Help Seeking Behavior of Women with Self-Discovered Breast Cancer Symptoms: A Meta-Ethnographic Synthesis of Patient Delay

Background and Objective

Patient delay makes a critical contribution to late diagnosis and poor survival in cases of breast cancer. Identifying the factors that influence patient delay could provide information for adopting strategies that shorten this delay. The aim of this meta-ethnography was to synthesize existing qualitative evidence in order to gain a new understanding of help seeking behavior in women with self-discovered breast cancer symptoms and to determine the factors that influence patient delay.

Methods

The design was a meta-ethnography approach. A systematic search of the articles was performed in different databases including Elsevier, PubMed, ProQuest and SCOPUS. Qualitative studies with a focus on help seeking behaviors in women with self-discovered breast cancer symptoms and patient delay, published in the English language between 1990 and 2013 were included. The quality appraisal of the articles was carried out using the Critical Appraisal Skills Programme qualitative research checklist and 13 articles met the inclusion criteria. The synthesis was conducted according to Noblit and Hare’s meta-ethnographic approach (1988), through reciprocal translational analysis and lines-of-argument.

Findings

The synthesis led to identification of eight repeated key concepts including: symptom detection, initial symptom interpretation, symptom monitoring, social interaction, emotional reaction, priority of medical help, appraisal of health services and personal-environmental factors. Symptom interpretation is identified as the important step of the help seeking process and which changed across the process through active monitoring of their symptoms, social interactions and emotional reactions. The perceived seriousness of the situation, priority to receive medical attention, perceived inaccessibility and unacceptability of the health care system influenced women’s decision-making about utilizing health services.

Conclusion

Help seeking processes are influenced by multiple factors. Educational programs aimed at correcting misunderstandings, erroneous social beliefs and improving self-awareness could provide key strategies to improve health policy which would reduce patient delay.     

Symptoms in Response to Controlled Diesel Exhaust More Closely Reflect Exposure Perception Than True Exposure

Background

Diesel exhaust (DE) exposures are very common, yet exposure-related symptoms haven’t been rigorously examined.

Objective

Describe symptomatic responses to freshly generated and diluted DE and filtered air (FA) in a controlled human exposure setting; assess whether such responses are altered by perception of exposure.

Methods

43 subjects participated within three double-blind crossover experiments to order-randomized DE exposure levels (FA and DE calibrated at 100 and/or 200 micrograms/m³ particulate matter of diameter less than 2.5 microns), and completed questionnaires regarding symptoms and dose perception.

Results

For a given symptom cluster, the majority of those exposed to moderate concentrations of diesel exhaust do not report such symptoms. The most commonly reported symptom cluster was of the nose (29%). Blinding to exposure is generally effective. Perceived exposure, rather than true exposure, is the dominant modifier of symptom reporting.

Conclusion

Controlled human exposure to moderate-dose diesel exhaust is associated with a range of mild symptoms, though the majority of individuals will not experience any given symptom. Blinding to DE exposure is generally effective. Perceived DE exposure, rather than true DE exposure, is the dominant modifier of symptom reporting.     

Low Levels of Blood Lipids Are Associated with Etiology and Lethal Outcome in Acute Liver Failure

Background/Aims

Emerging data links different aspects of lipid metabolism to liver regeneration. In patients with acute liver failure (ALF), low levels of lipids may correlate with disease severity. Thus, we determined whether there is an etiology-specific link between lipid levels in patients suffering from ALF and aimed to investigate an effect of lipid levels on the prognosis of ALF.

Methods

In this retrospective single center study, we reviewed 89 consecutive ALF patients, who met the criteria of the “Acute Liver Failure Study Group”. Patient characteristics, clinical data and laboratory parameters were individually analyzed at admission and correlated with the patients'' outcome after a four week follow up. Possible endpoints were either discharge, or death or liver transplantation.

Results

High-density lipoprotein (HDL), cholesterol and triglyceride levels were significantly lower in patients who died or required a liver transplant. HDL levels were significantly higher in patients with ALF caused by acetaminophen intoxication, compared to fulminant HBV infection or drug induced liver injury. HDL levels correlated with hepatic injury by ALT levels, and Albumin, and inversely correlated with the MELD score, INR, and bilirubin.

Conclusion

In our cohort of patients with ALF, we could show that HDL and cholesterol are suppressed. In addition novel etiology specific patterns between acteminophen and non-acteminophen induced liver failure were detected for serum lipid components. Further studies are needed to address the role of cholesterol and lipid metabolism and the according pathways in different etiologies of ALF.     

Modified Uterine Allotransplantation and Immunosuppression Procedure in the Sheep Model

Objective

To develop an orthotopic, allogeneic, uterine transplantation technique and an effective immunosuppressive protocol in the sheep model.

Methods

In this pilot study, 10 sexually mature ewes were subjected to laparotomy and total abdominal hysterectomy with oophorectomy to procure uterus allografts. The cold ischemic time was 60 min. End-to-end vascular anastomosis was performed using continuous, non-interlocking sutures. Complete tissue reperfusion was achieved in all animals within 30 s after the vascular re-anastomosis, without any evidence of arterial or venous thrombosis. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil and methylprednisolone tablets. Graft viability was assessed by transrectal ultrasonography and second-look laparotomy at 2 and 4 weeks, respectively.

Results

Viable uterine tissue and vascular patency were observed on transrectal ultrasonography and second-look laparotomy. Histological analysis of the graft tissue (performed in one ewe) revealed normal tissue architecture with a very subtle inflammatory reaction but no edema or stasis.

Conclusion

We have developed a modified procedure that allowed us to successfully perform orthotopic, allogeneic, uterine transplantation in sheep, whose uterine and vascular anatomy (apart from the bicornuate uterus) is similar to the human anatomy, making the ovine model excellent for human uterine transplant research.     

Psychopathological Profiles in Transsexuals and the Challenge of Their Special Status among the Sexes

Objective

Investigating psychopathological profiles of transsexuals raises a very basic methodological question: are control groups, which represent the biological or the phenotypic sex, most suited for an optimal evaluation of psychopathology of transsexuals?

Method

Male-to-female (MtF) (n=52) and female-to-male transsexuals (FtM) (n=32), receiving cross-sex hormone treatment, were compared with age matched healthy subjects of the same genetic sex (n=178) and with the same phenotypic sex (n=178) by means of the Symptom Check List-90-Revisited instrument (SCL-90-R). We performed analyses of covariance (ANCOVA) to test for group and sex effects. Furthermore, we used a profile analysis to determine if psychopathological symptom profiles of transsexuals more closely resemble genotypic sex or phenotypic sex controls.

Results

Transsexual patients reported more symptoms of psychopathological distress than did healthy control subjects in all subscales of the SCL-90-R (all p<0.001), regardless of whether they were compared with phenotype or genotype matched controls. Depressive symptoms were more pronounced in MtF than in FtM (SCL-90-R score 0.85 vs. 0.45, p = 0.001). We could demonstrate that FtM primarily reflect the psychopathological profile of biological males rather than that of biological females (r = 0.945), while MtF showed a slightly higher profile similarity with biological females than with biological males (r = 0.698 vs. r = 0.685).

Conclusion

Our findings suggest that phenotypic sex matched controls are potentially more appropriate for comparison with the psychopathology of transsexual patients than are genetic sex matched controls.     

History of Having a Macrosomic Infant and the Risk of Diabetes: The Japan Public Health Center-Based Prospective Diabetes Study

Objective

The aim of the present study was to test a hypothesis that a history of having a macrosomic infant (≥4000g) is associated with the risk of diabetes.

Methods

Data on the Japan Public Health Center-based Prospective diabetes cohort were analyzed, which is a population-based cohort study on diabetes. The survey of diabetes was performed at baseline and at the 5-year follow-up. A history of having a macrosomic infant was assessed using a self-administered questionnaire. A cross-sectional analysis was performed among 12,153 women who participated in the 5-year survey of the cohort. Logistic regression was used to examine the relationship between a history of having a macrosomic infant and the presence of diabetes. A longitudinal analysis was also conducted among 7,300 women without diabetes who participated in the baseline survey. Logistic regression was used to investigate the relationship between a history of having a macrosomic infant and the incidence of diabetes between the baseline survey and the 5-year survey.

Results

In the cross-sectional analysis, parous women with a positive history were more likely to have diabetes in relation to parous women without (OR = 1.44, 95% CI = 1.13-1.83). The longitudinal analysis showed a modest but non-significant increased risk of developing diabetes among women with a positive history (OR = 1.24, 95% CI = 0.80-1.94).

Conclusions

An increased risk of diabetes was implied among women with a history of having a macrosomic infant although the longitudinal analysis showed a non-significant increased risk.     

Psychological and Physical Co-Morbidity among Urban South African Women

Objectives

There is substantial evidence for the links between poverty and both physical and mental health; but limited research on the relationship of physical and mental health problems exists in low- and middle-income countries. The objective of this paper is to evaluate the prevalence and co-morbidity of psychological distress among women with common physical diseases in a socio-economically disadvantaged urban area of South Africa.

Methods

Women enrolled in the Birth to twenty (Bt20) cohort study were evaluated for this paper. Bt20 was founded in 1990 and has followed more than 3,000 children and their caregivers since birth; this study evaluates the health of the caregivers (average age 44) of these children. Psychological distress was evaluated by administering the General Health Questionnaire (GHQ-28) and we evaluated the presence of physical disease by self-report.

Results

Forty percent of the sample presented with psychological distress using the GHQ scoring method. More than half of the women who reported a history of a physical disease, including diabetes, heart attack, asthma, arthritis, osteoporosis, epilepsy, and tuberculosis, reported psychological disorder. Presence of one physical disease was not associated with increased rates of psychological distress. However, women who reported two diseases had increased rates of psychological symptoms, and this upward trend continued with each additional physical disease reported (measured to five).

Conclusions

These data indicate high prevalence rates of co-morbid psychological distress among women with physical disease. This argues for the need of greater mental health support for women living with physical diseases.     

Cirrhosis,Liver Transplantation and HIV Infection Are Risk Factors Associated with Hepatitis E Virus Infection

Background

Acute and chronic hepatitis E have been associated with high mortality and development of cirrhosis, particularly in solid-organ recipients and patients infected by human immunodeficiency virus. However, data regarding the epidemiology of hepatitis E in special populations is still limited.

Aims

Investigate seroprevalence and possible factors associated with HEV infection in a large cohort of immunosuppressed patients.

Methods

Cross-sectional study testing IgG anti-HEV in serum samples from 1373 consecutive individuals: 332 liver-transplant, 296 kidney-transplant, 6 dual organ recipients, 301 non-transplanted patients with chronic liver disease, 238 HIV-infected patients and 200 healthy controls.

Results

IgG anti-HEV was detected in 3.5% controls, 3.7% kidney recipients, 7.4% liver transplant without cirrhosis and 32.1% patients who developed post-transplant cirrhosis (p<0.01). In patients with chronic liver disease, IgG anti-HEV was also statistically higher in those with liver cirrhosis (2% vs 17.5%, p<0.01). HIV-infected patients showed an IgG anti-HEV rate of 9.2%, higher than those patients without HIV infection (p<0.03). Multivariate analysis showed that the factors independently associated with anti-HEV detection were liver cirrhosis, liver transplantation and HIV infection (OR: 7.6, 3.1 and 2.4). HCV infection was a protective factor for HEV infection (OR: 0.4).

Conclusions

HEV seroprevalence was high in liver transplant recipients, particularly those with liver cirrhosis. The difference in anti-HEV prevalence between Liver and Kidney transplanted cases suggests an association with advanced liver disease. Further research is needed to ascertain whether cirrhosis is a predisposing factor for HEV infection or whether HEV infection may play a role in the pathogeneses of cirrhosis.     

The Impact of Sexual Abuse in Patients Undergoing Colonoscopy

Background

Sexual abuse has been linked to strong effects on gastrointestinal health. Colonoscopy can provoke intense emotional reactions in patients with a sexual abuse history and may lead to avoidance of endoscopic procedures.

Objective

To determine whether care around colonoscopy needs adjustment for patients with sexual abuse experience, thereby exploring targets for the improvement of care around colonoscopic procedures.

Methods

Questionnaires were mailed to patients (n = 1419) from two centers within 11 months after colonoscopy. Differences in experience of the colonoscopy between patients with and without a sexual abuse history were assessed and patients'' views regarding physicians'' inquiry about sexual abuse and care around endoscopic procedures were obtained.

Results

A total of 768 questionnaires were analyzed. The prevalence of sexual abuse was 3.9% in male and 9.5% in female patients. Patients born in a non-western country reported more sexual abuse (14.9%) than those born in a western country (6.3%; p = 0.008). Discomfort during colonoscopy was indicated on a scale from 0 to 10, mean distress score of patients with sexual abuse was 4.8(±3.47) compared to 3.5(±3.11) in patients without a sexual abuse history (p = 0.007). Abdominal pain was a predictor for higher distress during colonoscopy (β = −0.019 (SE = 0.008); p = 0.02, as well as the number of complaints indicated as reason for colonoscopy (β = 0.738 (SE = 0.276); p = 0.008). Of patients with sexual abuse experience, 53.8% believed gastroenterologists should ask about it, 43.4% said deeper sedation during colonoscopy would diminish the distress.

Conclusions

Sexual abuse is prevalent in patients presenting for colonoscopy. Patients with a sexual abuse history experience more distress during the procedure and indicate that extra attention around and during colonoscopy may diminish this distress.     

A Shift towards Pro-Inflammatory CD16+ Monocyte Subsets with Preserved Cytokine Production Potential after Kidney Transplantation

Background

The presence of monocyte-macrophage lineage cells in rejecting kidney transplants is associated with worse graft outcome. At present, it is still unclear how the monocyte-macrophage related responses develop after transplantation. Here, we studied the dynamics, phenotypic and functional characteristics of circulating monocytes during the first 6 months after transplantation and aimed to establish the differences between kidney transplant recipients and healthy individuals.

Methods

Phenotype, activation status and cytokine production capacity of classical (CD14++CD16−), intermediate (CD14++CD16+) and non-classical (CD14+CD16++), monocytes were determined by flow cytometry in a cohort of 33 healthy individuals, 30 renal transplant recipients at transplantation, 19 recipients at 3 months and 16 recipients at 6 months after transplantation using a cross-sectional approach.

Results

The percentage of both CD16+ monocyte subsets was significantly increased in transplant recipients compared to healthy individuals, indicative of triggered innate immunity (p≤0.039). Enhanced production capacity of tumor necrosis factor-α, interferon-γ and interleukin-1β was observed by monocytes at transplantation compared to healthy individuals. Remarkably, three months post-transplant, in presence of potent immunosuppressive drugs and despite improved kidney function, interferon-γ, tumor necrosis factor-α and interleukin-10 production capacity still remained significantly increased.

Conclusion

Our data demonstrate a skewed balance towards pro-inflammatory CD16+ monocytes that is present at the time of transplantation and retained for at least 6 months after transplantation. This shift could be one of the important drivers of early post-transplant cellular immunity.     

Psychometric Assessment of the Chinese Version of the Supportive Care Needs Survey Short-Form (SCNS-SF34-C) among Hong Kong and Taiwanese Chinese Colorectal Cancer Patients

Background

Accurate assessment of unmet supportive care needs is essential for optimal cancer patient care. This study used confirmatory factor analysis (CFA) to test the known factor structures of the short form of Supportive Care Need Survey (SCNS-34) in Hong Kong and Taiwan Chinese patients diagnosed with colorectal cancer (CRC).

Methods

360 Hong Kong and 263 Taiwanese Chinese CRC patients completed the Chinese version of SCNS-SF34. Comparative measures (patient satisfaction, anxiety, depression, and symptom distress) tested convergent validity while known group differences were examined to test discriminant validity.

Results

The original 5-factor and recent 4-factor models of the SCNS demonstrated poor data fit using CFA in both Hong Kong and Taiwan samples. Subsequently a modified five-factor model with correlated residuals demonstrated acceptable fit in both samples. Correlations demonstrated convergent and divergent validity and known group differences were observed.

Conclusions

While the five-factor model demonstrated a better fit for data from Chinese colorectal cancer patients, some of the items within its domain overlapped, suggesting item redundancy. The five-factor model showed good psychometric properties in these samples but also suggests conceptualization of unmet supportive care needs are currently inadequate.     

Salvage Liver Transplantation for Recurrent Hepatocellular Carcinoma after Liver Resection: Retrospective Study of the Milan and Hangzhou Criteria

Background

Salvage liver transplantation (SLT) has recently been proposed for recurrent hepatocellular carcinoma after liver resection; however, criteria for candidate assessment in SLT have not been thoroughly evaluated.

Methods and Findings

We retrospectively analyzed outcomes and factors affecting survival of 53 recipients who received SLT in the Liver Transplantation Center, The First Affiliated Hospital of Zhejiang University between 2004 and 2012. Thirty recipients fulfilled the Hangzhou criteria, of which 16 also fulfilled the Milan criteria, while the remaining 23 exceeded both criteria. The 1-year, 3-year and 5-year overall survival rates and tumor-free survival rates were both superior in patients fulfilling Milan or Hangzhou criteria compared with those exceeding the criteria. For recipients outside Milan criteria but within Hangzhou criteria, the 1-year, 3-year overall survival rates were 70.1%, 70.1%, similar to recipients within Milan criteria, with the 1-year, 3-year and 5-year overall survival of 93.8%%, 62.1% and 62.1% (P = 0.586). The tumor-free survival rates were also similar between these two subgroups, with 51.9% and 51.9% vs. 85.6%, 85.6% and 64.2% during the same time interval, respectively (P = 0.054). Cox regression analysis identified Hangzhou criteria (within vs. outside, hazard ratio (HR) 0.376) and diameter of the largest tumor (HR 3.523) to be independent predictors for overall survival. The only predictor for tumor-free survival was diameter of the largest tumor (HR 22.289).

Conclusions

Hangzhou criteria safely expanded the candidate pool and are feasible in assessment of candidates for SLT. This is helpful in donor liver allocation in transplant practice.     

Psychological Sequelae of the Station Nightclub Fire: Comparing Survivors with and without Physical Injuries Using a Mixed-Methods Analysis

Background

Surveying survivors from a large fire provides an opportunity to explore the impact of emotional trauma on psychological outcomes.

Methods

This is a cross-sectional survey of survivors of The Station Fire. Primary outcomes were post-traumatic stress (Impact of Event Scale – Revised) and depressive (Beck Depression Inventory) symptoms. Linear regression was used to examine differences in symptom profiles between those with and without physical injuries. The free-response section of the survey was analyzed qualitatively to compare psychological sequelae of survivors with and without physical injuries.

Results

104 participants completed the study survey; 47% experienced a burn injury. There was a 42% to 72% response rate range. The mean age of respondents was 32 years, 62% were male, and 47% experienced a physical injury. No significant relationships were found between physical injury and depressive or post-traumatic stress symptom profiles. In the qualitative analysis, the emotional trauma that survivors experienced was a major, common theme regardless of physical injury. Survivors without physical injuries were more likely to experience survivor guilt, helplessness, self-blame, and bitterness. Despite the post-fire challenges described, most survivors wrote about themes of recovery and renewal.

Conclusions

All survivors of this large fire experienced significant psychological sequelae. These findings reinforce the importance of mental health care for all survivors and suggest a need to understand factors influencing positive outcomes.     

Course of Symptoms and Health-Related Quality of Life during Specialized Pre-Dialysis Care

Background

Concerns are present on the limited value of renal function alone in defining the optimal moment to start dialysis. Disease-related symptoms and health-related quality of life (HRQOL) may have additional clinical value in defining this moment, but little is known about how these parameters change during pre-dialysis care. The aims of our study were to describe the course of symptoms and HRQOL during pre-dialysis care and to investigate their association with poor health outcomes.

Methods

In the prospective PREPARE-2 cohort, incident patients starting specialized pre-dialysis care were included when referred to one of the 25 participating Dutch outpatient clinics (2004–2011). In the present analysis, 436 patients with data available on symptoms and HRQOL were included. Clinical data, symptoms (revised illness perception questionnaire), and HRQOL (short form-36 questionnaire; physical and mental summary score) were collected every 6-month interval. A time-dependent Cox proportional hazard model was used to associate symptoms and HRQOL with the combined poor health outcome (i.e. starting dialysis, receiving a kidney transplant, and death).

Results

All symptoms increased, especially fatigue and loss of strength, and both the physical and mental summary score decreased over time, with the most pronounced change during the last 6–12 months of follow-up. Furthermore, each additional symptom (adjusted HR 1.04 (95% CI, 1.00–1.09)) and each 3-point lower physical and mental summary score (adjusted HR 1.04 (1.02–1.06) and 1.04 (1.02–1.06) respectively) were associated with a higher risk of reaching the combined poor health outcome within the subsequent 6 months.

Conclusions

The number of symptoms increased and both the physical and mental HRQOL score decreased during pre-dialysis care and these changes were associated with starting dialysis, receiving a kidney transplant, and death. These results may indicate that symptoms and HRQOL are good markers for the medical condition and disease stage of pre-dialysis patients.     

Depression,Anxiety and Quality of Life in Long-Term Survivors of Malignant Melanoma: A Register-Based Cohort Study

Aim

The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma.

Methods

In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2%) completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7) and depression (PHQ-9) and the EORTC Quality of Life Questionnaire (EORTC QLQ 30). Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population.

Results

An average of 8.4 (5.7 to 12.2) years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients). Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women), but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases.

Conclusion

Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.     

Personality Traits,Education, Physical Exercise,and Childhood Neurological Function as Independent Predictors of Adult Obesity

Objective

To investigate whether personality traits, education, physical exercise, parental socio-economic conditions, and childhood neurological function are independently associated with obesity in 50 year old adults in a longitudinal birth cohort study.

Method

The sample consisted of 5,921 participants born in Great Britain in 1958 and followed up at 7, 11, 33, 42, and 50 years with data on body mass index measured at 42 and 50 years.

Results

There was an increase of adult obesity from 14.2% at age 42 to 23.6% at 50 years. Cohort members who were reported by teachers on overall clumsiness as “certainly applied” at age 7 were more likely to become obese at age 50. In addition, educational qualifications, traits Conscientiousness and Extraversion, psychological distress, and physical exercise were all significantly associated with adult obesity. The associations remained to be significant after controlling for birth weight and gestation, maternal and paternal BMI, childhood BMI, childhood intelligence and behavioural adjustment, as well as diet.

Conclusion

Neurological function in childhood, education, trait Conscientiousness, and exercise were all significantly and independently associated with adult obesity, each explained unique individual variability.     

Effect of Immunosuppressive Agents on Hepatocyte Apoptosis Post-Liver Transplantation

Introduction

Immunosuppressants are used ubiquitously post-liver transplantation to prevent allograft rejection. However their effects on hepatocytes are unknown. Experimental data from non-liver cells indicate that immunosuppressants may promote cell death thereby driving an inflammatory response that promotes fibrosis and raises concerns that a similar effect may occur within the liver. We evaluated apoptosis within the liver tissue of post-liver transplant patients and correlated these findings with in vitro experiments investigating the effects of immunosuppressants on apoptosis in primary hepatocytes.

Methods

Hepatocyte apoptosis was assessed using immunohistochemistry for M30 CytoDEATH and cleaved PARP in human liver tissue. Primary mouse hepatocytes were treated with various combinations of cyclosporine, tacrolimus, sirolimus, or MMF. Cell viability and apoptosis were evaluated using crystal violet assays and Western immunoblots probed for cleaved PARP and cleaved caspase 3.

Results

Post-liver transplant patients had a 4.9-fold and 1.7-fold increase in M30 CytoDEATH and cleaved PARP compared to normal subjects. Cyclosporine and tacrolimus at therapeutic concentrations did not affect hepatocyte apoptosis, however when they were combined with MMF, cell death was significantly enhanced. Cell viability was reduced by 46% and 41%, cleaved PARP was increased 2.6-fold and 2.2-fold, and cleaved caspase 3 increased 2.2-fold and 1.8-fold following treatment with Cyclosporine/MMF and Tacrolimus/MMF respectively. By contrast, the sirolimus/MMF combination did not significantly reduce hepatocyte viability or promote apoptosis.

Conclusion

Commonly used immunosuppressive drug regimens employed after liver transplantation enhance hepatocyte cell death and may thus contribute to the increased liver fibrosis that occurs in a proportion of liver transplant recipients.     

Tinnitus: distinguishing between subjectively perceived loudness and tinnitus-related distress

Objectives

Overall success of current tinnitus therapies is low, which may be due to the heterogeneity of tinnitus patients. Therefore, subclassification of tinnitus patients is expected to improve therapeutic allocation, which, in turn, is hoped to improve therapeutic success for the individual patient. The present study aims to define factors that differentially influence subjectively perceived tinnitus loudness and tinnitus-related distress.

Methods

In a questionnaire-based cross-sectional survey, the data of 4705 individuals with tinnitus were analyzed. The self-report questionnaire contained items about subjective tinnitus loudness, type of onset, awareness and localization of the tinnitus, hearing impairment, chronic comorbidities, sleep quality, and psychometrically validated questionnaires addressing tinnitus-related distress, depressivity, anxiety, and somatic symptom severity. In a binary step-wise logistic regression model, we tested the predictive power of these variables on subjective tinnitus loudness and tinnitus-related distress.

Results

The present data contribute to the distinction between subjective tinnitus loudness and tinnitus-related distress. Whereas subjective loudness was associated with permanent awareness and binaural localization of the tinnitus, tinnitus-related distress was associated with depressivity, anxiety, and somatic symptom severity.

Conclusions

Subjective tinnitus loudness and the potential presence of severe depressivity, anxiety, and somatic symptom severity should be assessed separately from tinnitus-related distress. If loud tinnitus is the major complaint together with mild or moderate tinnitus-related distress, therapies should focus on auditory perception. If levels of depressivity, anxiety or somatic symptom severity are severe, therapies and further diagnosis should focus on these symptoms at first.     

Sleep Apnea and the Risk of Dementia: A Population-Based 5-Year Follow-Up Study in Taiwan

Background

Sleep apnea (SA) has been associated with cognitive impairment. However, no data regarding the risk of dementia in patients with SA has been reported in the general population. This retrospective matched-control cohort study was designed to estimate and compare the risk of dementia in SA and non-SA patients among persons aged 40 and above over a 5-year period follow-up.

Methods

We conducted a nationwide 5-year population-based study using data retrieved from the Longitudinal Health Insurance Database 2005 (LHID2005) in Taiwan. The study cohort comprised 1414 patients with SA aged 40 years who had at least 1 inpatient service claim or 1 ambulatory care claim. The comparison cohort comprised 7070 randomly selected patients who were matched with the study group according to sex, age, and index year. We performed Cox proportional-hazards regressions to compute the 5-year dementia-free survival rates after adjusting for potentially confounding factors.

Results

The SA patients in this study had a 1.70-times greater risk of developing dementia within 5 years of diagnosis compared to non-SA age- and sex-matched patients, after adjusting for other risk factors (95% confidence interval (CI) = 1.26-2.31; P < .01). For the gender-dependent effect, only females with SA were more likely to develop dementia (adjust HR: 2.38, 95% CI =1.51–3.74; P < .001). For the age-dependent effect of different genders, males with SA aged 50-59 years had a 6.08 times greater risk for developing dementia (95% CI = 1.96-18.90), and females with SA aged ≥ 70 years had a 3.20 times greater risk of developing dementia (95% CI =1.71–6.00). For the time-dependent effect, dementia may be most likely to occur in the first 2.5 years of follow-up (adjusted HR:2.04, 95% CI =1.35-3.07).

Conclusions

SA may be a gender-dependent, age-dependent, and time-dependent risk factor for dementia.     

Risk of Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza Vaccine in Quebec

Context

An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.

Objective

To assess narcolepsy risk following administration of a similar vaccine in Quebec.

Design

Retrospective population-based study.

Setting

Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.

Population

Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.

Main Outcome Measures

Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1^st, 2009, and December 31^st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.

Results

A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009–2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50–11.12). RR was 2.07 (0.70–6.17) in the SCCS, and 1.48 (0.37–7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.

Conclusions

Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.