Post-stroke Quality of Life Index: A quality of life tool for stroke survivors from Sri Lanka.

BACKGROUND: Burden of stroke is rising due to the demographic and epidemiological transitions in Sri Lanka. Assessment of success of stroke-management requires tools to assess the quality of life (QOL) of stroke survivors. Most of currently used QOL tools are developed in high-income countries and may not reflect characteristics relevant to resource-constrained countries. The aim was to develop and validate a new QOL tool for stroke survivors in Sri Lanka. METHODS: The COnsensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist was referred. A conceptual framework was prepared. Item generation was done reviewing the existing QOL tools, inputs from experts and from stroke survivors. Non-statistical item reduction was done for the 36 generated items with modified-Delphi technique. Retained 21 items were included in the draft tool. A cross sectional study was done with 180 stroke survivors. Exploratory Factor Analysis was done and identified factors were subjected to varimax rotation. Further construct validity was tested with 6 a-priori hypothesis using already validated tools (SF-36, EQ-5D-3 L) and a formed construct. Internal consistency reliability was assessed with Cronbach alpha. RESULTS: Four factors identified with principal-component-analysis explained 72.02% of the total variance. All 21 items loaded with a level > 0.4. The developed tool was named as the Post-stroke QOL Index (PQOLI). Four domains were named as "physical and social function", "environment", "financial-independence" and "pain and emotional-wellbeing". Four domain scores of PQOLI correlated as expected with the SF-36, EQ-5D Index and EQ-5D-VAS scores. Higher domain scores were obtained for ambulatory-group than the hospitalized-group. Higher scores for financial-independence domain were obtained for the group without financial-instability. Five a-priori hypothesis were completely proven to be true. Cronbach-alpha level ranged from 0.682 to 0.906 for the four domains. CONCLUSIONS: There is first evidence for sufficient construct validity of the PQOLI as a valid QOL tool for measuring the QOL of stroke survivors with satisfactory internal consistency reliability.

Occupational hazards in medium and large scale industrial sectors in Sri Lanka: experience of a developing country.

OBJECTIVE: Occupational hazards is an area where many countries have begun to pay more emphasis as it affects the health of many particularly in developing countries. However, documented literature is scarce in this regard although occupational hazards are common in workplaces. The study was carried out with the objective of describing the physical hazards and control measures adopted in the formal medium and large-scale industrial sector in Sri Lanka. RESULTS: Of the 69 units of the 25 factories, physical hazards detected in the workplaces were; excessive noise (78.3%), poor light (58%), increased temperature (65.2%), and poor ventilation (68.1%). Over 50% of large machinery and 33% of medium-scale machinery were not adequately guarded. Nearly 41% of the machinery were difficult to operate, of them 36.2% had controls in positions which were hard to reach. Of safety measures adopted, only 34.8% had proper demarcation of areas with 28.9% displaying safety signs. Housekeeping was poor in 59.4% and less than 40% had safe storage of raw materials and end products.

Construct validity and reliability of EQ-5D-3L for stroke survivors in a lower middle income setting

Introduction: Stroke is a leading disease accounting for burden of chronic NCDs especially in lower and lower-middle income (LMI) settings. Quality of Life (QOL) is considered as an important facet of determination of success of patient management. EQ-5D-3L is a generic QOL tool. It provides an index score amalgamating responses for five descriptive questions and a visual analogue scale (VAS) value. Objectives: To assess the validity and reliability of EQ-5D-3L for stroke patients in Sri Lanka, which is a LMI setting. Methods: A descriptive cross sectional study was done among 100 stroke survivors among whom 50 each were managed at an ambulatory setting and an in-ward setting. A second wave of data collection was done for reliability analysis among one half of participants. The validity of EQ-5D-3L was assesses with five a-priori hypotheses. Reliability was assessed with test-retest method and with internal consistency. Non parametric Mann Whitney U test and Spearman correlation coefficients were used in the analysis. Results: The EQ-5D index scores had significant positive correlation with SF-36 domain scores (p<0.001). The EQ-5D VAS scores had significant positive correlation with SF-36 domain scores (p<0.01). Index and VAS values of the EQ-5D were proved to be valid in known-group comparison (p<0.001). Participants reporting some kind of impairment for EQ-5D-3L dimensions had lower SF-36 domain scores. All the kappa values in the analysis of test-retest method were significant (p<0.001). For the VAS score, the Spearman correlation coefficient in test-reter analysis was 0.993 (p<0.001). Cronbach's alpha value was 0.928. Conclusions: and Recommendations EQ-5D-3L questionnaire demonstrates construct validity and a is a reliable toolin measuring QOL among stoke survivors in Sri Lanka.

Factors influencing pre-stroke and post-stroke quality of life among stroke survivors in a lower middle-income country.

Quality of life (QOL) reflects the individual's perception of the position within living contexts. This study was done to describe pre- and post-stroke QOLs of stroke survivors. A prospective longitudinal study was done among stroke survivors admitted to 13 hospitals in the western province of Sri Lanka. The calculated sample size was 260. The pre-stroke and post-discharge one-month QOL was gathered using short form-36 (SF-36) QOL tool. SF-36 includes questions on eight domains: general health, physical functioning, pain, role limitation due to physical problems, social functioning, vitality, role limitations due to emotional problems, and mental health. Univariate analysis was followed by determining the independent risk factors through multivariate analysis. The response rate was 81%. The disability was measured by the modified Rankin scale which ranges from 0 (no symptoms) to 6 (fatal outcome). The median (IQR) disability score was 4 (3 to 5). The post-discharge QOL scores were significantly lower than pre-stroke values (p < 0.05). With a higher pre-stroke QOL, younger age was significantly associated in six domains and higher income and better health infrastructure in two domains (p < 0.05). Six factors were determined to be independent risk factors for lower post-discharge QOL scores of SF-36: younger age (for general health and role limitation-physical domains), female gender (for physical functioning and pain domains), lower health infrastructure (for general health, vitality, and mental health domains), lower education (for pain domain), higher disability (for general health, physical functioning, vitality, social functioning, and mental health domains), and hypercholesterolemia (for role limitation-emotional domain). Stroke survivors have not regained their pre-stroke QOL at 1 month following the hospital discharge irrespective of income level and pre-stroke QOL. Higher pre- and post-stroke QOLs are associated with better statuses of social determinants of health.

Financial burden of survivors of medically-managed myocardial infarction and its association with selected social determinants and quality of life in a lower middle income country.

BACKGROUND: Burden from ischemic heart disease is rising in Sri Lanka due to the demographic and epidemiological transitions. Documented literature is scarce on quality of life, financial burden and its determinants in relation to myocardial infarction (MI). This study was done to describe the financial burden among the survivors of MI managed only with drugs (i.e. those who did not undergo Percutaneous Coronary Intervention or Coronary Artery Bypass Graft) and its association with selected social determinants (SDHs) and quality of life (QOL). METHODS: A cross sectional study was done among MI survivors in 13 hospitals in the premier province of Sri Lanka. Out of 336 participants recruited at hospital stay, 270 responded through a self-administered questionnaire at 1 month post discharge. Questionnaire included sections on financial burden, selected SDHs and on QOL measured by the EQ-5D-3 L QOL tool. Presence of financial burden was determined using an operational definition. Associations were tested with Mann-Whitney-U test, Chi square test and Spearman-correlation-coefficient at 5% significant level. RESULTS: Around 40% (n = 116) had to seek financial support for out-of-pocket expenditure. Nearly 5% (n = 6) of previously employed participants had lost their job. Of the employed respondents (n = 139, 51.5%), 29% (n = 85) had limited physical activity and 40% (n = 115) had limitations of employment time. Of the respondents, 15.4% had to apply for a loan, 7.8% had to sell a property, 19.1% had an income loss and 33.8% had to restrict usual expenses. Financial burden was not significantly associated with gender (p = 0.146), ethnicity (p = 0.068), highest education (p = 0.184) and area of residence (p = 0.369). Influence of income (p = 0.001), social support (p = 0.002) and the health infrastructure (p < 0.001) were significantly associated with the occurrence of a financial burden. In the group with a financial burden, the index score (p = 0.002) and VAS score (p < 0.001) of EQ-5D-3 L were significantly lower. CONCLUSIONS: Financial burden is common among survivors of medically-managed occurring irrespective of the gender, ethnicity, education and the area. It is influenced significantly by the income, level of social support and the level of health infrastructure. The financial burden is influencing the post-discharge-1-month QOL.

Pre-event quality of life and its influence on the post-event quality of life among patients with ST elevation and non-ST elevation myocardial infarctions of a premier province of Sri Lanka.

BACKGROUND: Pre-event Quality of Life (QOL) reflects the true social circumstances in which people live prior to the onset of myocardial infarctions. It is believed to be a predictor of the post-event QOL. The aim of this study was to describe the pre-event QOL and its influence on the post-event Quality of Life among patients with ST elevation (STEMI) and Non-ST elevation myocardial infarctions (NSTEMI) using Short Form-36 (SF-36), a generic QOL tool with 8 domains. Documented literature is rare in this regard in Sri Lanka, which is a lower-middle-income country. METHODS: A cross-sectional study with a 28-day post-discharge follow-up was carried out in 13 hospitals. Three hundred and forty-four patients who were diagnosed with STEMI or NSTEMI were recruited during the hospital stay. The pre-event QOL was measured using an interviewer-administered questionnaire which included the SF-36 QOL tool and medical details. Follow-up QOL was gathered using a questionnaire that was filled and posted back by participants. Of the recruited sample, 235 responded for the follow-up component. Analysis was conducted for associations between pre- and post-discharge QOL. Furthermore, comparisons were made between the STEMI and NSTEMI groups. Mann Whiney U test, Wilcoxon signed rank test and chi square test were used in the analysis. RESULTS: The post-event QOL was lower in seven out of eight domains than the pre-event QOL (p < 0.05). The NSTEMI group had more risk factors and a significantly lower pre-event QOL for seven domains (p < 0.05), when compared to the STEMI group. For seven domains, the post-discharge QOL was not significantly different (p > 0.05) between the STEMI and NSTEMI groups. Post-discharge general-health QOL domain score was higher than the pre-MI score (p = 0.028) and was higher in the STEMI group compared to the NSTEMI group (p = 0.042). Regression analysis showed a significant beta coefficient between pre- and post-QOL for five domains in STEMI and for all domains in NSTEMI groups when adjusted for the disease severity. The R square values ranged from 12.3 to 62.3% for STEMI and 7.3 to 64.8% for NSTEMI. CONCLUSIONS: Pre-event QOL is lower in the NSTEMI group compared to the STEMI group. Patients do not regain the previous QOL within one month post-discharge. Post-discharge QOL can be predicted by the pre-event QOL for most domains.

Acute hepatic encephalopathy with diffuse cortical lesions.

Acute hepatic encephalopathy is a poorly defined syndrome of heterogeneous aetiology. We report a 49-year-old woman with alcoholic cirrhosis and hereditary haemorrhagic telangiectasia who developed acute hepatic coma induced by severe gastrointestinal bleeding. Laboratory analysis revealed excessively elevated blood ammonia. MRI showed lesions compatible with chronic hepatic encephalopathy and widespread cortical signal change sparing the perirolandic and occipital cortex. The cortical lesions resembled those of hypoxic brain damage and were interpreted as acute toxic cortical laminar necrosis.

High-dose intra-arterial cisplatin boost with hyperfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS: Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION: In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

Functional MRI in patients with band heterotopia.

Functional activation associated with a motor task (fist movements) was studied in three patients with band heterotopias by fMRI. In two patients, additional visual fMRI studies were performed using a flickering checkerboard stimulus. In all patients activation of the outer cortex and of the inner neuronal band could be found during performance of the motor task. Visual stimulation elicited a normal activation pattern without activation of the ectopic neuronal layer in one patient; in another patient activation extended toward the ventricular wall, i.e., along the route of embryonic neuronal migration. The potential participation of ectopic neuronal tissue in physiologic cerebral functions is of clinical impact in patients with neuronal heterotopias suffering from medically intractable seizures prior to epilepsy surgery.

Tuberculous meningoencephalitis in HIV-seronegative patients: variety of clinical presentation and impact on diagnostics and treatment.

UNLABELLED: Tuberculous meningoencephalitis (TBM), an infrequent disease in Western European countries, shows a wide heterogeneity of clinical symptoms. MATERIAL AND METHODS: We present 4 patients (age range 42-72 years) with the definite diagnosis of isolated TBM. All patients were HIV-seronegative, only 1 patient was known to be immunoincompetent on admission due to acute myelocytic leukemia; other reasons for immune suppression were detected in 2 other patients (leukemia and idiopathic CD4+ T-lymphocytopenia, respectively). RESULTS: The diagnosis of TBM was confirmed in 3 cases by culture from CSF, in 1 case Mycobacterium tuberculosis was proven only in tracheal aspirate. In 1 patient M. bovis was found, which is an extremely rare cause of TBM in Germany. We report the contributions of different diagnostic tools (CSF analysis, neuroimaging) in reaching the presumptive diagnosis and in monitoring the further course. All patients developed neurological complications despite prompt tuberculostatic treatment. Three of the patients presented a chronic severe loss of consciousness of unclear origin. CONCLUSION: The possible causative relationships of these complications and their impact on the prognosis are discussed.

Diagnosis and management of brain metastases.

In the past 15 years, significant advancement has been made in the diagnosis and treatment of brain metastases. The distinction between the management of single and multiple brain metastases is an important one. Although radiotherapy remains a mainstay of treatment, especially in multiple brain metastases, surgical resection and stereotactic radiosurgery also have their place in the management of selected patients. Rarely, interstitial radiation or chemotherapy also may be used to treat brain metastases in the setting of relapse.

High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation therapy in patients with locally advanced primary squamous cell carcinoma of the head and neck: report of a phase II study.

BACKGROUND: This phase II study evaluates the tolerability and efficacy of concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Between December 1995 and November 1997, 20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had T4 disease, and 14 (70%) had N2/ N3 disease. RESULTS: Grade 3-5 acute toxicity was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4 hematologic toxicity was observed. Median weight loss during therapy was 9% (range, 2%-16%). Eighteen patients had complete response (90%) at the primary site; 14 were confirmed pathologically. Among 17 patients with positive neck disease, 16 (94%) achieved complete response in the neck, including 12 of 13 patients with N2/N3 disease who underwent planned neck dissection. Active follow-up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients (90%) remained disease free at the primary site, and the locoregional control rate is 80%. CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in this study is feasible and warrants further investigation. The high complete response rate and low grade 4 toxicity in this highly unfavorable subset of patients appears better than previously reported chemoradiation regimens for more favorable patients.

Two homologues encoding human UDP-glucose:glycoprotein glucosyltransferase differ in mRNA expression and enzymatic activity.

UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that operates as a gatekeeper for quality control by preventing transport of improperly folded glycoproteins out of the ER. We report the isolation of two cDNAs encoding human UDP-glucose:glycoprotein glucosyltransferase homologues. HUGT1 encodes a 1555 amino acid polypeptide that, upon cleavage of an N-terminal signal peptide, is predicted to produce a soluble 173 kDa protein with the ER retrieval signal REEL. HUGT2 encodes a 1516 amino acid polypeptide that also contains a signal peptide and the ER retrieval signal HDEL. HUGT1 shares 55% identity with HUGT2 and 31-45% identity with Drosophila, Caenorhabditis elegans, and Schizosaccharomyces pombe homologues, with most extensive conservation of residues in the carboxy-terminal fifth of the protein, the proposed catalytic domain. HUGT1 is expressed as multiple mRNA species that are induced to similar extents upon disruption of protein folding in the ER. In contrast, HUGT2 is transcribed as a single mRNA species that is not induced under similar conditions. HUGT1 and HUGT2 mRNAs are broadly expressed in multiple tissues and differ slightly in their tissue distribution. The HUGT1 and HUGT2 cDNAs were expressed by transient transfection in COS-1 monkey cells to obtain similar levels of protein localized to the ER. Extracts from HUGT1-transfected cells displayed a 27-fold increase in the transfer of [(14)C]glucose from UDP-[(14)C]glucose to denatured substrates. Despite its high degree of sequence identity with HUGT1, the expressed recombinant HUGT2 protein was not functional under the conditions optimized for HUGT1. Site-directed alanine mutagenesis within a highly conserved region of HUGT1 identified four residues that are essential for catalytic function.

Expression of p53, bcl-2, E-cadherin, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinases-1 in paired primary tumors and brain metastasis.

The objectives of this study were to: (a) characterize the immunohistochemical expression of p53, bcl-2, E-cadherin (EC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) in brain metastases; (b) compare immunohistochemical (IHC) expression of brain metastases with their primary tumors; and (c) assess the prognostic value of expression of these markers. Tumors from 35 patients with brain metastasis were studied for IHC expression of p53, bcl-2, EC, MMP-9, and TIMP-1. In 17 cases, primary tumors were also available for study. In brain metastases, p53 was positive in 91% of cases and intermediate in 9%, MMP-9 was positive in all cases, TIMP-1 was intermediate in 6% and negative in 94% of cases, EC expression was positive in 86% of cases and intermediate in 14%, and bcl-2 was variable. All primary tumors were positive for p53 and MMP-9, 3% were intermediate for TIMP-1 and 97% were negative, 65% were positive for EC and 35% were intermediate, whereas bcl-2 expression was variable. Neither p53, bcl-2, TIMP-1, or EC staining correlated with overall survival or survival with brain metastases. No assessment of survival differences could be made for MMP-9 because of its overexpression in all tissues. This study found that MMP-9 and p53 were markedly overexpressed in primary tumors and matched brain metastasis, TIMP-1 expression was negative in the majority of specimens, whereas EC expression was maintained in both primary tumors and brain metastases and bcl-2 expression was variable. This study suggests that the functional balance of MMP-9 and TIMP-1 is shifted toward extracellular matrix degradation in brain metastases and that deregulation of cell cycle control by p53 also exists in brain metastases. The high expression of EC may indicate the importance of adherence at late stages of metastasis but requires further study.

Bi-phasic CD34+ cell mobilization of a syngeneic donor during prolonged G-CSF delivery.

BACKGROUND: G-CSF administration over 10 days and neutrophil cytapheresis have been reported in the literature, but the kinetics of CD34+ cells in this situation is unclear. CASE: A 42-year-old female underwent syngeneic transplantation for metastatic breast cancer. The recipient was in critical condition peri-transplant, therefore the donor received G-CSF for 13 days, during which eight cytaphereses for both PBPC and neutrophils were performed. Two peaks in CD34+ cells were noted; the first on Day 5 and the second on Days 10-13 of G-CSF administration; a total of 11.6 x 10(6)/kg CD34+ cells and 38.11 x 10(8)/kg neutrophils were infused. The recipient's ANC exceeded 0.1 x 10(9)/L on Day +3. DISCUSSION: To our knowledge, this is the longest reported cytapheresis of CD34+ cells from a normal donor The bi-phasic pattern in the cytapheresis product is also of interest. It is an unusual pattern that suggests a profound and complicated alteration in the marrow progenitor cell pool. If substantiated, this finding may offer an alternative cytapheresis schedule for donors.

Spinal cord compression due to extramedullary hematopoiesis in beta-thalassemia intermedia.

BACKGROUND: Extramedullary hematopoiesis (EMH) occurs in many disorders, including thalassemias and other hemoglobinopathies, and commonly presents in the spleen and liver. We present a case of spinal cord compression in a patient with beta-thalassemia intermedia, and review the literature and available treatment options. PATIENT AND METHODS: A 35-year-old black female with beta-thalassemia intermedia presented with a 3-week history of back pain and lower extremity weakness. Neurologic examination was consistent with spinal cord compression, and gadolinium enhanced magnetic resonance imaging (MRI) confirmed this diagnosis. She was given intravenous steroids and radiotherapy was begun in 200 cGy fractions to a total dose of 2000 cGy. RESULTS: At the completion of radiotherapy the patient was ambulatory with mild residual weakness. MRI scans 16 months later showed smaller, but persistent masses, and she remains asymptomatic 5 years from her diagnosis. CONCLUSION: Recognition of spinal cord EMH requires prompt physical examination and MRI for accurate diagnosis. EMH can be managed with radiation, surgery, transfusions, or a combination of these therapies. Radiation in conservative doses of (750-3500 cGy) is non-invasive, avoids the surgical risks of potentially severe hemorrhage and incomplete resection, and has a high complete remission rate in the majority of patients. Relapse rates are moderate (37.5%), but retreatment provides excellent chance for second remission.

Two siblings poisoned with diphenhydramine: a case of factitious disorder by proxy.

We report a case of factitious disorder by proxy (FDBP), formerly known as Munchausen syndrome by proxy, in which 2 siblings were poisoned with diphenhydramine. Although diphenhydramine is a readily available medication, no report of its use as the sole agent in an FDBP case was found in a literature search. Although sibling involvement in FDBP is well documented, this is the first case report of 2 siblings hospitalized simultaneously because of intentional poisoning with the same substance. Finally, the use of physostigmine to definitively diagnose anticholinergic poisoning in a case of FDBP has not previously been described.