Caries Experience in Elderly People Consuming a Milk-Based Drink Nutritional Supplement: A Cross-Sectional Study.

Nutritional supplements have been recommended to cope with malnutrition in elderly persons. In Chile, the Supplementary Nutrition Program for the Elderly (PACAM, for its Spanish acronym) consists in a monthly distribution of a low-fat-milk-based drink that contains 8% sucrose. The aim of this study was to determine whether older persons consuming the milk-based drink have a higher caries experience when compared to those not receiving the supplement. A cross-sectional study was conducted in the Maule Region in Chile. The representative sample comprised two groups: (a) PACAM consumers (CS) (n = 60) and (b) nonconsumers (NCS) (n = 60). Participants received intraoral examination and coronal (DMFT/DMFS) and root caries (RCI index) experience were recorded. Additionally, questionnaires regarding acceptability and consumption habits of PACAM and a 24-h diet recall were applied. The influence of predictors was calculated using binary logistic regression for a dichotomized DMFS and Poisson Regression for root caries lesions. A p value <0.05 was considered significant. No differences were detected in food consumption patterns between study groups (p > 0.05). CS participants had increased dairy product consumption. Higher DMFS mean value was observed in the CS (85.35 ± 39.0) compared with NCS (77.28 ± 28.9) (p = 0.043). The multivariate analysis showed nonconsumers of the milk-based product (ß = -0.41, p = 0.02) are less likely to have root surfaces affected by caries. Additionally, CS show higher RCI, compared to nonconsumers (ß = -0.17, p = 0.02). Daily consumption of a PACAM's milk-based drink supplement seems to increase coronal and root caries risk. Based on these results, composition modification of milk-based drinks with added sucrose appears mandatory.

Cariogenicity of a Milk-Based Drink Used as a Dietary Supplement for Older Adults Using a Root Caries Experimental Model.

The aim of this study was to evaluate the cariogenicity of a milk-based drink intended for older adults that was used as part of a governmental initiative in Chile to improve their nutritional conditions. This drink contains a high concentration of sugars, which can contribute to root caries development. To test this hypothesis, an experimental biofilm/caries model was used. Dentin slabs were used to grow biofilms of Streptococcus mutans UA159. Slabs/biofilms were exposed 3× per day to bovine milk with different fat content, the milk-based drink, and the milk-based drink supplemented with 10 g of sucrose added per serving. Slabs exposed to 10% sucrose or 0.9% NaCl were used as positive and negative controls, respectively. Biofilms were analyzed for bacterial counts and acidogenicity. Dentin demineralization was estimated by the loss of surface microhardness and integrated mineral loss. Results were compared by analysis of variance and Tukey's test. The milk-based drink showed higher acidogenicity than milk with its entire (whole) or reduced total fat content (skim). The milk-based drink supplemented with -sucrose had similar acidogenicity as the 10% sucrose positive control (p = 0.506). Whole milk exposure elicited lower bacterial counts than the positive control, the milk-based drink, and the milk-based drink supplemented with sucrose (p = 0.002; 0.006 and 0.014 respectively). Although skim milk induced higher demineralization than whole milk, both milk types produced lower demineralization than the milk-based drink. Regarding integrated mineral loss, demineralization induced by the milk-based drink and the milk-based drink supplemented with sucrose was similar to that induced by the positive control and skim milk (p > 0.05). Sugar-containing milk-based drinks used as dietary supplements for older adults may be highly cariogenic and could represent a potential risk for root caries.

The Effect of Dutasteride on Magnetic Resonance Imaging Defined Prostate Cancer: MAPPED-A Randomized, Placebo Controlled, Double-Blind Clinical Trial.

PURPOSE: Dutasteride, which is licensed for symptomatic benign prostatic hyperplasia, has been associated with a lower progression rate of low risk prostate cancer. We evaluated the effect of dutasteride on prostate cancer volume as assessed by T2-weighted magnetic resonance imaging. MATERIALS AND METHODS: In this randomized, double-blind, placebo controlled trial, men with biopsy proven, low-intermediate risk prostate cancer (up to Gleason 3 + 4 and PSA up to 15 ng/ml) who had visible lesion of 0.2 ml or greater on T2-weighted magnetic resonance imaging sequences were randomized to daily dutasteride 0.5 mg or placebo for 6 months. Lesion volume was assessed at baseline, and 3 and 6 months with image guided biopsy to the lesion at study exit. The primary end point was the percent reduction in lesion volume over 6 months. This trial was registered with the European Clinical Trials register (EudraCT 2009-102405-18). RESULTS: A total of 42 men were recruited between June 2010 and January 2012. In the dutasteride group, the average volumes at baseline and 6 months were 0.55 and 0.38 ml, respectively and the average reduction was 36%. In the placebo group, the average volumes at baseline and 6 months were 0.65 and 0.76 ml, respectively, and the average reduction was -12%. The difference in percent reductions between the groups was 48% (95% CI 27.4-68.3, p <0.0001). The most common adverse event was deterioration in erectile function, which was 25% in men randomized to dutasteride and 16% in men randomized to placebo. CONCLUSIONS: Dutasteride was associated with a significant reduction in prostate cancer volume on T2-weighted magnetic resonance imaging compared to placebo.

MRI findings in men on active surveillance for prostate cancer: does dutasteride make MRI visible lesions less conspicuous? Results from a placebo-controlled, randomised clinical trial.

OBJECTIVES: To investigate changes in the Apparent Diffusion Coefficient (ADC) using diffusion-weighted imaging (DWI) in men on active surveillance for prostate cancer taking dutasteride 0.5 mg or placebo. METHODS: We analysed 37 men, randomised to 6 months of daily dutasteride (n = 18) or placebo (n = 19), undergoing 3T multi-parametric Magnetic Resonance Imaging (mpMRI) scans at baseline and 6 months. Images were reviewed blind to treatment allocation and clinical information. Mean ADC of peripheral (PZ) and transition (TZ) zones, and MR-suspicious lesions were compared between groups over 6 months. Conspicuity was defined as the PZ divided by tumour ADC, and its change over 6 months was assessed. RESULTS: A decrease in mean conspicuity in the dutasteride group (but not the controls) was seen over 6 months (1.54 vs 1.38; p = 0.025). Absolute changes in ADC and conspicuity were significantly different between placebo and dutasteride groups at 6 months: (-0.03 vs 0.08, p = 0.033) and (0.11 vs -0.16, p = 0.012), as were percentage changes in the same parameters: (-2.27% vs 8.56% p = 0.048) and (9.25% vs -9.89% p = 0.013). CONCLUSIONS: Dutasteride was associated with increased tumour ADC and reduced conspicuity. A lower threshold for triggering biopsy might be considered in men on dutasteride undergoing mpMRI for prostate cancer. KEY POINTS: • Dutasteride increases ADC and reduces conspicuity in small mpMRI-visible prostate cancers. • Knowledge of dutasteride exposure is important in the interpretation of prostate mpMRI. • A lower threshold for triggering biopsy may be appropriate on dutasteride.

Influence of baseline variables on changes in International Prostate Symptom Score after combined therapy with dutasteride plus tamsulosin or either monotherapy in patients with benign prostatic hyperplasia and lower urinary tract symptoms: 4-year results of the CombAT study.

OBJECTIVE: To examine, using post hoc analysis, the influence of baseline variables on changes in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax ) and IPSS quality of life (QoL) in patients with moderate-to-severe lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) treated with either the α-blocker tamsulosin or the dual 5-alpha reductase inhibitor dutasteride, alone or in combination, as part of the 4-year Combination of Avodart and Tamsulosin (CombAT) study. PATIENTS AND METHODS: CombAT was a 4-year, multicentre, randomized, double-blind, parallel-group study in 4844 men ≥50 years of age with a clinical diagnosis of BPH by medical history and physical examination, an IPSS ≥12 points, prostate volume (PV) ≥30 mL, total serum PSA level ≥1.5 ng/mL, and Qmax >5 mL/s and ≤15 mL/s with a minimum voided volume ≥125 mL. Eligible subjects were randomized to receive oral daily tamsulosin, 0.4 mg; dutasteride, 0.5 mg; or a combination of both. Baseline variable subgroups analysed were as follows: PV (30 to <40; 40 to <60; 60 to <80; ≥80 mL), PSA level (1.5 to <2.5; 2.5 to <4; ≥4 ng/mL), age (median: <66, ≥66 years), IPSS (median: <16, ≥16; IPSS thresholds, <20, ≥20), IPSS QoL score (question 8, Q8) (median: <4, ≥4), Qmax (median: <10.4, ≥10.4 mL/s), BPH impact index (BII) (median: <5, ≥5) and body mass index (BMI, median: <26.8, ≥26.8 kg/m(2) ). Within each baseline variable subgroup, changes in IPSS, Qmax and IPSS QoL Q8 from baseline were evaluated using a generalized linear model with effects for baseline IPSS, Qmax or IPSS QoL Q8 and treatment group at each post-baseline assessment up to and including the month 48 visit using a last observation carried forward approach. The treatment comparisons of combination therapy vs dutasteride and combination therapy vs tamsulosin were performed from the general linear model with statistical significance defined as P ≤ 0.01. RESULTS: Combination therapy resulted in a significantly greater improvement from baseline IPSS at 48 months vs tamsulosin monotherapy across all baseline subgroups. The benefit of combination therapy over dutasteride was confined to groups with lower baseline PV (<60 mL) and PSA (<4 ng/mL). In groups with baseline PV ≥60 mL and PSA ≥4 ng/mL, dutasteride and combination therapy show similar improvements in symptoms. Combination therapy resulted in significantly improved Qmax compared with tamsulosin but not dutasteride monotherapy. Qmax improvement appeared to increase with PV and PSA level in combination therapy subjects. The proportion of subjects with an IPSS QoL ≤2 (at least mostly satisfied) at 48 months was significantly higher with combination therapy than with dutasteride for subgroups with PV 40-60 mL and PSA level <4 ng/mL and than with tamsulosin for all PSA subgroups and PV subgroups ≥40 mL. CONCLUSIONS: CombAT data support the use of long-term combination therapy with dutasteride and tamsulosin in patients considered at risk for progression of BPH, as determined by high PV (≥30 mL) and high PSA (≥1.5 ng/mL). Combination therapy, dutasteride monotherapy and tamsulosin monotherapy all improved Qmax , but to different extents (combination therapy > dutasteride >> tamsulosin), suggesting that dutasteride contributes most to the Qmax benefit in combination therapy. Combination therapy provided consistent improvement over tamsulosin in LUTS across all analysed baseline variables at 48 months. Compared with dutasteride, the superiority of combination therapy at 48 months was shown in patients with PV <60 mL or PSA <4 ng/mL.

Impact of dutasteride on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH): a pooled analysis of three phase III studies.

PURPOSE: To assess the impact of dutasteride compared with placebo on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia, using pooled data from dutasteride phase III studies. METHODS: Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included: mean change in nocturia at 24 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with baseline score ≥ 2. RESULTS: In total, 4,321 patients with a mean age of 66 years were evaluated. From month 12 onwards, mean nocturia improvements were significantly superior with dutasteride than with placebo (p ≤ 0.05). Reduction in nocturia was significantly better with dutasteride than with placebo across all baseline subgroups tested (p ≤ 0.05). Also at month 24, dutasteride therapy resulted in a greater proportion of subjects with nocturia improvement compared with placebo (p ≤ 0.05), with the largest treatment group differences in subjects with a baseline nocturia score of 2 or 3. Among patients with significant nocturia at baseline (score ≥ 2), significantly more subjects with dutasteride versus placebo had a score <2 at month 24 (26 vs. 19 %, p < 0.001). CONCLUSIONS: After 24 months of treatment, dutasteride treatment provided significantly greater improvements in nocturia, and less worsening, compared with placebo, primarily in subjects with two or three nocturia episodes per night. Studies specifically designed to assess nocturia are required to prospectively confirm these findings.

Nocturia improvement in the combination of Avodart(®) and tamsulosin (CombAT) study.

PURPOSE: The purpose of the study was to assess the impact of dutasteride plus tamsulosin combination therapy, compared with dutasteride or tamsulosin monotherapy, on nocturia in men with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) using data from the 4-year CombAT study. METHODS: Nocturia was assessed using Question 7 of the International Prostate Symptom Score questionnaire. Efficacy measures included as follows: mean change in nocturia at 3-month intervals up to 48 months; proportion of patients with improvement/worsening in nocturia; nocturnal voiding frequency at baseline and study end, overall and by baseline subgroups; and nocturnal voiding frequency <2 at study end in patients with a baseline score ≥ 2. RESULTS: In total, 4,722 patients with a mean age of 66 years were included. Mean nocturia improvements were significantly superior (p ≤ 0.01) with combination therapy than with either monotherapy (adjusted mean change from baseline in IPSS Question 7 score at month 48: combination therapy -0.5, dutasteride -0.4, tamsulosin -0.3). Reduction in nocturia score with combination therapy was significantly (p ≤ 0.01) better than tamsulosin monotherapy across all baseline subgroups tested, except for men with previous 5ARI use. Among those with a baseline IPSS Q7 score ≥ 2, more patients with combination therapy had a score <2 at month 48 (34 %) compared with dutasteride (30 %, p = 0.018) or tamsulosin (26 %, p < 0.0001). CONCLUSIONS: Combination therapy provided greater improvements and less worsening of nocturia compared with both dutasteride and tamsulosin monotherapies. These analyses are the first to show greater improvement with a 5ARI/α-blocker combination versus either agent alone for the management of nocturia in patients with LUTS/BPH.

Predictors of pathological progression among men with localized prostate cancer undergoing active surveillance: a sub-analysis of the REDEEM study.

PURPOSE: We identify risk factors for pathological progression among men on active surveillance in the REDEEM (REduction by Dutasteride of clinical progression Events in Expectant Management trial). MATERIALS AND METHODS: REDEEM was a 3-year, randomized, double-blind study of patients in 65 North American academic centers. Eligible men were 48 to 82 years old, with low risk prostate cancer (T1c-T2a), Gleason score 6 or less, 3 or fewer cores positive, tumor less than 50% of any 1 core, serum prostate specific antigen 11 ng/ml or less, life expectancy greater than 5 years and undergoing active surveillance. Entry biopsies (10 cores or more) were required. The analysis included 276 patients with 1 biopsy or more after the start of study treatment. Patients received dutasteride 0.5 mg per day or placebo for 3 years. Time to pathological progression (volume [4 or more cores positive or 50% or greater of 1 core] or grade progression [Gleason score 7 or greater]) in a post-baseline biopsy (not preceded by therapeutic intervention), and baseline variables were analyzed using a Cox proportional hazard model. RESULTS: In total 94 of 276 patients with a post-baseline biopsy (34.1%) had pathological progression, 54 (19.6%) had volume progression only, 19 (6.9%) had grade progression only and 21 (7.6%) had both types of progression. Older age (HR 1.05, 95% CI 1.01-1.08, p=0.009) and higher prostate specific antigen density (HR 1.06, 95% CI 1.04-1.09, p<0.001) were associated with pathological progression. Post-baseline prostate specific antigen identified grade, but not volume progression in patients treated with placebo and dutasteride. CONCLUSIONS: Older age and higher prostate specific antigen density were independent predictors of pathological progression. Post-baseline measurements as predictors of pathological progression could not be established. Further studies are needed to evaluate the role of dutasteride and establish better markers of pathological progression in active surveillance.

The REDUCE Follow-Up Study: low rate of new prostate cancer diagnoses observed during a 2-year, observational, followup study of men who participated in the REDUCE trial.

PURPOSE: The primary objective of the REDUCE (REduction by DUtasteride of prostate Cancer Events) Follow-Up Study was to collect data on the occurrence of newly diagnosed prostate cancers for 2 years beyond the 4-year REDUCE study. MATERIALS AND METHODS: The 4-year REDUCE study evaluated prostate cancer risk reduction in men taking dutasteride. This 2-year observational study followed men from REDUCE with a clinic visit shortly after study conclusion and with up to 2 annual telephone calls during which patient reported data were collected regarding prostate cancer events, chronic medication use, prostate specific antigen levels and serious adverse events. No study drug was provided and all biopsies during the 2-year followup were performed for cause. The primary objective was to collect data on the occurrence of new biopsy detectable prostate cancers. Secondary end points included assessment of Gleason score and serious adverse events. RESULTS: A total of 2,751 men enrolled in the followup study with numbers similar to those of the REDUCE former treatment groups (placebo and dutasteride). Few new prostate cancers were detected during the 2-year followup period in either former treatment group. A greater number of cancers were detected in the former dutasteride group than in the former placebo group (14 vs 7 cases). No Gleason score 8-10 prostate cancers were detected in either former treatment group based on central pathology review. No new safety issues were identified during the study. CONCLUSIONS: Two years of followup of the REDUCE study cohort demonstrated a low rate of new prostate cancer diagnoses in the former placebo and dutasteride treated groups. No new Gleason 8-10 cancers were detected.

Usefulness of prostate-specific antigen (PSA) rise as a marker of prostate cancer in men treated with dutasteride: lessons from the REDUCE study.

OBJECTIVES: To determine if dutasteride-treated men can be monitored safely and adequately for prostate cancer based on data from the Reduction by Dutasteride in Prostate Cancer Events (REDUCE) study. To analyse whether the use of treatment-specific criteria for repeat biopsy maintains the usefulness of prostate-specific antigen (PSA) level for detecting high grade cancers. PATIENTS AND METHODS: The REDUCE study was a randomized, double-blind, placebo-controlled investigation of whether dutasteride (0.5 mg/day) reduced the risk of biopsy-detectable prostate cancer in men with a previous negative biopsy. The usefulness of PSA was evaluated using biopsy thresholds defined by National Comprehensive Cancer Network guidelines in the placebo group and any rise in PSA from nadir (the lowest PSA level achieved while in the study) in the dutasteride group. The number of cancers detected on biopsy in the absence of increased/suspicious PSA level as well as sensitivity, specificity, positive predictive value and negative predictive value for high grade prostate cancer detection were analysed by treatment group. Prostate cancer pathological characteristics were compared between men who did and did not meet biopsy thresholds. RESULTS: Of 8231 men randomized, 3305 (dutasteride) and 3424 (placebo) underwent at least one prostate biopsy during the study and were included in the analysis. If only men meeting biopsy thresholds underwent biopsy, 25% (47/191) of Gleason 7 and 24% (7/29) of Gleason 8-10 cancers would have been missed in the dutasteride group, and 37% (78/209) of Gleason 7 and 22% (4/18) Gleason 8-10 cancers would have been missed in the placebo group. In both groups, the incidence of Gleason 7 and Gleason 8-10 cancers generally increased with greater rises in PSA. Sensitivity of PSA kinetics was higher and specificity was lower for the detection of Gleason 7-10 cancers in men treated with dutasteride vs placebo. Men with Gleason 7 and Gleason 8-10 cancer meeting biopsy thresholds had greater numbers of positive cores, percent core involvement, and biopsy cancer volume vs men not meeting thresholds. CONCLUSION: Using treatment-specific biopsy thresholds, the present study shows that the ability of PSA kinetics to detect high grade prostate cancer is maintained with dutasteride compared with placebo in men with a previous negative biopsy. The sensitivity of PSA kinetics with dutasteride was similar to (Gleason 8-10) or higher than (Gleason 7-10) the placebo group; however, biopsy decisions based on a single increased PSA measurement from nadir in the dutasteride group resulted in a lower specificity compared with using a comparable biopsy threshold in the placebo group, indicating the importance of confirmation of PSA measurements.

Understanding dental caries as a non-communicable and behavioral disease: Management implications.

New paradigms in caries conceptualization have emerged during the last decades, leading to intense debate and discussion on how to approach the disease, both from a preventive and a therapeutic perspective. Among many new ideas, research discoveries and technologies, one major concept can be highlighted that created a deep frontier between the old and the new paradigm in caries conceptualization; the non-communicable nature of the disease, firmly associated with behaviors and lifestyles. This article synthetizes the conceptual construction of dental caries as a non-communicable disease (NCD) based on the current evidence and discusses the appropriate management of the disease in this context. Dental caries has shifted from being considered transmissible and infectious to an ecological and non-communicable disease. Environmental factors such as frequent sugars intake, disrupt the symbiosis of the dental biofilm leading to a dysbiosis, which favors caries lesion initiation and progression. As an NCD, dental caries shares characteristics with other NCDs such as cardiovascular and chronic respiratory diseases, cancer and diabetes, including long duration and slow progression, not being transmissible from person-to-person, being strongly related to modifiable behavioral risk factors, and affecting preferentially disadvantaged populations with a strong inequality gradient. Given the high prevalence of dental caries, and its consequences on people's health and quality of life, a recognizable conceptual view of caries as a NCD is required to target an effective management. Current understanding of dental caries supports prevention through acting on the modifiable risk factors (behaviors) and involves management based on an interdisciplinary approach. Communicating these modern concepts among researchers, clinicians and policymakers is needed to decrease the global high burden of the disease.

The effect of dutasteride on the usefulness of prostate specific antigen for the diagnosis of high grade and clinically relevant prostate cancer in men with a previous negative biopsy: results from the REDUCE study.

PURPOSE: We assessed whether dutasteride enhances the usefulness of total prostate specific antigen for diagnosing clinically significant prostate cancer. MATERIALS AND METHODS: The 4-year REDUCE study evaluated the efficacy and safety of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative prostate biopsy. Specificity, sensitivity, and positive and negative predictive values of prostate specific antigen for the diagnosis of prostate cancer were assessed. RESULTS: Final prostate specific antigen before biopsy and change from month 6 to final prostate specific antigen performed better for the diagnosis of Gleason score 7-10 tumors in men who received dutasteride vs placebo as assessed by the area under the ROC curves (0.700 vs 0.650, p = 0.0491; and 0.699 vs 0.593, p = 0.0001, respectively). Increases in prostate specific antigen were associated with a higher likelihood of biopsy detectable, Gleason score 7-10 and clinically significant (modified Epstein criteria) prostate cancer. Percentage decreases in prostate specific antigen from baseline to month 6 in the dutasteride arm did not predict prostate cancer overall or Gleason score 7-10 cancer. CONCLUSIONS: In men with a previously negative prostate biopsy, prostate specific antigen performed better during the 4-year study as a marker of prostate cancer in men who received dutasteride vs placebo. The degree of prostate specific antigen increase after 6 months was a better indicator of clinically significant cancer in the dutasteride arm than in the placebo arm. Conversely, the initial decrease in prostate specific antigen in men taking dutasteride did not predict the likelihood of prostate cancer.

Treatment costs of prostate cancer in the first year after diagnosis: a short-term cost of illness study for France, Germany, Italy, Spain and the UK.

OBJECTIVE: To calculate the total cost per patient of prostate cancer treatment and the economic cost burden by stage, in the first year after diagnosis, for five European countries. METHODS: Data from the Information Management Systems, Inc. database, survival data, expert opinion, published data and unit costs from various published official sources were used to calculate total costs per patient by stage for each country, from a payer's perspective. Diagnostic costs, first surgery, radio-, chemo- and hormonal therapy costs were included. Costs were aggregated for incident cases. RESULTS: The mean direct costs per patient for initial treatment were euro3698 in Germany, euro3256 in Spain, euro3682 in the UK, euro5226 in Italy and euro5851 in France. The total costs for all diagnosed patients in the first year from diagnosis were (million euro) 116.7 (UK), 244 (Germany), 385 (France), 202 (Italy) and 114.6 (Spain). CONCLUSIONS: The direct initial healthcare cost burden of the most common non-skin-related male cancer, prostate cancer, in France, Germany, Italy, Spain and the UK is considerable. Given the high and increasing prevalence of prostate cancer due to ageing populations in Europe, and the significant cost burden of the disease, national health policy makers should be aware of prostate cancer as a priority disease area.

A broader role for 5ARIs in prostate disease? Existing evidence and emerging benefits.

5ARIs are recommended for men who have moderate-to-severe lower urinary tract symptoms (LUTS) and benign prostatic enlargement (BPE) secondary to benign prostatic hyperplasia. Studies have confirmed the utility of combining 5ARIs with alpha-blockers; the MTOPS study showed that risk of overall clinical progression was significantly reduced after 4.5 years with combination therapy (finasteride/doxazosin) in comparison with either monotherapy, while the ongoing CombAT trial (dutasteride/tamsulosin) has for the first time shown benefit in improving symptoms for combination therapy over monotherapies within 12 months of treatment. Data also suggest roles for 5ARIs in prostate cancer. Several studies indicate that treatment with a 5ARI improves the performance of PSA testing for identifying men with prostate cancer, while the PCPT showed a significant reduction in the risk of developing prostate cancer with finasteride. However, widespread use of finasteride in this setting has been tempered by an apparent increase in high-grade disease observed in the study. The ongoing REDUCE study will provide further insight into prostate cancer prevention with 5ARIs. 5ARI-containing regimens may have utility as less aggressive treatment options for patients who only have rising PSA after definitive local therapy, and in patients with disease resistant to androgen deprivation therapy who have PSA progression. Current evidence therefore shows that 5ARIs are effective in treating LUTS/BPE and preventing disease progression, and may also have a role in the prevention of prostate cancer. The overlap between BPE and prostate cancer may allow a more unified approach to managing these conditions, with 5ARIs having a central role.

Can dutasteride delay or prevent the progression of prostate cancer in patients with biochemical failure after radical therapy? Rationale and design of the Avodart after Radical Therapy for Prostate Cancer Study.

OBJECTIVE: To describe the Avodart after Radical Therapy for prostate cancer Study (ARTS), investigating the use of dutasteride (a dual 5alpha-reductase inhibitor that suppresses intraprostatic dihydrotestosterone, reduces tumour volume and improves other markers of tumour regression in prostate cancer) to prevent or delay disease progression in patients with biochemical recurrence after therapy with curative intent. PATIENTS AND METHODS: An increasing serum prostate-specific antigen (PSA) level after radical prostatectomy (RP) or radiotherapy (RT) is indicative of recurrent prostate cancer and typically pre-dates clinically detectable metastatic disease by several years. ARTS is an ongoing European multicentre trial in which patients are stratified by previous therapy (RP with or without salvage RT vs primary RT) and randomized to double-blind treatment with dutasteride 0.5 mg or placebo once daily for 2 years. Eligible patients will have a PSA doubling time (DT) of 3-24 months. Biochemical recurrence is defined as three increases in PSA level from the nadir, with each increase > or =4 weeks apart and each PSA level > or =0.2 ng/mL, and a final PSA level of > or =0.4 ng/mL (after RP) or > or =2 ng/mL (after primary RT). Study endpoints include time to PSA doubling, time to disease progression, treatment response (PSA decrease or an increase of < or =15% from baseline), changes in PSA and PSADT, and changes in anxiety (Memorial Anxiety Scale for Prostate Cancer). CONCLUSIONS ARTS: will be the first study to evaluate the effects of dutasteride on PSADT, disease progression and treatment response in patients with biochemical failure after RP or RT, and should help to elucidate the potential role of dual 5alpha-reductase inhibition in prostate cancer.

¿Cómo Intervenir el Proceso de Caries en Personas Mayores? Adaptación del Consenso de ORCA/EFCD/DGZ

Los cambios demográficos y epidemiológicos actuales determinarán un aumento en la prevalencia e incidencia de caries, específicamente lesiones de caries radicular (RCLs, por sus siglas en inglés) en personas mayores, por lo que la necesidad de tratamiento de mayor cobertura y efectividad será también cada vez mayor. Este artículo resume en español la evidencia actual disponible acerca de las recomendaciones clínicas para las intervenciones preventivas, no invasivas, micro o mínimamente invasivas e invasivas para el manejo de la caries dental en personas mayores, con especial énfasis en RCLs. La presente publicación se basa en un taller de consenso, seguido de un proceso de consenso e-Delphi, realizado por un panel de expertos nominados por la Organización Europea para la Investigación en Caries (ORCA), la Federación Europea de Odontología Conservadora (EFCD) y la Federación Alemana de Odontología Conservadora (DGZ). El propósito de este artículo es presentar las principales conclusiones alcanzadas en el consenso de ORCA/EFCD/DGZ para permitir una mejor difusión del conocimiento y la aplicación de estos conceptos en la práctica clínica, orientando la correcta toma de decisiones en el manejo de la enfermedad y RCLs en las personas mayores.

Current demographic and epidemiological changes will condition increased caries prevalence and incidence, specifically root caries lesions (RCLs) in the elderly. There will be a need, therefore, for therapeutic approaches with greater coverage and effectiveness. This article summarizes, in Spanish, the current available evidence leading to clinical recommendations for preventive, non-invasive, micro or minimally invasive and invasive interventions for the management of dental caries in older people, with special emphasis on RCLs. This publication is based on a consensus workshop, followed by an e-Delphi consensus process, conducted by a panel of experts nominated by the European Organization for Caries Research (ORCA), the European Federation of Conservative Dentistry (EFCD) and the German Federation of Conservative Dentistry (DGZ). The purpose of this article is to present the main conclusions reached in the ORCA/EFCD/DGZ consensus to allow a better dissemination of knowledge and the application of these concepts in clinical practice, guiding the correct decision-making for the disease management and the RCLs in the elderly.

Salivary protein characteristics from saliva of carious lesionfree and high caries adults.

It has been argued that specific salivary proteins could have a protective effect against caries, but data from the many available studies are rather contradictory. The purpose of this study was to analyze whether there is a relationship between protein concentration, electrophoretic profile and concentration of salivary IgA and the presence or absence of caries in adults. Adults with high caries activity (HC) and without caries lesions (CF), assessed by ICDAS criteria, were asked to provide unstimulated saliva samples. Protein concentration (µg/mL) was determined using the Bradford method. Western blotting was used to detect IgA. Data were compared using Student's t test at p<0.05. Total protein concentration in CF was higher (50.65±7.5 µg/mL) than in HC individuals (26.80±2.5 µg/mL) (p=0.001). More protein bands were visualized in the gels from CF than the HC group (p=0.001). CF subjects showed higher salivary IgA concentration (11.27±0.5 µg) than HC individuals (1.71±0.2µg) (p=0.001).Salivary composition in high caries experience and cariesfree young adults seems to differ in terms of the type and amount of proteins. Further research is needed to expand these findings.

Se ha descrito que proteínas salivales específicas podrían tener un efecto protector sobre la caries, sin embargo, los datos de losnumerosos estudios disponibles son contradictorios. El propósito de este trabajo fue analizar si existe una relación entre la concentración total de proteínas, perfil electroforético y la concentración de IgA salival y la presencia o ausencia de lesiones de caries en adultos. Se obtuvieron muestras de flujo salival no estimulado de adultos con alta actividad de caries (HC) y sin lesiones de caries (CF), evaluados según criterios ICDAS. La concentración total de proteínas (mg / ml) se determinó utilizando el método de Bradford. Para detección de IgA se empleó Western Blot. Los datos se compararon mediante la prueba t student, estableciendo diferencias significativas si p<0,05. La concentración total de proteínas en CF fue mayor (50,65 ± 7,5 mg / ml) que en individuos HC (26,80 ± 2,5 mg / ml) (p=0,001). En los geles, se visualizó un mayor número de bandas de proteínas en CF que en el grupo HC (p=0,001). Los Sujetos CF mostraron mayor concentración de IgA salival (11,27 ± 0,5 µg) que los individuos HC (1,71 ± 0,2 µg) (p=0,001). La composición salival de sujetos adultos jóvenes con alta experiencia y libres de caries, parece ser diferente en función del tipo y la cantidad de proteínas. Se requiere de más investigación para profundizar estos resultados.

Characteristics of female outpatients with urinary incontinence participating in a 6-month observational study in 14 European countries.

OBJECTIVE: To describe the characteristics of women seeking treatment for symptoms of urinary incontinence (UI) in European countries. DESIGN: Prospective urinary incontinence research (PURE) was a 6-month, observational, pan-European study, primarily aimed at determining the direct costs of urinary incontinence treatment. The secondary objectives of PURE were to describe the impact of UI on health-related quality of life (HRQoL) in treatment seeking patients and to illustrate the treatment patterns for UI in Europe. SETTING: One thousand and Fifty-five physicians from 14 European countries, including general practitioners (GPs), gynaecologists, urologists and geriatricians, observed women seeking treatment for their UI and recorded data at the first observation and then prospectively at 3 and 6 months after the first observation during the normal course of therapy. SUBJECTS: Women of at least 18 years of age who had experienced urinary leakage in the 12 months prior to enrolment in the study, who were seeking treatment or under treatment for UI and who presented within the normal course of UI care were included in the 6 months study. The first observation characteristics of the patients are described here. METHODS: Demographic characteristics, as well as disease and treatment status at first observation were explored using descriptive summary statistics to gain an understanding of the population studied. RESULTS: In total, 9487 women took part in PURE, with the largest patient groups from Germany, Spain and the UK/Ireland. The majority of women were post-menopausal and had a mean age of 60.7 years, were not current smokers and tended to be overweight (BMI > 25.0). Overall, mixed UI symptoms were more common than SUI and UUI, as defined by clinical opinion (SUI 38%, MUI 42% and UUI 18%), and by a two-item questionnaire, the S/UIQ (SUI 29%, MUI 58% and UUI 13%). Around half of the patients (48%) suffered from their symptoms for less than 2 years before consulting a physician; 28% delayed seeking treatment for 3-5 years, with 13% waiting for 6-10 years and the remaining 11% waiting for 11 or more years. CONCLUSIONS: Some of the described patients' characteristics may provide important information to clinicians to enable them to take a more active approach to case-finding, which will ultimately benefit the incontinent patient.

Burden of Illness in Prostate Cancer Patients with a Low-to-Moderate Risk of Progression: A One-Year, Pan-European Observational Study.

Objective. To assess the impact of low-to-moderate risk prostate cancer on patients' quality of life (QoL) at diagnosis and within the first year of treatment. Subjects and Methods. Men (n = 672) aged 50-75 years with prostate cancer (Gleason score ≤7, PSA ≤20 ng/mL and clinical staging T1c-T2b) were enrolled in five European countries. Patients completed five questionnaires, including EORTC Quality of Life Questionnaire-Prostate Cancer 25 (QLQ-PR25) and EORTC Quality of Life Questionnaire-Cancer 30 (QLQ-C30). Questionnaires were completed at baseline, at 3 months and 12 months after starting treatment. The primary endpoint was the change in QLQ-PR25 urinary symptoms subscale score from baseline to the assessment at 3 months. Results. Mean (SD) age was 65.0 (5.7) years and 400 (66%) men had Gleason score ≤6 prostate cancer. The most frequently used initial treatment was radical prostatectomy (71% of patients). QLQ-PR25 urinary symptoms subscale score was significantly increased at 3 months (P < 0.001), indicating that urinary symptoms worsened after treatment. The score was lower at 12 months than at 3 months, but it was still significantly higher than at baseline (P < 0.001). Hormonal treatment-related symptoms, sexual functioning, and sexual activity scores significantly worsened at 3 and 12 months (all P < 0.001). For the QLQ-C30 questionnaire, global health status/QoL score significantly decreased at month 3 but was not different from baseline by month 12. Scales for physical, role, and social functioning, and fatigue, showed significant deterioration at 3 and 12 months. Conclusions. Low-to-moderate risk prostate cancer may have a substantial effect on patients' QoL within one year following treatment.

Modeling and analysis of Gleason score 8-10 prostate cancers in the REDUCE study.

OBJECTIVE: To explore explanations for the numerical imbalance of biopsy-detected Gleason 8-10 prostate cancers (PCa) diagnosed in years 3-4 in the dutasteride and placebo groups of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study. METHODS: REDUCE was a 4-year, randomized, double-blind, placebo-controlled trial of dutasteride (0.5 mg/d) vs placebo for PCa risk reduction. We modeled the incidence of Gleason 8-10 cancer and used logistic regression analysis to evaluate the effects of baseline predictors of PCa, as well as post-baseline prostate volume at the time of biopsy, on PCa diagnosis. We compared needle biopsy Gleason scores with corresponding surgery Gleason scores. All statistical tests conducted were 2-sided. RESULTS: Had there been a scheduled biopsy occurring only at year 4, we estimated a similar incidence of Gleason 8-10 PCa in the dutasteride (n = 45) and placebo (n = 46) groups. Two biopsy Gleason 7 cancers in the placebo group (n = 150) were upgraded to Gleason 8-10 cancer on prostatectomy, and no patients in the dutasteride group (n = 111) were upgraded. Logistic regression analysis demonstrated the effect of prostate volume on Gleason 8-10 cancer diagnosis. CONCLUSION: Although modeling of REDUCE data showed a similar incidence of Gleason 8-10 cancer in the dutasteride and placebo groups at year 4, an association between dutasteride and Gleason 8-10 cancer cannot be definitely excluded. It is likely that several biases, notably study design and prostate size at the time of biopsy, contributed to the numerical imbalance in Gleason 8-10 cancers observed between the treatment groups in years 3-4.