bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Tp-e interval, Tp-e/QT ratio and Tp-e/QTc ratio in patients with acute myocarditis
Authors: Ucar Fatih Mehmet , Ozturk Cihan , Yılmaztepe Mustafa Adem
Published: October 2019

Background

Acute myocarditis (AM) can be defined as an inflammatory disease of the myocardium and characterized by large heterogeneity of clinical presentation. Myocarditis is becoming increasingly recognized as a contributor to unexplained mortality, and is thought to be a major cause of sudden cardiac death in the first two decades of life. The present study aimed to search the assessment of repolarization dispersion measured from the 12-lead surface electrocardiogram (including Tp-e interval, Tp-e/QT and Tp-e/QTc ratios) in AM patients.

Methods

Totally 56 patients (mean age was 22 ± 3.7 years and 67% of the patients were male) with AM and 56 control subjects (23 ± 4.7 years and 64% of the patients were male) were enrolled. Tp-e intervals, Tp-e/QT and Tp-e/corrected QT (QTc) ratios were calculated from 12-lead electrocardiogram.

Results

Heart rate, QT and QTc values were similar between groups. QRS interval was lower in AM group compared to the control group (p <  0.001). Tp-e, Tp-e/QT and Tp-e/ QTc were significantly higher in AM group (p <  0.001, p <  0.001, p = 0.03 respectively) and they were significantly correlated with high troponin and high sensitive C reactive protein levels. In hospital follow-up time was 6 ± 2 days. Four patients have non sustained ventricular tachyarrhythmias and 1 patient dead because of cardiac arrest.

Conclusions

Our study demonstrated that Tp-e intervals, Tp-e/QT and Tp-e/QTc ratios were higher in patients with AM than control subjects. The increased frequency of ventricular arrhythmias can be clarified by increased indexes of ventricular repolarization parameters in patients with AM.
Radiofrequency catheter ablation of ventricular arrhythmias arising from the region above pulmonary valve
Authors: Li Jin , Zheng Cheng , Liu Zhi-Rui , Ma Jun , Jin Ge , Lin Wei-Qian , Wang Yao-Yao , Lin Jia-Feng
Published: October 2019

Background

Ventricular arrhythmias (VAs) arising from the origin above pulmonary valve lack comprehensive investigation. This study aimed to disclose the characteristics and radiofrequency catheter ablation (RFCA) outcomes for those VAs.

Methods

One hundred six VAs arising from the region above pulmonary valve treated with RFCA were included in this study.

Results

Seventy-five cases were identified in the pulmonary sinus cusps (PSCs, 32 in left sinus cusp (PLC), 15 in right (PRC), 28 in anterior (PAC)) and 31 cases were in the main stem of pulmonary artery (MSPA, 18 above PLC (LMSPA), 3 above PRC (RMSPA), 10 above PAC (AMSPA)). Compared with PSCs VAs, MSPA VAs exhibited a higher R wave amplitude in the inferior leads, a total inferior R amplitude > 5.1 mV predicting MSPA origins. LMSPA, RMSPA and AMSPA VAs resembled PLC, PRC and PAC VAs in electrocardiographic characteristics respectively. No electrophysiological differences were found between PSCs and MSPA VAs. The irrigated-up catheter and R0 Swartz long sheath were more utilized for ablation of PSCs VAs than for MSPA VAs. All these VAs were successfully eliminated by RFCA.

Conclusion

VAs arising from the origin above pulmonary valve were common. Based on certain electrocardiographic characteristics, they could be roughly located, which contributed to an effective RFCA.
Perceptions of time constraints among primary care physicians in Germany
Authors: von dem Knesebeck Olaf , Koens Sarah , Marx Gabriella , Scherer Martin
Published: October 2019

Background

Time constraints during patient visits play a major role for the work stress of primary care physicians. Several studies suggest that there is a critical situation in terms of time constraints in primary care in Germany. Therefore, the following research questions are addressed: (1) What is the time allocated and needed for different types of consultations among primary care physicians in an urban area in Germany? (2) What is the extent of time stress? (3) Are there differences in time stress according to physician characteristics (gender and length of experience) and practice type (single vs. group/shared practice)?

Methods

Data stem from a face-to-face survey of primary care doctors in Hamburg and adjacent regions. A sample of 128 physicians stratified by a combination of physicians’ gender and length of experience (≤15 years or > 15 years) was used. Physicians were asked about the time needed (in minutes) to provide high quality of care for patients regarding six types of consultations: (1) new patient appointment, (2) routine consultation, (3) complete physical examination, (4) symptom-oriented examination, (5) check-up, and (6) home visit (without drive). Afterwards, they were asked about the average minutes allocated for the six consultations. Time stress was measured by calculating minutes needed minus minutes available.

Results

Average perceived time needed was higher than time allocated for all six types of consultation. However, there were differences in the magnitude of time stress between the consultation types. Time stress was most pronounced and most prevalent in case of a new patient visit. No significant differences in time stress between male and female primary care physicians were found, while less experienced physicians reported more time stress than those with more experience (> 15 years). Physicians working in a single practice had less time stress than those working in a group or shared practice in case of a check-up visit.

Conclusions

Perceived time needed is higher than time allocated for various types of consultation among primary care physicians in Germany. Time stress in primary care is particularly pronounced in case of new patient appointments. Early-career physicians are particularly affected by time stress.
Peer-to-peer support model to improve quality of life among highly vulnerable, low-income older adults in Cape Town, South Africa
Authors: Geffen Leon N. , Kelly Gabrielle , Morris John N. , Howard Elizabeth P.
Published: October 2019

Background

Developing countries are experiencing rapid population ageing. Many do not have the resources or formal structures available to support the health and wellbeing of people as they age. In other contexts, the use of peer support programmes have shown favourable outcomes in terms of reducing loneliness, increasing physical activity and managing chronic disease. Such programmes have not been previously developed or tested in African countries. We piloted a peer-to-peer support model among vulnerable community-dwelling adults in a developing country (South Africa) to examine the program’s effect on wellbeing and social engagement.

Methods

A pre-post, pilot design was used to evaluate targeted outcomes, including wellbeing, social support, social interaction, mood, loneliness and physical activity. A total of 212 persons, aged 60+ years and living independently in a low-income area in Cape Town were recruited and screened for eligibility by trained assessors. Participants were assessed using the interRAI CheckUp, WHO-5 Wellbeing index, and the MOS-SS 8 instruments before and after the 5-month intervention, during which they received regular visits and phone calls from trained peer volunteers. During visits volunteers administered a wellness screening, made referrals to health and social services; built friendships with clients; encouraged social engagement; promoted healthy living; and provided emotional and informational support.

Results

Volunteer visits with clients significantly increased levels of self-reported wellbeing by 58%; improved emotional and informational support by 50%; decreased reports of reduced social interaction by 91%; reduced loneliness by 70%; improved mood scores represented as anxiety, depression, lack of interest or pleasure in activities, and withdrawal from activities of interest; and increased levels of physical activity from 49 to 66%.

Discussion

The intervention led to demonstrable improvement in client wellbeing. Policymakers should consider integrating peer-support models into existing health programs to better address the needs of the elderly population and promote healthy ageing in resource-poor community settings. Longer-term and more rigorous studies with a control group are needed to support these findings and to investigate the potential impact of such interventions on health outcomes longitudinally.
Disseminated cytomegalovirus disease after bendamustine: a case report and analysis of circulating B- and T-cell subsets
Authors: Cona Andrea , Tesoro Daniele , Chiamenti Margherita , Merlini Esther , Ferrari Daris , Marti Antonio , Codecà Carla , Ancona Giuseppe , Tincati Camilla , d’Arminio Monforte Antonella , Marchetti Giulia
Published: October 2019

Background

Bendamustine, used for the treatment of indolent B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, is known to cause prolonged myelosuppression and lymphocytopenia and has been associated with the risk of developing serious and fatal infections. While reports of localized CMV infections in asymptomatic patients exist, disseminated CMV disease has not been described.

Case presentation

We report the first case of disseminated CMV infection in a 75-year-old male diagnosed with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia with massive bone marrow infiltration. Despite 6-cycle R-bendamustine chemotherapy resulted in a good partial response, the patient developed persistent fever and severe weight loss. Analysis of cerebrospinal fluid and peripheral blood revealed the presence of CMV-DNA, while the fundus oculi examination revealed bilateral CMV retinitis. Treatment with induction and maintenance drugs was complicated by neutropenia and deterioration of renal function with electrolyte imbalance. From an immunological standpoint, we observed a profound imbalances in phenotype and function of B- and T-cell subsets, with a high proportion of circulating total, activated CD69+ and CD80+ B-cells, a low γ/δ T-cell frequency with a high proportion of CD69- and CD38-expressing cells, and hyperactivated/exhausted CD4+ and CD8+ T-cell phenotypes unable to face CMV challenge.

Conclusions

We hereby describe a severe form of disseminated CMV disease after R-bendamustine treatment. Our observations strongly support the careful clinical monitoring of CMV reactivation/infection in oncologic patients undergoing this therapeutic regimen.
Bacterial vaginosis, vulvovaginal candidiasis and trichomonal vaginitis among reproductive-aged women seeking primary healthcare in Sana’a city, Yemen
Authors: Abdul-Aziz Maha , Mahdy Mohammed A. K. , Abdul-Ghani Rashad , Alhilali Nuha A. , Al-Mujahed Leena K. A. , Alabsi Salma A. , Al-Shawish Fatima A. M. , Alsarari Noura J. M. , Bamashmos Wala , Abdulwali Shahad J. H. , Al Karawani Mahdi , Almikhlafy Abdullah A.
Published: October 2019

Background

In Yemen, the underlying causes of infectious vaginitis have been neglected. Therefore, this study aimed to determine the prevalence and risk factors associated with bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) and trichomonal vaginitis (TV) among non-pregnant reproductive-aged women.

Methods

A cross-sectional study was conducted among 347 non-pregnant reproductive-aged women seeking primary healthcare in Sana’a city, Yemen. Data about sociodemographic characteristics, lifestyle-related behaviors, routine hygienic practices, menstrual care and history and type of contraceptive intake were collected using a structured questionnaire. Vaginal discharge samples were collected and examined for discharge characteristics and pH by a gynecologist. Then, samples were examined for BV, VVC and TV. Data were analyzed using suitable statistical tests.

Results

Vaginal infections were prevalent among 37.6% of reproductive-aged women, where BV was the most prevalent (27.2%). VVC was significantly higher among symptomatic women and significantly associated with itching (P = 0.005). Using bivariate analysis, the age of < 25 years (odds ratio [OR] = 1.9, 95% confidence interval [CI]: 1.16–3.10;P = 0.010) and using intrauterine contraceptive devices (IUCDs) (OR = 1.8, 95% CI: 1.09–2.89;P = 0.020) were significantly associated with BV, while history of miscarriage was significantly associated with a lower risk of BV (OR = 0.5, 95% CI: 0.31–0.85,P = 0.009). However, polygyny was significantly associated with VVC (OR = 3.4, 95% CI: 1.33–8.66;P = 0.007). Multivariable analysis confirmed that age of < 25 years and using IUCD were the independent predictors of BV, while history of miscarriage was an independent protective factor against BV. On the other hand, marriage to a polygamous husband was the independent predictor of VVC.

Conclusions

More than a third of non-pregnant reproductive-aged women seeking PHC in Sana’a have single or mixed infections with BV, VVC or TV. BV is the most frequent cause of vaginitis and is significantly associated with the age of < 25 years and using IUCDs, while VVC is significantly higher among women with polygamous husbands. Health education of polygamous husbands and their wives, regular monitoring of BV among IUCD users and screening women for vaginitis before treatment are recommended.
Clinical outcomes among hospital patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection
Authors: Habib Abdulrahman Mohammed G. , Ali Mohamed Abd Elghafour , Zouaoui Baha R. , Taha Mustafa Ahmed H. , Mohammed Bassem Sahsah , Saquib Nazmus
Published: October 2019

Background

Mortality is high among patients with Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. We aimed to determine hospital mortality and the factors associated with it in a cohort of MERS-CoV patients.

Methods

We reviewed hospital records of confirmed cases (detection of virus by polymerase chain reaction from respiratory tract samples) of MERS-CoV patients (n = 63) admitted to Buraidah Central Hospital in Al-Qassim, Saudi Arabia between 2014 and 2017. We abstracted data on demography, vital signs, associated conditions presented on admission, pre-existing chronic diseases, treatment, and vital status. Bi-variate comparisons and multiple logistic regressions were the choice of data analyses.

Results

The mean age was 60 years (SD = 18.2); most patients were male (74.6%) and Saudi citizens (81%). All but two patients were treated with Ribavirin plus Interferon. Hospital mortality was 25.4%. Patients who were admitted with septic shock and/or organ failure were significantly more likely to die than patients who were admitted with pneumonia and/or acute respiratory distress syndrome (OR = 47.9, 95% CI = 3.9, 585.5, p-value 0.002). Age, sex, and presence of chronic conditions were not significantly associated with mortality.

Conclusion

Hospital mortality was 25%; septic shock/organ failure at admittance was a significant predictor of mortality.
The use of non-contrast-enhanced MRI to evaluate serial changes in endoleaks after aortic stenting: a case report
Authors: Lee Yu-Li , Huang Yao-Kuang , Hsu Li-Sheng , Chen Pang-Yen , Chen Chien-Wei
Published: October 2019

Background

Aortic dissection is a life-threatening syndrome that sometimes requires emergency intervention, and endovascular aortic aneurysm repair (EVAR) is a treatment option. Long-term image follow-up is also required for patients after EVAR due to possible complications.

Case presentation

We present the case of a 73-year-old male with underlying chronic renal disease diagnosed with a type A aortic dissection who underwent EVAR. Four-dimensional (three spatial dimensions combined with time) phase-contrast magnetic resonance imaging (4D PC-MRI) was performed during regular follow-up in preference to contrast-enhanced computed tomography or simple MRI while taking his poor renal function into consideration.

Conclusions

We considered this preferable given his issues with renal function.
Analysis of misdiagnosed cases of hemorrhagic fever with renal syndrome in children: two cases and literature review
Authors: Zhang Li , Ma Qing-shan , Zhang Yan , Sun Bai-chao , Zhao Leng-yue
Published: October 2019

Background

Hemorrhagic fever with renal syndrome (HFRS) is an acute disease caused by hantavirus infection and is clinically characterized by fever, various hemorrhagic manifestations and transient renal and hepatic dysfunctions. Although various cases of HFRS have been reported, cases in children have rarely been described. Herein, we report two atypical cases of HFRS in children without distinctive manifestations and typical disease clinically progresses.

Case presentation

Patient 1 was a 11-year-old girl who attended our clinic for fever accompanying with acute renal failure, proteinuria and decreased level of complement 3 (C3) and thrombocytopenia without any hemorrhagic manifestations, acute glomerulonephritis was suspected first, especially lupus nephritis. Patient 2 was misdiagnosed as encephalitis at local hospital because of fever and headache for 4 days. With elevated liver transaminases, proteinuria and normal cerebrospinal fluid examination, HFRS was taken into consideration. Both of the two cases were supported and confirmed by serological test for Hantavirus.

Conclusions

Clinical manifestations of HFRS in children often presented atypically and were milder than adults. Febrile disease accompanying with thrombocytopenia may lead to the suspected diagnosis of HFRS.
Mid-life serum Vitamin D concentrations were associated with incident dementia but not late-life neuropsychological performance in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Fashanu Oluwaseun E. , Zhao Di , Schneider Andrea L. C. , Rawlings Andreea M. , Sharrett A. Richey , Lutsey Pamela L. , Gottesman Rebecca F. , Gross Alden L. , Guallar Eliseo , Alonso Alvaro , Mosley Thomas H. , Michos Erin D.
Published: October 2019

Background

Activated Vitamin D has anti-inflammatory properties and adequate 25-hydroxyvitamin D [25(OH)D] concentrations may be important for neurocognitive function and protection against neurologic injury. We examined whether mid-life 25(OH) D concentrations were associated with later-life performance on neuropsychological testing, functional ability, depressive symptoms, and incident dementia.

Methods

We studied 13,039 white and black ARIC participants who had serum 25(OH) D measured mid-life at visit 2 (1990–1992). Over the next ~ 20 years through visit 5 (2011–2013), participants underwent 3 additional in-person visits, annual telephone calls, and hospitalization surveillance. An extensive battery of neuropsychological outcomes were assessed at visit 5 using standardized protocols. Incident dementia was ascertained through a formal algorithm that included data from in-person cognitive testing, telephone interviews, hospital discharge codes, and death certificate codes. Diagnoses of dementia were adjudicated by expert clinician committee. For the primary cognitive analyses, we imputed for missing covariates and outcomes and used linear regression to evaluate non-concurrent cross-sectional associations of mid-life 25(OH) D (visit 2) with late-life neuropsychological outcomes (visit 5). We also used Cox regression models to examine associations of mid-life 25(OH) D and incident dementia.

Results

In mid-life, the mean (SD) age of participants was 57 (6) years, 57% were women, and 24% black. Mean (SD) 25(OH) D was 24.3 (8.6) ng/mL; 33% had deficient (< 20 ng/mL), 44% intermediate (20- < 30 ng/mL), and 23% sufficient (≥30 ng/mL) 25(OH) D concentrations. Association between mid-life 25(OH) D and late-life performance on neuropsychological testing were mostly null. There was no significant association with functional ability or depressive symptoms. Results were similar in a sensitivity analysis using complete-case data (no imputation). However, after a median follow-up of 20 years, low 25(OH) D concentrations were associated with increased risk for incident dementia (p = 0.01 for trend across categories), with HR of 1.26 (95% CI 1.06, 1.49) for participants with deficient 25(OH) D, compared to sufficient concentrations.

Conclusion

In this community cohort, mid-life serum 25(OH) D concentrations were associated with incident dementia but not with performance on neuropsychological testing, functional ability, or depressive symptoms, 20 years later. Whether serum 25(OH) D concentrations are causally related to dementia or confounded by poorer health status remains uncertain.

Trial registration

Registered on clinicaltrials.gov NCT00005131.
Palbociclib in combination with simvastatin induce severe rhabdomyolysis: a case report
Authors: Nersesjan Vardan , Hansen Klaus , Krag Thomas , Duno Morten , Jeppesen Tina D.
Published: October 2019

Background

Palbociclib is a selective well-tolerated antineoplastic drug used in the treatment of advanced HER2-negative, estrogen-receptor positive breast cancer that has shown significant improvement in progression-free survival. We present a patient that developed severe rhabdomyolysis with tetra-affection and loss of gait after initiating the first cycle of Palbociclib concomitantly with Simvastatin 40 mg treatment.

Case presentation

A 71-year-old woman with metastatic breast cancer developed tetraparesis and near fatal rhabdomyolysis after initiation of first cycle Palbociclib. For 10 years prior to this treatment, the patient had been treated with Simvastatin without myalgia or other neuromuscular complaints prior to the first cycle of Palbociclib. The patient was admitted at the neurology department, where Palbociclib and Simvastatin were discontinued. The patient was aggressively hydrated and treated with intravenous immunoglobulin therapy with slowly remission and finally regaining independent gait function. Evaluation showed a negative myositis antibody work-up. Muscle magnetic resonance imaging showed edema in multiple foci, but skeletal muscle biopsy did not show necrosis. Post discharge genetic analysis showed single heterozygosity for nucleotide polymorphism rs4149056.

Conclusion

We present a patient who developed severe rhabdomyolysis induced by a combination of Palbociclib and Simvastatin treatment. Rhabdomyolysis was most likely induced by toxic plasma concentrations of Simvastatin due to Palbociclibs inhibition of the CYP3A4 enzyme in combination with a decreased hepatic uptake of Simvastatin due to single nucleotide polymorphism rs4149056. The study underscores that combining Simvastatin and Palbociclib should be done cautiously and genetic testing of the rs4149056 SNP is warranted. If present, Simvastatin should be discontinued or replaced with a lesser myopathic statin in regard to patients risk of cardiovascular events.
Pregnancy following kidney transplantation - impact on mother and graft function and focus on childrens’ longitudinal development
Authors: Bachmann Friederike , Budde Klemens , Gerland Marie , Wiechers Cornelia , Heyne Nils , Nadalin Silvio , Brucker Sara , Bachmann Cornelia
Published: October 2019

Background

Pregnancy after kidney transplantation has been considered as high risk for maternal and fetal complications. After careful patient selection successful pregnancies are described. Little is known about fetal outcomes and data is particularly scarce on childrens´ early development up to two years when born to kidney/−pancreas transplant recipients.

Here, we analyzed maternal and fetal risk and evaluated graft function during pregnancy in transplanted women. We aimed to identify factors affecting the outcomes of mothers and their grafts during pregnancy and of children up to 2 years after delivery/ birth.

Methods

All consecutive pregnancies in kidney/ kidney-pancreas recipients with live-born children from 2002 to 2016 were evaluated in two transplant centers (Charité Berlin/ University Tuebingen). All data was gathered from medical records. Impact of pregnancy on obstetrical risks, graft function and fetal development was evaluated. Additionally, for the first time development of children, including physical examination and assessment of neurological function were evaluated at 12 and 24 months.

Results

Thirty-two pregnancies in 28 patients with a median duration of 34 gestational weeks (range, 24–38) were analyzed. 13 patients (46.4%) developed deterioration of kidney graft function > 10 ml/min during pregnancy. In majority, caesarean section was performed (75%). Twenty-five (78.1%) children were born prematurely, thereof (16%) < 28 weeks. Almost 70% had low birth weights (LBW) (< 2.500 g); median birth weight was 2.030 g. General health and physical constitution of children were unremarkable with normal development in 94% at 12 and 24 months of corrected age, respectively.

Conclusion

Despite the high rate of preterm birth and LBW, development up to two years was age-appropriate in this cohort. Due to low absolute numbers, increasing efforts in centralized counseling, diagnostics and committed specialist support are required. Decisive treatment of these high-risk patients in specialized units leading to better performance of these patients (mother/ fetus) is deemed superior. In order to confirm this, prospective studies on neonatal and pediatric outcomes with a standard-of-care comparator arm will be conducted.
A hospital-based birth defects surveillance system in Kampala, Uganda
Authors: Mumpe-Mwanja Daniel , Barlow-Mosha Linda , Williamson Dhelia , Valencia Diana , Serunjogi Robert , Kakande Ayoub , Namale-Matovu Joyce , Nankunda Jolly , Birabwa-Male Doreen , Okwero Margaret Achom , Nsungwa-Sabiiti Jesca , Musoke Philippa
Published: October 2019

Background

In 2010, the World Health Assembly passed a resolution calling upon countries to prevent birth defects where possible. Though birth defects surveillance programs are an important source of information to guide implementation and evaluation of preventive interventions, many countries that shoulder the largest burden of birth defects do not have surveillance programs. This paper shares the results of a hospital-based birth defects surveillance program in Uganda which, can be adopted by similar resource-limited countries.

Methods

All informative births, including live births, stillbirths and spontaneous abortions; regardless of gestational age, delivered at four selected hospitals in Kampala from August 2015 to December 2017 were examined for birth defects. Demographic data were obtained by midwives through maternal interviews and review of hospital patient notes and entered in an electronic data collection tool. Identified birth defects were confirmed through bedside examination by a physician and review of photographs and a narrative description by a birth defects expert. Informative births (live, still and spontaneous abortions) with a confirmed birth defect were included in the numerator, while the total informative births (live, still and spontaneous abortions) were included in the denominator to estimate the prevalence of birth defects per 10,000 births.

Results

The overall prevalence of birth defects was 66.2/10,000 births (95% CI 60.5–72.5). The most prevalent birth defects (per 10,000 births) were: Hypospadias, 23.4/10,000 (95% CI 18.9–28.9); Talipes equinovarus, 14.0/10,000 (95% CI 11.5–17.1) and Neural tube defects, 10.3/10,000 (95% CI 8.2–13.0). The least prevalent were: Microcephaly, 1.6/10,000 (95% CI 0.9–2.8); Microtia and Anotia, 1.6/10,000 (95% CI 0.9–2.8) and Imperforate anus, 2.0/10,000 (95% CI 1.2–3.4).

Conclusion

A hospital-based surveillance project with active case ascertainment can generate reliable epidemiologic data about birth defects prevalence and can inform prevention policies and service provision needs in low and middle-income countries.
Global patterns and trends in ovarian cancer incidence: age, period and birth cohort analysis
Authors: Zhang Yanting , Luo Ganfeng , Li Mengjie , Guo Pi , Xiao Yuejiao , Ji Huanlin , Hao Yuantao
Published: October 2019

Background

Ovarian cancer (OC) is the seventh most common malignancy worldwide and the most lethal gynaecological malignancy. We aimed to explore global geographical patterns and temporal trends from 1973 to 2015 for 41 countries in OC incidence and especially to analyse the birth cohort effect to gain further insight into the underlying causal factors of OC and identify countries with increasing risk of OC.

Methods

OC data were drawn from the Cancer Incidence in Five Continents databases and online databases published by governments. The joinpoint regression model was applied to detect changes in OC trends. The age–period–cohort model was applied to explore age and birth cohort effects.

Results

The age-standardized rate of OC incidence ranged from 3.0 to 11.4 per 100,000 women worldwide in 2012. The highest age-standardized rate was observed in Central and Eastern Europe, with 11.4 per 100,000 women in 2012. For the most recent 10-year period, the increasing trends were mainly observed in Central and South America, Asia and Central and Eastern Europe. The largest significant increase was observed in Brazil, with an average annual percentage change of 4.4%. For recent birth cohorts, cohort-specific increases in risk were pronounced in Estonia, Finland, Iceland, Lithuania, the United Kingdom, Germany, the Netherlands, Italy, Malta, Slovenia, Bulgaria, Russia, Australia, New Zealand, Brazil, Costa Rica, Ecuador, India, Japan, the Philippines and Thailand.

Conclusions

Disparities in the incidence and risk of OC persist worldwide. The increased risk of birth cohort in OC incidence was observed for most countries in Asia, Central and Eastern Europe, and Central and South America. The reason for the increasing OC risk for recent birth cohorts in these countries should be investigated with further epidemiology studies.
Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study
Authors: Perkhofer L. , Berger A. W. , Beutel A. K. , Gallmeier E. , Angermeier S. , Fischer von Weikersthal L. , Goetze T. O. , Muche R. , Seufferlein T. , Ettrich T. J.
Published: October 2019

Background

Biliary tract cancer (BTC) has a high mortality. Primary diagnosis is frequently delayed due to mostly unspecific symptoms, resulting in a high number of advanced cases at the time of diagnosis. Advanced BTCs are in principle chemotherapy sensitive as determined by improved disease control, survival and quality of life (QoL). However, median OS does not exceed 11.7 months with the current standard of care gemcitabine plus cisplatin. Thereby, novel drug formulations like nanoliposomal-irinotecan (nal-IRI) in combination with 5- fluorouracil (5-FU)/leucovorin may have the potential to improve therapeutic outcomes in this disease.

Methods

NIFE is an interventional, prospective, randomized, controlled, open label, two-sided phase II study. Within the study, 2 × 46 patients with locally advanced, non-resectable or metastatic BTC are to be enrolled by two stage design of Simon. Data analysis will be done unconnected for both arms. Patients are allocated in two arms: Arm A (experimental intervention) nal-IRI mg/m2, 46 h infusion)/5-FU (2400 mg/m2, 46 h infusion)/leucovorin (400 mg/m2, 0.5 h infusion) d1 on 14 day-cycles; Arm B (standard of care) cisplatin (25 mg/m2, 1 h infusion)/gemcitabine (1000 mg/m2, 0.5 h infusion) d1 and d8 on 21 day-cycles. The randomization (1:1) is stratified for tumor site (intrahepatic vs. extrahepatic biliary tract), disease stage (advanced vs. metastatic), age (≤70 vs. > 70 years), sex (male vs. female) and WHO performance score (ECOG 0 vs. ECOG 1). Primary endpoint of the study is the progression free survival (PFS) rate at 4 months after randomization by an intention-to-treat analysis in each of the groups. Secondary endpoints are the overall PFS rate, the 3-year overall survival rate, the disease control rate after 2 months, safety and patient related outcome with quality of life. The initial assessment of tumor resectability for locally advanced BTCs is planned to be reviewed retrospectively by a central surgical board. Exploratory objectives aim at establishing novel biomarkers and molecular signatures to predict response. The study was initiated January 2018 in Germany.

Discussion

The NIFE trial evaluates the potential of a nanoliposomal-irinotecan/5-FU/leucovorin combination in the first line therapy of advanced BTCs and additionally offers a unique chance for translational research.

Trial registration

Clinicaltrials.gov NCT03044587. Registration Date February 7th 2017.
Consensus in determining the resectability of locally progressed pancreatic ductal adenocarcinoma – results of the Conko-007 multicenter trial
Authors: Wittel U. A. , Lubgan D. , Ghadimi M. , Belyaev O. , Uhl W. , Bechstein W. O. , Grützmann R. , Hohenberger W. M. , Schmid A. , Jacobasch L. , Croner R. S. , Reinacher-Schick A. , Hopt U. T. , Pirkl A. , Oettle H. , Fietkau R. , Golcher H.
Published: October 2019

Background

One critical step in the therapy of patients with localized pancreatic cancer is the determination of local resectability. The decision between primary surgery versus upfront local or systemic cancer therapy seems especially to differ between pancreatic cancer centers. In our cohort study, we analyzed the independent judgement of resectability of five experienced high volume pancreatic surgeons in 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer.

Methods

Pretherapeutic CT or MRI scans of 200 consecutive patients with borderline resectable or locally advanced pancreatic cancer were evaluated by 5 independent pancreatic surgeons. Resectability and the degree of abutment of the tumor to the venous and arterial structures adjacent to the pancreas were reported. Interrater reliability and dispersion indices were compared.

Results

One hundred ninety-four CT scans and 6 MRI scans were evaluated and all parameters were evaluated by all surgeons in 133 (66.5%) cases. Low agreement was observed for tumor infiltration of venous structures (κ = 0.265 and κ = 0.285) while good agreement was achieved for the abutment of the tumor to arterial structures (interrater reliability celiac trunk κ = 0.708 P < 0.001). In patients with vascular tumor contact indicating locally advanced disease, surgeons highly agreed on unresectability, but in patients with vascular tumor abutment consistent with borderline resectable disease, the judgement of resectability was less uniform (dispersion index locally advanced vs. borderline resectable p < 0.05).

Conclusion

Excellent agreement between surgeons exists in determining the presence of arterial abutment and locally advanced pancreatic cancer. The determination of resectability in borderline resectable patients is influenced by additional subjective factors.

Trial registration

EudraCT:2009-014476-21 (2013-02-22) and NCT01827553 (2013-04-09).
A new indocyanine green fluorescence lymphography protocol for identification of the lymphatic drainage pathway for patients with breast cancer-related lymphoedema
Authors: Suami Hiroo , Heydon-White Asha , Mackie Helen , Czerniec Sharon , Koelmeyer Louise , Boyages John
Published: October 2019

Background

Breast cancer related lymphoedema (BCRL) is a common side effect of cancer treatment. Recently indocyanine green (ICG) fluorescent lymphography has become a popular method for imaging the lymphatics, however there are no standard protocols nor imaging criteria. We have developed a prospective protocol to aid in the diagnosis and therapeutic management of BCRL.

Methods

Lymphatic imaging procedures were conducted in three phases. Following initial observation of spontaneous movement of ICG in phase one, manual lymphatic drainage (MLD) massage was applied to facilitate ICG transit via the lymphatics in phase two. All imaging data was collected in phase three. Continuous lymphatic imaging of the upper limb was conducted for approximately an hour and lymphatic drainage pathways were determined. Correlations between the drainage pathway and MD Anderson Cancer Centre (MDACC) ICG lymphoedema stage were investigated.

Results

One hundred and three upper limbs with BCRL were assessed with this new protocol. Despite most of the patients having undergone axillary node dissection, the ipsilateral axilla drainage pathway was the most common (67% of upper limbs). We found drainage to the ipsilateral axilla decreased as MDACC stage increased. Our results suggest that the axillary pathway remained patent for over two-thirds of patients, rather than completely obstructed as conventionally thought to be the case for BCRL.

Conclusions

We developed a new ICG lymphography protocol for diagnosing BCRL focusing on identification of an individual patient’s lymphatic drainage pathway after lymph node surgery. The new ICG lymphography protocol will allow a personalised approach to manual lymphatic drainage massage and potentially surgery.
External quality assessment (EQA) program for the immunohistochemical detection of ER, PR and Ki-67 in breast cancer: results of an interlaboratory reproducibility ring study in China
Authors:   China Anticancer Association Professional Committee of Tumour Pathology, Pu Tianjie , Shui Ruohong , Shi Jie , Liang Zhiyong , Yang Wentao , Bu Hong , Li Qin , Zhang Zhang
Published: October 2019

Background

An External Quality Assessment (EQA) program was developed to investigate the status of estrogen receptor (ER), progesterone receptor (PR), and Ki-67 immunohistochemical (IHC) detection in breast cancer and to evaluate the reproducibility of staining and interpretation in 44 pathology laboratories in China.

Methods

This program was implemented through three specific steps. In study I, three revising centres defined the reference value for 11 sections. In study II, 41 participating centres (PC) stained and interpreted 11 sections by their own daily practice IHC protocols. In study III, all cases received second interpretation opinions.

Results

The stained slides of 44 laboratories were up to the interpretation standard. The overall interpretation concordance rate of this study was over 90%. A perfect agreement was reached among the PCs for the cases with ER+ and PR+ > 50% and Ki-67 > 30%, whereas a moderate agreement was observed for intermediate categories. After second interpretations, the misclassification rates for ER were reduced by 12.20%, for PR were reduced by 17.07%, and for Ki-67 were reduced by 4.88%. Up to 31 PCs observed a benefit from the second opinion strategy.

Conclusions

This project is the first EQA study performed on a national scale for assessment of ER, PR and Ki-67 status by IHC in China. In the whole IHC evaluation process, the intermediate categories were less reproducible than those with high expression rates. Second opinions can significantly improve the diagnostic agreement of pathologists’ interpretations.
Prenatal alcohol history – setting a threshold for diagnosis requires a level of detail and accuracy that does not exist
Authors: Petryk Susan , Siddiqui Muhammad A. , Ekeh Juliet , Pandey Mamata
Published: October 2019

Background

The revised 2015 Canadian Guidelines requires a more specific prenatal alcohol exposure (PAE) threshold for a Fetal Alcohol Spectrum Disorder (FASD) diagnosis. The unintended consequences of adhering to the suggested PAE threshold for an FASD diagnosis and the challenges professionals face in obtaining an accurate PAE history were explored.

Methods

Using a mixed methods study design, the study was carried out in two parts (Quantitative and Qualitative). PAE history and FASD diagnosis was reviewed retrospectively from 146 patient charts referred for an FASD assessment between 2011 and 2016. The challenges experienced when collecting the PAE history were explored through interviews with 23 professionals. Statistical analysis was performed using SPSS (IBM SPSS Statistics 20.0).

Results

Of 146 assessments, only 21.9% met the revised 2015 PAE guidelines while 79.4% met the previous 2005 PAE criteria. Of 146 clients, 54.1% met brain criteria for FASD yet of those only 29.1% met the revised PAE criteria whereas 70.9% did not and therefore could lose their FASD diagnosis under a diligent application of PAE level suggested in the 2015 Guidelines. Thematic analysis of the interview data indicated that obtaining a reliable PAE history was challenging and a combination of methods are employed to get credible information.

Conclusion

Confirming PAE history can be difficult, but ensuring reliable and accurate details on quantity, frequency, and timing of exposure is impossible in a clinical setting. Three out of every four individuals in the present study lost their FASD diagnosis following implementation of 2015 Canadian FASD Guidelines. A threshold might also imply that alcohol consumption below threshold is safe. The 2015 Canadian Guidelines need further refinement regarding the PAE criteria.
Serum folate levels in bipolar disorder: a systematic review and meta-analysis
Authors: Hsieh Yung-Chi , Chou Li-Shiu , Lin Ching-Hua , Wu Hung-Chi , Li Dian-Jeng , Tseng Ping-Tao
Published: October 2019

Background

Bipolar disorder (BD) is a major psychiatric illness, however its physiopathology is unclear. The role of folate in the physiopathology of BD is controversial. We conducted this systematic review and meta-analysis to investigate the effect of folate in BD patients.

Methods

We performed a thorough literature study of the PubMed, Embase, ScienceDirect, ClinicalKey, Cochrane Library, ProQuest, Web of Science, andClinicalTrials.govdatabases until December 21st, 2018. Random effects meta-analysis was conducted.

Results

Six articles involving 481 patients with BD and 760 controls were included. The meta-analysis results suggested that serum folate levels in the patients with BD were significantly lower than those in the controls (Hedges’ g = − 0.211, 95% confidence interval = − 0.391 to − 0.031,p = 0.021).

Conclusion

The current meta-analysis show it might be association between lower serum folate levels and patient with BD. However, we could not distinguish the potentially confounding effects of mood states on the folate levels. Further prospective studies including subjects with different mood states and possible physiopathology are warranted to investigate the association between folate deficiency and the etiology of BD.
Problem gambling in adolescents: what are the psychological, social and financial consequences?
Authors: Livazović Goran , Bojčić Karlo
Published: October 2019

Background

The paper examines the roles of sociodemographic traits, family quality and risk behaviour in adolescent problem gambling, with focus on the psychological, social and financial consequences from the socio-ecological model approach. This model emphasizes the most important risk-protective factors in the development and maintenance of problem gambling on an individual level, a relationship level, as well as a community and societal level.

Methods

The research was done using theCanadian Adolescent Gambling Inventorywith a sample of 366 participants, 239 females (65.3%) using descriptive statistics and t-test, ANOVA, correlation and hierarchical regression analysis.

Results

Males reported significantly higher gambling consequences on all scales (p < .001) and significantly more risk behaviour (p < .05). Age was significant for psychological consequences (p < .01), problem gambling (p < .01) and risk behaviour (p < .001) with older participants scoring higher. Students with lower school success reported significantly higher psychological consequences of gambling (p < .01), higher risk behaviour activity (p < .001) and lower family life satisfaction (p < .001). The psychological, financial and social consequences were positively correlated with problem gambling (p < .001). Age (p < .05), gender (p < .001), school success (p < .01) and the father’s education level (p. < 05) were significant predictors of problem gambling, with older male adolescents who struggle academically and have lower educated fathers being at greater risk.

Conclusions

Results indicate an important relation between adolescent gambling behaviour and very serious psychological, social and financial consequences. There is a constellation of risk factors that likely place certain individuals at high risk for problem gambling.
Persistent physical symptoms reduction intervention: a system change and evaluation in secondary care (PRINCE secondary) – a CBT-based transdiagnostic approach: study protocol for a randomised controlled trial
Authors: Chalder Trudie , Patel Meenal , James Kirsty , Hotopf Matthew , Frank Philipp , Watts Katie , McCrone Paul , David Anthony , Ashworth Mark , Husain Mujtaba , Garrood Toby , Moss-Morris Rona , Landau Sabine
Published: October 2019

Background

Persistent physical symptoms (PPS), also known as medically unexplained symptoms (MUS), affect approximately 50% of patients in secondary care and are often associated with disability, psychological distress and increased health care costs. Cognitive behavioural therapy (CBT) has demonstrated both short- and long-term efficacy with small to medium effect sizes for PPS, with larger treatment effects for specific PPS syndromes, including non-cardiac chest pain, irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS). Research indicates that PPS conditions share similar cognitive and behavioural responses to symptoms, such as avoidance and unhelpful beliefs. This suggests that a transdiagnostic approach may be beneficial for patients with PPS.

Methods

A randomised controlled trial (RCT) will be conducted to evaluate the efficacy and cost-effectiveness of a transdiagnostic CBT-based intervention for PPS. 322 participants with PPS will be recruited from secondary care clinics. Participants stratified by clinic and disability level will be randomised to CBT plus standard medical care (SMC) versus SMC alone. The intervention consists of 8 CBT sessions delivered by a qualified therapist over a period of 20 weeks. Outcomes will be assessed at 9, 20, 40- and 52-weeks post randomisation. Efficacy will be assessed by examining the difference between arms in the primary outcome Work and Social Adjustment Scale (WSAS) at 52 weeks after randomisation. Secondary outcomes will include mood, symptom severity and clinical global impression at 9, 20, 40 and 52 weeks. Cost-effectiveness will be evaluated by combining measures of health service use, informal care, loss of working hours and financial benefits at 52 weeks.

Discussion

This trial will provide a powered evaluation of the efficacy and cost-effectiveness of a transdiagnostic CBT approach versus SMC for patients with PPS. It will also provide valuable information about potential healthcare pathways for patients with PPS within the National Health Service (NHS).

Trial registration

ClinicalTrials.gov NCT02426788. Registered 27 April 2015. Overall trial status: Ongoing; Recruitment status: No longer recruiting.