. RESULTS: Number of annually performed abdominal CT scans in this demographically stable regional population increased by a factor 4.3 from 15 in 2005 to 65 in 2018 per 1,000 inhabitants. The audit revealed that 31% of the secondabdominal CT scans within a 28 days period were categorized as either doubtful whether justified or not justified. Moreover, 20% of theCT scans were considered replaceable by ultrasonography. CONCLUSIONS: Annual performance of abdominal CT scans increased fourfold during the 14 years period. This tendency is probably attributable to changes in the Danish health care sector by which CT scan examination are used more frequently aiming at more accelerated patient investigation flow in conjunction with shorter length of hospitalization stay. Alertness is strongly warranted towards the associated risk of cancer due to life-time cumulative ionising radiation exposure by this strategy.

Impact of Low-Dose Dronabinol Therapy on Cognitive Function in Cancer Patients Receiving Palliative Care: A Case-Series Intervention Study.

Background: Cannabis may offer therapeutic benefits to patients with advanced cancer not responding adequately to conventional palliative treatment. However, tolerability is a major concern. Cognitive function is a potential adverse reaction to tetrahydrocannabinol containing regimens. The aim of this study was to test cognitive function in patients being prescribed dronabinol as an adjuvant palliative therapy. Methods: Adult patients with advanced cancer and severe related pain refractory to conventional palliative treatment were included in this case-series study. Patients were examined at baseline in conjunction with initiation of dronabinol therapy and at a two-week follow-up using three selected Wechsler's adult intelligence scale III neurocognitive tests: Processing Speed Index (PSI), Perceptual Organization Index (POI), and Working Memory Index (WMI). Patients were also assessed using pain visual analog scale, Major Depression Inventory, and Brief Fatigue Inventory. Results: Eight patients consented to take part in the study. Two patients discontinued dronabinol therapy, one due to a complaint of dizziness and another critical progression of cancer disease, respectively. The remaining six patients were successfully treated with a daily dosage of 12.5 mg dronabinol (p = 0.039). PSI (p = 0.020), POI (p = 0.034.), and WMI (p = 0.039). Conclusions: Cognitive function improved in this group of patients with advanced cancer in conjunction with low-dose dronabinol therapy. The cause is likely multifactorial including reported relief of cancer-associated symptoms. Further clinical investigation is required.

Prospective pilot study on the relationship between seminal HIV-1 shedding and genital schistosomiasis in men receiving antiretroviral therapy along Lake Malawi.

Male genital schistosomiasis (MGS) is hypothesized to increase seminal shedding of HIV-1. This prospective pilot study assessed seminal HIV-1 RNA shedding in men on long-term ART with and without a diagnosis of MGS. Study visits occurred at 0, 1, 3, 6 and 12 months. MGS was diagnosed by egg positivity on semen microscopy or PCR of seminal sediment. After optimization of the HIV-RNA assay, we examined 72 paired plasma and semen samples collected from 31 men (15 with and 16 without MGS) over 12 months. HIV-1 RNA was detected in 7/72 (9.7%) seminal samples and 25/72 (34.7%) plasma samples. When comparing sample pairs, 5/72 (6.9%) showed HIV-1 RNA detection only in the seminal sample. Overall, 3/31 (9.7%) participants, all with MGS, had detectable HIV-1 RNA in semen while plasma HIV-1 RNA was undetectable (< 22 copies/mL), with seminal levels ranging up to 400 copies/mL. Two participants showing HIV-1 RNA in seminal fluid from the MGS-negative group also had concomitant HIV-1 RNA detection in plasma. The findings suggest that MGS can be associated with low-level HIV-1 RNA shedding despite virologically suppressive ART. Further studies are warranted to confirm these observations and assess its implications.

Discrepant findings between proton magnetic resonance spectroscopy and magnetic resonance imaging in an immunocompetent patient with herpes simplex virus type 1 encephalitis.

The authors report discrepant findings between proton magnetic resonance spectroscopy and conventional magnetic resonance imaging in a 67-y-old woman with herpes simplex virus type 1 encephalitis. The sparse amount of literature on proton magnetic resonance spectroscopy in patients with herpes simplex type 1 encephalitis is discussed.

Different types of foot orthoses effect on gait mechanics in patients with rheumatoid arthritis.

Foot orthoses are a first line conservative treatment for foot impairments in patients with rheumatoid arthritis (RA), however their effect on gait mechanics is poorly understood. We aimed to compare changes in lower limb and foot mechanics between two types of commonly used foot orthoses (FO) with a control. Twenty-seven patients with rheumatoid arthritis participated in this crossover study. Two different types of FO (a medially wedged custom-made FO and a prefabricated FO with a metatarsal dome, respectively), were compared against a control insole. During gait, lower limb mechanics were analyzed using 3D motion capture, force plates, and an in-shoe pressure system. Inverse dynamics models were created in the Anybody Modeling System to calculate joint angles and joint moments during gait. Gait variables were analyzed using statistical parametric mapping. Compared to the control, the prefabricated FO had limited effect on gait mechanics. Compared to the control the custom-made FO reduced ankle plantarflexion moment with 0.4 %body weight * body height (BW * BH) between 66 and 76% of stance and ankle eversion moment was reduced 0.16% BW*BH between 3 and 40% of stance. Furthermore, it also reduced the average forefoot plantar pressure by 9 kPa between 20 and 62% of stance compared to the control. Changes in foot pressure distribution, joint moments and angles were most pronounced for custom-made FO compared to the prefabricated FO. The findings suggest that patients with RA and foot impairments may benefit more from an individualized FO strategy, if the aim of the treatment is to alter gait mechanics. (NCT03561688).

The effect of foot orthoses on gait biomechanics and pain among people with rheumatoid arthritis: A quasi-experimental study.

BACKGROUND: Foot pain is frequent among people with rheumatoid arthritis (RA). Foot orthoses (FO) are commonly prescribed with the intention to reduce pain symptoms and improve function. RESEARCH QUESTION: How do a custom-made FO affect pain, gait biomechanics and daily activity among people with RA? METHODS: Twenty-five participants with RA and foot pain completed this quasi-experimental study using a control insole for four weeks and then a custom-made FO in the following four weeks. The foot orthoses were customized by plantar foot shape targeting optimal restoration of normal arch height. A visual analog scale was used to monitor changes in ankle/foot, knee, hip joints, and global arthritis pain. In addition, the perceived pain area was measured using a body chart analysis. Kinematics and kinetics of the hip, knee and ankle joints during gait were analyzed using 3D-motion capture. Daily steps were measured with a wrist-based activity tracker for both the control insole and custom-made FO period, respectively. RESULTS: In comparison to the control insole, the custom-made FO reduced ankle/foot pain intensity (p < 0.001) in addition to a reduction of the perceived pain areas in the feet (p < 0.001), legs (p = 0.012), as well as the arms and hands (p = 0.014). Ankle plantar flexion and eversion moments were also reduced (p < 0.001). No difference in daily steps was observed between the two periods (p = 0.657). SIGNIFICANCE: This study has demonstrated an ankle/foot pain-relieving effect in conjunction with alterations of the ankle joint moments in people with RA using custom-made FO. The pain relief is plausibly attributed to alterations of the ankle joint moments when using the custom-made FO. However, future studies are needed to explore further into therapeutic implication of custom-made FO in pain management of people with RA.

Cervical lesion proportion measure using a digital gridded imaging technique to assess cervical pathology in women with genital schistosomiasis.

Female genital schistosomiasis (FGS) is characterized by a pattern of lesions which manifest at the cervix and the vagina, such as homogeneous and grainy sandy patches, rubbery papules in addition to neovascularization. A tool for quantification of the lesions is needed to improve FGS research and control programs. Hitherto, no tools are available to quantify clinical pathology at the cervix in a standardized and reproducible manner. This study aimed to develop and validate a cervical lesion proportion (CLP) measure for quantification of cervical pathology in FGS. A digital imaging technique was applied in which a grid containing 424 identical squares was positioned on high resolution digital images from the cervix of 70 women with FGS. CLP was measured for each image by observers counting the total number of squares containing at least one type of FGS associated lesion. For assessment of inter- and intra-observer reliability, three different observers measured CLP independently. In addition, a rubbery papule count (RPC) was determined in a similar manner. The intraclass correlation coefficient was 0.94 (excellent) for the CLP inter-rater reliability and 0.90 (good) for intra-rater reliability and the coefficients for the RPC were 0.88 and 0.80 (good), respectively. The CLP facilitated a reliable and reproducible quantification of FGS associated lesions of the cervix. In the future, grading of cervical pathology by CLP may provide insight into the natural course of schistosome egg-induced pathology of the cervix and may have a role in assessing praziquantel treatment efficacy against FGS. Trial Registration: ClinicalTrials.gov, trial number NCT04115072; trial URL https://clinicaltrials.gov/ct2/show/NCT04115072?term=Female+genital+schistosomiasis+AND+Madagascar&draw=2&rank=1.

Evaluation of depression as a risk factor for treatment failure in chronic hepatitis C.

UNLABELLED: The Major Depression Inventory (MDI) was used to estimate the value of routine medical interviews in diagnosing major depression among patients receiving peginterferon alfa-2a and ribavirin therapy for chronic hepatitis C virus (HCV) infection (n = 325). According to criteria from the MDI and Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), 19 patients (6%) had major depression at baseline. An additional 114 (37%) developed depression while on HCV combination therapy, with baseline MDI score and female sex independently predicting the emergence of major depression during treatment in a multivariate analysis. Only 36 (32%) of the 114 patients developing major depression according to MDI/DSM-IV criteria were correctly diagnosed during routine medical interviews. The emergence of major depression frequently led to premature discontinuation of peginterferon/ribavirin therapy, and an on-treatment MDI score increment exceeding 30 points (i.e., a validated marker of idiopathic DSM-IV major depression) was correlated with impaired outcome of HCV therapy (P = 0.02). This difference was even more pronounced among patients with an on-treatment increase in MDI score greater than 35 points (P = 0.003). CONCLUSION: We conclude that (1) depressive symptoms among patients undergoing HCV therapy are commonly overlooked by routine clinical interviews, (2) the emergence of depression compromises the outcome of HCV therapy, and (3) the MDI scale may be useful in identifying patients at risk for treatment-induced depression.

HIV late presenters in Denmark: need for increased diagnostic awareness among general practitioners.

INTRODUCTION: The study objective was to describe demographic and clinical characteristics among HIV late presenters in a Danish university hospital. MATERIAL AND METHODS: Patients > 15 years of age were enrolled in this retrospective study. Data from the medical patient records were analyzed in accordance with the CD4 count at the time of HIV diagnosis. RESULTS: Among 194 HIV patients (138 men and 56 women), 63 (33%) were diagnosed with a CD4 count below 200 cells/microlitre (late presenters). Heterosexuals constituted a larger proportion of patients in the late presenter group than did homosexual men (MSM) (p = 0.02), whereas a higher proportion of MSM than heterosexuals were diagnosed with HIV during primary infection (p < 0.01). Half of the late presenters had consulted a general practitioner three to 12 months prior to their HIV diagnosis. HIV antibody testing had not been performed although complaints consistent with possible underlying immune deficiency had been reported. Twenty per cent of the late presenters had a persistently low CD4 count below 200 cells/microlitre at follow-up despite having received HAART therapy for more than two years. CONCLUSION: One third of the HIV patients in this study were diagnosed as late presenters, and this group featured a higher proportion of heterosexuals than of MSM. The HIV antibody test should be performed more consistently on solid clinical ground by general practitioners.