Prevalence of Prolonged Grief Disorder (PGD) among bereaved relatives in a Malaysia Palliative Care Unit (PCU).

INTRODUCTION: Prolonged grief disorder (PGD) is a diagnosis characterised by severe, persistent and disabling grief beyond 6 months post-death of a loved one. The new text revision of DSM-5 (DSM-5-TR) approved a new diagnosis PGD on March 2022. In Malaysia, PGD is not routinely screened in healthcare settings and hence goes untreated. The aim of this study is to identify prevalence and factors related to PGD among bereaved relatives whose loved ones had access to PCU services. MATERIALS AND METHODS: A cross-sectional study involving bereaved individuals in Palliative Care Unit Hospital Selayang. Participants (n=175) were recruited through telephone, and a validated tool Prolonged Grief Disorder Scale (PG-13) was asked to identify PGD. Further data collected were concomitant stressors in life and support system in the bereaved individual. RESULTS: Prevalence of PGD was 2.9% (n=5), and subthreshold PGD was 4% (n=7). A model of multiple logistic regression calculated most of the traditional risk factors were not significant except having an increased responsibility as a single parent after passing of a spouse or loved one, had 10 times increased odds of PGD (Odds Ratios: 10.93; 95% Confidence Interval: 2.937, 40.661). Otherwise, immediate family support (80%), religion (60%) and community (40%) support were the top three coping mechanisms of our PGD cohort, although they were not significant in a multiple logistic regression model. CONCLUSION: Our PGD percentage may not be as high as those of other countries, but nonetheless they exist and their needs are just as important. The authors hope that this paper may create an awareness among the healthcare clinicians about PGD in our society, for a greater access of service to understand them and better public awareness.

Characteristics, symptom management and outcomes in Covid-19 patients referred to palliative care in a tertiary hospital: A retrospective observational study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) variants pose unique challenges with inevitable premature death when cases of severe disease exponentially rise in a healthcare system. It is imperative that palliative care is provided with a proactive approach to symptom recognition, assessment, management and treatment escalation to ensure comfort throughout the course of this illness. OBJECTIVES: To evaluate the characteristics, symptom burden, palliative care management and outcomes of COVID-19 patients referred to a palliative care unit (PCU) in a single tertiary hospital. Clinical outcomes specifically observed the management of agitation in these patients based on their Richmond Agitation and Sedation Scale (RASS) scores. METHODS: A retrospective observational study was conducted in a tertiary hospital by reviewing electronic medical records and extracting data from 1st June 2021to 31st July 2021 of all COVID-19 patients referred to the PCU. RESULTS: A cohort of 154 (75 males, 79 females) COVID-19 patients was referred to the PCU with a mean age of 67 (20- 95) years. The median number of days of COVID-19 illness before referral was 7(4-11), with 79.3% of patients being in categories 4 and 5. The median duration of the PCU involvement was 4(1-24) days; 74% of families were engaged in virtual platform communication. The most prevalent symptoms were dyspnoea (73.4%) and agitation (41.6%). Common medications used were opioids, antipsychotics and benzodiazepines. Among agitated patients, none had RASS scores above +2 in the last encounter. Palliative care doctors in the team reported complete effectiveness in patient's symptom control in 74% of patients. CONCLUSIONS: A hallmark of severe COVID-19 is rapid deterioration, which calls for proactive assessment and urgent palliation. Breathlessness and agitation are priority symptoms to address. Among agitated patients, benzodiazepines and antipsychotics are highly effective in addressing agitation and reducing RASS scores. Communication with families using virtual platforms is effective in providing a supportive presence and closure when face-to-face communication is not possible.

Effects of cost surface uncertainty on current density estimates from circuit theory.

BACKGROUND: Conservation practitioners are often interested in developing land use plans that increase landscape connectivity, which is defined as the degree to which the landscape facilitates or impedes movement among resource patches. Landscape connectivity is often estimated with a cost surface that indicates the varying costs experienced by an organism in moving across a landscape. True, or absolute costs are rarely known however, and therefore assigning costs to different landscape elements is often a challenge in creating cost surface maps. As such, we consider it important to understand the sensitivity of connectivity estimates to uncertainty in cost estimates. METHODS: We used simulated landscapes to test the sensitivity of current density estimates from circuit theory to varying relative cost values, fragmentation, and number of cost classes (i.e., thematic resolution). Current density is proportional to the probability of use during a random walk. Using Circuitscape software, we simulated electrical current between pairs of nodes to create current density maps. We then measured the correlation of the current density values across scenarios. RESULTS: In general, we found that cost values were highly correlated across scenarios with different cost weights (mean correlation ranged from 0.87 to 0.92). Changing the spatial configuration of landscape elements by varying the degree of fragmentation reduced correlation in current density across maps. We also found that correlations were more variable when the range of cost values in a map was high. DISCUSSION: The low sensitivity of current density estimates to relative cost weights suggests that the measure may be reliable for land use applications even when there is uncertainty about absolute cost values, provided that the user has the costs correctly ranked. This finding should facilitate the use of cost surfaces by conservation practitioners interested in estimating connectivity and planning linkages and corridors.

A comparison of single-dose dexmedetomidine or propofol on the incidence of emergence delirium in children undergoing general anaesthesia for magnetic resonance imaging.

Emergence delirium is a significant problem in children regaining consciousness following general anaesthesia. We compared the emergence characteristics of 120 patients randomly assigned to receive a single intravenous dose of dexmedetomidine 0.3 µg.kg(-1) , propofol 1 mg.kg(-1) , or 10 ml saline 0.9% before emerging from general anaesthesia following a magnetic resonance imaging scan. Emergence delirium was diagnosed as a score of 10 or more on the Paediatric Anaesthesia Emergence Delirium scale. The incidence of emergence delirium was 42.5% in the dexmedetomidine group, 33.3% in the propofol group and 41.5% in the saline group (p = 0.671). Three patients in the dexmedetomidine group, none in the propofol group and two in the saline group required pharmacological intervention for emergence delirium (p = 0.202). Administration of neither dexmedetomidine nor propofol significantly reduced the incidence, or severity, of emergence delirium. The only significant predictor for emergence delirium was the time taken to awaken from general anaesthesia, with every minute increase in wake-up time reducing the odds of emergence delirium by 7%.

Ferriman-Gallwey scores, serum androgen and mullerian inhibiting substance levels in hirstute adolescent girls.

OBJECTIVE: To study Ferriman-Gallwey (FG) scoring in adolescents with an aim to correlate these scores with serum androgens and mullerian inhibiting substance (MIS). DESIGN: Cross sectional study. SETTING: Pediatric and Adolescent Gynecology Clinic of a university hospital. PATIENTS: Twenty-four hirsute adolescent girls age 12-19 with a FG score of 6 or greater. INTERVENTIONS: FG examination and collection of serum levels of MIS, total testosterone, free testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, cortisol, and androstenedione. MAIN OUTCOME MEASURES: Correlation between FG scores in adolescents and serum androgens and MIS. RESULTS: Weak correlations were seen between FG score and FSH, free-testosterone, total testosterone, and cortisol. Increasing FG scores correlated with an increase in cortisol. As FG score increased, FSH, free-testosterone, and total testosterone decreased. There was no statistical relationship between FG score and LH, androstenedione, prolactin, and MIS. There were weak positive correlations between MIS levels and FSH, total testosterone, and androstenedione. There was no evidence for a linear relationship between MIS levels and LH, free testosterone, cortisol, prolactin, and FG score. CONCLUSIONS: The utility of FG scoring in adolescents is unknown. There were no direct correlations found with MIS levels and FG score. MIS was not found to be a predictor of hirsutism. A larger study is needed to assess the clinical relevance of FG scoring and presence of underlying causes of hirsutism in adolescents.

Methylene blue related sterile endophthalmitis.

To report a case of methylene blue related endophthalmitis. Observational case report. Review of clinical record, photographs. A 60 year old man developed endophthalmitis after methylene blue was accidentally used to stain the anterior capsule during phacoemulsification of cataract. His left visual acuity deteriorated from 6/12 to 6/36 two weeks after the operation. Despite intensive treatment with topical and intravitreal antibiotics, his condition deteriorated. A vitrectomy and silicone oil injection eventually managed to control the progression of the disease and salvage the eye. However the visual outcome remained poor due to corneal decompensation and retinal ischemia. Both vitreous tap and vitreous biopsy were negative for any organism. Methylene blue is extremely toxic to ocular structures and should not be used intraocularly.

Bilateral corneal perforation in a sexually active adult male with gonococcal conjunctivitis.

A 41 year-old Malay man had been treated by general practitioners for bilateral red eyes with profuse discharge of three weeks' duration with no improvement. He then presented to an ophthalmologist who noted profuse purulent discharge, bilateral corneal perforation, lid swelling and chemosis. Culture of the ocular discharge grew Neisseria gonorrhoeae. Treatment with systemic and topical antibiotics prevented microperforations in the right eye from progressing to overt perforation and was able to control disease in the left eye.

Cervical myelopathy caused by an exostosis of the posterior arch of C1.

We report a case of vertebral osteochondroma of C1 causing cord compression and myelopathy in a patient with hereditary multiple exostosis. We highlight the importance of early diagnosis and the appropriate surgery in order to obtain a satisfactory outcome.

Symptomatology and health status in patients with chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD) is a growing health problem worldwide and in Malaysia. Until recently, research on COPD has been slow and difficult, partly due to the huge heterogeneity of this disease, and its variable and imprecise definitions. To perform a descriptive study on a convenient sample of local patients with COPD treated in a state hospital in Malaysia. Fifty-two patients [mean (95% CI) age: 67 (63-70) years; 86% male: 38% Malays, 36% Chinese, 25% Indians; mean (95% CI) PEFR: 45 (40-51) % predicted normal] were interviewed. Clinico-demographic data was collected using a structured questionnaire and health-related quality of life was scored using St George's Respiratory Questionnaire (SGRQ). For analysis, patients were also divided into moderate (n=17) [PEFR 50% to 80%] and severe (n=35) [PEFR < 50%] disease groups. Except for education and total family income, demographic and comorbidity variables were comparable between the two groups of COPD severity. All except 9% of patients were current or ex-smokers. Breathlessness, not chronic bronchitis (i.e. cough and sputum), was the first ranking respiratory symptom in over 70% of the patients, whether currently or at early disease manifestation. Between 5 and 15% of the patients denied any symptom of chronic bronchitis as current or early stage symptoms. Duration of symptoms prior to the diagnosis varied considerably with about 9% having symptoms for over 10 years. Over 80% of the patients smoked for over 15 years before the onset of symptoms. Quality of life in patients with COPI) was generally poor and similar between both COPD severity groups. About one fifth of the patients had exacerbations more than 12 times a year. While many features described in our local patients are well recognized in COPD, the finding that 'chronic bronchitis' is not a prominent symptom in the current or past history may have important implications in the diagnosis of at risk individuals and patients with early disease requiring attention. More research is required to confirm and to understand this.

Hyperhomocysteinemia and impaired vasomotor function in type 2 diabetes mellitus.

BACKGROUND: Hyperhomocysteinemia has been shown to adversely affect vascular function. The aim of this study was to determine whether hyperhomocysteinemia was independently associated with changes in endothelium-dependent and -independent vasomotor functions in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Fasting homocysteine (tHcy) was measured in 123 patients with type 2 diabetes and in 61 nondiabetic controls. Endothelium-dependent and -independent vasodilation was measured using high-resolution vascular ultrasound. RESULTS: Plasma tHcy concentration was increased in the diabetic patients (11.1 +/- 3.7 micromol L(-1) vs. 9.8 +/- 2.9, P < 0.05). The prevalence of hyperhomocysteinemia (defined as tHcy > 15 micromol L(-1)) was higher in the diabetic patients (P < 0.05). Within group comparisons showed that both the abnormalities in endothelium-dependent and -independent vasodilation were significantly more severe in diabetic patients with tHcy 10-15 (P < 0.05) and tHcy > 15 micromol L(-1) (P < 0.05) than in those patients with tHcy < 10 micromol L(-1). When compared with nondiabetic controls matched for tHcy levels, impairment of endothelium-dependent and -independent vasodilation were already evident, even in patients with normal tHcy levels (P < 0.01). Despite significant univariate relationships between tHcy and endothelium-dependent (r = -0.24, P < 0.01) and -independent vasodilation (r = -0.33, P < 0.01) in patients with diabetes, only the relationship between tHcy and endothelium-independent vasodilation remained significant after adjusting for other cardiovascular risk factors in multiple regression analysis. CONCLUSIONS: Impairment of endothelium-dependent and -independent vasodilation was already present in diabetic patients with normal tHcy levels, and these abnormalities became more severe with increasing tHcy levels. Only the association between tHcy and endothelium-independent vasodilation was free of other cardiovascular risk factors.

Effect of postmenopausal hormone replacement therapy on lipoprotein and homocysteine levels in Chinese women.

Epidemiological studies have revealed that postmenopausal estrogen replacement therapy results in a marked reduction in the risk for cardiovascular diseases. In the present study, we evaluated plasma lipoprotein profile as well as homocysteine levels in 145 postmenopausal and premenopausal Chinese women living in Hong Kong. We also investigated the effect of hormone-replacement therapy (HRT) with estrogen or estrogen combined with progestin on plasma lipoprotein profile and homocysteine concentrations in those individuals. Postmenopausal women displayed significantly higher plasma levels of total cholesterol, LDL-cholesterol and apoB as well as higher plasma homocysteine levels than that of premenopausal women. HRT with either estrogen (17beta-estradiol or conjugated equine estrogen) alone or estrogen combined with progestin for 3.5-4.5 years significantly improved the lipoprotein profile in postmenopausal women by decreasing the levels of total cholesterol (12-20% reduction), LDL-cholesterol (26-29% reduction) and apoB (21-25% reduction). In women treated with 17beta-estradiol or conjugated equine estrogens their plasma levels of apoAl were significantly elevated (18% elevation) as compared to non-users. HRT also reduced plasma concentrations of homocysteine (13-15% reduction). In conclusion, we found that long-term HRT was associated with improvement in plasma lipoprotein profile and a reduction in homocysteine concentration in postmenopausal women. These results support the notion that the improvement of lipoprotein profile and a reduction in homocysteine concentration may contribute to the beneficial effect of HRT on cardiovascular risk.

Lipoprotein-X stimulates monocyte chemoattractant protein-1 expression in mesangial cells via nuclear factor-kappa B.

BACKGROUND: Lipoprotein-X (Lp-X) is an abnormal lipoprotein found in the plasma of patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency. The majority of patients with this disorder develop progressive glomerulosclerosis. One key event in the pathogenesis of glomerulosclerosis is the infiltration of monocytes into affected glomeruli. Mesangial cells can synthesize and secrete monocyte chemoattractant protein-1 (MCP-1), an important chemoattractant for monocytes. The objective of the present study was to examine the effect of Lp-X on MCP-1 expression in mesangial cells leading to an enhanced monocyte chemotaxis and to elucidate the mechanisms involved in this process. METHODS: Lp-X was isolated from the plasma of a patient with familial LCAT deficiency. After rat mesangial cells were incubated with Lp-X for four or six hours, the expression of MCP-1 mRNA was determined by nuclease protection assay, and MCP-1 protein was measured by Western immunoblotting analysis. Monocyte chemotaxis was determined by using a Micro Chemotaxis Chamber. RESULTS: Lp-X (50 to 100 nmol/mL) stimulated mesangial cell MCP-1 mRNA expression (137 to 220%) and MCP-1 protein levels (233 to 375%). Conditioned media collected from Lp-X-treated mesangial cells stimulated human acute monocytic leukemia (THP-1) monocyte chemotaxis (165 to 200%). The increase in MCP-1 expression in mesangial cells was associated with an elevation of intracellular diacylglycerol levels, and activation of protein kinase C (PKC) as well as nuclear factor-kappa B (NF-kappa B). CONCLUSION: These results suggest that Lp-X participates in the pathogenesis of glomerulosclerosis and subsequent renal failure in familial LCAT deficient patients by stimulating monocyte infiltration via a mechanism involving mesangial MCP-1 expression.

Inhibition of stress-activated protein kinase in the ischemic/reperfused heart: role of magnesium tanshinoate B in preventing apoptosis.

The activation of stress-activated protein (SAP) kinase may lead to an induction of apoptosis that is responsible for part of the cardiomyocyte death in reperfusion injury. The objective of the present study was to investigate the mechanism by which magnesium tanshinoate B (MTB), a bioactive compound isolated from Danshen, prevents apoptosis in cardiomyocytes in the ischemic/reperfused heart. Isolated adult rat hearts were perfused by the Langendorff mode with medium containing MTB prior to the induction of normothermic global ischemia. At the end of the 30-min ischemic period, the heart was reperfused with the same medium with or without MTB for an additional 20 min. In the MTB-treated ischemic/reperfused heart, the number of apoptotic nuclei was reduced by 2.5-fold in comparison to that in untreated ischemic/reperfused controls [23 +/- 4 vs 57 +/- 7 (mean +/- SD) TUNEL-positive cells, respectively, N = 3-4, P < 0.001]. SAP kinase activity was elevated 1.7-fold in ischemic/reperfused rat hearts [35.6 +/- 3.8 vs 21.2 +/- 3.3 (control) (mean +/- SEM) relative densitometric units, N = 4-6, P < 0.05]. Treatment with MTB abolished this elevation in SAP kinase activity (25.0 +/- 5.2 relative densitometric units), which was also decreased by 40% in the nucleus. When the heart was subjected to ischemia alone, there was no significant change in SAP kinase activity in the presence or absence of MTB. MTB did not appear to affect the p38 mitogen-activated protein kinase activity in this model system. In conclusion, MTB was shown to have cardioprotective activity against apoptosis, probably through the inhibition of SAP kinase activity.

Homocysteine induces monocyte chemoattractant protein-1 expression by activating NF-kappaB in THP-1 macrophages.

Homocysteinemia is an independent risk factor for cardiovascular disorders. The recruitment of monocytes is an important event in atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates monocyte migration into the intima of arterial walls. The objective of the present study was to investigate the effect of homocysteine on MCP-1 expression in macrophages and the underlying mechanism of such effect. Human monocytic cell (THP-1)-derived macrophages were incubated with homocysteine. By nuclease protection assay and ELISA, homocysteine (0.05-0.2 mM) was shown to significantly enhance the expression of MCP-1 mRNA (up to 2.6-fold) and protein (up to 4.8-fold) in these cells. Homocysteine-induced MCP-1 expression resulted in increased monocyte chemotaxis. The increase in MCP-1 expression was associated with activation of nuclear factor (NF)-kappaB due to increased phosphorylation of the inhibitory protein (IkappaB-alpha) as well as reduced expression of IkappaB-alpha mRNA in homocysteine-treated cells. In conclusion, our results demonstrate that homocysteine, at pathological concentration, stimulates MCP-1 expression in THP-1 macrophages via NF-kappaB activation.

Inhibition by ginkgolides and bilobalide of the production of nitric oxide in macrophages (THP-1) but not in endothelial cells (HUVEC).

Nitric oxide (NO) is a principal mediator in many physiological and pathological processes. NO produced by constitutive nitric oxide synthase in endothelial cells (eNOS) acts as a vasodilator, whereas excess NO production due to elevated expression of inducible nitric oxide synthase (iNOS) may produce cytotoxic effects to cells in the vascular wall. We demonstrated in our previous work that the extract of Ginkgo biloba leaves (EGb) inhibits iNOS-mediated NO production. The objective of the present study was to investigate the effects of several active EGb components on iNOS-mediated NO production in macrophages derived from a human monocytic cell line (THP-1), as well as on eNOS-mediated NO production in human umbilical vein endothelial cells (HUVEC). Ginkgolide A, ginkgolide B, or bilobalide (0.25 to 1.0 microg/mL) caused a 30-65% reduction in the levels of NO metabolites released by THP-1 macrophages after 4 hr of incubation, with a corresponding decrease in iNOS activity. Western immunoblotting analysis coupled with a nuclease protection assay and reverse transcription-polymerase chain reaction revealed a concomitant reduction in the levels of iNOS protein mass and mRNA in ginkgolide A-, ginkgolide B-, or bilobalide-treated macrophages. On the other hand, these compounds did not affect eNOS-mediated NO production or the expression of eNOS protein and mRNA in HUVEC. Taken together, these results suggest that ginkgolide A, ginkgolide B, and bilobalide may contribute to the selective inhibitory effect of EGb on iNOS expression without affecting eNOS-mediated NO production.

Magnesium tanshinoate B (MTB) inhibits low density lipoprotein oxidation.

Danshen, a Chinese herbal medicine has been widely used for the treatment of cardiovascular diseases. Magnesium tanshinoate B (MTB) is an active compound purified from Danshen. The objective of this study was to investigate the effect of MTB on the susceptibility of low density lipoproteins (LDL) to oxidative modification as well as on the accumulation of lipids in THP-1 derived macrophages. Aliquots of LDL were incubated with copper sulfate in the absence or presence of MTB. The degrees of oxidative modification of LDL were assessed by examining the relative gel electrophoretic mobility, by measuring the amount of thiobarbituric acid reactive substances (TBARS), and by continuous monitoring of the formation of conjugated dienes upon the increase in absorbency at 234 nm. MTB at concentrations of 1-10 microM significantly inhibited oxidative modification of LDL. Such inhibitory effect resulted in a decrease in the uptake of LDL by THP-1 derived macrophages. Taken together, these results clearly demonstrate that MTB inhibits oxidative modification of LDL and hence prevents the uptake of LDL by cultured macrophages. Such effect may be therapeutically relevant in protecting cells from lipid peroxidation in vascular disorders.

Homocysteine stimulates nuclear factor kappaB activity and monocyte chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible role for protein kinase C.

Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates the migration of monocytes into the intima of arterial walls. Although many factors that induce MCP-1 expression have been identified, the effect of homocysteine on the expression of MCP-1 in atherogenesis and the underlying mechanisms are not entirely clear. The objective of the present study was to investigate the role of homocysteine in MCP-1 expression in human aorta vascular smooth-muscle cells (VSMCs). After VSMCs were incubated with homocysteine for various time periods, a nuclease protection assay and ELISA were performed. Homocysteine (0.05-0.2 mM) significantly increased the expression of MCP-1 mRNA (up to 2. 7-fold) and protein (up to 3.3-fold) in these cells. The increase in MCP-1 expression was associated with the activation of protein kinase C (PKC) as well as nuclear factor kappaB (NF-kappaB). Further investigation demonstrated that the activation of NF-kappaB was the result of a PKC-mediated reduction in the expression of inhibitory protein (IkappaBalpha) mRNA and protein in homocysteine-treated cells. Oxidative stress might also be involved in the activation of NF-kappaB by homocysteine in VSMCs. In conclusion, the present study has clearly demonstrated that the activation of PKC as well as superoxide production followed by activation of NF-kappaB is responsible for homocysteine-induced MCP-1 expression in VSMCs. These results suggest that homocysteine-stimulated MCP-1 expression via NF-kappaB activation may play an important role in atherogenesis.