Anti-VEGF treatment of patients with diabetic macular edema : Studies of visual acuity, macular edema and patient-reported outcomes

The aim of this thesis was to describe and evaluate visual acuity, macular edema and patientreported outcomes (PRO) following anti-VEGF treatment of diabetic macular edema (DME) patients in a real-world setting. Using a longitudinal study design, a cohort of DME patients was followed from baseline to 1 year after treatment start. Data were collected from two eye clinics at two county hospitals. Social background characteristics, medical data and PRO were measured before treatment initiation, at four month and after 1 year. A total of 57 patients completed the study. Mean age was 69 years and the sample was equally distributed regarding sex. At baseline, the patients described their general health as low. One year after treatment initiation, 30 patients had improved visual acuity and 27 patients had no improvement in visual acuity. The patients whose visual acuity improved reported an improvement in several subscales in patient-reported outcome measures (PROM), which was in contrast to the group that experienced a decline in visual acuity, where there was no improvement in PROM. Outcomes from the study can be useful for developing and providing relevant information and support to patients undergoing this treatment.

Exercise Prescription for Patients with Non-specific Chronic Low Back Pain: a Qualitative Study of Patients' Experiences in Decision Making

Background The culture of current clinical practice calls for collaboration between therapists and patients, sharing power and responsibility. This paper reports on the findings of a qualitative study of exercise prescription for patients with NSCLBP, taking into account issues such as decision making and how this accords with patient preferences and experiences. Objective To understand the treatment decision making experiences, information and decision support needs of patients with NSCLBP who have been offered exercise as part of their management plan. Design A qualitative study using a philosophical hermeneutic approach. Methods Semi-structured interviews with eight patients (including use of brief patient vignettes) was undertaken to explore their personal experiences of receiving exercise as part of the management of their NSCLBP, and their involvement in decisions regarding their care. Findings The findings provide a detailed insight into patients’ perceptions and experiences of receiving exercise-based management strategies. Four themes were formed from the texts: (1) patients’ expectations and patients’ needs are not synonymous, (2) information is necessary but often not sufficient, (3) not all decisions need to be shared, and (4) wanting to be treated as an individual. Conclusions Shared decision making did not appear to happen in physiotherapy clinical practice, but equally may not be what every patient wants. The overall feeling of the patients was that the therapist was dominant in structuring the interactions, leaving the patients feeling disempowered to question and contribute to the decision making.

Exploring the potential role of allostatic load biomarkers in risk assessment of patients presenting with depressive symptoms

Background: Depression is a major health problem worldwide and the majority of patients presenting with depressive symptoms are managed in primary care. Current approaches for assessing depressive symptoms in primary care are not accurate in predicting future clinical outcomes, which may potentially lead to over or under treatment. The Allostatic Load (AL) theory suggests that by measuring multi-system biomarker levels as a proxy of measuring multi-system physiological dysregulation, it is possible to identify individuals at risk of having adverse health outcomes at a prodromal stage. Allostatic Index (AI) score, calculated by applying statistical formulations to different multi-system biomarkers, have been associated with depressive symptoms. Aims and Objectives: To test the hypothesis, that a combination of allostatic load (AL) biomarkers will form a predictive algorithm in defining clinically meaningful outcomes in a population of patients presenting with depressive symptoms. The key objectives were: 1. To explore the relationship between various allostatic load biomarkers and prevalence of depressive symptoms in patients, especially in patients diagnosed with three common cardiometabolic diseases (Coronary Heart Disease (CHD), Diabetes and Stroke). 2 To explore whether allostatic load biomarkers predict clinical outcomes in patients with depressive symptoms, especially in patients with three common cardiometabolic diseases (CHD, Diabetes and Stroke). 3 To develop a predictive tool to identify individuals with depressive symptoms at highest risk of adverse clinical outcomes. Methods: Datasets used: ‘DepChron’ was a dataset of 35,537 patients with existing cardiometabolic disease collected as a part of routine clinical practice. ‘Psobid’ was a research data source containing health related information from 666 participants recruited from the general population. The clinical outcomes for 3 both datasets were studied using electronic data linkage to hospital and mortality health records, undertaken by Information Services Division, Scotland. Cross-sectional associations between allostatic load biomarkers calculated at baseline, with clinical severity of depression assessed by a symptom score, were assessed using logistic and linear regression models in both datasets. Cox’s proportional hazards survival analysis models were used to assess the relationship of allostatic load biomarkers at baseline and the risk of adverse physical health outcomes at follow-up, in patients with depressive symptoms. The possibility of interaction between depressive symptoms and allostatic load biomarkers in risk prediction of adverse clinical outcomes was studied using the analysis of variance (ANOVA) test. Finally, the value of constructing a risk scoring scale using patient demographics and allostatic load biomarkers for predicting adverse outcomes in depressed patients was investigated using clinical risk prediction modelling and Area Under Curve (AUC) statistics. Key Results: Literature Review Findings. The literature review showed that twelve blood based peripheral biomarkers were statistically significant in predicting six different clinical outcomes in participants with depressive symptoms. Outcomes related to both mental health (depressive symptoms) and physical health were statistically associated with pre-treatment levels of peripheral biomarkers; however only two studies investigated outcomes related to physical health. Cross-sectional Analysis Findings: In DepChron, dysregulation of individual allostatic biomarkers (mainly cardiometabolic) were found to have a non-linear association with increased probability of co-morbid depressive symptoms (as assessed by Hospital Anxiety and Depression Score HADS-D≥8). A composite AI score constructed using five biomarkers did not lead to any improvement in the observed strength of the association. In Psobid, BMI was found to have a significant cross-sectional association with the probability of depressive symptoms (assessed by General Health Questionnaire GHQ-28≥5). BMI, triglycerides, highly sensitive C - reactive 4 protein (CRP) and High Density Lipoprotein-HDL cholesterol were found to have a significant cross-sectional relationship with the continuous measure of GHQ-28. A composite AI score constructed using 12 biomarkers did not show a significant association with depressive symptoms among Psobid participants. Longitudinal Analysis Findings: In DepChron, three clinical outcomes were studied over four years: all-cause death, all-cause hospital admissions and composite major adverse cardiovascular outcome-MACE (cardiovascular death or admission due to MI/stroke/HF). Presence of depressive symptoms and composite AI score calculated using mainly peripheral cardiometabolic biomarkers was found to have a significant association with all three clinical outcomes over the following four years in DepChron patients. There was no evidence of an interaction between AI score and presence of depressive symptoms in risk prediction of any of the three clinical outcomes. There was a statistically significant interaction noted between SBP and depressive symptoms in risk prediction of major adverse cardiovascular outcome, and also between HbA1c and depressive symptoms in risk prediction of all-cause mortality for patients with diabetes. In Psobid, depressive symptoms (assessed by GHQ-28≥5) did not have a statistically significant association with any of the four outcomes under study at seven years: all cause death, all cause hospital admission, MACE and incidence of new cancer. A composite AI score at baseline had a significant association with the risk of MACE at seven years, after adjusting for confounders. A continuous measure of IL-6 observed at baseline had a significant association with the risk of three clinical outcomes- all-cause mortality, all-cause hospital admissions and major adverse cardiovascular event. Raised total cholesterol at baseline was associated with lower risk of all-cause death at seven years while raised waist hip ratio- WHR at baseline was associated with higher risk of MACE at seven years among Psobid participants. There was no significant interaction between depressive symptoms and peripheral biomarkers (individual or combined) in risk prediction of any of the four clinical outcomes under consideration. Risk Scoring System Development: In the DepChron cohort, a scoring system was constructed based on eight baseline demographic and clinical variables to predict the risk of MACE over four years. The AUC value for the risk scoring system was modest at 56.7% (95% CI 55.6 to 57.5%). In Psobid, it was not possible to perform this analysis due to the low event rate observed for the clinical outcomes. Conclusion: Individual peripheral biomarkers were found to have a cross-sectional association with depressive symptoms both in patients with cardiometabolic disease and middle-aged participants recruited from the general population. AI score calculated with different statistical formulations was of no greater benefit in predicting concurrent depressive symptoms or clinical outcomes at follow-up, over and above its individual constituent biomarkers, in either patient cohort. SBP had a significant interaction with depressive symptoms in predicting cardiovascular events in patients with cardiometabolic disease; HbA1c had a significant interaction with depressive symptoms in predicting all-cause mortality in patients with diabetes. Peripheral biomarkers may have a role in predicting clinical outcomes in patients with depressive symptoms, especially for those with existing cardiometabolic disease, and this merits further investigation.

Profile and treatment outcomes of patients with tuberculosis in Northeastern Ethiopia: a cross sectional study.

Background: Data on the epidemiology of tuberculosis and its treatment outcomes were incomplete in the study area and this study was done to fill this gap. Methods: Institution based cross sectional study was conducted from January 2011 to December 2014. A total of 949 TB patients who were on treatment in North Eastern Ethiopia, Eastern Amhara region were included. Data was analyzed using SPSS version 20. Frequency, percentages and means were used to present data. To assess the associations of treatment outcomes with sex, age, type of TB and human immunodeficiency virus (HIV), logistic regression was used. Results: The proportion of smear positive and negative pulmonary TB, and extra pulmonary TB were 187/949 (19.7%), 322/949 (33.9%) and 440/949 (46.4%), respectively. Treatment success rate was 853/949 (89.9%). Smear positive pulmonary TB and TB/HIV co-infections were significantly associated with unsuccessful treatment outcome, P≤ 0.002. Conclusion: Extra pulmonary TB was the most prevalent types of TB followed by smear negative pulmonary TB. Treatment success rate was above the WHO target of 85%. The causes for the high proportion of smear negative PTB and EPTB should be further investigated. Special emphasis should be put on smear positive PTB patients and TB/HIV co-infected patients to decrease unsuccessful treatment outcome and TB transmissions.

Experiences of patients undergoing chemotherapy - a qualitative study of adults attending Uganda Cancer Institute

Background: Cancer is a global public health challenge and how patients in countries with poor healthcare infrastructure experience cancer treatment is largely unknown. Purpose: The objective of this study was to describe adult Ugandan cancer patients’ experiences of undergoing chemotherapy treatment. Methodology: Using a qualitative descriptive design, seven in-patients with varying cancer diagnoses at the Uganda Cancer Institute were interviewed about their experiences of undergoing chemotherapy treatment; the interviews were transcribed and analysed thematically. Results: The analysis resulted in nine subthemes, which were categorized under three main themes: ‘experiences related to the body’, with the subthemes dry and sensitive skin, changes in eating and bowel habits, fever and feelings of abnormal body sensation; ‘thoughts and feelings’, with four subthemes reflecting the psychosocial impact of chemotherapy; and ‘actively dealing with discomfort’, with three subthemes describing how patients dealt with side effects, such as by sticking to a diet. Conclusion: Receiving chemotherapy treatment is difficult, and the side effects negatively influenced patients’ bodies and moods. Dealing actively with discomfort and accepting negative impacts in hope of a cure helped the participants manage the acute complications related to the treatment. We recommend the development of interventions to ease discomfort due to chemotherapy.

Buruli Ulcer in South Western Nigeria: A Retrospective Cohort Study of Patients Treated in Benin

International audience

A review of patients with advanced cervical cancer presenting to palliative care services at Queen Elizabeth Central Hospital in Blantyre, Malawi

Background Cervical cancer is the commonest cancer affecting women in Malawi, which has the highest rate of this disease in the world. Most cases are diagnosed at an advanced stage. Aim To describe the symptom burden, palliative care interventions, and outcomes of cervical cancer patients who entered care at Tiyanjane Clinic in Blantyre, Malawi, between January and December 2012. Methods We reviewed the case files of 72 patients presenting to our hospital-based palliative care service over one year. Results The mean age was 49.5 years. Twenty-six patients (36%) were HIVpositive and the majority of these (n = 22; 85%) were on antiretroviral medication at presentation to palliative care. Pain (n = 66; 92%), vaginal discharge (n = 44; 61%), and unpleasant odour (n = 37; 51%) were commonly reported. Over a third of patients (n = 26; 36%) reported pain in two or more sites. Fourteen patients (19%) reported vaginal bleeding. Spousal breakdown (through widowhood or divorce) was noted in over half (n = 41; 57%) of all cases. Pain relief was provided to 69 (96%) of the patients (morphine to 40 patients; 56%). Common interventions provided included metronidazole tablets (used vaginally), sanitary items, and counselling. At the end of the study period, 18 patients (25%) were still under the care of palliative services. Conclusions Access to medications such as morphine, metronidazole and tranexamic acid can improve quality of life, even when radiotherapy is limited. Health care teams require necessary skills and training, including how to perform a comprehensive assessment, with an emphasis on the provision of psychosexual counselling, to assist with the complexity of symptoms occurring in this vulnerable group.

Characterization of patients undergoing noninvasive ventilation admitted in unit intermediate care

Non-invasive ventilation (NIV) is the application of a ventilatory support without resorting to invasive methods. Today it’s considered a credible therapeutic option, with enough scientiic evidence to support its application in various situations and clinical settings related to the treatment of acute respiratory disease, as well as chronic respiratory disease. Objectives: Characterize patients undergoing NIV admitted in Unit Intermediate Care (ICU) in the period from October 1st 2015 to June 30th 2016. Methods: Prospective study conducted in ICU between October 2015 and June 2016. In this study were included all patients hospitalized in this unit (ICU) and in that time period a sample of 57 participants was obtained. As data collection instruments we used a questionnaire for sociodemographic and clinical data and the Braden scale. Results: Participants were mostly male 38 (66.7%), the average age 69.5 ± 11.3 years, ranging between 43 and 92 years. They weighed on average 76.6 kg (52 and 150), with an average body mass index of 28.5 kg/m2 (20 to 58.5). With skin intact 28 (49.1%) with abnormal perfusion 12 (21.1%), with altered sensitivity 11 (19.3%) and a high risk of ulcer on the scale of Braden 37 (65%). The admission diagnosis was respiratory failure 33 (57.3%) and had different backgrounds. We used reused mask 53 (93.0%), the average time of NIV was 7.1 days (1-28), 4.8 days of hospitalization (1-18) and an average of 7.8 IPAP pressure. 11 (19.3%) of the participants developed face ulcer pressure.Conclusions: The NIV is used in patients with advanced age, obesity, respiratory failure and high risk of face ulcer development.

Serological based monitoring of a cohort of patients with chronic Chagas disease treated with benznidazole in a highly endemic area of northern Argentina

This study aimed to evaluate well-documented diagnostic antigens, named B13, 1F8 and JL7 recombinant proteins, as potential markers of seroconversion in treated chagasic patients. Prospective study, involving 203 patients treated with benznidazole, was conducted from endemic areas of northern Argentina. Follow-up was possible in 107 out of them and blood samples were taken for serology and PCR assays before and 2, 3, 6, 12, 24 and 36 months after treatment initiation. Reactivity against Trypanosoma cruzi lysate and recombinant antigens was measured by ELISA. The rate of decrease of antibody titers showed nonlinear kinetics with an abrupt drop within the first three months after initiation of treatment for all studied antigens, followed by a plateau displaying a low decay until the end of follow-up. At this point, anti-B13, anti-1F8 and anti-JL7 titers were relatively close to the cut-off line, while anti-T. cruzi antibodies still remained positive. At baseline, 60.8% (45/74) of analysed patients tested positive for parasite DNA by PCR and during the follow-up period in 34 out of 45 positive samples (75.5%) could not be detected T. cruzi DNA. Our results suggest that these antigens might be useful as early markers for monitoring antiparasitic treatment in chronic Chagas disease.

The influence of the initial state of nutrition on the lifespan of patients with amyotrophic lateral sclerosis (ALS) during home enteral nutrition

Aim: Amyotrophic lateral sclerosis (ALS) is a chronic, neurodegenerative disease, which leads to development of malnutrition. The main purpose of this research was to analyze the impact of malnutrition on the course of the disease and long-term survival. Material and methods: A retrospective analysis has been performed on 48 patients (22 F [45,83%] and 26 M [54,17%], the average age of patients: 66,2 [43-83]) in 2008-2014.The analysis of the initial state of nutrition was measured by body mass index (BMI), nutritional status according to NRS 2002, SGA and concentration of albumin in blood serum. Patients were divided into two groups, depending on the state of nutrition: well-nourished and malnourished. The groups were created separately for each of these, which allowed an additional comparative analysis of techniques used for the assessment of nutritional status. Results: Proper state of nutrition was interrelated with longer survival (SGA: 456 vs. 679 days, NRS: 312 vs. 659 vs. 835 days, BMI: respectively, 411, 541, 631 days, results were statistically significant for NRS and BMI). Concentration of albumin was not a prognostic factor, but longer survival was observed when level of albumin was increased during nutritional therapy. Conclusions: The initial nutrition state and positive response to enteral feeding is associated with better survival among patients with ALS. For this reason, nutritional therapy should be introduced as soon as possible.

One-year follow-up of the nutritional status of patients undergoing liver transplantation

Background: Choosing the method of nutritional assessment is essential for proper follow-up of the nutritional status of patients undergoing liver transplantation. Objectives: Evaluate and compare the nutritional status of cirrhotic patients before and after liver transplantation over a year by different methods of nutritional assessment. Methods: Patients undergoing liver transplantation were assessed in five phases: pre-transplant, 1, 3, 6 and 12 months after transplantation at the hospital Santa Casa de Misericordia de Porto Alegre, RS, Brazil. The methods used for nutritional assessment were anthropometry, grip strength of the non-dominant hand (HGS) by dynamometry, thickness of the adductor pollicis muscle (APM) and phase angle (PA) by bioelectrical impedance analysis (BIA). In all evaluations, the same measurements were taken. Results: Evaluations were performed in 22 patients. Methods that showed a higher prevalence of malnourished patients before transplantation were PA by BIA (25%), arm muscle circumference (AMC) (21.9%) and arm circumference (AC) (18.8%). When comparing the nutritional status of patients during follow-up, there was a significant difference only in the evaluation methods AC, triceps skinfold thickness and PA by BIA. At the end, the methods of nutritional assessment were compared again. They showed a significant statistical difference, with HGS being the best method for detecting malnutrition. Conclusions: In conclusion, it is suggested that the method PA by BIA could be widely used with this population since the results are consistent with other findings in the literature and they are significant, reliable, and reproducible.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment.

Epidemiological features of patients with nonsyndromic cleft lip and/or palate in Western Parana

Aim:To describe the clinical, demographic and environmental features associated with NSCL/P (nonsyndromic cleft lip and/or palate) patients born in western Parana state, Brazil. Methods: This cross-sectional, observational, retrospective study included 188 patients attended at the Association of Carriers of Cleft Lip and Palate - APOFILAB, Cascavel-Parana, between 2012 and 2014. Information on demographic characteristics, medical and dental histories and life style factors were obtained from records and personal interviews. Results: Among the 188 patients, cleft lip and palate (CLP) was the most frequent subtype (55.8%), followed by cleft lip only (CLO, 25.0%) and cleft palate only (CPO, 19.2%). Caucasian males were the most affected, although no differences among types of cleft were observed. The otorhinolaryngologic and respiratory alterations were the most frequent systemic alterations in NSCL/P patients, and more than 80% of the NSCL/P mothers reported no vitamin supplements during the first trimester of pregnancy. Conclusions: This study revealed that the prevalence of nonsyndromic oral cleft types in this cohort was quite similar to previously reported prevalence rates. Systemic alterations were identified among 23.4% of the patients and patients with CLP were the most affected. History of maternal exposition to environmental factors related to nonsyndromic oral clefts was frequent and most mothers reported no vitamin supplements during the pregnancy. This study highlights the importance of identifying systemic alterations and risk factors associated with NSCL/P in the Brazilian population for planning comprehensive strategies and integrated actions for the development of preventive programs and treatment.

Development of the Andalusian Registry of Patients Receiving Community Case Management, for the follow-up of people with complex chronic diseases.

Background: Complex chronic diseases are a challenge for the current configuration of Health services. Case management is a service frequently provided for people with chronic conditions and despite its effectiveness in many outcomes, such as mortality or readmissions, uncertainty remains about the most effective form of team organization, structures, and the nature of the interventions. Many processes and outcomes of case management for people with complex chronic conditions cannot be addressed with the information provided by electronic clinical records. Registries are frequently used to deal with this weakness. The aim of this study was to generate a registry-based information system of patients receiving case management to identify their clinical characteristics, their context of care, events identified during their follow-up, interventions developed by case managers, and services used. Methods and design: The study was divided into three phases, covering the detection of information needs, the design and its implementation in the healthcare system, using literature review and expert consensus methods to select variables that would be included in the registry. Objective: To describe the essential characteristics of the provision of ca re lo people who receive case management (structure, process and outcomes), with special emphasis on those with complex chronic diseases. Study population: Patients from any District of Primary Care, who initiate the utilization of case management services, to avoid information bias that may occur when including subjects who have already been received the service, and whose outcomes and characteristics could not be properly collected. Results: A total of 102 variables representing structure, processes and outcomes of case management were selected for their inclusion in the registry after the consensus phase. Total sample was composed of 427 patients, of which 211 (49.4%) were women and 216 (50.6%) were men. The average functional level (Barthel lndex) was 36.18 (SD 29.02), cognitive function (Pfeiffer) showed an average of 4.37 {SD 6.57), Chat1son Comorbidity lndex, obtained a mean of 3.03 (SD 2.7) and Social Support (Duke lndex) was 34.2 % (SD 17.57). More than half of patients include in the Registry, correspond lo immobilized or transitional care for patients discharged from hospital (66.5 %). The patient's educational level was low or very low (50.4%). Caregivers overstrain (Caregiver stress index), obtained an average value of 6.09% (SD 3.53). Only 1.2 % of patients had declared their advanced directives, 58.6 had not defined the tutelage and the vast majority lived at home 98.8 %. Regarding the major events recorded at RANGE Registry, 25.8 % of the selected patients died in the first three months, 8.2 % suffered a hospital admission at least once time, 2.3%, two times, and 1.2% three times, 7.5% suffered a fall, 8.7% had pressure ulcer, 4.7% had problems with medication, and 3.3 % were institutionalized. Stroke is the more prevalent health problem recorded (25.1%), followed by hypertension (11.1%) and COPD (11.1%). Patients registered by NCMs had as main processes diabetes (16.8%) and dementia (11.3 %). The most frequent nursing diagnoses referred to the self-care deficit in various activities of daily living. Regarding to nursing interventions, described by the Nursing Intervention Classification (NIC), dementia management is the most used intervention, followed by mutual goal setting, caregiver and emotional support. Conclusions: The patient profile who receive case management services is a chronic complex patient with severe dependence, cognitive impairment, normal social support, low educational level, health problems such as stroke, hypertension or COPD, diabetes or dementia, and has an informal caregiver. At the first follow up, mortality was 19.2%, and a discrete rate of readmissions and falls.