[Surgical treatment of pseudomyxoma peritonei-Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. / Chirurgische Therapie des Pseudomyxoma-peritonei-Syndroms ­ zytoreduktive Chirurgie und hypertherme intraperitoneale Chemotherapie.

BACKGROUND: Pseudomyxoma peritonei syndrome (PMP) is an orphan disease. Surgery is the fundament of treatment. METHOD: Short review summarizing the state of the art treatment. RESULTS: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) form the foundations of treatment for PMP. The peritoneal cancer index should be preoperatively determined based on imaging and/or laparoscopy, intraoperatively validated and both should be documented. An extraperitoneal surgical preparation technique leads to effective en bloc resection of the peritoneum and the affected abdominal area. The HIPEC technique should be performed with mitomycin C for 60-90 min. Complete CRS (CC = 0, CC = 1) and the histological subtype are relevant for the prognosis. Structured educational programs and mentoring can optimize the learning curve. The aftercare should be performed at the surgical center. After follow-up imaging at 3 months after CRS, in the first 2 years a control should be carried out every 6 months. Thereafter, the intervals can be extended to 1 year. CONCLUSION: Standardized surgical treatment and HIPEC, optimized specific surgical training and structured follow-up at the center lead to an excellent long-term prognosis for patients with PMP.

Benefit-risk analysis of maintaining essential Reproductive, Maternal, Newborn, and Child Health (RMNCH) services against risk of COVID-19 infection.

With the COVID-19 pandemic spreading across the world, its disruptive effect on the provision and utilization of non- COVID related health services have become well-documented. As countries developed mitigation strategies to help continue the delivery of essential health services through the pandemic, they needed to carefully weigh the benefits and risks of pursuing these strategies. In an attempt to assist countries in their mitigation efforts, a Benefit-Risk model was designed to provide guidance on how to compare the health benefits of sustained essential reproductive, maternal, newborn and child (RMNCH) services against the risk of SARS-CoV-2 infections incurred by the countries' populations when accessing these services. This article describes how two existing models were combined to create this model, the field-testing process carried out from November 2020 through March 2021 in six countries and the findings. The overall Benefit-Risk Ratio in the 6 countries analyzed was found to be between 13.7 and 79.2, which means that for every 13.7 to 79.2 lives gained due to increased RMNCH service coverage, there was one loss of a life related to COVID-19. In all cases and for all services, the benefit of maintaining essential health services far exceeded the risks associated with additional COVID-19 infections and deaths. This modelling process illustrated how essential health services can continue to operate during a pandemic and how mitigation measures can reduce COVID-19 infections and restore or increase coverage of essential health services. Overall, this Benefit-Risk analysis underscored the importance and value of maintaining coverage of essential health services even during public health emergencies, including the recent COVID-19 pandemic.

Protein-loss of SWI/SNF-complex core subunits influences prognosis dependent on histological subtypes of intra- and extrahepatic cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive malignancy with a 5-year-survival rate of <10%, mainly due to diagnosis in advanced stages and limited therapeutic options in case of progressive disease. Recently, evidence has indicated that alterations in the SWI/SNF-complex (SWI/SNF) may have an important role in the tumorigenesis of CCA. SWI/SNF-related chromatin remodeling has been reported to be crucial for differentiation and tumor suppression, and loss-of-function mutations of SWI/SNF are present in 20% of human malignancies; however, at present, little is known about its relevance in CCA. In the present study, a cohort of 52 patients with the diagnosis of primary CCA was retrospectively collected. All patients underwent surgery with curative intent. Tissue microarray analysis was performed on each tumor for immunohistochemical loss-of-protein analysis of the SWI/SNF core subunits ARID1A, INI-1, BRG1, PBRM-1 and BRM, corresponding to the following CCA subtypes: Extrahepatic CCA (ECCA), small duct or large duct intrahepatic CCA (ICCA). Kaplan-Meier analysis was used to determine survival distribution and survival differences were evaluated by log-rank test. In total, 14 of 52 patients (~35%) exhibited protein-loss of any tested SWI/SNF core subunit. Notably, 17% of patients exhibited a loss of ARID1a; this was the protein loss with the highest frequency. Patients with small and large duct ICCA with protein-loss of any tested SWI/SNF subunit exhibited significantly worse survival compared with the wild-type cohort with proficient protein expression (P=0.013 and P=0.002), whereas no significant survival difference was detected for patients with ECCA. SWI/SNF and its core subunits may be considered promising predictive and therapeutic targets, and require further investigation in patients with CCA.

Hand-Assisted Retroperitoneoscopic Donor Nephrectomy Compared to Anterior Approach Open Donor Nephrectomy: Improved Long-Term Physical Component Score in Health-Related Quality of Life in Living Kidney Donors.

BACKGROUND: Health-related quality of life (HRQL), fatigue, anxiety, and depression are crucial for the living kidney donor (LKD). Follow-up data for HRQL of LKDs comparing surgical techniques, especially regarding hand-assisted retroperitoneoscopic donor nephrectomy (HARP), are sparse. The aim of this study was to evaluate the influence of abdominal wall trauma minimized by HARP in comparison to open anterior approach donor nephrectomy (AA) on HRQL and additional psychosocial aspects of LKDs during the long-term follow-up. MATERIAL AND METHODS: This is a cross-sectional study comparing psychosocial aspects of LKD between HARP and AA. RESULTS: This study included 100 LKDs (68 HARP, 28 AA, and 4 were excluded secondary to incomplete data). The time to follow-up was 22.6 ± 11.7 (HARP) vs 58.7 ± 13.9 (AA) months (P < .005). Complications ≥3a° due to Clavien-Dindo classification was 0% in both groups. There were higher scores in all physical aspects for HARP donors vs AA donors at that time (physical function: 89.8 ± 14.6 vs 80.0 ± 19.9, P = .008, and the physical component score: 53.9 ± 7.6 vs 48.6 ± 8.5, P = .006). One year later (follow-up time + 12 months), HRQL for HARP donors was still higher. Mental items showed no significant differences. HARP donors showed better physical scores compared to the age-matched nondonor population (AA donors had lower scores). Neither the Multidimensional Fatigue Inventory-20 (MFI-20) or the Hospital Anxiety and Depression Scale (HADS) showed any differences between the 2 groups. Fatigue scores were higher for HARP and for AA compared to the age-matched population. CONCLUSIONS: LKDs undergoing HARP showed better physical performance as part of HRQL in the long-term follow-up.

The proteomic landscape of small urinary extracellular vesicles during kidney transplantation.

Kidney transplantation is the preferred renal replacement therapy available. Yet, long-term transplant survival is unsatisfactory, partially due to insufficient possibilities of longitudinal monitoring and understanding of the biological processes after transplantation. Small urinary extracellular vesicles (suEVs) - as a non-invasive source of information - were collected from 22 living donors and recipients. Unbiased proteomic analysis revealed temporal patterns of suEV protein signature and cellular processes involved in both early response and longer-term graft adaptation. Complement activation was among the most dynamically regulated components. This unique atlas of the suEV proteome is provided through an online repository allowing dynamic interrogation by the user. Additionally, a correlative analysis identified putative prognostic markers of future allograft function. One of these markers - phosphoenol pyruvate carboxykinase (PCK2) - could be confirmed using targeted MS in an independent validation cohort of 22 additional patients. This study sheds light on the impact of kidney transplantation on urinary extracellular vesicle content and allows the first deduction of early molecular processes in transplant biology. Beyond that our data highlight the potential of suEVs as a source of biomarkers in this setting.

Circulating tumor DNA as an emerging liquid biopsy biomarker for early diagnosis and therapeutic monitoring in hepatocellular carcinoma.

As one of the most common malignant tumors worldwide, hepatocellular carcinoma (HCC) is known for its poor prognosis due to diagnosis only in advanced stages. Nearly 50% of the patients with the first diagnosis of HCC die within a year. Currently, the advancements in the integration of omics information have begun to transform the clinical management of cancer patients. Molecular profiling for HCC patients is in general obtained from resected tumor materials or biopsies. However, the resected tumor tissue is limited and can only be obtained through surgery, so that dynamic monitoring of patients cannot be performed. Compared to invasive procedures, circulating tumor DNA (ctDNA) has been proposed as an alternative source to perform molecular profiling of tumor DNA in cancer patients. The detection of abnormal forms of circulating cell-free DNA (cfDNA) that originate from cancer cells (ctDNA) provides a novel tool for cancer detection and disease monitoring. This may also be an opportunity to optimize the early diagnosis of HCC. In this review, we summarized the updated methods, materials, storage of sampling, detection techniques for ctDNA and the comparison of the applications among different biomarkers in HCC patients. In particular, we analyzed ctDNA studies dealing with copy number variations, gene integrity, mutations (RAS, TERT, CTNNB1, TP53 and so on), DNA methylation alterations (DBX2, THY1, TGR5 and so on) for the potential utility of ctDNA in the diagnosis and management of HCC. The biological functions and correlated signaling pathways of ctDNA associated genes (including MAPK/RAS pathway, p53 signaling pathway and Wnt-ß catenin pathway) are also discussed and highlighted. Thus, exploration of ctDNA/cfDNA as potential biomarkers may provide a great opportunity in future liquid biopsy applications for HCC.

Global health electives: Ethical engagement in building global health capacity.

Purpose: Little is known about the impact medical trainees undertaking global health electives (GHEs) have on host institutions and their communities in low-and middle-income countries. The goal of this study was to explore the relationship dynamics associated with GHEs as perceived by host stakeholders at three sites in sub-Saharan Africa.Method: This case-based interpretive phenomenological study examined stakeholder perspectives in Mwanza, Tanzania, and Mbarara and Rugazi, Uganda, where the University of Calgary, Alberta, Canada has long-standing institutional collaborations. Between September and November 2017, 33 host stakeholders participated in semi-structured interviews and 28 host stakeholders participated in focus group discussions. Participant experiences were analyzed using interpretive phenomenological techniques.Results: The findings revealed that, although GHEs are well-established and a common experience for host stakeholders, their perceptions about who visiting medical trainees (VMTs) are remains indistinct. Participants acknowledged that there are a variety of benefits to GHEs, but overall VMTs appear to benefit the most from this unique learning opportunity. Host stakeholders described significant challenges and burdens of GHEs and recommended ways in which GHEs could be improved.Conclusions: GHEs need to be designed to better embrace ethical engagement and reciprocity with host stakeholders to ensure equity in benefits and responsibilities.

A cross-sectional study to identify the distribution and characteristics of licensed and unlicensed private drug shops in rural Eastern Uganda to inform an iCCM intervention to improve health outcomes for children under five years.

INTRODUCTION: Malaria, pneumonia and diarrhea are leading causes of death in young children in Uganda. Between 50-60% of sick children receive treatment from the private sector, especially drug shops. There is an urgent need to improve quality of care and regulation of private drug shops in Uganda. This study was conducted to determine the distribution, the licensing status and characteristics of drug shops in four sub-districts of Kamuli district. METHODS: This study was part of a pre-post cross sectional study that examined the implementation of an integrated Community Case Management (iCCM) intervention for common childhood illness in rural private drug shops in Kamuli District in Eastern Uganda. This mapping exercise used a snowball sampling technique to identify licensed and unlicensed drug shops and collect information about their characteristics. Data were collected using a questionnaire. GPS data were collected for all drug shops. ANALYSIS: Quantitative data were analyzed using SPSS for descriptive statistics. Open ended questions were entered into NVivo 10 and analyzed using thematic analysis strategies. RESULTS: In total, 215 drug shops in 284 villages were located. Of these, 123 (57%) were open and consented to an interview. Only 12 (10%) drug shops were licensed, 93 (76%) were unlicensed, and the licensing status of 18 (15%) was unknown. Most respondents were the owner of the drug shop (88%); most drug sellers reported their qualification as nursing assistants (70%). Drug sellers reported licensing fees and costs of contracting an "in-charge" as barriers to licensing. Nearly all drug shops sold drugs for malaria (91%) and antibiotics (79%).

First reported case of a collision tumor composed of pancreatic adenocarcinoma and retroperitoneal liposarcoma: a case report.

BACKGROUND: Collision tumors are rare cases with two different tumor entities growing synchronously. While adenocarcinoma of the pancreas is the most common pancreatic tumor with an incidence of 10 per 100.000, retroperitoneal liposarcoma remains very rare. This is the first report of a collision tumor between these two tumor entities. CASE PRESENTATION: Demographic details: The tumor was diagnosed in a 64 male Caucasian patient. Besides atrial fibrillation, arterial hypertension and a hypothyroidism there is no relevant medical history especially no history of cancer. Clinical details: During a routine check-up an unclassified tumor of the pancreatic tail was diagnosed. The lab showed no pathologies. Tumor markers were negative for carbohydrate antigen 19-9 and 72-4 (CA 19-9, CA 72-4) and carcinoembryonic antigen (CEA). Alpha-fetoprotein (AFP) and neuron specific enolase (NSE) were both elevated (AFP 97kU/l, (< 5,8kU/l) and NSE 30,0 µg/l (16,4 µg/l)). A computed tomography-guided core needle biopsy was performed which revealed a low-grade liposarcoma (G1). A CT scan showed no metastases. A surgical resection was recommended by the interdisciplinary tumor board. INTERVENTIONS: A systematic left sided retroperitoneal compartment resection including en-bloc-left sided pancreatectomy, splenectomy, nephrectomy, hemicolectomy, adrenalectomy, partial gastrectomy and partial resection of the diaphragm was performed. Pathology revealed a collision tumor consisting of pancreatic adenocarcinoma that was classified pT3, pN2 (11/33 ece+) L1 V0 Pn0, R0; G2 [UICC Stage III] and a liposarcoma pT2, pN0 (0/33) L0 V0 Pn0, G1 [UICC Stage Ib]. The postoperative tumor board recommended an adjuvant chemotherapy with gemcitabine and capecitabine for the locally advanced pancreatic adenocarcinoma. OUTCOME: At the latest follow-up (1 year after surgery) the patient was in good clinical condition and without evidence of tumor recurrence. CONCLUSION: Collision tumors are rare and difficult to diagnose. This is the first description of a collision tumor composed of pancreatic adenocarcinoma and retroperitoneal liposarcoma. The reported case demonstrates that inconsistent diagnostic results (e.g. imaging and pathology) should raise suspicion concerning the diagnosis. Awareness of these rare cases might protect us from underdiagnosing patients and therefore leading to better patient care. There is evolving evidence that will lead to more personalized treatment options for somatic BRCA mutated pancreatic cancer.

Exclusive Phlebosclerosis of Submucosal Veins Leading to Ischemic Necrosis and Perforation of the Large Bowel: First European Case.

Phlebosclerotic colitis (PC) is a rare, potentially life-threatening disease of unclear pathogenesis almost exclusively reported in Asian patients of both genders. A fibrous degeneration of venous walls leads to threadlike calcifications along mesenteric vessels and colonic wall thickening, detectable by CT. This causes disturbed blood drainage and hemorrhagic infarction of the right-sided colonic wall. This is a report of PC in a Caucasian woman in Europe without Asian background and no history of herbal medications, a suspected cause in Asian patients. CT revealed no calcification of the mesenteric vein or its tributaries. Instead, submucosal veins of the left-sided colonic wall were calcified, leading to subsequent transmural necrosis. Clinically, the patient developed a paralytic ileus and sigmoidal perforation during a 2-week hospitalization due to a bleeding cerebral vascular aneurysm. This case of a European woman with PC is unique in its course as well as its radiologic, clinical, and pathologic presentation.

Where there is no doctor: can volunteer community health workers in rural Uganda provide integrated community case management?

INTRODUCTION: Integrated community case management (iCCM) involves assessment and treatment of common childhood illnesses by community health workers (CHWs). Evaluation of a new Ugandan iCCM program is needed. OBJECTIVES: The objectives of this study were to assess if iCCM by lay volunteer CHWs is feasible and if iCCM would increase proportions of children treated for fever, pneumonia, and diarrhoea in rural Uganda. METHODS: This pre/post study used a quasi-experimental design and non-intervention comparison community. CHWs were selected, trained, and equipped to assess and treat children under five years with signs of the three illnesses. Evaluation included CHW-patient encounter record review plus analysis of pre/post household surveys. RESULTS: 196 iCCM-trained CHWs reported 6,276 sick child assessments (45% fever, 46% pneumonia, 9% diarrhoea). 93% of cases were managed according to algorithm recommendations. Absolute proportions of children receiving treatment significantly increased post-intervention: antimalarial for fever (+24% intervention versus +4% control) and oral rehydration salts/zinc for diarrhoea (+14% intervention versus +1% control). CONCLUSION: In our limited-resource, rural Ugandan setting, iCCM involving lay CHWs was feasible and significantly increased the proportion of young children treated for malaria and diarrhoea.

Optimizing a living kidney donation program: transition to hand-assisted retroperitoneoscopic living donor nephrectomy and introduction of a passive polarizing three-dimensional display system.

BACKGROUND: Optimizing a living kidney donation program is important to guarantee a high grade of acceptance among potential donors. Hand-assisted retroperitoneoscopic donor nephrectomy (HARP) is an alternative to the open anterior approach (AA) technique. Problems associated to the learning curve could hinder a transition. 3D display technique seems to ease minimally invasive surgery. Aim of this study was to evaluate the learning curve during the transition from AA to HARP and the influence of the 3D display system on the established technique. METHODS: Observational study (n = 207) during transition to HARP and introduction of 3D display technique. RESULTS: Operation time (OT), warm ischemia time (WIT) and blood loss (BL) of HARP decreased during transition. Pairwise group comparison for OT showed a significant learning effect for the first 30 out of 50 HARPs without influence on graft function. Between AA and HARP no significant difference in OT (133 ± 24 vs. 127 ± 19 min, p = 0.25) but for WIT (23 ± 28 vs. 126 ± 40 s, p < 0.005) and BL (328 ± 207 vs. 54 ± 35 ml, p < 0.005) was seen. There was neither a significant difference in donors' nor recipients' eGFR. OT (98 ± 16 vs. 106 ± 19 min, p = 0.036) and WIT (97 ± 37 vs. 120 ± 57 s, p = 0.023) were significantly shorter for the 3D technique compared to 2D. CONCLUSION: A transition to HARP is possible without additional risk for the donor or loss of quality for the recipient. The learning curve for HARP is steep and short. The introduction of 3D display technique after transition facilitates the surgical preparation and could further help to optimize HARP.

A demonstration of mobile phone deployment to support the treatment of acutely ill children under five in Bushenyi district, Uganda.

BACKGROUND: Benefits of mobile phone deployment for children <5 in low-resource settings remain unproven. The target population of the current demonstration study in Bushenyi District, Uganda, presented with acute fever, pneumonia, or diarrhoea and were treated by community health workers (CHWs) providing integrated community case management (iCCM). METHODS: An observational study was conducted in five parishes (47 villages) served by CHWs well versed in iCCM with supplemental training in mobile phone use. Impact was assessed by quantitative measures and qualitative evaluation through household surveys, focus group discussions, and key informant interviews. RESULTS: CHWs in targeted sites improved child healthcare through mobile phone use coupled with iCCM. Of acutely ill children, 92.6% were correctly managed. Significant improvements in clinical outcomes compared to those obtained by CHWs with enhanced iCCM training alone were unproven in this limited demonstration. Nonetheless, qualitative evaluation showed gains in treatment planning, supply management, and logistical efficiency. Provider confidence and communications were enhanced as was ease and accuracy of record keeping. CONCLUSION: Mobile phones appear synergistic with iCCM to bolster basic supportive care for acutely ill children provided by CHWs. The full impact of expanded mobile phone deployment warrants further evaluation prior to scaling up in low-resource settings.

Protocol to describe the analysis of text-based communication in medical records for patients discharged from intensive care to hospital ward.

INTRODUCTION: Effective communication during hospital transitions of patient care is fundamental to ensuring patient safety and continuity of quality care. This study will describe text-based communication included in patient medical records before, during and after patient transfer from the intensive care unit (ICU) to a hospital ward (n=10 days) by documenting (1) the structure and focus of physician progress notes within and between medical specialties, (2) the organisation of subjective and objective information, including the location and accessibility of patient data and whether/how this changes during the hospital stay and (3) missing, illegible and erroneous information. METHODS: This study is part of a larger mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. Medical records will be collected and photocopied for each consenting patient for a period of up to 10 consecutive days, including the final 2 days in the ICU, the day of transfer and the first 7 days on the ward (n=10 days). Textual analysis of medical record data will be completed by 2 independent reviewers to describe communication between stakeholders involved in ICU transfer. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained at all study sites, including the coordinating study centre (which covers 4 Calgary-based sites; UofC REB 13-0021) and 6 additional study sites (UofA Pro00050646; UBC PHC Hi4-01667; Sunnybrook 336-2014; QCH 20140345-01H; Sherbrooke 14-172; Laval 2015-2171). Findings from this study will inform the development of an evidence-based tool that will be used to systematically analyse the series of notes in a patient's medical record.

A protocol for engaging unlicensed private drug shops in Rural Eastern Uganda for Integrated Community Case Management (ICCM) of malaria, pneumonia and diarrhoea in children under 5†years of age.

INTRODUCTION: Malaria, pneumonia and diarrhoea are leading causes of death in young children in Uganda. In 2010, Integrated Community Case Management (ICCM) was adopted in Uganda for community level diagnosis and treatment of these diseases through community health workers. However, 50-60% of sick children will receive treatment from the private sector, especially drug shops. Only about half of drug shops are licensed and the quality of care is poor. There is an urgent need to improve quality of care and regulation of drug shops in Uganda. METHODS: This is a pre-post cross-sectional study with before and after measurement in an intervention area in Kamujli district. A snowball mapping exercise, exit interviews, focus group discussions and interviews will be used. 25 randomly selected drug shops will be selected for an intervention that will assist drug shops to become licensed, and provide five days of ICCM training, subsidised prepackaged medicines (artemisinin-based combination therapies for malaria, amoxicillin for pneumonia, Oral Rehydration Salts/zinc for diarrhoea) and free diagnostic tools (rapid diagnostic tests, respiratory timers, thermometers, algorithms). We anticipate a sample size of 1200 (600 at baseline and 600 at the end of the study). ANALYSIS: Quantitative data will be analysed using SPSS for proportions and CIs. Bivariate and multiple logistic regression analysis with adjustment for clustering of data will be performed to adjust for confounding and determine intervention effect. Qualitative data will be entered into NVivo 10 and analysed using content analysis. ETHICS AND DISSEMINATION: Research ethics approval is received from the University of Calgary (REB 14-0269), and Makerere University (IRB00011353). Findings from this study will be disseminated through journal articles and conference presentations, and will illustrate the feasibility of introducing ICCM for drug shops.

Prospective cohort study protocol to describe the transfer of patients from intensive care units to hospital wards.

INTRODUCTION: The transfer of patient care between the intensive care unit (ICU) and the hospital ward is associated with increased risk of medical error and adverse events. This study will describe patient transfer from ICU to hospital ward by documenting (1) patient, family and provider experiences related to ICU transfer, (2) communication between stakeholders involved in ICU transfer, (3) adverse events that follow ICU transfer and (4) opportunities to improve ICU to hospital ward transfer. METHODS: This is a mixed methods prospective observational study of ICU to hospital ward transfer practices in 10 ICUs across Canada. We will recruit 50 patients at each site (n=500) who are transferred from ICU to hospital ward, and distribute surveys to enrolled patients, family members, and healthcare providers (ICU and ward physicians and nurses) after patient transfer. A random sample of 6 consenting study participants (patients, family members, healthcare providers) from each study site (n=60) will be offered an opportunity to participate in interviews to further describe stakeholders' experience with ICU to hospital ward transfer. We will abstract information from patient health records to identify clinical data and use of transfer tools, and identify adverse events that are related to the transfer. ETHICS AND DISSEMINATION: Research ethics board approval has been obtained at the coordinating study centre (UofC REB13-0021) and 5 study sites (UofA Pro00050646; UBC-PHC H14-01667; Sunnybrook 336-2014; QCH 14-07; Sherbrooke 14-172). Dissemination of the findings will provide a comprehensive description of transfer from ICU to hospital ward in Canada including the uptake of validated or local transfer tools, a conceptual framework of the experiences and needs of stakeholders in the ICU transfer process, a summary of adverse events experienced by patients after transfer from ICU to hospital ward, and opportunities to guide quality improvement efforts.

Drugs for some but not all: inequity within community health worker teams during introduction of integrated community case management.

BACKGROUND: The Ugandan health system now supports integrated community case management (iCCM) by community health workers (CHWs) to treat young children ill with fever, presumed pneumonia, and diarrhea. During an iCCM pilot intervention study in southwest Uganda, two CHWs were selected from existing village teams of two to seven CHWs, to be trained in iCCM. Therefore, some villages had both 'basic CHWs' who were trained in standard health promotion and 'iCCM CHWs' who were trained in the iCCM intervention. A qualitative study was conducted to investigate how providing training, materials, and support for iCCM to some CHWs and not others in a CHW team impacts team functioning and CHW motivation. METHODS: In 2012, iCCM was implemented in Kyabugimbi sub-county of Bushenyi District in Uganda. Following seven months of iCCM intervention, focus group discussions and key informant interviews were conducted alongside other end line tools as part of a post-iCCM intervention study. Study participants were community leaders, caregivers of young children, and the CHWs themselves ('basic' and 'iCCM'). Qualitative content analysis was used to identify prominent themes from the transcribed data. RESULTS: The five main themes observed were: motivation and self-esteem; selection, training, and tools; community perceptions and rumours; social status and equity; and cooperation and team dynamics. 'Basic CHWs' reported feeling hurt and overshadowed by 'iCCM CHWs' and reported reduced self-esteem and motivation. iCCM training and tools were perceived to be a significant advantage, which fueled feelings of segregation. CHW cooperation and team dynamics varied from area to area, although there was an overall discord amongst CHWs regarding inequity in iCCM participation. Despite this discord, reasonable personal and working relationships within teams were retained. CONCLUSIONS: Training and supporting only some CHWs within village teams unexpectedly and negatively impacted CHW motivation for 'basic CHWs', but not necessarily team functioning. A potential consequence might be reduced CHW productivity and increased attrition. CHW programmers should consider minimizing segregation when introducing new program opportunities through providing equal opportunities to participate and receive incentives, while seeking means to improve communication, CHW solidarity, and motivation.

Stakeholders' perceptions of integrated community case management by community health workers: a post-intervention qualitative study.

BACKGROUND: Integrated community case management (iCCM) involves delivery of simple medicines to children with pneumonia, diarrhea and/or malaria by community health workers (CHWs). Between 2010 and 2012, an iCCM intervention trial was implemented by Healthy Child Uganda. This study used qualitative tools to assess whether project stakeholders perceived that iCCM improved access to care for children under five years of age. METHODS: The intervention involved training and equipping 196 CHWs in 98 study villages in one sub-county in Uganda in iCCM. During the eight-month intervention, CHWs assessed sick children, provided antimalarials (coartem) for fever, antibiotics (amoxicillin) for cough and fast breathing, oral rehydration salts/zinc for diarrhea, and referred very sick children to health facilities. In order to examine community perceptions and acceptability of iCCM, post-intervention focus groups and key respondent interviews involving caregivers, health workers, CHWs and local leaders were carried out by experienced facilitators using semi-structured interview guides. Data were analyzed using thematic analysis techniques. RESULTS: Respondents reported increased access to health care for children as a result of iCCM. Access was reportedly closer to home, available more hours in a day, and the availability of CHWs was perceived as more reliable. CHW care was reported to be trustworthy and caring. Families reported saving money especially due to reduced transportation costs, and less time away from home. Respondents also perceived better health outcomes. Linkages between health facilities and communities were reportedly improved by the iCCM intervention due to the presence of trained CHWs in the community. CONCLUSIONS: iCCM delivered by CHWs may improve access to health care and is acceptable to families. Policymakers should continue to seek opportunities to implement and support iCCM, particularly in remote communities where there are health worker shortages.

Heat shock protein 27 as a prognostic and predictive biomarker in pancreatic ductal adenocarcinoma.

A role of heat shock protein 27 (HSP27) as a potential biomarker has been reported in various tumour entities, but comprehensive studies in pancreatic cancer are lacking. Applying tissue microarray (TMA) analysis, we correlated HSP27 protein expression status with clinicopathologic parameters in pancreatic ductal adenocarcinoma specimens from 86 patients. Complementary, we established HSP27 overexpression and RNA-interference models to assess the impact of HSP27 on chemo- and radiosensitivity directly in pancreatic cancer cells. In the TMA study, HSP27 expression was found in 49% of tumour samples. Applying univariate analyses, a significant correlation was found between HSP27 expression and survival. In the multivariate Cox-regression model, HSP27 expression emerged as an independent prognostic factor. HSP27 expression also correlated inversely with nuclear p53 accumulation, indicating either protein interactions between HSP27 and p53 or TP53 mutation-dependent HSP27-regulation in pancreatic cancer. In the sensitivity studies, HSP27 overexpression rendered HSP27 low-expressing PL5 pancreatic cancer cells more susceptible towards treatment with gemcitabine. Vice versa, HSP27 protein depletion in HSP27 high-expressing AsPC-1 cells caused increased gemcitabine resistance. Importantly, HSP27 expression was inducible in pancreatic cancer cell lines as well as primary cells. Taken together, our study suggests a role for HSP27 as a prognostic and predictive marker in pancreatic cancer. Assessment of HSP27 expression could thus facilitate the identification of specific patient subpopulations that might benefit from individualized treatment options. Additional studies need to clarify whether modulation of HSP27 expression could represent an attractive concept to support the incorporation of hyperthermia in clinical treatment protocols for pancreatic cancer.