16.9.2005

Depressive disorders in primary care: recurrent, chronic, and co-morbid

Vuorilehto, M; Melartin, T; Isometsä, E.

PSYCHOLOGICAL MEDICINE 35 (5): 673-682.

Background - Preceding longitudinal course and current somatic and psychiatric co-morbidity of depression have been little investigated in primary care.

Methods - Consecutive patients (n = 1111) in primary care in the city of Vantaa, Finland, were screened for depression with the PRIME-MD, and positive cases interviewed by telephone. Cases with current depressive symptoms were diagnosed face-to-face with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I/P). A cohort of 137 patients with unipolar depressive disorders, comprising all patients with at least two depressive symptoms and clinically significant distress or disability, was recruited. The Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II), medical records, rating scales, and a retrospective life-chart were used to obtain comprehensive cross-sectional and longitudinal information.

Results - Current major depressive disorder (MDD) was the most prevalent depressive disorder (66 %); it was usually mild to moderate but recurrent. A quarter of cases (23 %) had MDD in partial remission or prodromal phase, and only 10 % had true minor depression. Axis I co-morbidity was present in 59 %, Axis 11 in 52 %, and chronic Axis III disorders in 47 %; only 12 % had no co-morbidity. One third of patients presented with a psychological complaint, predicted by higher depression severity and younger age.

Conclusion - From a lifetime perspective, the majority of primary-care patients with depressive disorders suffer from recurrent MDD, although they are currently often in prodromal or residual phase. Psychiatric and somatic co-morbidity are highly prevalent. Treatment of depression in primary care should not rely on an assumption of short-lived, uncomplicated mild disorders.

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Mortality among patients with schizophrenia and reduced psychiatric hospital care.

Heila, H; Haukka, J; Suvisaari, J; Lönnqvist, J.

PSYCHOLOGICAL MEDICINE 35 (5): 725-732.

Background - There are suggestions that mortality, especially that due to suicide, increases among schizophrenia patients during a period of declining psychiatric beds. We investigated the mortality of schizophrenia patients in the general population of Finland during the reduction of psychiatric beds during 1980-1996.

Method - Patients hospitalized for schizophrenia before 31 December 1996, and alive on I January 1980 (n = 58 76 1) were identified via the National Hospital Discharge Register. General population data came from the National Population Register, and mortality data from the National Causes of Death Register. We calculated relative risks (RR) for total mortality, mortality due to natural causes (cancer, ischaemic heart disease, respiratory disease), unnatural causes (accident, homicide, suicide), and suicide.

Results. Patients with schizophrenia had an increased mortality both from natural causes (RR 2-59, 95 % CI 2-55-2-63) and from suicide (RR 9-9, 95 % CI 9-43-10-30). The RR for both natural and unnatural deaths was highest among patients with < 5 years since onset of schizophrenia. Among them all-cause mortality rose in the 1990s, but decreased among patients with > 10 years from onset. Otherwise no major changes or linear trends were found in mortality during deinstitutionalization.

Conclusions. Reduction of psychiatric beds did not generally increase the mortality of patients with schizophrenia. However, patients in their early years of illness experienced increased mortality after the steepest bed reduction. Improved recognition and treatment of somatic illness would benefit patients with schizophrenia.


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Sample type is crucial to the diagnosis of Mycoplasma pneumoniae pneumonia by PCR.

Räty, R; Rönkkö, E; Kleemola, M.

JOURNAL OF MEDICAL MICROBIOLOGY 54 (3): 287-291.

Sensitive and specific methods for rapid laboratory diagnosis of Mycoplasma pneumoniae were not available until nucleic acid amplification methods were developed. The choice of sample type and method of sampling are crucial to optimal diagnostic efficacy. Three types of respiratory samples from 32 young military conscripts with pneumonia were collected during an outbreak of M. pneumoniae infection. Sputum, nasopharyngeal aspirate and throat swab specimens were tested by 16S rRNA gene-based PCR with liquid-phase probe hybridization, and the results were compared with serology. The PCR result was positive for 22 (69%) of the sputa, 16 (50%) of the aspirates and 12 (37(.)5%) of the swabs. Serology with increasing or high titres supported the positive findings in all instances. Sputum, when available, is clearly the best sample type for young adults with pneumonia.

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Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: Implications for clinical management.

Wensing, AMJ; van de Vijver, DA; Angarano, G; Asjo, B; Balotta, C; Boeri, E; Camacho, R; Chaix, ML; Costagliola, D; De Luca, A; Derdelinckx, I; Grossman, Z; Hamouda, O; Hatzakis, A; Hemmer, R; Hoepelman, A; Horban, A; Korn, K; Kucherer, C; Leitner, T; Loveday, C; MacRae, E; Maljkovic, I; de Mendoza, C; Meyer, L; Nielsen, C; de Coul, ELO; Ormaasen, V; Paraskevis, D; Perrin, L; Puchhammer-Stockl, E; Ruiz, L; Salminen, M; Schmit, JC; Schneider, F; Schuurman, R; Soriano, V; Stanczak, G; Stanojevic, M; Vandamme, AM; Van Laethem, K; Violin, M; Wilbe, K; Yerly, S; Zazzi, M; Boucher, CA. SPREAD Programme.

JOURNAL OF INFECTIOUS DISEASES 192 (6): 958-966.


Background. Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis.

Methods. We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002.

Results. In Europe, 1 of 10 antiretroviral-naive patients carried viruses with >= 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P = .006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%;). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from P <.01 2.0% (1/49) in 1996-1998 to 8.2% (16/194) in 2000-2001.

Conclusions. Drug-resistant variants are frequently present in both recently and chronically infected therapy-naive patients. Drug-resistant variants are most commonly seen in patients infected with subtype B virus, probably because of longer exposure of these viruses to drugs. However, an increase in baseline resistance in non-B viruses is observed. These data argue for testing all drug-naive patients and are of relevance when guidelines for management of postexposure prophylaxis and first-line therapy are updated.

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Searching for an assessment instrument to determine temporomandibular disorder pain profiles for the purposes of primary health care.

Forssell, H; Santalahti, P; Puukka, P; Talo, S.

INTERNATIONAL JOURNAL OF REHABILITATION RESEARCH, 28 (3): 203-209 SEP 2005

Mutations in the catalytic subunit of the mitochondrial DNA polymerase g ( POLG) have been found to be an important cause of neurological disease. Recently, we and collaborators reported a new neurodegenerative disorder with autosomal recessive ataxia in four patients homozygous for two amino acid changes in POLG: W748S in cis with E1143G. Here, we studied the frequency of this allele and found it to be among the most common genetic causes of inherited ataxia in Finland. We identified 27 patients with mitochondrial recessive ataxia syndrome ( MIRAS) from 15 Finnish families, with a carrier frequency in the general population of 1:125. Since the mutation pair W748S+E1143G has also been described in European patients, we examined the haplotypes of 13 non-Finnish, European patients with the W748S mutation. Haplotype analysis revealed that all the chromosomes carrying these two changes, in patients from Finland, Norway, the United Kingdom, and Belgium, originate from a common ancient founder. In Finland and Norway, long, common, northern haplotypes, outside the core haplotype, could be identified. Despite having identical homozygous mutations, the Finnish patients with this adult-or juvenile-onset disease had surprisingly heterogeneous phenotypes, albeit with a characteristic set of features, including ataxia, peripheral neuropathy, dysarthria, mild cognitive impairment, involuntary movements, psychiatric symptoms, and epileptic seizures. The high carrier frequency in Finland, the high number of patients in Norway, and the ancient European founder chromosome indicate that this newly identified ataxia should be considered in the first-line differential diagnosis of progressive ataxia syndromes.

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A review of the efficacy of rosuvastatin in patients with type 2 diabetes.

Tuomilehto, J; Leiter, LA; Kallend, D.

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE 58: 30-40, Suppl. 143.

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes melhtUS), ANDROMEDA (A raNdomized, Double-bhnd study to compare Rosuvastatin [10 & 20 mg] and -atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.
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A new definition for myocardial infarction: what difference does it make?

Salomaa, V; Koukkunen, H; Ketonen, M; Immonen-Raiha, P; Karja-Koskenkari, P; Mustonen, J; Lehto, S; Torppa, J; Lehtonen, A; Tuomilehto, J; Kesaniemi, YA; Pyorala, K. FINAMI Study Grp.

EUROPEAN HEART JOURNAL 26 (17): 1719-1725.
Open Access Article available 12 months after publication

Aims - As a response to changing diagnostic tools of myocardial infarction (MI), new case definitions for acute coronary events were published in 2003 as the American Heart Association Scientific Statement. We assessed the new definition in hospitalized patients in a large population-based MI register study.

Methods and results - We identified all suspected acute coronary syndromes with data either on troponin T or on troponin I and at least one of the enzymatic markers of myocardial injury (n=6104). The 2003 definition with the use of troponins identified 83% more definite MIs than the WHO MONICA definition using cardiac enzymes. The additional patients were older, had more often diabetes, and received less often thrombolysis and revascularization than those having MI by both definitions. Adjusting for age, sex, study area, and study year, the additional patients with their first MI aged 25-74 had a higher risk of cardiovascular death within 1 year than patients having definite MI by both definitions (hazard ratio 1.6, 95% CI 1.1-2.2).

Conclusion - The changing diagnostic criteria present a considerable challenge for the assessment of long-term trends in MI events in the community as well as for longitudinal studies of the natural history of MI. The 2003 definition, when applied using troponins, identified a sizable new group of MI patients, among persons with suspected acute coronary syndrome, at high risk of a recurrent event.
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The burden of mortality attributable to diabetes - Realistic estimates for the year 2000.

Roglic, G; Unwin, N; Bennett, PH; Mathers, C; Tuomilehto, J; Nag, S; Connolly, V; King, H.

DIABETES CARE, 28 (9): 2130-2135 SEP 2005
Open Access Article

OBJECTIVE- To estimate the global number of excess deaths due to diabetes in the year 2000.

RESEARCH DESIGN AND METHODS- We used a computerized generic formal disease model (DisMod 11), used by the World Health Organization to assess disease burden through modeling the relationships between incidence, prevalence, and disease-specific mortality. Baseline input data included population structure, age- and sex-specific estimates of diabetes prevalence, and available published estimates of relative risk of death for people with diabetes compared with people without diabetes. The results were validated with population-based observations and independent estimates of relative risk of death.

RESULTS- The excess global mortality attributable to diabetes in the year 2000 was estimated to be 2.9 million deaths, equivalent to 5.2% of all deaths. Excess mortality attributable to diabetes accounted for 2-3% of deaths in poorest countries and over 8% in the U.S., Canada, and the Middle East. In people 35-64 years old, 6-27% of deaths were attributable to diabetes.

CONCLUSIONS- These are the first global estimates of mortality attributable to diabetes. Globally, diabetes is likely to be the fifth leading cause of death.

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The diagnosis, symptomatology, and epidemiology of seasonal affective disorder.

Magnusson, A; Partonen, T.

CNS SPECTRUMS, 10 (8): 625-+ AUG 2005

KeyWords Plus: PATTERN-ASSESSMENT-QUESTIONNAIRE; DEFICIT HYPERACTIVITY DISORDER; NONSEASONAL MOOD DISORDERS; DSM-III-R; WINTER DEPRESSION; BULIMIA-NERVOSA; FOLLOW-UP; PRIMARY-CARE; MAJOR DEPRESSION; COLLEGE-STUDENTS
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Overexpression of OSBP-related protein 2 (ORP2) induces changes in cellular cholesterol metabolism and enhances endocytosis.

Hynynen, R; Laitinen, S; Kakela, R; Tanhuanpaa, K; Lusa, S; Ehnholm, C; Somerharju, P; Ikonen, E; Olkkonen, VM.

BIOCHEMICAL JOURNAL, 390: 273-283 Part 1 AUG 15 2005

Open Access Article

ORP2 [OSBP (oxysterol-binding protein)-related protein 2] belongs to the 12-member mammalian ORP gene/protein family. We characterize in the present study the effects of inducible ORP2 overexpression on cellular cholesterol metabolism in HeLa cells and compare the results with those obtained for CHO cells (Chinese-hamster ovary cells) that express ORP2 constitutively. In both cell systems, the prominent phenotype is enhancement of [C-14]cholesterol efflux to all extracellular acceptors, which results in a reduction of cellular free cholesterol. No change was observed in the plasma membrane cholesterol content or distribution between raft and non-raft domains upon ORP2 expression. However, elevated HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase activity and LDL (low-density lipoprotein) receptor expression, as well as enhanced transport of newly synthesized cholesterol to a cyclodextrin-accessible pool, suggest that the ORP2 expression stimulates transport of cholesterol out of the endoplasmic reticulum. In contrast with ORP2/CHO cells, the inducible ORP2/HeLa cells do not show down-regulation of cholesterol esterification, suggesting that this effect represents an adaptive response to long-term cholesterol depletion in the CHO cell model. Finally, we provide evidence that ORP2 binds PtdIns(3,4,5)P-3 and enhances endocytosis, phenomena that are probably interconnected. Our results suggest a function of ORP2 in both cholesterol trafficking and control of endocytic membrane transport.
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Effects of diet and simvastatin on fatty acid composition in hypercholesterolemic men - A randomized controlled trial.

Jula, A; Marniemi, J; Ronnemaa, T; Virtanen, A; Huupponen, R.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 25 (9): 1952-1959.

Objective - To explore the separate and combined effects of simvastatin and a low-saturated diet rich in alpha-linolenic acid on serum fatty acids.

Methods and Results - 120 hypercholesterolemic men were randomly allocated to a habitual diet or dietary treatment group and to receive, in random order, simvastatin 20 mg/d or placebo, each for 12 weeks, in a double-blind manner. Dietary treatment decreased proportions from total fatty acids of palmitic acid (C16: 0) by 3.3% ( P < 0.05), stearic acid (C18: 0) by 3.7% ( P < 0.05) and increased proportions of oleic acid (C18: 1n-9) by 4.2% ( P < 0.01), and alpha-linolenic acid ( C18: 3n-3) by 29.8% ( P < 0.001). Simvastatin decreased proportions from total fatty acids of palmitic acid by 2.0% ( P < 0.01), linoleic acid (C18: 2n-6) by 5.3% ( P < 0.001), and alpha-linolenic acid by 6.8% ( P < 0.05), and increased proportions of gamma-linolenic acid (C18: 3n- 6) by 11.1% ( P < 0.001), dihomo-gamma-linolenic acid (C20: 3n- 6) by 4.2% ( P < 0.01), arachidonic acid ( C20: 4n-6) by 14.2% ( P < 0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% ( P < 0.001). Simvastatin increased ratios of stearic to palmitic, gamma-linolenic to linoleic, and arachidonic to dihomo- gamma-linolenic acid by 7.6%, 17.0%, and 10.0% ( P < 0.001 for all), respectively, suggesting increased fatty acid elongase and Delta 6- and Delta 5-desaturase enzyme activities.

Conclusions - Increased formation of long-chain polyunsaturated fatty acids and their metabolites may contribute a substantial part of the pleiotropic effects of simvastatin.

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Effect of simvastatin, an established lipid-lowering drug, on pulmonary Chlamydia pneumoniae infection in mice.

Erkkilä, L; Jauhiainen, M; Laitinen, K; Haasio, K; Tiirola, T; Saikku, P; Leinonen, M.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY 49 (9): 3959-3962.
Open Access Article

The effects of simvastatin treatment on Chlamydia pneumoniae lung infection, inflammation, and serum lipids in mouse model were studied. Simvastatin decreased viable chlamydial counts and increased inflammatory cell infiltrates in the lung tissue, suggesting that simvastatin treatment had both antichlamydial and immunomodulatory effects during an acute C pneumoniae infection. ========================================================================