Presentation, Diagnosis and Treatment Delays in Breast Cancer Care and Their Associations in Sri Lanka, a Low-resourced Country.

AIMS: Delays in breast cancer care, one important attributable factor for breast cancer being diagnosed at advanced stages, are not systematically studied in many countries. This study assessed the magnitude and factors associated with delays in breast cancer care in Sri Lanka, from symptom detection to treatment initiation. MATERIALS AND METHODS: We interviewed 800 consecutively sampled female breast cancer patients, diagnosed within the last 12 months, using context-specific questionnaires and medical records. We defined the cut-off times for delays using international guidelines and features of the national health system and care-seeking patterns in the country. Delays were estimated as proportions with 95% confidence intervals and presented for: (i) presentation delay; (ii) diagnosis delay and (iii) treatment delay. We looked at how sociodemographic and healthcare availability and accessibility at the individual level were associated with delays using multivariate logistic regression, with a P value of 0.05 to define statistical significance. RESULTS: Nearly two-thirds of patients reported a presentation delay (63.3%, 95% confidence interval 59.9-66.6%). A diagnosis delay (36.7%, 95% confidence interval 33.4-40.0%) was also seen among one-third, whereas treatment delays (13.2%, 95% confidence interval 10.8-15.5%) were less common. Low family monthly income (odds ratio 6.3; 95% confidence interval 4.2-9.3) and poor knowledge on breast cancer (odds ratio 2.7; 95% confidence interval 1.8-3.8) were associated with presentation delay. Poor health literacy (odds ratio 1.7; 95% confidence interval 1.1-2.7) and the need to make more than two visits to the first contact health provider prior to diagnosis (odds ratio 7.2; 95% confidence interval 4.6-11.1) were associated with diagnosis delays, whereas directly contacting an appropriate specialised health provider once the lump was detected reduced diagnosis delay (odds ratio 0.3; 95% confidence interval 0.2-0.4). Having undergone a core biopsy (odds ratio 0.5; 95% confidence interval 0.3-0.8) and having a mammogram (odds ratio 0.6; 95% confidence interval 4.7-32.7) reduced the likelihood of treatment delays. CONCLUSIONS: Our study findings show that delays in breast cancer care in Sri Lanka are much lower than those in other lower-middle income countries. However, there is significant room for improvement, especially in relation to the excellence in quality of care, such as improving access to mammography services. Periodical estimation of breast cancer delays enabling temporal comparisons will probably provide useful information to policy makers in improving care delivery for breast cancer patients and, hence, is recommended. Such future assessments designed for comparisons between different treatment modalities would provide more information to assist policy decisions in care improvement.

Genetic and other risk factors for suicidal ideation and the relationship with depression.

BACKGROUND: There is a genetic contribution to the risk of suicide, but sparse prior research on the genetics of suicidal ideation. METHODS: Active and passive suicidal ideation were assessed in a Sri Lankan population-based twin registry (n = 3906 twins) and a matched non-twin sample (n = 2016). Logistic regression models were used to examine associations with socio-demographic factors, environmental exposures and psychiatric symptoms. The heritability of suicidal ideation was assessed using structural equation modelling. RESULTS: The lifetime prevalence of any suicidal ideation was 13.0% (11.7-14.3%) for men; 21.8% (20.3-23.2%) for women, with no significant difference between twins and non-twins. Factors that predicted suicidal ideation included female gender, termination of marital relationship, low education level, urban residence, losing a parent whilst young, low standard of living and stressful life events in the preceding 12 months. Suicidal ideation was strongly associated with depression, but also with abnormal fatigue and alcohol and tobacco use. The best fitting structural equation model indicated a substantial contribution from genetic factors (57%; CI 47-66) and from non-shared environmental factors (43%; CI 34-53) in both men and women. In women this genetic component was largely mediated through depression, but in men there was a significant heritable component to suicidal ideation that was independent of depression. CONCLUSIONS: These are the first results to show a genetic contribution to suicidal ideation that is independent of depression outside of a high-income country. These phenomena may be generalizable, because previous research highlights similarities between the aetiology of mental disorders in Sri Lanka and higher-income countries.

Screening patients with tuberculosis for diabetes mellitus in Ampara, Sri Lanka.

Given the well-known linkage between diabetes mellitus (DM) and tuberculosis (TB), the World Health Organization recommends bidirectional screening. Here we report the first screening effort of its kind from a chest clinic in the Ampara district of Sri Lanka. Of 112 TB patients registered between January 2013 and October 2014, eight had pre-existing DM. Of those remaining, 83 (80%) underwent fasting plasma glucose testing, of whom two (2%) and 17 (20%) were found to have diabetes and impaired fasting glucose, respectively. All of these were enrolled in care. Screening TB patients for DM was found to be feasible at the district level. Further studies at the provincial/country level are required before making any decision to scale up bidirectional screening.

Etant donné le lien bien connu entre diabète (DM) et tuberculose (TB), l'Organisation Mondiale de la Santé recommande un dépistage bidirectionnel. Nous rapportons ici le premier effort de dépistage de ce type au Sri Lanka dans un centre de maladies respiratoires du district d'Ampara. Sur 112 patients TB enregistrés entre janvier 2013 et octobre 2014, huit avaient un DM préexistant. Parmi les autres, 83 (80%) ont eu une glycémie à jeun et parmi eux, respectivement deux (2%) et 17 (20%) ont eu un diabète et une glycémie à jeun trop élevée; tous ont été enrôlés dans un programme de soins. Le dépistage du DM chez des patients TB s'est avéré faisable au niveau du district. D'autres études au niveau provincial/national sont nécessaires avant de décider l'extension de la stratégie.

Dado el vínculo reconocido entre la diabetes (DM) y la tuberculosis (TB), la Organización Mundial de la Salud recomienda la detección sistemática bidireccional. En el presente estudio se comunica la primera campaña de detección de este tipo emprendida en Sri Lanka, en un consultorio de neumología del distrito de Ampara. De los 112 pacientes notificados al registro de TB de enero del 2013 a octubre del 2014, en ocho prexistía el diagnóstico de DM. De los casos restantes (80%), en 83 se practicó la glucemia plasmática en ayunas y se puso en evidencia el diagnóstico de DM en dos de ellos (2%) y 17 pacientes presentaron una glucemia basal alterada (20%); todos los pacientes ingresaron a un programa de atención. Se confirmó que es factible practicar la detección sistemática de la DM en los pacientes con diagnóstico de TB a escala distrital. Será necesario realizar estudios a escala de la provincia y del país antes de adoptar decisiones de ampliación de escala de la medida.

Modeling and analysis of repeat RNA toxicity in Drosophila.

Expansion of repeat sequences beyond a pathogenic threshold is the cause of a series of dominantly inherited neurodegenerative diseases that includes Huntington's disease, several spinocerebellar ataxias, and myotonic dystrophy types 1 and 2. Expansion of repeat sequences occurring in coding regions of various genes frequently produces an expanded polyglutamine tract that is thought to result in a toxic protein. However, in a number of diseases that present with similar clinical symptoms, the expansions occur in untranslated regions of the gene that cannot encode toxic peptide products. As expanded repeat-containing RNA is common to both translated and untranslated repeat expansion diseases, this repeat RNA is hypothesized as a potential common toxic agent.We have established Drosophila models for expanded repeat diseases in order to investigate the role of multiple candidate toxic agents and the potential molecular pathways that lead to pathogenesis. In this chapter we describe methods to identify candidate pathogenic pathways and their constituent steps. This includes establishing novel phenotypes using Drosophila and developing methods for using this system to screen for possible modifiers of pathology. Additionally, we describe a method for quantifying progressive neurodegeneration using a motor functional assay as well as small RNA profiling techniques, which are useful in identifying RNA intermediates of pathogenesis that can then be used to validate potential pathogenic pathways in humans.

Characteristics and outcomes of tuberculosis patients who fail to smear convert at two months in Sri Lanka.

SETTING: Five districts in Sri Lanka. OBJECTIVES: To determine: 1) the proportion of sputum smear-positive pulmonary tuberculosis (PTB) cases who failed to smear convert at 2 months, 2) their management, and 3) whether baseline characteristics and final treatment outcomes were different from those who did smear convert. DESIGN: Cross-sectional retrospective review of medical files, tuberculosis (TB) registers and TB treatment records of new smear-positive PTB patients registered from January to December 2010. RESULTS: Of 925 patients, 840 were available to submit sputum at 2 months, of whom 137 (16%) were smear-positive. Baseline sputum smears showing 3+ acid-fast bacilli and missing doses of anti-tuberculosis drugs during the initial phase of treatment were significantly associated with being smear-positive at 2 months. Management was poor: of 137 patients, 46 (34%) submitted sputum for culture and drug susceptibility testing and Mycobacterium tuberculosis was cultured in six cases; 120 (88%) received a 1-month extension of the initial phase, and of the 30 patients still smear-positive at 3 months there were no culture results available. Final treatment outcomes were similar, regardless of smear conversion at 2 or 3 months. CONCLUSION: Certain characteristics were risk factors for failure to smear convert at 2 months. However, treatment outcomes for all patients were good. These findings have implications for the modification of national programme recommendations.

Delayed gastric emptying rates and impaired antral motility in children fulfilling Rome III criteria for functional abdominal pain.

BACKGROUND: Gastric sensorymotor dysfunctions have been implicated in the pathophysiology of some functional gastrointestinal disorders, such as functional dyspepsia and irritable bowel syndrome. Therefore, we hypothesized that abnormal gastric emptying and impaired antral motility are possible underlying mechanisms of symptoms in children with functional abdominal pain (FAP). METHODS: Hundred and two children [37 (36.3%) males, 4-14 years, mean 7.8 years, SD 2.7 years] fulfilling Rome III criteria for FAP were recruited for this study. An age and sex compatible group of healthy children (n = 20) were selected as controls [8 (40%) males, 4-14 years, mean 8.4 years, SD 3.0 years]. Liquid gastric emptying rate (GER) and antral motility parameters (amplitude of antral contractions, frequency of antral contractions and antral motility index) were assessed using a previously reported ultrasound method. KEY RESULTS: Average GER (42.1% vs 66.2% in controls), amplitude of antral contractions (56.5% vs 89%), frequency of contractions per 3 min (8.5 vs 9.3), and antral motility index (4.9 vs 8.3) were significantly lower in patients with FAP compared with controls (P < 0.01). Fasting antral area was higher in patients (1.4 vs 0.6, P < 0.0001). GER negatively correlated with the scores obtained for severity of abdominal pain (r = -0.29, P = 0.004). CONCLUSIONS & INFERENCES: Gastric emptying rate and antral motility parameters were significantly impaired in patients with FAP and GER negatively correlated with symptom severity. These findings highlight the possible role of gastrointestinal motility abnormalities in the pathophysiology of childhood FAP.

Developmental interventions in infancy during lengthy hospitalizations.

A review of concepts related to infant development, care, and stimulation is presented. A description is provided of the development of an infant with small bowel syndrome during her hospitalization from birth until age 19 months. Interventions which facilitated feeding, sitting, walking, fine motor and language development are described. In addition, interventions are reviewed which focus on enhancing the infant's attachment to her cartakers, object permanence, and object constancy, and helping the normal unfolding of the individuation process. Efforts to "normalize" the hospital environment for the infant are stressed. The implications of the infant's hospitalizations and her future psychological development are discussed.