Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Disease-modifying genes and monogenic disorders: experience in cystic fibrosis

The mechanisms responsible for the determination of phenotypes are still not well understood; however, it has become apparent that modifier genes must play a considerable role in the phenotypic heterogeneity of Mendelian disorders. Significant advances in genetic technologies and molecular medicine allow huge amounts of information to be generated from individual samples within a reasonable time frame. This review focuses on the role of modifier genes using the example of cystic fibrosis, the most common lethal autosomal recessive disorder in the white population, and discusses the advantages and limitations of candidate gene approaches versus genome-wide association studies. Moreover, the implications of modifier gene research for other monogenic disorders, as well as its significance for diagnostic, prognostic, and therapeutic approaches are summarized. Increasing insight into modifying mechanisms opens up new perspectives, dispelling the idea of genetic disorders being caused by one single gene.

Disease evolution and outcomes in familial AML with germline CEBPA mutations

In-depth molecular investigation of familial leukemia has been limited by the rarity of recognized cases. This study examines the genetic events initiating leukemia and details the clinical progression of disease across multiple families harboring germ-line CEBPA mutations. Clinical data were collected from 10 CEBPA-mutated families, representing 24 members with acute myeloid leukemia (AML). Whole-exome (WES) and deep sequencing were performed to genetically profile tumors and define patterns of clonal evolution. Germline CEBPA mutations clustered within the N-terminal and were highly penetrant, with AML presenting at a median age of 24.5 years (range, 1.75-46 years). In all diagnostic tumors tested (n = 18), double CEBPA mutations (CEBPAdm) were detected, with acquired (somatic) mutations preferentially targeting the C-terminal. Somatic CEBPA mutations were unstable throughout the disease course, with different mutations identified at recurrence. Deep sequencing of diagnostic and relapse paired samples confirmed that relapse-associated CEBPA mutations were absent at diagnosis, suggesting recurrence was triggered by novel, independent clones. Integrated WES and deep sequencing subsequently revealed an entirely new complement of mutations at relapse, verifying the presentation of a de novo leukemic episode. The cumulative incidence of relapse in familial AML was 56% at 10 years (n = 11), and 3 patients experienced ≥3 disease episodes over a period of 17 to 20 years. Durable responses to secondary therapies were observed, with prolonged median survival after relapse (8 years) and long-term overall survival (10-year overall survival, 67%). Our data reveal that familial CEBPA-mutated AML exhibits a unique model of disease progression, associated with favorable long-term outcomes.

The Process-Outcome Mindfulness Effects in Trainees (PrOMET) study: protocol of a pragmatic randomized controlled trial

Background Mindfulness has its origins in an Eastern Buddhist tradition that is over 2500 years old and can be defined as a specific form of attention that is non-judgmental, purposeful, and focused on the present moment. It has been well established in cognitive-behavior therapy in the last decades, while it has been investigated in manualized group settings such as mindfulness-based stress reduction and mindfulness-based cognitive therapy. However, there is scarce research evidence on the effects of mindfulness as a treatment element in individual therapy. Consequently, the demand to investigate mindfulness under effectiveness conditions in trainee therapists has been highlighted. Methods/Design To fill in this research gap, we designed the PrOMET Study. In our study, we will investigate the effects of brief, audiotape-presented, session-introducing interventions with mindfulness elements conducted by trainee therapists and their patients at the beginning of individual therapy sessions in a prospective, randomized, controlled design under naturalistic conditions with a total of 30 trainee therapists and 150 patients with depression and anxiety disorders in a large outpatient training center. We hypothesize that the primary outcomes of the session-introducing intervention with mindfulness elements will be positive effects on therapeutic alliance (Working Alliance Inventory) and general clinical symptomatology (Brief Symptom Checklist) in contrast to the session-introducing progressive muscle relaxation and treatment-as-usual control conditions. Treatment duration is 25 therapy sessions. Therapeutic alliance will be assessed on a session-to-session basis. Clinical symptomatology will be assessed at baseline, session 5, 15 and 25. We will conduct multilevel modeling to address the nested data structure. The secondary outcome measures include depression, anxiety, interpersonal functioning, mindful awareness, and mindfulness during the sessions. Discussion The study results could provide important practical implications because they could inform ideas on how to improve the clinical training of psychotherapists that could be implemented very easily; this is because there is no need for complex infrastructures or additional time concerning these brief session-introducing interventions with mindfulness elements that are directly implemented in the treatment sessions.

Risk factors for developing complications while awaiting a cholecystectomy

Background. Laparoscopic Cholecystectomy is the gold standard for patients who are diagnosed with biliary colic (NIH, 1993). It has been demonstrated that individuals who wait a longer time between diagnosis and treatment are at increased risk of having complications (Rutledge et al., 2000; Contini et al., 2004; Eldar et al., 1999). County hospitals, such as Ben Taub General Hospital (BTGH), have a particularly high population of uninsured patients and consequently long surgical wait periods due to limited resources. This study evaluates patients the risk factors involved in their progression to complications from gallstones in a county hospital environment. ^ Methods. A case-control study using medical records was performed on all patients who underwent a cholecystectomy for gallstone disease at BTGH during the year of 2005 (n=414). The risk factors included in the study are obesity, gender, age, race, diabetes, and amount of time from diagnosis to surgery. Multivariate analysis and logistical regression were used to assess factors that potentially lead to the development of complications. ^ Results. There were a total of 414 patients at BTGH who underwent a cholecystectomy for gallstone disease during 2005. The majority of patients were female, 84.3% (n=349) and Hispanic, 79.7% (n=330). The median wait time from diagnosis to surgery was 1.43 weeks (range: 0-184.71). The majority of patients presented with complications 72.5% (n=112). The two factors that impacted development of complications in our study population were Hispanic race (OR=1.81; CI 1.02, 3.23; p=0.04) and time from diagnosis to surgery (OR=0.98; CI 0.97, 0.99; p<0.01). Obesity, gender, age, and diabetes were not predictive of development of complications. ^ Conclusions. An individual's socioeconomic status potentially influences all aspects of their health and subsequent health care. The patient population of BTGH is largely uninsured and therefore less likely to seek care at an early stage in their disease process. In order to decrease the rate of complications, there needs to be a system that increases patient access to primary care clinics. Until the problem of access to care is solved, those who are uninsured will likely suffer more severe complications and society will bear the cost. ^

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

Process evaluation of intervention program for prevention of early sexual activity and alcohol use among Hispanic teenagers

Hispanic teens are a high-risk population for initiation of early sexual activity and alcohol use which in turn has numerous social and health consequences. One strategy to address prevention of these behaviors is to implement a capacity building intervention that promotes parent child communication, encompasses their cultural values and community participation. This study describes the process evaluation of a pilot intervention program amongst Hispanic teens and their families living along the Texas-Mexico border. “Girls Lets Talk” is a small group intervention with 10-14 year old teens and their female adult family members that involves education regarding effects of alcohol use and sexual activity as well as activities for monitoring and refusal skills to prevent risky behaviors. Two waves of the program each consisting of at least seven mother daughter dyads were conducted. During the designing process, community advisory board meetings and focus groups were held to review course materials and ensure they were appropriate to the Mexican American culture. Parent and adolescent surveys were administered at the beginning and end of the intervention to assess for psychosocial outcome variables. All sessions received high mean satisfactory scores (mean of 4.00 or better on a five point scale) for both adult and adolescent participants. Qualitative feedback was obtained via debriefing sessions to evaluate experience as well as alter recruitment strategies. A Wilcoxon Sign Rank analysis of the pre and post intervention surveys was done that showed significant changes in some outcome variables such as intentions and confidence for monitoring behaviors for adults and beliefs regarding sexual activity. “Girls Lets Talk” is a promising example of how a process evaluation plan can help develop a theory based health promotion program using the community based participatory research approach. The intervention may also be effective in altering intentions and enhancing self-efficacy among parents and teens in order to decrease risky behaviors such as early sexual activity and alcohol use.^

DISEASE-RELATED INFORMATION NEEDS OF CANCER PATIENTS AGES 11-20: A COMPARISON OF PATIENT-PARENT AND PATIENT-PHYSICIAN PERCEPTIONS

Innovative, aggressive treatments and prolonged survival rates for patients with childhood cancers have placed new demands on the patient, parent and physician. As a result, counterproductive coping behaviors are often noted in adolescent cancer patients.^ One of the main ways the environment is manipulated by the individual to achieve personal comfort is through selectivity of information. An individual will usually pull the support personally needed to cope from the environment if sufficient resources are available. However, information provided young cancer patients is often filtered through the physicians and parents perspectives of the patient's needs without systematic input from the patient. In order to ensure that adequate information resources are available to help teenage patients cope with their illness, health professionals must have insights into the information needs of those patients. No previous efforts to address this subject were found in the literature.^ This study was designed to identify adolescent perspectives of their disease-related information needs and to compare their viewpoints with those of their parents and physicians. Sixty-five outpatient cancer patients (ages 11-20) receiving treatment at the University of Texas M. D. Anderson Hospital and Tumor Institute in Houston, Texas, 60 of their parents, and 53 physicians, who were involved in the treatment of pediatric patients at M. D. Anderson, were asked to complete self-administered questionnaires. The questionnaires used were developed, administered and analyzed by the investigator. Specific areas addressed in the questionnaires included: Perceptions of cancer-related tests and treatments, the importance of 30 disease-related items of information, responses evoked by receipt of information, current and preferred sources of information, delivery of information at the time of diagnosis, and disease-related information requested for patients, family, friends and teachers.^ Adolescent perceptions of their information needs and their preferences for delivery of information were determined. The relationships between patient-parent and patient-physician perceptions were then analyzed to determine areas in which agreements and disparities in viewpoint existed. Programmatic and research recommendations were then provided.^ Hopefully, through these efforts, the adolescent patient will be helped to receive relevant information support from those deemed to be most important to his/her efforts to cope with cancer. ^

Prevención de complicaciones orales en personas con discapacidad severa

La salud, como derecho primordial de toda persona, adquiere una connotación especial cuando la persona tiene una discapacidad. El término Discapacidad describe una restricción o ausencia, debido a una deficiencia, de la capacidad de realizar una actividad en la forma o dentro del margen que se considera normal para el ser humano. Si nos referimos concretamente a la salud bucal, podemos decir, que presentan alta incidencia de patologías por lo que constituyen un grupo de riesgo con una gran necesidad de cuidados dentales. Es importante destacar que gran parte de las personas con Discapacidad, no pueden expresar en palabras o determinar claramente su proceso patológico y así toleran importantes dolores demostrados mediante el aumento de la irritabilidad, la inactividad, la pérdida de apetito, los problemas de sueño, la autoagresión, etc. Esta falta de certeza y reacciones adversas genera una situación familiar de alteración de la vida cotidiana y desconcierto, además de comenzar a realizar una serie de consultas a psiquiatra, otorrinolaringólogo, neurólogo, clínico, entre otros especialistas. Dicha situación puede ser previsible mediante controles odontológicos periódicos, derivación temprana a exámenes bucales por parte de médicos y/u otros especialistas tratantes, interconsulta con odontólogo ante cambios de conducta o autoagresión. La prevención y el cuidado de la salud dental en los pacientes con discapacidad favorecen el mantenimiento de la salud general y proporcionan una mayor calidad de vida. La intervención del odontólogo en patologías ya instaladas consiste en la eliminación de la sintomatología, detención y tratamiento de las lesiones, restauración de la función y la estética.

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Territorio, trabajo y salud : Una mirada desde dos actividades productivas. Producción granífera en Zona Núcleo y producción ladrillera en el sudeste santiagueño

El objetivo de este artículo es analizar los cambios en la dinámica territorial de la producción de ladrillos en el sudeste santiagueño y de granos en la Zona Núcleo Granífera, y su impacto en la relación urbano-rural y en la salud de los trabajadores. Para ello, recurrimos a técnicas cuantitativas (elaboración de bases de datos sobre la base de registros epidemiológicos institucionales) y a técnicas cualitativas de investigación (entrevistas, observación participante, análisis documental y bibliográfico). En el marco del avance de la frontera agrícola, la sojización y la agriculturización, analizamos la relación entre trabajo y territorio para comprender el proceso de salud-enfermedad-atención en dos zoonosis regionales: enfermedad de Chagas y Fiebre Hemorrágica Argentina

Disease sequence from mutant rhodopsin allele to rod and cone photoreceptor degeneration in man

Mutations in the gene encoding rhodopsin, the visual pigment in rod photoreceptors, lead to retinal degeneration in species from Drosophila to man. The pathogenic sequence from rod cell-specific mutation to degeneration of rods and cones remains unclear. To understand the disease process in man, we studied heterozygotes with 18 different rhodopsin gene mutations by using noninvasive tests of rod and cone function and retinal histopathology. Two classes of disease expression were found, and there was allele-specificity. Class A mutants lead to severely abnormal rod function across the retina early in life; topography of residual cone function parallels cone cell density. Class B mutants are compatible with normal rods in adult life in some retinal regions or throughout the retina, and there is a slow stereotypical disease sequence. Disease manifests as a loss of rod photoreceptor outer segments, not singly but in microscopic patches that coalesce into larger irregular areas of degeneration. Cone outer segment function remains normal until >75% of rod outer segments are lost. The topography of cone loss coincides with that of rod loss. Most class B mutants show an inferior-nasal to superior-temporal retinal gradient of disease vulnerability associated with visual cycle abnormalities. Class A mutant alleles behave as if cytotoxic; class B mutants can be relatively innocuous and epigenetic factors may play a major role in the retinal degeneration.

O cuidado no espaço de intermedicalidade em uma aldeia indígena

O objetivo deste estudo foi interpretar a realidade social e política, na qual se estabelece o cuidado intercultural vivenciado por indivíduos na zona de intermedicalidade de uma aldeia, partindo da perspectiva dos usuários indígenas e dos profissionais de saúde ameríndios e não-indígenas. As bases teóricas que ancoraram a coleta e análise interpretativa dos dados incluíram: a Etnografia, Antropologia Interpretativa, Modelos explanatórios e abordagem cultural safety. Mediante aprovação do Comitê Nacional de Ética em Pesquisa, procedeu-se trabalho de campo na Terra Indígena Buriti, localizada nos munícipios Sidrolândia e Dois Irmãos do Buriti, Mato Grosso do Sul, Brasil. Realizou-se observação participante nas unidades de saúde e no cotidiano das famílias nas aldeias, bem como no Pólo de Sidrolândia. Realizaram-se entrevistas semiestruturadas com 16 indígenas usuários do serviço, 12 profissionais de saúde terenas e seis trabalhadores de saúde não-indígenas. A análise dos dados, simultânea à coleta, ocorreu na perspectiva da Hermenêutica Dialética por meio da análise temática. Os preceitos éticos foram seguidos. Neste estudo, identificaram-se dois temas: 1) \"Doença é pior que a morte: explicações sobre o processo de adoecimento\" retrata como o processo saúde-doença é interpretado pelos participantes. Saúde, para os terenas, é um aspecto primordial na vida deles. O processo de adoecer envolve a perda e/ou a redução da disposição física, psíquica e espiritual para desenvolver atividades cotidianas. Espiritualidade, higiene, alimentação e a questão da posse de terra impactam o processo de adoecimento terena. 2) \"A intermedicalidade do sistema de cuidado em saúde terena\" que retrata os significados atribuídos pelos participantes à coexistência e intercomunicações (intermedicalidade) entre as formas de cuidados em saúde terena: medicina terena, espiritualidade, modo de vida e o serviço oficial de atenção à saúde (sistema Pólo/Posto). O sistema de cuidado dos terenas revela o processo de indigenização dos serviços de saúde. A medicina terena é entendida sob dois âmbitos: um centralizado no conhecimento tradicional indígena, que inclui uso de ervas, atividades de parteiras e de \"puxadores de pernas\"; e outro nos aspectos místicos e sobrenaturais para sua execução: rezas e prática da pajelança, com destaque para redução do número de pajés. A espiritualidade como opção terapêutica é representada pela fé do terena em Deus, concretizada pela oração. O modo de vida do terena engloba principalmente dois aspectos: centralidade na família e o cuidado com higiene individual e ambiental. O sistema Polo/Posto é procurado pelo terena conforme a cartela de serviços ofertada pelas unidades e segundo suas necessidades peculiares, os casos que o terena \"não consegue resolver\". Neste âmbito de cuidado, há a produção de encontros do cuidado pautados pelo vínculo, confiança, diálogo e agir dos profissionais culturalmente sensível. Há, também, desencontros do cuidado favorecidos por prioridades estabelecidas em metas, atendimento queixa-conduta e precária infraestrutura. Observou-se um processo maciço do uso de medicação. Os aspectos identificados nos relatos dos participantes sobre o sistema de cuidado terena são atravessados pela historicidade do povo terena, questão da posse de terra, medicalização da sociedade, higienismo, integração entre corpo, cosmos e terra, espiritualidade com diversidade religiosa, cultura terena centrada na família, atividades programáticas de saúde na atenção básica, biomedicina, transporte precário e baixa resolutividade. Diabetes e hipertensão arterial foram as doenças registradas pelo Pólo e significadas pelos participantes como as principais enfermidades da população. Há a coexistência de medicinas híbridas em todos âmbitos de cuidado em saúde terena. É importante que a intermedicalidade ocorra nos espaços do sistema Pólo/Posto sem sobreposição do saber médico e/ou da lógica institucional à sabedoria terena

Patients' and professionals' views on managing fibromyalgia

BACKGROUND: Managing fibromyalgia is a challenge for both health care systems and the professionals caring for these patients, due, in part, to the fact that the etiology of this disease is unknown, its symptoms are not specific and there is no standardized treatment. OBJECTIVE: The present study examines three aspects of fibromyalgia management, namely diagnostic approach, therapeutic management and the health professional-patient relationship, to explore specific areas of the health care process that professionals and patients may consider unsatisfactory. METHODS: A qualitative study involving semistructured interviews with 12 fibromyalgia patients and nine health professionals was performed. RESULTS: The most commonly recurring theme was the dissatisfaction of both patients and professionals with the management process as a whole. Both groups expressed dissatisfaction with the delay in reaching a diagnosis and obtaining effective treatment. Patients reported the need for greater moral support from professionals, whereas the latter often felt frustrated and of little help to patients. Patients and professionals agreed on one point: the uncertainty surrounding the management of fibromyalgia and, especially, its etiology. CONCLUSION: The present study contributes to a better understanding regarding why current management of fibromyalgia is neither effective nor satisfactory. It also provides insight into how health professionals can support fibromyalgia patients to achieve beneficial results. Health care services should offer greater support for these patients in the form of specific resources such as fibromyalgia clinics and health professionals with increased awareness of the disease.