Internalizing and externalizing symptoms and suicidal behaviour in young people: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess internalizing and externalizing symptoms as risk factors for suicidal behaviour and suicide among adolescents and young adults. METHOD: We conducted a systematic review of articles published until January 2017. We identified 26 883 potential papers; 1701 full-text articles were assessed for eligibility, of which 1479 were excluded because of methodological reasons. Diverse meta-analyses were performed for each group of symptoms. Odds ratios (ORs) and 95% confidence intervals (95% CI) or beta coefficients for categorical variables, and effect size (ES) were calculated for continuous variables. RESULTS: Finally, 41 studies were included, involving participants aged 12-26 years for a systematic review, and 24 articles were included for meta-analysis. The meta-analysis showed that youths with any internalizing (ES = 0.93) or externalizing symptoms (ES = 0.76 and OR = 2.59) were more likely to attempt suicide in future. This effect was also seen in depression symptoms (OR = 6.58 and ES = 1.00), legal problems (OR = 3.36), and anxiety (ES = 0.65). CONCLUSION: Reported internalizing and externalizing symptoms are predictors of suicide behaviour in young people; therefore, the detection and management of these symptoms in young populations could be a crucial strategy for preventing suicidality in this group.

Sexual orientation and suicidal behaviour in adolescents and young adults: systematic review and meta-analysis.

BackgroundResearch suggests that lesbian, gay and bisexual (LGB) adolescents have a higher risk of suicidal behaviours than their heterosexual peers, but little is known about specific risk factors.AimsTo assess sexual orientation as a risk factor for suicidal behaviours, and to identify other risk factors among LGB adolescents and young adults.MethodA systematic search was made of six databases up to June 2015, including a grey literature search. Population-based longitudinal studies considering non-clinical populations aged 12-26 years and assessing being LGB as a risk factor for suicidal behaviour compared with being heterosexual, or evaluating risk factors for suicidal behaviour within LGB populations, were included. Random effect models were used in meta-analysis.ResultsSexual orientation was significantly associated with suicide attempts in adolescents and youths (OR = 2.26, 95% CI 1.60-3.20). Gay or bisexual men were more likely to report suicide attempts compared with heterosexual men (OR = 2.21, 95% CI 1.21-4.04). Based on two studies, a non-significant positive association was found between depression and suicide attempts in LGB groups.ConclusionsSexual orientation is associated with a higher risk of suicide attempt in young people. Further research is needed to assess completed suicide, and specific risk factors affecting the LGB population.

Exposure to violence, a risk for suicide in youths and young adults. A meta-analysis of longitudinal studies.

OBJECTIVE: To assess the association and magnitude of the effect of early exposure to different types of interpersonal violence (IPV) with suicide attempt and suicide death in youths and young adults. METHOD: We searched six databases until June 2015. Inclusion criteria were as follows: (1) assessment of any type of IPV as risk factor of suicide attempt or suicide: (i) child maltreatment [childhood physical, sexual, emotional abuse, neglect], (ii) bullying, (iii) dating violence, and (iv) community violence; (2) population-based case-control or cohort studies; and (3) subjects aged 12-26 years. Random models were used for meta-analyses (Reg: CRD42013005775). RESULTS: From 23 682 articles, 29 articles with 143 730 subjects for meta-analyses were included. For victims of any IPV, OR of subsequent suicide attempt was 1.99 (95% CI: 1.73-2.28); for child maltreatment, 2.25 (95% CI: 1.85-2.73); for bullying, 2.39 (95% CI: 1.89-3.01); for dating violence, 1.65 (95% CI: 1.40-1.94); and for community violence, 1.48 (95% CI: 1.16-1.87). Young victims of IPV had an OR of suicide death of 10.57 (95% CI: 4.46-25.07). CONCLUSION: Early exposure to IPV confers a risk of suicide attempts and particularly suicide death in youths and young adults. Future research should address the effectiveness of preventing and detecting early any type of IPV exposure in early ages.

Obesity reduces the pro-angiogenic potential of adipose tissue stem cell-derived extracellular vesicles (EVs) by impairing miR-126 content: impact on clinical applications.

BACKGROUND/OBJECTIVES: Soluble factors and cell-derived extracellular vesicles (EVs) are crucial tissue repair mediators in cell-based therapy. In the present study, we investigate the therapeutic impact of EVs released by adipose tissue-derived stem cells (ASCs) recovered from obese subjects' visceral and subcutaneous tissues. METHODS: ASCs were recovered from 10 obese (oASCs) and 6 non-obese (nASCs) participants and characterized. In selected experiments, nASCs and oASCs were cultured with palmitic acid (PA) or high glucose (HG), respectively. EVs from obese (oEVs) and non-obese (nEVs) subjects' visceral and subcutaneous ASCs were collected after ultracentrifugation and analyzed for their cargo: microRNA-126 (miR-126), vascular endothelial growth factor (VEGF), and matrix metalloproteinase 2 (MMP-2), and for their biological effects on endothelial cells (ECs). Western blotting analysis and loss- and gain-of function experiments were performed. RESULTS: oEVs show impaired angiogenic potential compared with nEVs. This effect depends on EV cargo: reduced content of VEGF, MMP-2 and, more importantly, miR-126. We demonstrate, using gain- and loss-of-function experiments, that this reduced miR-126 content leads to Spred1 upregulation and the inhibition of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway in ECs. We also show that PA treatment of nASCs translates into the release of EVs that recapitulate oEV cargo. Moreover, HG treatment of oASCs further reduces miR-126 EV content and EV-mediated in vitro angiogenesis. Finally, impaired pro-angiogenic potential is also detected in EVs released from obese subcutaneous adipose tissue-derived ASCs. CONCLUSIONS: These results indicate that obesity impacts on EV pro-angiogenic potential and may raise concerns about the use of adipose tissue-derived EVs in cell-based therapy in the obese setting.

Comparative efficacy of two interventions to discontinue long-term benzodiazepine use: cluster randomised controlled trial in primary care.

BACKGROUND: Benzodiazepines are extensively used in primary care, but their long-term use is associated with adverse health outcomes and dependence. AIMS: To analyse the efficacy of two structured interventions in primary care to enable patients to discontinue long-term benzodiazepine use. METHOD: A multicentre three-arm cluster randomised controlled trial was conducted, with randomisation at general practitioner level (trial registration ISRCTN13024375). A total of 532 patients taking benzodiazepines for at least 6 months participated. After all patients were included, general practitioners were randomly allocated (1:1:1) to usual care, a structured intervention with follow-up visits (SIF) or a structured intervention with written instructions (SIW). The primary end-point was the last month self-declared benzodiazepine discontinuation confirmed by prescription claims at 12 months. RESULTS: At 12 months, 76 of 168 (45%) patients in the SIW group and 86 of 191 (45%) in the SIF group had discontinued benzodiazepine use compared with 26 of 173 (15%) in the control group. After adjusting by cluster, the relative risks for benzodiazepine discontinuation were 3.01 (95% CI 2.03-4.46, P<0.0001) in the SIW and 3.00 (95% CI 2.04-4.40, P<0.0001) in the SIF group. The most frequently reported withdrawal symptoms were insomnia, anxiety and irritability. CONCLUSIONS: Both interventions led to significant reductions in long-term benzodiazepine use in patients without severe comorbidity. A structured intervention with a written individualised stepped-dose reduction is less time-consuming and as effective in primary care as a more complex intervention involving follow-up visits.

A diabetic milieu promotes OCT4 and NANOG production in human visceral-derived adipose stem cells.

AIMS/HYPOTHESIS: Successful outcomes have been obtained by exploiting adipose-derived stem cells (ASCs) in regenerative medicine. NADPH oxidase (NOX)-generated reactive oxygen species (ROS) are known to control stem cell self-renewal. Several high glucose (HG)-mediated effects depend on NOX-generated ROS. In this study, we investigated whether, and how mechanistically, HG concentrations control ASC fate in patients with diabetes. METHODS: ASCs from the visceral adipose tissue of non-diabetic (N-ASCs) and diabetic participants (D-ASCs), identified by surface markers, were counted and evaluated for ROS generation and stem cell properties. Their ability to release soluble factors was assessed by BioPlex analysis. To reproduce an in vitro diabetic glucose milieu, N-ASCs were cultured in HG (25 mmol/l) or normal glucose (NG) concentration (5 mmol/l), as control. ASC pluripotency was assessed by in vitro study. The p47(phox) NOX subunit, AKT and octamer-binding transcription factor 4 (OCT4; also known as POU5F1) were knocked down by small-interfering RNA technology. Stem-cell features were evaluated by sphere cluster formation. RESULTS: The ASC number was higher in diabetic patients than in non-diabetic controls. Production of OCT4 and NANOG, stem-cell-specific transcription factors, was upregulated in D-ASCs compared with N-ASCs. Moreover, we found that ROS production and AKT activation drove D-ASC, but not N-ASC, secretion. When N-ASCs were cultured in vitro in the presence of HG, they also expressed OCT4/NANOG and formed spheres. By knock-down of the p47(phox) NOX subunit, AKT and OCT4 we demonstrated that NOX-generated ROS and their downstream signals are crucial for HG-mediated ASC de-differentiation and proinflammatory cytokine production. CONCLUSIONS/INTERPRETATION: We herein provide a rationale for exploiting D-ASCs in regenerative medicine and/or exploiting HG preconditioning to increase ASCs ex vivo.

Stressful life events severity in patients with first and recurrent depressive episodes.

BACKGROUND: Stressful life events are associated with depression and their role in first onset and recurrences is a promising but controversial perspective of research. The objective is to analyze the role of number of previous episodes and life events exposure in a large sample of primary care depressive patients taking into account life events severity. METHOD: 10,257 patients with DSM-IV criteria for a current single or recurrent major depressive episode were recruited by 2,056 general practitioners in a cross-sectional epidemiological study. Patients answered the Montgomery-Asberg Depression Rating Scale, the Patient Health Questionnaire and the Social Readjustment Rating Scale (SRRS). Stressful life events were categorized into three levels of severity (severe, moderate and mild). All relevant confounding variables were analyzed: age, gender, depression severity, somatic symptoms severity and length of episode. RESULTS: We found a significant positive correlation with number of episodes and depression severity. There was no significant correlation of SRRS scores with age, gender and length of episode. ANOVA exploring life events severity with regard to number of episodes showed statistically differences in SRRS total score, moderate life events and mild life events (F = 15.14, p < 0.001) but not for severe life events. CONCLUSIONS: Prevention and treatment strategies for recurrent depression need to manage life stressful events during mild and long-term periods and not just in the initial recurrences of the disease.

Medical comorbidity in recurrent versus first-episode depressive patients.

OBJECTIVE: This study compares the comorbidity of affective disorders and medical diseases in primary care patients with either a first or recurrent depressive episode. METHOD: A cross-sectional epidemiological study in primary care centres in Spain was designed. A total of 10,257 primary care patients suffering a DSM-IV major depressive episode (MDD) were analysed. Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS), and World Health Organization (WHO) medical diagnoses were provided by the patient's general practitioner according to medical records revised on the basis of radiology or laboratory test data. RESULTS: A total of 88.6% of recurrent patients and 71.1% of first-episode depressive patients reported a medical condition (aOR = 2.61, CI = 2.31-2.93). All medical conditions were more prevalent in the recurrent group than in first-episode group, and with the exception of myocardial infarction, psoriasis and migraine, all other crude ORs showed statistically significant differences between first- and recurrent episodes patients after adjusting for gender, age, education, socioeconomic status and body mass index (BMI). CONCLUSION: Recurrent depression is associated with a decrement in health that is significantly greater than in first-episode depression. Special attention needs to be paid to the physical health in the middle- and long-term management of patients with affective disorders.

Retrospective data analysis of animal poisoning events in Liguria.

Intentional poisoning represents a serious risk to domestic and wild animals, and it can be an environmental and human health issue as well . This paper is a retrospective study, which covers a decade, based on animal poisoning cases and poisoned baits that were submitted for diagnostic examinations to the Veterinary Medical Research Institute for Piedmont, Liguria and the Aosta Valley (IZS-PLVA) in Liguria region. All data were collected through a passive surveillance system introduced in Italy by a decree of the Ministry of Health in January 2009. 43.2% of the animal poisoning cases were confirmed by toxicological analysis, whereas toxic agents were detected in 31.1% of the baits. The most affected animal species were dogs and cats, followed by synanthropic birds,. Only 4% of the total poisoning events analysed involved wild animals and cases of livestock poisoning were minimal. An increased number of cases in January, March, April and August was noticed, but no seasonal trend was detected. The most affected areas were the ones with the highest level of urbanization and population density. The major cause of the poisonings and the most common substances detected in the examined baits were anticoagulants whereas cholinesterase inhibitors, organochlorine pesticides and carbamates were detected in a minor number of cases. This study raises concerns about deliberate animal poisoning in ligurian region and highlights the necessity to fight this phenomenon as it endangers animals, humans and environment.

Validation of a Spanish language version of the pain self-perception scale in patients with fibromyalgia.

BACKGROUND: The Pain Self-Perception Scale (PSPS) is a 24-item questionnaire used to assess mental defeat in chronic pain patients. The aim of this study was to develop a Spanish language version of the PSPS (PSPS-Spanish), to assess the instrument's psychometric properties in a sample of patients with fibromyalgia and to confirm a possible overlapping between mental defeat and pain catastrophizing. METHODS: The PSPS was translated into Spanish by three bilingual content and linguistic experts, and then back-translated into English to assess for equivalence. The final Spanish version was administered, along with the Hospital Anxiety Depression Scale (HADS), Pain Visual Analogue Scale (PVAS), Pain Catastrophizing Scale (PCS) and Fibromyalgia Impact Questionnaire (FIQ), to 250 Spanish patients with fibromyalgia. RESULTS: PSPS-Spanish was found to have high internal consistency (Cronbach's α = 0.90 and the item-total r correlation coefficients ranged between 0.68 and 0.86). Principal components analysis revealed a one-factor structure which explained 61.4% of the variance. The test-retest correlation assessed with the intraclass correlation coefficient, over a 1-2 weeks interval, was 0.78. The total PSPS score was significantly correlated with all the questionnaires assessed (HADS, PVAS, PCS, and FIQ). CONCLUSIONS: The Spanish version of the PSPS appears to be a valid tool in assessing mental defeat in patients with fibromyalgia. In patients with fibromyalgia and Post-Traumatic Stress Disorder (PTSD), PSPS-Spanish correlates more intensely with FIQ than in patients without PTSD. Mental defeat seems to be a psychological construct different to pain catastrophizing.

Dietary changes and colorectal cancer trends in Spain during 1951-2007.

OBJECTIVES: Analysis of the evolution of colorectal cancer in Spain during the period 1951-2007 and its relationship with diet. MATERIAL AND METHODS: Calculation of incidence rates, standardized mortality and years of potential life lost (world population) and per capita consumption of different foods. RESULTS: Red and processed meats, poultry, fish and fruits intake has increased and consumption of vegetables, cereals and legumes has decreased. The incidence of colorectal cancer has steadily increased in both genders, more markedly among men, and across all age groups, in contrast to what has been observed in other countries. Mortality increased during the period 1951-2000, but from that time until 2007 these rates have kept steady in men and fallen in women. The years of potential life lost (YPLL) shows a similar distribution to mortality. The correlation coefficients have values close to one for consumption of red meat, poultry, fish, vegetables and fruits and strongly negative values for the consumption of cereals and vegetables with the incidence and mortality in both genders, and the YPLL, but only among men, with weaker correlations for women. CONCLUSIONS: In colorectal cancer, a minimal time span of ten-fifteen years is necessary for changes in exposure to risk factors to be able to modify the incidence of this tumour. Therefore, Spanish State and Regional Governments should implement legislative and educational measures in the field of Health Promotion regarding the diet urgently.

Longitudinal association between self-injurious thoughts and behaviors and suicidal behavior in adolescents and young adults: A systematic review with meta-analysis.

BACKGROUND: Adolescents with previous self-injurious thoughts and behaviors (SITB) have over 2-fold risk of dying by suicide, higher than older ages. This meta-analysis aims to disentangle the association of each SITB with subsequent suicidal behavior in adolescence/young adulthood, the contribution of each SITB, and the proportion of suicide deaths with no previous suicide attempt. METHODS: We searched 6 databases until June 2015. INCLUSION CRITERIA: 1. Assessment of any previous SITB [a) suicidal thoughts and behaviors (ideation; threat/gesture; plan; attempt); b) non-suicidal thoughts and behaviors (thoughts; threat/gesture; self-injury); c) self-harm] as a risk factor of suicide attempt or suicide death; 2. Case-control or cohort studies; 3. Subjects aged 12-26y. Random effect models, metaregression analyses including mental health and environmental variables, and population attributable risks (PAR)s were estimated. RESULTS: From 23,682 potentially eligible articles, 29 were included in the meta-analysis (1,122,054 individuals). While 68% of all youth suicide deaths had no previous suicide attempt, suicide death was very strongly associated with any previous SITB (OR=22.53, 95%CI: 18.40-27.58). Suicide attempts were also associated with a history of previous SITB (OR=3.48, 95%CI: 2.71-4.43). There were no moderating effects for mental health and environmental features. The PAR of previous SITB to suicide attempts is 26%. LIMITATIONS: There is considerable heterogeneity between the available studies. Due to limitations in the original studies, an over-estimation of the proportion dying at their first attempt cannot be ruled out, since they might have missed unrecognized previous suicide attempts. CONCLUSIONS: Although more than two thirds of suicide deaths in adolescence/young adulthood have occurred with no previous suicidal behavior, previous SITBs have a much higher risk of dying by suicide than previously reported in this age group.

NF1 mutation rather than individual genetic variability is the main determinant of the NF1-transcriptional profile of mutations affecting splicing.

A significant number of neurofibromatosis type 1 (NF1) mutations result in exon skipping. The majority of these mutations do not occur in the canonical splice sites and can produce different aberrant transcripts whose proportions have not been well studied. It has been hypothesized that differences in the mutation-determined NF1-transcriptional profile could partially explain disease variability among patients bearing the same NF1 splice defect. In order to gain insight into these aspects, we analyzed the proportion of the different transcripts generated by nine NF1-splicing mutations in 30 patients. We assessed the influence of the mutation in the NF1-related transcriptional profiles and investigated the existence of individual differences in a global manner. We analyzed potential differences in tissue-specific transcriptional profiles and evaluated the influence of sample processing and mRNA nonsense-mediated decay (NMD). Small transcriptional differences were found in neurofibromas and neurofibroma-derived Schwann cells (SC) compared to blood. We also detected a higher cell culture-dependent NMD. We observed that mutation per se explains 93.5% of the profile variability among mutations studied. However, despite the importance of mutation in determining the proportion of NF1 transcripts generated, we found certain variability among patients with the same mutation. From our results, it seems that genetic factors influencing RNA processing play a minor role in determining the NF1-transcriptional profile. Nevertheless neurofibromin studies would clarify whether these small differences translate into significant functional changes that could explain the great clinical expressivity observed in the disease or any of the disease-related traits.

Male sexual behavior and human papillomavirus DNA: key risk factors for cervical cancer in Spain.

BACKGROUND: It is now established that certain types of human papillomaviruses (HPVs) are the sexually transmitted agents etiologically linked to cervical cancer. Studies assessing the contribution of the male's sexual behavior and genital HPV DNA status to the risk of development of cervical neoplasia in sexual partners have yielded inconsistent results. PURPOSE: This study evaluates the role of men's sexual behavior and the presence of HPV DNA in the penis on the development of cervical cancer in their sexual partners in Spain, a low-risk area for cervical neoplasia. METHODS: Husbands (n = 633) of women participating in two case-control studies of cervical neoplasia were interviewed to obtain information on lifestyle habits, including sexual practices. Cytologic samples were taken from the distal urethra and the surface of the glans penis of 183 husbands of case women and of 171 husbands of control women. These samples were analyzed by a polymerase chain reaction-based system using a generic probe and 25 type-specific probes for the detection and typing of HPV DNA. Serologic specimens were also obtained and analyzed for antibodies to Chlamydia trachomatis, Treponema pallidum, herpes simplex virus type II, and Neisseria gonorrhoeae. RESULTS: The presence of HPV DNA in the husbands' penis conveyed a fivefold risk of cervical cancer to their wives (adjusted odds ratio [OR] for HPV DNA positivity = 4.9; 95% confidence interval [CI] = 1.9-12.6). The risk of cervical cancer was strongly related to HPV type (adjusted OR for HPV type 16 = 9.0; 95% CI = 1.1-77.5), to the husbands' number of extramarital partners (adjusted OR = 11.0; 95% CI = 3.0-40.0; for > or = 21 women versus one), and to the number of prostitutes as extramarital sexual partners (adjusted OR = 8.0; 95% CI = 2.9-22.2; for > or = 10 women versus none). Presence of antibodies to C. trachomatis (adjusted OR = 2.6; 95% CI = 1.4-4.6) and an early age at first sexual intercourse of the husband (adjusted OR = 3.2; 95% CI = 1.7-5.9; for < or = 15 years versus > or = 21 years) were also associated with cervical neoplasia in the wife. After adjustment for these variables and for the wife's pack-years of smoking, the husband's smoking was moderately associated with cervical cancer in his wife (adjusted OR = 2.5; 95% CI = 1.4-4.4; for > or = 26.2 pack-years versus none). CONCLUSIONS: The study supports the role of men as vectors of the HPV types that are related to cervical cancer. Life-time number of female sexual partners, number of female prostitutes as sexual partners, and detection of HPV DNA in the penis of husbands are all surrogate markers of exposure to HPV during marriage. IMPLICATIONS: Men who report multiple sexual partners or who are carriers of HPV DNA may be vectors of high-risk HPV types and may place their wives at high risk of developing cervical cancer. Prostitutes are an important reservoir of high-risk HPVs.

Obesity, metabolic syndrome and Mediterranean diet: Impact on depression outcome.

OBJECTIVE: Obesity, metabolic syndrome (MetS) and low adherence to Mediterranean diet are frequent in major depression patients and have been separately related with prognosis. The aim of this study is to analyse their predictive power on major depression outcome, at 6 and 12 months. METHODS: 273 Major depressive patients completed the Beck Depression Inventory for depressive symptoms and the 14-item Mediterranean diet adherence score. MetS was diagnosed according to the International Diabetes Federation (IDF). RESULTS: At the baseline Mediterranean diet adherence was inversely associated with depressive symptoms (p=0.007). Depression response was more likely in those patients with normal weight (p=0.006) and not MetS (p=0.013) but it was not associated with Mediterranean diet adherence (p=0.625). Those patients with MetS and obesity were less likely to improve symptoms of depression than patients with obesity but not MetS. CONCLUSIONS: Obesity and MetS, but not low adherence to the Mediterranean diet at baseline, predicted a poor outcome of depression at 12 months. Our study suggests that MetS is the key factor that impacts negatively in depression prognosis, rather than obesity or diet. If this finding is confirmed, clinicians should be aware about MetS diagnosis and treatment in overweight depressed patients, especially if outcome is not being satisfactory enough.

Human papillomavirus DNA and antibodies to human papillomaviruses 16 E2, L2, and E7 peptides as predictors of survival in patients with squamous cell cervical cancer.

PURPOSE: To assess whether human papillomavirus (HPV) DNA detection in cervical cancer specimens, or antibodies to selected HPV 16 peptides are predictors of tumor recurrence and long-term survival in patients with squamous cell invasive cervical cancer. SUBJECTS AND METHODS: Four hundred seventy-one cases included in two population-based case-control studies underwent follow-up evaluation. The survival and cause of death were ascertained for 410 cases (87%), with a median follow-up time of 4.6 years after diagnosis. HPV DNA was assessed using an L1 polymerase chain reaction (PCR)-based system and Southern hybridization (SH) on scraped cytologic specimens or biopsies. HPV 16 antibodies to E2, L2, and E7 peptides were detected with enzyme-linked immunosorbent assay (ELISA). RESULTS: Clinical stage was the only independent prognostic factor for recurrence or survival. Although seropositivity to HPV 16 E7/3 peptide predicted a twofold excess risk of mortality (adjusted hazards ratio [HRa] = 2.0; 95% confidence interval [CI], 1.2 to 3.3), the association was restricted to stage I (HRa = 6.6; 95% CI, 1.2 to 37.6) and II (HRa = 5.9; 95% CI, 2.1 to 16.5) patients. The presence of HPV DNA (HRa = 0.9; 95% CI, 0.5 to 1.5), different estimates of the HPV viral load and the HPV type identified were not predictors of tumor recurrence or survival. CONCLUSION: The presence of antibodies to HPV 16 E7 proteins is of prognostic value in early-stage cervical cancer. Our results provide strong evidence that detection and typing of HPV DNA in cervical cells or tissues is not a prognostic factor for recurrence or survival.

Lifestyle change recommendations in major depression: Do they work?

BACKGROUND: Modifying some lifestyle factors can be useful in depression, at least as an adjuvant treatment. Combining different lifestyle interventions seems to be an adequate strategy to increase their antidepressant efficacy according with preliminary studies, but this issue has not been enough investigated. METHODS: The present study is a randomized, double-blinded, multicentre, two arm-parallel clinical trials, with a 12 month follow-up. The sample consisted of 273 Primary Care patients. Four combined hygienic-dietary written recommendations were given to the patients about diet, exercise, light exposure and sleep hygiene. RESULTS: Both active and control interventions were associated with improvement on BDI (Beck Depression Inventory) scores. However, there were not statistically significant differences (7.0 vs. 7.6; p=0.594). LIMITATIONS: We were unable to monitor whether patients carry out recommendations. Intervention could be too difficult to accomplish for depressed patients without enough support and supervision. CONCLUSIONS: Just giving written lifestyle recommendations are not enough for depressive patients to benefit from them, so perhaps lifestyle change recommendations work or do not work on Depression depending on how they are presented to patients and on monitoring systems of their implementation.

Risk factors for cervical intraepithelial neoplasia grade III/carcinoma in situ in Spain and Colombia.

A case-control study of 525 histologically confirmed cases of cervical intraepithelial neoplasia grade III and 512 controls was done in Spain and Colombia to assess the role of various risk factors taking into account the effect of human papillomavirus (HPV). The presence of HPV DNA, assessed by a polymerase chain reaction-based method, was the strongest risk factor identified. In Spain the adjusted odds ratio (OR) and 95% confidence interval (CI) (numbers in parentheses) were 56.9 (24.8-130.6) and, in Colombia, were 15.5 (8.2-29.4). In addition to HPV, the multivariate analysis revealed independent effects of early age at first intercourse (in Spain ORa, 4.3; 95% CI, 2.0-9.3 for ages < 17 versus 20+ years and in Colombia ORa, 9.0; 95% CI, 2.6-30.9 for ages < 14 versus 20+ years), and antibodies to Chlamydia trachomatis (in Spain ORa, 2.3; 95% CI, 1.1-4.5; and in Colombia ORa, 1.7; 95% CI, 1.1-2.7). High parity showed a significant effect only in Colombia (ORa, 2.0; 95% CI, 1.0-5.0 for > or = 6 versus 1) while number of partners of the woman and specially of her husband showed a strong effect in Spain only (ORa, 6.9; 95% CI, 3.1-15.3 for partners of the husband > or = 21 versus 1-5). Smoking and use of oral contraceptives did not show significant or consistent associations. Among HPV-DNA positive women early age at first intercourse and high parity increased the risk of cervical intraepithelial neoplasia III but the effect was statistically significant only for the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Human papillomavirus and cervical intraepithelial neoplasia grade III/carcinoma in situ: a case-control study in Spain and Colombia.

A case-control study of 525 cases of cervical intraepithelial neoplasia grade III (CIN III) and 512 controls was conducted in Spain and Colombia between 1985 and 1988 to assess the role of human papillomavirus (HPV) in the etiology of CIN III. HPV DNA in cytological scrapes from the cervix was assessed by Virapap and by polymerase chain reaction (PCR) based on the L1 consensus primers. A subsample of 268 specimens was also tested for HPV DNA using Southern hybridization. In Spain, the PCR-based prevalences of HPV DNA were 70.7% among cases and 4.7% among controls. Odds ratio (OR) and 95% confidence interval (numbers in parentheses) for HPV DNA were 56.9 (24.8-130.6). In Columbia HPV DNA was detected by PCR in 63.2% of the cases and in 10.5% of the controls. The OR was 15.5 (8.2-29.4). The estimated fractions of CIN III attributable to HPV were 72.4% in Spain and 60.3% in Colombia. HPV 16 was the predominant viral type and showed the strongest association with CIN III; in Spain the OR was 295.5 (44.8-1946.4) and in Colombia the OR was 27.1 (10.6-69.5). HPV DNA of unknown type was frequent in HPV-positive cases (18.3% in Spain and 38.0% in Colombia) and controls (66.7% in Spain and 47.4% in Colombia). The comparison of results from Virapap and PCR indicated that PCR is the method of choice for epidemiological studies. These data strongly support the hypothesis of the viral origin of CIN III, the common etiology of CIN III and invasive cervical cancer, and the causal nature of the association between HPV and CIN III.

Risk factors for progression of cervical intraepithelial neoplasm grade III to invasive cervical cancer.

Data from four case-control studies on invasive cervical cancer and on cervical intraepithelial neoplasia grade III (CIN III) that were concurrently conducted in Spain and Colombia were used to look for factors that might favor the progression from CIN III to the invasive stage. These studies were compared in two ways; a case-case comparison and an estimation of the ratio of odds ratios with the use of of special logistic regression model that took into account the different design of each study and possible confounding factors. Variables studied were human papillomavirus status, viral load, viral types, sexual behavior, sexually transmitted diseases, reproductive patterns, oral contraceptives, and smoking. Both CIN III and invasive cervical cancer have a very similar profile of risk factors and none of them was different in a consistent way to suggest a role in the progression from CIN III to invasive cervical cancer. Some methodological problems such as cohort-specific differences and some selection biases could be adjusted for with a careful statistical analysis. Other problems derived from the cross-sectional nature of the design are unavoidable and should be considered in the interpretation of the results.