Cancer-associated fibroblasts of the prostate promote a compliant and more invasive phenotype in benign prostate epithelial cells.

Reciprocal interactions between prostate epithelial cells and their adjacent stromal microenvironment not only are essential for tissue homeostasis but also play a key role in tumor development and progression. Malignant transformation is associated with the formation of a reactive stroma where cancer-associated fibroblasts (CAFs) induce matrix remodeling and thereby provide atypical biochemical and biomechanical signals to epithelial cells. Previous work has been focused on the cellular and molecular phenotype as well as on matrix stiffness and remodeling, providing potential targets for cancer therapeutics. So far, biomechanical changes in CAFs and adjacent epithelial cells of the prostate have not been explored. Here, we compared the mechanical properties of primary prostatic CAFs and patient-matched non-malignant prostate tissue fibroblasts (NPFs) using atomic force microscopy (AFM) and real-time deformability cytometry (RT-FDC). It was found that CAFs exhibit an increased apparent Young's modulus, coinciding with an altered architecture of the cytoskeleton compared with NPFs. In contrast, co-cultures of benign prostate epithelial (BPH-1) cells with CAFs resulted in a decreased stiffness of the epithelial cells, as well as an elongated morphological phenotype, when compared with co-cultures with NPFs. Moreover, the presence of CAFs increased proliferation and invasion of epithelial cells, features typically associated with tumor progression. Altogether, this study provides novel insights into the mechanical interactions between epithelial cells with the malignant prostate microenvironment, which could potentially be explored for new diagnostic approaches.

EAU-ESMO consensus statements on the management of advanced and variant bladder cancer-an international collaborative multi-stakeholder effort: under the auspices of the EAU and ESMO Guidelines Committees†.

BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. SETTING: Online Delphi survey and consensus conference. PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.

Associations between functional polymorphisms in the NFκB signaling pathway and response to anti-TNF treatment in Danish patients with inflammatory bowel disease.

Antitumor necrosis factor-α (TNF-α) is used for treatment of severe cases of inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, one-third of the patients do not respond to the treatment. Genetic markers may predict individual response to anti-TNF therapy. Using a candidate gene approach, 39 mainly functional single nucleotide polymorphisms (SNPs) in 26 genes regulating inflammation were assessed in 738 prior anti-TNF-naive Danish patients with IBD. The results were analyzed using logistic regression (crude and adjusted for age, gender and smoking status). Nineteen functional polymorphisms that alter the NFκB-mediated inflammatory response (TLR2 (rs3804099, rs11938228, rs1816702, rs4696480), TLR4 (rs5030728, rs1554973), TLR9 (rs187084, rs352139), LY96 (MD-2) (rs11465996), CD14 (rs2569190), MAP3K14 (NIK) (rs7222094)), TNF-α signaling (TNFA (TNF-α) (rs361525), TNFRSF1A (TNFR1) (rs4149570), TNFAIP3(A20) (rs6927172)) and other cytokines regulated by NFκB (IL1B (rs4848306), IL1RN (rs4251961), IL6 (rs10499563), IL17A (rs2275913), IFNG (rs2430561)) were associated with response to anti-TNF therapy among patients with CD, UC or both CD and UC (P ⩽ 0.05). In conclusion, the results suggest that polymorphisms in genes involved in activating NFκB through the Toll-like receptor (TLR) pathways, genes regulating TNF-α signaling and cytokines regulated by NFκB are important predictors for the response to anti-TNF therapy among patients with IBD. Genetically strong TNF-mediated inflammatory response was associated with beneficial response. In addition, the cytokines IL-1ß, IL-6 and IFN-γ may be potential targets for treating patients with IBD who do not respond to anti-TNF therapy. These findings should be examined in independent cohorts before these results are applied in a clinical setting.

Should cavitation in proximal surfaces be reported in cone beam computed tomography examination?

AIM: A clinical study was done to assess the clinical diagnostic accuracy of cone beam computed tomography (CBCT) in detecting proximal cavitated carious lesions in order to determine whether cavitation should be reported when a CBCT examination is available. MATERIALS AND METHODS: 79 adjacent proximal surfaces without restorations in permanent teeth were examined. Patients suspected to have carious lesions after a visual clinical and a bitewing examination participated in a CBCT examination (Kodak 9000 3D, 5 × 3.7 cm field of view, voxel size 0.07 mm). Ethical approval and informed consent were obtained according to the Helsinki Declaration. Radiographic assessment recording lesions with or without cavitation was performed by two observers in bitewings and CBCT sections. Orthodontic separators were placed interdentally between two lesion-suspected surfaces. The separator was removed after 3 days and the surfaces recorded as cavitated (yes/no), i.e. validated clinically. Differences between the two radiographic modalities (sensitivity, specificity and overall accuracy) were estimated by analyzing the binary data in a generalized linear model. RESULTS: For both observers, sensitivity was significantly higher for CBCT than for bitewings (average difference 33%, p < 0.001) while specificity was not significantly different between the methods (p = 0.19). The overall accuracy was also significantly higher for CBCT (p < 0.001). CONCLUSION: CBCT was more accurate in detecting cavitation in proximal surfaces than bitewing radiographs; therefore a CBCT examination performed for other clinical applications should also be assessed for proximal surface cavities in teeth without restorations, and when detected, this pathology must be part of the dentist's report.

Association between Attention-Deficit Hyperactivity Disorder in childhood and schizophrenia later in adulthood.

PURPOSE: To estimate the risk of schizophrenia in adulthood among children and adolescents with ADHD compared to the background population. SUBJECTS/MATERIALS AND METHODS: Two hundred and eight youths with ADHD (183 boys; 25 girls) were followed prospectively. Diagnoses of schizophrenia were obtained from The Danish Psychiatric Central Register. The relative risk (RR) of schizophrenia for cases with ADHD, compared to the normal population, was calculated as risk ratios. Hazard ratios (HR's) by Cox regression were calculated in the predictor analyses. RESULTS: Mean age for ADHD cases at follow-up was 31.1years. Schizophrenia diagnoses were given to 3.8% of these cases. Compared to the general population, RR of schizophrenia in cases with ADHD was 4.3 (95% CI 1.9-8.57). DISCUSSION AND CONCLUSION: This prospective follow-up study found children with ADHD to be at higher risk of later schizophrenia than controls. If replicated, these results warrant increased focus on the possible emergence symptoms of schizophrenia or schizophreniform psychosis during clinical follow-up of patients with ADHD.

Fluctuations in sedation levels may contribute to delirium in ICU patients.

BACKGROUND: Delirium in patients admitted to the intensive care unit (ICU) is a serious complication potentially increasing morbidity and mortality. The aim of this study was to investigate the impact of fluctuating sedation levels on the incidence of delirium in ICU. METHODS: A prospective cohort study of adult patients at three multidisciplinary ICUs. The Richmond Agitation and Sedation Scale (RASS) and the Confusion Assessment Method for the ICU were used at least twice a day. RESULTS: Delirium was detected at least once in 65% of the patients (n = 640). Delirious patients were significantly older, more critically ill, more often intubated, had longer ICU stays, and had higher ICU mortality than non-delirious patients. The median duration of delirium was 3 days (interquartile range: 1;10), and RASS was less than or equal to 0 (alert and calm) 91% of the time. The odds ratio (OR) for development of delirium if RASS changed more than two levels was 5.19 when adjusted for gender, age, severity of illness, and ICU site and setting. Continuous infusion of midazolam was associated with a decrease in delirium incidence (OR: 0.38; P = 0.002). CONCLUSIONS: Fluctuations in sedation levels may contribute to development of delirium in ICU patients. The risk of developing delirium might be reduced by maintaining a stable sedation level or by non-sedation.

Detection of cavitated approximal surfaces using cone beam CT and intraoral receptors.

OBJECTIVES: The aim of this study was to compare cone beam CT (CBCT) in a small field of view (FOV) with a solid-state sensor and a photostimulable phosphor plate system for detection of cavitated approximal surfaces. METHODS: 257 non-filled approximal surfaces from human permanent premolars and molars were recorded by two intraoral digital receptors, a storage phosphor plate (Digora Optime, Soredex) and a solid-state CMOS sensor (Digora Toto, Soredex), and scanned in a cone beam CT unit (3D Accuitomo FPD80, Morita) with a FOV of 4 cm and a voxel size of 0.08 mm. Image sections were carried out in the axial and mesiodistal tooth planes. Six observers recorded surface cavitation in all images. Validation of the true absence or presence of surface cavitation was performed by inspecting the surfaces under strong light with the naked eye. Differences in sensitivity, specificity and agreement were estimated by analysing the binary data in a generalized linear model using an identity link function. RESULTS: A significantly higher sensitivity was obtained by all observers with CBCT (p < 0.001), which was not compromised by a lower specificity. Therefore, a significantly higher overall agreement was obtained with CBCT (p < 0.001). There were no significant differences between the Digora Optime phosphor plate system and the Digora Toto CMOS sensor for any parameter. CONCLUSIONS: CBCT was much more accurate in the detection of surface cavitation in approximal surfaces than intraoral receptors. The differences are interpreted as clinically significant. A CBCT examination performed for other reasons should also be assessed for approximal surface cavities in teeth without restorations.

Time to diagnosis and mortality in colorectal cancer: a cohort study in primary care.

BACKGROUND: The relationship between the diagnostic interval and mortality from colorectal cancer (CRC) is unclear. This association was examined by taking account of important confounding factors at the time of first presentation of symptoms in primary care. METHODS: A total of 268 patients with CRC were included in a prospective, population-based study in a Danish county. The diagnostic interval was defined as the time from first presentation of symptoms until diagnosis. We analysed patients separately according to the general practitioner's interpretation of symptoms. Logistic regression was used to estimate 3-year mortality odds ratios as a function of the diagnostic interval using restricted cubic splines and adjusting for tumour site, comorbidity, age, and sex. RESULTS: In patients presenting with symptoms suggestive of cancer or any other serious illness, the risk of dying within 3 years decreased with diagnostic intervals up to 5 weeks and then increased (P=0.002). In patients presenting with vague symptoms, the association was reverse, although not statistically significant. CONCLUSION: Detecting cancer in primary care is two sided: aimed at expediting ill patients while preventing healthy people from going to hospital. This likely explains the counterintuitive findings; but it does not explain the increasing mortality with longer diagnostic intervals. Thus, this study provides evidence for the hypothesis that the length of the diagnostic interval affects mortality in CRC patients.

Case report: renal cell carcinoma segregating with a t(2;3)(q37.3;q13.2) chromosomal translocation in an Ashkenazi Jewish family.

Chromosome translocations involving chromosome 3 have previously been associated with the development of renal cell carcinoma. In this report we describe an Ashkenazi Jewish family with a previously unreported balanced constitutional translocation (t(2;3)(q37.3;q13.2)) segregating with the development of clear cell renal carcinomata in three family members spanning two generations. We outline the difficulties with the clinical utility of this finding for genetic counselling and risk management strategies. We suggest that an additional renal cancer susceptibility gene may exist at 3q13.2, and review known breakpoints in the autosomes which are associated with clear cell renal cell carcinoma.

Empirical support for a reclassification of eating disorders NOS.

OBJECTIVE: To explore the empirical support for a reclassification of the eating disorders NOS (EDNOS) category. METHODS: In a cross-sectional design eight specific subgroups of EDNOS were compared to anorexia nervosa (AN) and bulimia nervosa (BN) on interview-based data and questionnaire measures. The sample consisted of 965 patients in the age 13-54 years admitted to treatment for an eating disorder. RESULTS: According to the DSM-IV 176(18%) presented with AN, 290(30%) with BN and 499(52%) with EDNOS. Of all EDNOS cases 34% could be reclassified as AN or BN. Three specific subgroups emerged as separate diagnostic entities. A heterogeneous subgroup of 122 patients (13% of all) was proposed as 'true' EDNOS. Implications of the results on the DSM-V are discussed. CONCLUSIONS: The results support a broader definition of AN and BN and suggest subgroups of EDNOS as separate diagnostic entities. This results in a substantial reduction of the heterogeneous EDNOS group.

Trans-diagnostic outcome of eating disorders: A 30-month follow-up study of 629 patients.

OBJECTIVE: To assess the 30-month outcome and predictors of outcome in a cohort of patients with any eating disorder (ED). METHOD: A naturalistic design was used to determine time to remission, predictors of remission, relapse, diagnostic cross-over and mortality of 629 patients. RESULTS: At follow-up (FU) 312 patients attended, 42% obtained full remission and 72% partial remission. No differences were found between diagnostic groups for adolescents. Adult patients with anorexia-like eating disorder not otherwise specified-anorexia nervosa (EDNOS-AN) had the poorest outcome. Bulimia-like EDNOS was the most frequent relapse diagnosis. Bingeing/purging behaviour predicted a poorer outcome for individuals with bulimic disorders. Desired low BMI predicted a poorer outcome for individuals with anorexia. Comorbid personality disorder was a common predictor of a worse outcome. CONCLUSION: Adults with EDNOS-AN had the poorest prognosis. Bulimic symptoms emerged frequently during FU regardless of diagnosis. Remission rates and outcome predictors were similar to previous findings.

Effect of monitor display on detection of approximal caries lesions in digital radiographs.

OBJECTIVES: The aim was to compare the accuracy of five flat panel monitors for detection of approximal caries lesions. METHODS: Five flat panel monitors, Mermaid Ventura (15 inch, colour flat panel, 1024 x 768, 32 bit, analogue), Olórin VistaLine (19 inch, colour, 1280 x 1024, 32 bit, digital), Samsung SyncMaster 203B (20 inch, colour, 1024 x 768, 32 bit, analogue), Totoku ME251i (21 inch, greyscale, 1400 x 1024, 32 bit, digital) and Eizo FlexScan MX190 (19 inch, colour, 1280 x 1024, 32 bit, digital), were assessed. 160 approximal surfaces of human teeth were examined with a storage phosphor plate system (Digora FMX, Soredex) and assessed by seven observers for the presence of caries lesions. Microscopy of the teeth served as validation for the presence/absence of a lesion. RESULTS: The sensitivities varied between observers (range 7-25%) but the variation between the monitors was not large. The Samsung monitor obtained a significantly higher sensitivity than the Mermaid and Olórin monitors (P<0.02) and a lower specificity than the Eizo and Totoku monitors (P<0.05). There were no significant differences between any other monitors. The percentage of correct scores was highest for the Eizo monitor and significantly higher than for the Mermaid and Olórin monitors (P<0.03). CONCLUSIONS: There was no clear relationship between the diagnostic accuracy and the resolution or price of the monitor. The Eizo monitor was associated with the overall highest percentage of correct scores. The standard analogue flat panel monitor, Samsung, had higher sensitivity and lower specificity than some of the other monitors, but did not differ in overall accuracy for detection of carious lesions.

Sex steroids modulate alpha 1-adrenoceptor-stimulated Ca2+ elevation in human cultured prostatic stromal cells.

BACKGROUND: Benign prostatic hyperplasia is an age- and androgen-dependent condition of urethral compression caused by prostatic contractility and glandular enlargement. In this study we investigate whether testosterone, dihydrotestosterone and estradiol modulate the ability of human cultured prostatic stromal cells (HCPSCs) to respond to the adrenoceptor agonists, noradrenaline (30 microM) and phenylephrine (100 microM), the protein kinase C activating phorbol ester, phorbol diacetate (PDA, 10 microM), and the L-type Ca(2+) channel activator, (-)-Bay K8644 (Bay K, 10 microM) with elevations of intracellular Ca(2+) ([Ca(2+)](i)). METHODS: Cells were loaded with the Ca(2+) sensitive fluorophore, FURA-2AM (10 microM) and changes in intracellular Ca(2+) determined before and 8-12 min after ligand addition. RESULTS: Compared to steroid-free (SF) controls, the incubation of HCPSC with testosterone (30 and 300 pM) significantly increased responses to both noradrenaline and phenylephrine. Responses to Bay K were significantly reduced between 30 nM to 300 pM but responses to PDA were not greatly affected. Compared to SF the addition of estradiol (E(2), 100 pM) did not affect responses to phenylephrine. The concomitant addition of dihydrotestosterone (DHT) and E(2) (to give ratios from 1:1 to 1,000:1) elevated the responses to noradrenaline and phenylephrine at the extreme ranges. Responses to PDA and Bay K generally increased as DHT:E(2) approached unity. CONCLUSIONS: These results indicate that sex steroids modulate the activities of HCPSCs through the regulation of both receptors and signal transduction processes.

Having children with different men and subsequent cancer risk. A nationwide study in Denmark.

The more men by whom a woman has children, the more diverse will be the foetal antigens of paternal origin introduced into her bloodstream, and we investigated whether this has an impact on subsequent cancer risks. By using population registries we identified 64704 women who had children with at least two different partners from 1973 to 1996 in Denmark. We compared their cancer incidence with that of women who during the same time period had at least two births with no indication of partner change, adjusting for age, parity, socioeconomic factors and residence. The overall cancer incidence was more than 50% higher in women with two or more partners. Women having children with multiple partners had a higher incidence of cancer of the cervix and corpus uteri, a lower incidence of melanoma but a similar incidence of breast and ovarian cancer. Uncontrolled differences in lifestyle factors may explain the higher cancer risk associated with having multiple partners. The strong protective effect for melanoma was unexpected and deserves further study.

A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells.

1. This study investigated the possibility that adenosine receptors modulate the alpha(1)-adrenoceptor-mediated contractility of human cultured prostatic stromal cells (HCPSC). 2. The nonselective adenosine receptor agonist, 5'-N-ethylcarboxamido-adenosine (NECA; 10 nm-10 microm), and the A(1) adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nm-10 microm), elicited significant contractions in HCPSC, with maximum contractile responses of 18+/-3% and 17+/-2% reduction in initial cell length, respectively. 3. In the presence of a threshold concentration of phenylephrine (PE) (100 nm), CPA (1 nm-10 microm) caused contractions, with an EC(50) of 124+/-12 nm and maximum contractile response of 37+/-4%. The A(1) adenosine receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX 100 nm) blocked this effect. In the presence of DPCPX (100 nm), NECA (1 nm-10 microm) inhibited contractions elicited by a submaximal concentration of PE (10 microm), with an IC(50) of 48+/-2 nm. The A(2A) adenosine receptor-selective antagonist 4-(2-[7-amino-2-[furyl][1,2,4]triazolo[2,3-alpha][1,3,5,]triazin-5-yl amino]ethyl)phenol (Zm241385 100 nm) blocked this effect. 4. In BCECF-AM (10 microm)-loaded cells, both CPA (100 pM-1 microm) and NECA (100 pm-10 microm) elicited concentration-dependent decreases in intracellular pH (pH(i)), with EC(50) values of 3.1+/-0.3 and 6.0+/-0.3 nm, respectively. The response to NECA was blocked by Zm241385 (100 nm; apparent pK(B) of 9.4+/-0.4), but not by DPCPX (100 nm). The maximum response to CPA was blocked by DPCPX (100 nm), and unaffected by Zm241385 (100 nm). 5. NECA (10 nm-10 microm) alone did not increase [(3)H]-cAMP in HCPSC. In the presence of DPCPX (100 nm), NECA (10 nm-10 microm) caused a concentration dependent increase in [(3)H]-cAMP, with an EC(50) of 1.2+/-0.1 microm. This response was inhibited by Zm241385 (100 nm). CPA (10 nm-10 microm) had no effect on cAMP, in the presence or absence of forskolin (1 microm). 6. These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor-mediated contractility in human prostate-derived cells.

Head injury as a risk factor for bipolar affective disorder.

BACKGROUND: Case reports have associated head injury with psychoses including affective disorders, but little is known regarding head injury as a risk factor for the onset of bipolar affective disorder. METHODS: The Danish Psychiatric Case Register and the Danish National Patients Register were linked together with the Danish Population Register, thus identifying 10,242 patients with bipolar affective disorder, and 102,420 matched controls. History regarding head injury was recorded from the National Patients Register data. Data were analysed using conditional logistic regression. RESULTS: Bipolar affective disorder was associated with an increased risk of a history of head injury (IRR=1.55; 95% CI 1.36-1.77). The increased risk was confined to head injury occurring less than 5 years before the first psychiatric admission. The finding could not be ascribed to increased accident proneness (as evaluated through the occurrence of other fractures not involving the skull). LIMITATIONS: In studies based on clinical diagnoses only and limited to patients who were hospitalised for psychiatric disorder, exposure was limited to injuries leading to admission to hospital. CONCLUSIONS: Head injury may be a contributing factor to the onset of bipolar affective illness. However, this factor is probably only relevant to a relatively small minority of cases.

Gyrus bipolar electrovaporization vs transurethral resection of the prostate: a randomized prospective single-blind trial with 1 y follow-up.

The Gyrus system uses bipolar electrocautery with saline irrigation to vaporize prostatic tissue and is compared to transurethral resection of the prostate (TURP) in a randomized prospective study with 1 y follow-up. Outcomes measured were fluid absorption, blood loss, period of catheterization, hospital stay, symptom scores, quality of life, flow rates, and post-void residual volumes at 3, 6, and 12 months. All measured parameters were similar, although re-catheterization rates were higher (30% vs 5%) in the Gyrus group. Clot evacuation rates were higher in the TURP group (19% vs 0%). The Gyrus device is safe and produces results that are similar to TURP at 1 y.

Mental illness in new neurological patients.

OBJECTIVE: To determine the prevalence of psychiatric disorders in new neurological inpatients and outpatients, and examine whether they are recognised, treated, or referred to psychiatric consultation. METHODS: 198 consecutive patients referred for the first time to a neurologist were studied using a two phase design. ICD-10 psychiatric diagnoses were established by means of the SCAN (Schedules for Clinical Assessment in Neuropsychiatry). RESULTS: The overall prevalence of current mental disorders was 55.1% (95% CI: 46.2 to 63.8), and 65.0% (95% CI: 56.1 to 73.0) had at least once in their life had a psychiatric disorder. The most frequent current diagnoses were somatoform disorders (33.8%, (95% CI: 25.9 to 42.7%)), followed by phobias (21.8%; 95% CI: 15.3 to 30.0), substance use disorders (13.3%; 95% CI: 8.3 to 20.6) and depression/dysthymia (14.4; 95% CI: 9.1 to 21.8). The psychiatric morbidity markedly declined with increasing age. Compared with 63.5% of the women, 46.4% of the men had a psychiatric disorder. Substance use disorders were more frequent in men than women (p=0.002). Patients with a psychiatric disorder were more frequently seen in the outpatients' clinic than those without. The neurologists detected 14%-40% of the cases, 16.9% were in treatment, and only 4.6% were referred to mental health care. CONCLUSION: Psychiatric disorders, in particular somatoform disorders, are extremely common in neurological patients, especially in young and middle aged patients, outpatients, and women. The results call for more research on mental illness' impact on care and outcome in neurological patients.

The effect of choosing different units of analysis when estimating risk of presence of dental caries in the primary dentition.

BACKGROUND: Data on caries are usually collected with the tooth surface or the tooth as the unit, but subsequently analysed by aggregating the data at the level of the individual. AIMS: To evaluate how different units of analysis may affect the result of the statistical analyses in a study of the association between deciduous dental caries and a set of risk factors. METHOD: 293 children (mean age: 7.5 yrs) from two primary schools in Dar es Salaam, Tanzania were examined. Thus the study design was cross-sectional. Logistic regression analysis was used to determine the association between caries experience and nutritional status, socioeconomic background, and microbiological and salivary characteristics using the subject, the tooth, and the tooth surface as unit of analysis, allowing for the fact that teeth and surfaces within the same individual must be considered non-independent. RESULTS: When aggregated data were used, point estimates were larger in some instances. The precision of the estimates increased considerably when the tooth as compared to the individual was used as the unit of analysis. No or limited gain in precision was obtained when the tooth surface as compared to the tooth was used as unit of analysis. CONCLUSIONS: The choice of unit of analysis may strongly influence the result of the statistical analyses and thus the conclusion of an investigation.