An exploratory analysis of individuals with multiple episodes of different reportable diseases, Montreal, 1990-2012.

OBJECTIVES: Studies of public health reporting have only examined multiple episodes of the same communicable disease within an individual. We aimed to characterize Montreal residents with multiple reportable disease episodes from 1990 to 2012, while accounting for all types of reportable diseases. STUDY DESIGN: Retrospective cohort study. METHODS: We performed an exploratory analysis using descriptive statistics, contingency tables, and logistic regression. RESULTS: There were 157,839 individuals with at least one disease report and a total of 179,455 disease reports. The 9.8% of subjects with more than one episode accounted for 20.7% of all reported episodes. Among subjects with four or fewer episodes, 54.0% were women, while 74.3% of subjects with five or more episodes were men. Subjects with multiple episodes were more likely to be reported for sexually transmitted infections than were persons with a single episode [difference of proportions: 10.4% (95% CI: 10.0%-10.9%)] and to reside in the neighbourhood encompassing Montreal's gay village. CONCLUSIONS: Individuals with multiple communicable disease reports place a large burden on public health officials. These results may help guide investigation and prevention efforts to reduce the number of excess episodes.

Characterization of a novel founder MSH6 mutation causing Lynch syndrome in the French Canadian population.

We identified an MSH6 mutation (c.10C>T, p.Gln4*) causing Lynch syndrome (LS) in 11 French Canadian (FC) families from the Canadian province of Quebec. We aimed to investigate the molecular and clinical implications of this mutation among FC carriers and to assess its putative founder origin. We studied 11 probands and 27 family members. Additionally 6433 newborns, 187 colorectal cancer (CRC) cases, 381 endometrial cancer (EC) cases and 179 additional controls, all of them from Quebec, were used. Found in approximately 1 of 400 newborns, the mutation is one of the most common LS mutations described. We have found that this mutation confers a greater risk for EC than for CRC, both in the 11 studied families and in the unselected cases: EC [odds ratio (OR) = 7.5, p < 0.0001] and CRC (OR = 2.2, p = 0.46). Haplotype analyses showed that the mutation arose in a common ancestor, probably around 430-656 years ago, coinciding with the arrival of the first French settlers. Application of the results of this study could significantly improve the molecular testing and clinical management of LS families in Quebec.

Influence of skin ageing features on Chinese women's perception of facial age and attractiveness.

OBJECTIVES: Ageing leads to characteristic changes in the appearance of facial skin. Among these changes, we can distinguish the skin topographic cues (skin sagging and wrinkles), the dark spots and the dark circles around the eyes. Although skin changes are similar in Caucasian and Chinese faces, the age of occurrence and the severity of age-related features differ between the two populations. Little is known about how the ageing of skin influences the perception of female faces in Chinese women. The aim of this study is to evaluate the contribution of the different age-related skin features to the perception of age and attractiveness in Chinese women. METHODS: Facial images of Caucasian women and Chinese women in their 60s were manipulated separately to reduce the following skin features: (i) skin sagging and wrinkles, (ii) dark spots and (iii) dark circles. Finally, all signs were reduced simultaneously (iv). Female Chinese participants were asked to estimate the age difference between the modified and original images and evaluate the attractiveness of modified and original faces. RESULTS: Chinese women perceived the Chinese faces as younger after the manipulation of dark spots than after the reduction in wrinkles/sagging, whereas they perceived the Caucasian faces as the youngest after the manipulation of wrinkles/sagging. Interestingly, Chinese women evaluated faces with reduced dark spots as being the most attractive whatever the origin of the face. The manipulation of dark circles contributed to making Caucasian and Chinese faces being perceived younger and more attractive than the original faces, although the effect was less pronounced than for the two other types of manipulation. CONCLUSION: This is the first study to have examined the influence of various age-related skin features on the facial age and attractiveness perception of Chinese women. The results highlight different contributions of dark spots, sagging/wrinkles and dark circles to their perception of Chinese and Caucasian faces.

MC1R major variants are a risk factor of sleep lines in Caucasian women.

BACKGROUND: Sleep lines are caused by individual's sleeping positions and should be differentiated from expression wrinkles. OBJECTIVE: The aim of the study was to investigate possible risk factors for sleep lines on a sizeable sample of middle-aged Caucasian women. METHODS: This study involved a sample of 542 French middle-aged women (44 to 70 years old) from Paris area. Three standardized facial photographs (face and profiles) were examined independently by two dermatologists allowing the identification of sleep lines and the evaluation of the severity of several facial skin features. Possible impacts of MC1R gene polymorphisms were tested using logistic regression models. RESULTS: Sixty women (11%) had facial sleep lines and showed generally more than one sleep line. The sleep lines were often located on the forehead, along the nose, on the cheeks and under the eyes, and more rarely on the chin. As expected, the sleep lines were associated with age, and the women with sleep lines showed also more severe signs of skin ageing. After adjustment on possible confounders, the presence of two major diminished function variants of the MC1R gene was identified as a strong risk factor for sleep lines [adjusted odds ratios (AOR) (95% CI): 8.25 (2.62-25.97)]. DISCUSSION/CONCLUSION: The data in the literature are scarce and this study is the first to be conducted on a sizeable sample of women. Our results suggest that genetic variations of MC1R are important determinants of the development of sleep lines.

Freckles and solar lentigines have different risk factors in Caucasian women.

BACKGROUND: To date, few epidemiological data on the relationships between solar lentigines, freckles and behavioural and constitutional risk factors in Caucasian populations exist. OBJECTIVES: To investigate the potential impact of behavioural and phenotypic variables, as well as the MC1R genetic background, on the history of facial freckles and the severity of solar lentigines in Caucasian women. METHODS: The severity of solar lentigines was graded from facial digital images of 523 French middle-aged women by a dermatologist and summarized by a score afterwards. The history of facial freckles was assessed and the sun-exposure behaviour was characterized using a six-category typology. Risk factors including MC1R polymorphism were evaluated using logistic regression models. RESULTS: Two constitutive host factors were found to be independently associated with a history of facial freckles: frequent sunburns and the presence of diminished function variants of the MC1R gene. In addition to age, five factors were independently associated with solar lentigines: constitutive host factors (dark skin colour and tanning capacity), a history of freckles, sun-exposure behaviour and current intake of oral contraceptive or progestogen treatments. CONCLUSION: These results strengthen the hypothesis that solar lentigines are markers of photoaging, whereas freckles are mainly determined by genetic factors. The finding that hormonal treatment is associated with a higher risk for solar lentigines merits further investigations.

Impact of filaggrin mutations on Raman spectra and biophysical properties of the stratum corneum in mild to moderate atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is associated with null mutations in the filaggrin (FLG) gene. OBJECTIVE: To assess the impact of FLG null mutations on biophysical properties and the molecular composition of the stratum corneum (SC) in healthy individuals and AD patients. METHODS: A total of 196 French adults, including 97 with a history of mild to moderate AD, were genotyped for the three major European FLG mutations. Components of the natural moisturizing factor (NMF), lipids and water content in the SC were determined using Raman spectroscopy. In addition, trans-epidermal water loss, capacitance and pH of the SC were measured. RESULTS: Stratum corneum concentrations of total NMF, water, ornithine and urocanic acid (UCA) were significantly lower in AD patients than in healthy controls. Null mutations of FLG were detected in 4% of controls and 10% of AD patients. FLG mutations were associated with increased SC levels of lactate, reduced concentrations of most other NMF components and higher disease severity in AD patients. In AD patients without FLG mutations, the content of NMF constituents decreased with increasing disease severity. The concomittant presence of low concentrations of histidine, alanine and either glycine or pyrrolidone-5-carboxylic acid (PCA) in the SC was associated with FLG mutations with 92% specificity. CONCLUSIONS: Our findings suggest a low prevalence of FLG mutations in mild AD and support an important role for filaggrin in determining the physicochemical parameters of the SC. The combined measurement of several filaggrin breakdown products in the SC may be useful to specifically predict the presence of FLG mutations.

[MC1R polymorphisms and facial photoaging]. / Polymorphismes du MC1R et photovieillissement du visage.

BACKGROUND: The objective of this study was to assess the association between melanocortin-1 receptor (MC1R) variants and the severity of facial skin photoaging. METHODS: The study population comprised 530 French middle-aged women between 44 and 70 years. A trained dermatologist graded the severity of facial skin photoaging from photographs using Larnier's global scale. Logistic regressions were performed to assess the influence of MC1R polymorphism on severe photoaging (grades 1-3 vs. 4-6), with adjustment for possible confounders (demographic and phenotypic data, and sun exposure intensity). RESULTS: Overall, 35% of the women were wild-type homozygotes, 49% had one variant, 15% had two variants, and 1% had at least one rare variant. After adjustment for possible confounders, the presence of two major diminished function variants was found to be a risk factor for photoaging (adjusted odds ratio=5.61; 95% confidence interval [1.43-21.96]). DISCUSSION: Our results suggest that genetic variations of MC1R are important determinants for severe photoaging.

Guideline adaptation: an approach to enhance efficiency in guideline development and improve utilisation.

BACKGROUND: Developing and updating high-quality guidelines requires substantial time and resources. To reduce duplication of effort and enhance efficiency, we developed a process for guideline adaptation and assessed initial perceptions of its feasibility and usefulness. METHODS: Based on preliminary developments and empirical studies, a series of meetings with guideline experts were organised to define a process for guideline adaptation (ADAPTE) and to develop a manual and a toolkit made available on a website (http://www.adapte.org). Potential users, guideline developers and implementers, were invited to register and to complete a questionnaire evaluating their perception about the proposed process. RESULTS: The ADAPTE process consists of three phases (set-up, adaptation, finalisation), 9 modules and 24 steps. The adaptation phase involves identifying specific clinical questions, searching for, retrieving and assessing available guidelines, and preparing the draft adapted guideline. Among 330 registered individuals (46 countries), 144 completed the questionnaire. A majority found the ADAPTE process clear (78%), comprehensive (69%) and feasible (60%), and the manual useful (79%). However, 21% found the ADAPTE process complex. 44% feared that they will not find appropriate and high-quality source guidelines. DISCUSSION: A comprehensive framework for guideline adaptation has been developed to meet the challenges of timely guideline development and implementation. The ADAPTE process generated important interest among guideline developers and implementers. The majority perceived the ADAPTE process to be feasible, useful and leading to improved methodological rigour and guideline quality. However, some de novo development might be needed if no high quality guideline exists for a given topic.

Decorative tattoos and reasons for their removal: a prospective study in 151 adults living in South of France.

BACKGROUND: Despite increasing demands for decorative tattooing in people of all ages, occupations and social classes, little is known regarding individuals' characteristics and behaviour with respect to tattooing. OBJECTIVE: The objective was to describe a large sample of French people asking for tattoo laser removal, to investigate their reasons for being tattooed and for tattoo removal, and to identify groups of subjects sharing similar characteristics. METHODS: A prospective exploratory study was conducted on 151 consecutive subjects asking for tattoo removal. RESULTS: The study population was composed of 65 women and 86 men, aged between 18 and 60 years. The reasons mentioned for tattoo removal included aesthetic, social, employment, family or partner pressure, change of lifestyle or partner and incompatibility with present attitudes and values. Four profiles were identified. Types 1 and 3 correspond to subjects with amateur tattoos more frequently reporting social reasons for tattoo removal, whereas types 2 and 4 correspond to subjects with studio tattoos who more frequently report aesthetic reasons. Types 1 and 4 are mainly composed of men (aged over forty and under forty, respectively), type 2 of women under thirty and type 3 of subjects of either sex aged over forty. CONCLUSIONS: These profiles could be used to target information campaigns about tattooing and tattoo removal techniques to avoid unwanted tattoos, and afterwards, possible disappointment after removal, as well as to target education programs on possible health risks. Furthermore, our findings open the way to focus further studies on more homogenous group of tattooed subjects.

Optimizing the management of HER2-positive early breast cancer: the clinical reality.

Breast cancer positive for HER2 (human epidermal growth factor receptor 2) is associated with a poor prognosis for patients with both early-stage and metastatic breast cancer. Trastuzumab has been shown to be effective and is now considered the standard of care for early-stage patients with HER2-positive breast cancer. In that population, trastuzumab has been studied in six randomized clinical trials. Overall, use of this agent leads to a significant reduction in risk of disease recurrence and improvement in overall survival. Despite the strong evidence for the use of trastuzumab in managing HER2-positive early breast cancer (EBC), a number of clinical controversies remain. The authors of this paper undertook a review of the available scientific literature on adjuvant trastuzumab to produce practical considerations from Canadian oncologists. The panel focused their discussion on five key areas: Management of node-negative disease with tumours 1 cm or smaller in size. Management of HER2-positive EBC across the spectrum of the disease (that is, nodal and steroid hormone receptor status, tumour size) Timing of trastuzumab therapy with chemotherapy for early-stage disease: concurrent or sequential. Treatment duration of trastuzumab for EBC. The role of non-anthracycline trastuzumab-based regimens.

Aggravating factors for melasma: a prospective study in 197 Tunisian patients.

BACKGROUND: Melasma is a frequent cause of consultations at dermatology departments by dark-skinned patients in Tunisia. OBJECTIVE: To investigate factors that influence melasma severity in a large Tunisian population. METHODS: A total of 197 patients (188 women and 9 men), who attended Tunis Military Hospital for a consultation were included prospectively from August 2005 to August 2006. Disease severity was estimated using the Melasma Area and Severity Index (MASI). Aggravating factors were investigated using multiple logistic regressions. RESULTS: Of the women included, 14% presented phototype III, 45% phototype IV and 41% phototype V; 76% presented a centrofacial melasma phenotype, 23% a malar and 1% a mandibular phenotype. About 60% developed melasma before thirty. Sun exposure was reported as a triggering factor by 51% of women and as an aggravating factor by 84%. Pregnancy was reported as an aggravating factor by 51% of women who had been pregnant, and oral contraceptive use reported by 38% of women exposed to oral contraceptives. The risk of severe melasma was about three times higher for women with age at onset under 30, phototype V and major lifetime sun exposure and about 8 times higher for women exposed to oral contraceptives. CONCLUSION: This study identifies a number of factors associated with the severity of melasma. Further epidemiological studies in this type of population, in particular, to investigate triggering factors, are justified by the aesthetic damage caused by melasma in dark-skinned patients, lack of efficacy of existing treatments, non-compliance with photoprotection recommendations and the challenge of treatment.

The role of neoadjuvant (HER)2-targeted therapies in (HER)2-overexpressing breast cancers.

Women receiving neoadjuvant systemic therapy for primary operable or inoperable breast cancer can potentially benefit in a number of ways, but the main advantage, which has been consistently demonstrated, is improved tumour resectability. Given the improvement in outcomes with the adjuvant use of trastuzumab in patients with early-stage breast cancer positive for the human epidermal growth factor receptor 2 (HER2), questions have been raised about the use of trastuzumab in the neoadjuvant setting. The present paper reviews the currently available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other HER2-targeted agents in the neoadjuvant setting.The panel focussed on the use of trastuzumab and other HER2-targeted agents as neoadjuvant therapy in primary operable, locally advanced, and inflammatory breast cancer; and possible choices of chemotherapeutic regimens with trastuzumab.The suggestions described here will continue to evolve as data from current and future trials with trastuzumab and other HER2-targeted agents emerge.

The role of HER2-targeted therapies in women with HER2-overexpressing metastatic breast cancer.

The role of targeted therapies in the treatment of women with breast cancer has been rapidly evolving. Trastuzumab, a monoclonal antibody against the human epidermal growth factor receptor 2 (HER2), was the first HER2-targeted therapy that clearly demonstrated a significant clinical benefit for women with HER2-overexpressing metastatic breast cancer (mbc). However, in recent years it has become increasingly apparent that, when trastuzumab is used in the first-line setting in combination with chemotherapy, most women eventually develop progressive disease. Determining the treatment options available to women who have progressed while on trastuzumab therapy has been hampered by a paucity of high-quality published data. In addition, with the standard use of trastuzumab in the adjuvant setting (for eligible HER2-positive patients), the role of anti-HER2 agents for patients who experience a breast cancer relapse has become a clinically relevant question. This manuscript reviews current available data and outlines suggestions from a panel of Canadian oncologists about the use of trastuzumab and other HER2-targeted agents in two key mbc indications:Treatment for women with HER2-positive mbc progressing on trastuzumab (that is, treatment beyond progression)Treatment for women with HER2-positive mbc recurring following adjuvant trastuzumab (that is, re-treatment)The suggestions set out here will continue to evolve as data and future trials with trastuzumab and other HER2-targeted agents emerge.

Reference ranges of skin micro-relief according to age in French Caucasian and Japanese women.

BACKGROUND/PURPOSE: The variation of skin surface morphological indicators according to age has not been frequently studied. The aim of this work was to establish French Caucasian and Japanese reference ranges of these indicators according to age. METHODS: Two studies were performed simultaneously in Paris and Sendai on 356 Caucasian and 120 Japanese healthy women aged from 20 to 80 years. Skin replicas were obtained from the volar forearm and analysed by interferometry. This analysis yielded 16 morphological indicators. Reference ranges according to age were established using the statistical methodology defined by Royston. RESULTS/DISCUSSION: Reference ranges were found for 15 out of the 16 parameters for the French women as well as for the Japanese women. The models' truthfulness will have to be confirmed using new samples, larger if possible. Moreover, non-parametric methods will be used in order to compare the results provided by these approaches.

Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach.

Escherichia coli is a model laboratory bacterium, a species that is widely distributed in the environment, as well as a mutualist and pathogen in its human hosts. As such, E. coli represents an attractive organism to study how environment impacts microbial genome structure and function. Uropathogenic E. coli (UPEC) must adapt to life in several microbial communities in the human body, and has a complex life cycle in the bladder when it causes acute or recurrent urinary tract infection (UTI). Several studies designed to identify virulence factors have focused on genes that are uniquely represented in UPEC strains, whereas the role of genes that are common to all E. coli has received much less attention. Here we describe the complete 5,065,741-bp genome sequence of a UPEC strain recovered from a patient with an acute bladder infection and compare it with six other finished E. coli genome sequences. We searched 3,470 ortholog sets for genes that are under positive selection only in UPEC strains. Our maximum likelihood-based analysis yielded 29 genes involved in various aspects of cell surface structure, DNA metabolism, nutrient acquisition, and UTI. These results were validated by resequencing a subset of the 29 genes in a panel of 50 urinary, periurethral, and rectal E. coli isolates from patients with UTI. These studies outline a computational approach that may be broadly applicable for studying strain-specific adaptation and pathogenesis in other bacteria.

Self-reported skin sensitivity in a general adult population in France: data of the SU.VI.MAX cohort.

OBJECTIVE: This study aimed to examine the frequency of self-assessed facial skin sensitivity and its different patterns, and the relationship with gender and sun sensitivity in a general adult population. METHODS: A standardized 11-item questionnaire investigating reactions experienced during the past year was developed. The questions explored different patterns of skin sensitivity: pattern I (blushing related to vascular reactivity), pattern II (skin reactions to certain environmental conditions), pattern III (skin reactions after substance contact), and for women pattern IV ('breakout of spots' related to menstrual cycle). Additional items were addressed for women and men, including sun sensitivity. The questionnaire was administered to a large middle-aged population involved in the 'Supplément en Vitamines et Minéraux Antioxydants' (SU.VI.MAX) cohort. RESULTS: Sensitive facial skin was reported by 61% of the women (n = 5074) and 32% of the men (n = 3448), and the frequency decreased with age. The frequency of patterns I, II and III was greater for women (78, 72 and 58%, respectively) than for men (56, 48 and 28%) of comparable classes of age. The frequency of pattern IV was reported by 49% of premenopausal women, and skin reactions after shaving by 41% of the men. Sun sensitivity was found to be a major component of skin sensitivity. Factor analysis showed that individuals with fair phototype frequently evoked reactions associated with pattern I, and skin redness and burning sensations were related to certain environmental conditions (pattern II). CONCLUSION: Skin sensitivity is a common concern that declines with age and is relevant for men as well as for women.

[Phototype, vitamin D status and bone mineral density among women at risk of osteoporosis]. / Phototype, statut en vitamine D et densité minérale osseuse chez des femmes à risque d'ostéoporose.

PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.

The benefit of participating to clinical research.

We assessed the impact of participating to clinical research among 1727 women with localized breast cancer. Using as referent individuals not treated according to guidelines for systemic therapy, the adjusted hazard ratio of death was 0.70 (95% confidence interval (CI): 0.54,0.90, p-value: 0.006) in those treated according to current guidelines and 0.45 (95% CI: 0.27,0.73, p-value: 0.001) in participants to research. Participation to clinical trials results in a substantial gain in survival.

Docetaxel and Gemcitabine administered on days 1 and 8 for metastatic non-small cell lung carcinoma (NSCLC): a phase II multicenter trial.

Docetaxel and Gemcitabine are active agents in non-small cell lung carcinoma (NSCLC). They have different mechanism of action, minimal overlapping toxicity, and are easily administered on an outpatient basis. This phase II study evaluated Docetaxel administered with Gemcitabine on days 1 and 8 in a 3-week cycle, to determine its efficacy, while attempting to lower the regimen's toxicity, especially myelosuppression which can occur when Docetaxel is administered at full dose on day 1 only. Forty-three chemonaive patients, 40 evaluable, were entered in this trial between May 2001 and March 2002. Thirty-seven patients had stage IV and three patients had stage III B NSCLC, median age 58 (ages 32-78), median performance status (PS) 1 (range 0-2). They were treated with Docetaxel 36mg/m(2) and Gemcitabine 1000mg/m(2) intravenously on days 1 and 8 in a 3-week cycle. No growth factors were administered. Of 40 evaluable patients, 4 achieved partial response (10%), 25 stable disease (62.5%) and 11 progressive disease (27.5%). Median time-to-disease progression was 15 weeks. Median survival was 7.75 months. One year survival was 32.5% (13 patients). Hematologic toxicity was minimal, non-hematologic toxicity was easily treatable. Docetaxel, when given with Gemcitabine on days 1 and 8 every 3 weeks, is less myelotoxic, yet still an effective treatment for metastatic NSCLC.

Daily variations in skin surface properties using mixed model methodology.

In order to explore the variations over the course of a day in certain skin biophysical properties, a study was conducted on 8 female volunteers. An assessment of several skin biophysical properties was carried out on the face and the volar forearm every 4 h over a period of 48 h. The biophysical parameters were assessed on the face for sebum secretion, skin surface pH, skin colour, transepidermal water loss, capacitance and skin surface temperature. The same parameters were measured on the volar forearm (excepted for sebum secretion). A statistical analysis based on mixed effect models was conducted. Four models, with different covariance structures, were successively tested. The analysis allowed us to identify a structure that repeated itself over time in the same way over each 24-hour period for capacitance on the forearm and for sebum secretion, skin surface pH and skin colour (L* and a* parameters) on the face. Mixed effect methodology is a powerful tool to analyse longitudinal data involving correlations among repeated measurements made on the same subject.