Epstein-Barr virus-associated acute pancreatitis.

Epstein-Barr virus (EBV) infection is mostly subclinical and resolves spontaneously without complications. Gastroenterology involvement usually manifests as asymptomatic liver enzymes elevation. We report a new case of acute pancreatitis complicating EBV infection and review the literature. EBV-associated acute pancreatitis is rare, usually develops in the setting of clinically clear EBV infection, occurs mostly in children and young adults, has mild-to-moderate severity, and has excellent prognosis with conservative management. It should be suspected when patients with an EBV infection picture develop unexplained abdominal pain.

Lay People's Ethical Attitudes To Placebo Treatment: A Q-Methodology Study.

BACKGROUND: Placebo-treatment acceptability is debated among ethicists, mostly due to conflict between respect-to-autonomy and beneficence principles. It is not clear how lay people balance these and other ethical principles. METHODS: One hundred and eighty-seven respondents rank-ordered 42 opinion statements covering various ethical aspects of placebo-treatment, according to a 9-category symmetrical distribution. We analyzed statements' scores using averaging-analysis and by-person factor analysis (Q-methodology). RESULTS: Respondents' mean (SD) age was 34.6 (10.6) years, 54% were women, 40% healthcare-related, 68% Muslims (31% Christians), and 39% received general education in Saudi Arabia (24% in the Philippines). On averaging-analysis, the most-agreeable statements were "Acceptable if benefit to patient large" and "Acceptable with physician intent to benefit patient". The most-disagreeable statements were "Acceptable with physician self-benefit intent" and "Acceptable with large harm to other patients". Muslims gave a higher rank to "Giving no description is acceptable", "Acceptable with small benefit to patient", and "Acceptable with physician intent to benefit patient" and a lower rank to "Acceptable to describe as inactive drug", "Acceptable with physician intent to please patient caring relative", and "Acceptable with moderate harm to other patients" (p<0.01). Q-methodology detected several ethical attitude models that were mostly multi-principled and consequentialism-dominated. The majority of Christian and Philippines-educated women loaded on a "relatively family and deception-concerned" model, whereas the majority of Muslim and Saudi Arabia-educated women loaded on a "relatively common-good-concerned" model. The majority of Christian and healthcare men loaded on a "relatively deception-concerned" model, whereas the majority of Muslim and non-healthcare men loaded on a "relatively motives-concerned" model. Of nine intent-related statements, ≥2 received extreme rank on averaging-analysis and in 100% of women and men models. CONCLUSION: 1) On averaging-analysis, patient's beneficence (consequentialism) followed by physician's intent (virtue ethics) were more important than deception (respect-to-autonomy). 2) Q-methodology identified several ethical attitude models that were mostly multi-principled and associated with respondents' demographics.

Vitamin-D2 treatment-associated decrease in 25(OH)D3 level is a reciprocal phenomenon: a randomized controlled trial.

BACKGROUND: Vitamin-D2 (D2) treatment has been associated with a decrease in 25-hydroxy (25(OH)) vitamin-D3 (D3) level, suggesting that D3 treatment would be preferred to raise total 25(OH) vitamin-D (D) level. We postulated that D2 treatment-associated decrease in 25(OH)D3 level is related to the increase in 25(OH)D level rather than being D2-specific, and thus there would be a similar D3 treatment-associated decrease in 25(OH)D2 level. METHODS: Fifty volunteers were block-randomized to 50,000 IU D2 or placebo orally once (study-1) and fifty volunteers received 50,000 IU D2 orally once and 4 days later block-randomized to 50,000 IU D3 or placebo orally once (study-2). Interventions were concealed from volunteers and research coordinators and blindly-administered. Serum 25(OH)D2 and 25(OH)D3 levels were blindly-determined at baseline and days 14, 28, 42, and 56, post-randomization by high performance liquid chromatography assay. Results of 97 participants were analyzed. Primary outcome measure was day-28 D2-associated change in 25(OH)D3 level in study-1 and D3-associated change in 25(OH)D2 level in study-2, adjusted for baseline levels. RESULTS: Mean (95% confidence interval) difference between the active and placebo arms in the decrease in day-28 25(OH)D3 (study-1) and 25(OH)D2 (study-2) levels was 13.2 (9.7 to 16.6) and 9.8 (5.2 to 14.4) nmol/L, respectively. Corresponding differences at day-56 were 10.8 (6.8 to 14.8) and 1.7 (- 7.6 to 11.1) nmol/L, respectively. The difference between the placebo and active arms in area-under-the-curve at day-28 (AUC28) and day-56 (AUC56) were 262.3 (197.8 to 326.7) and 605.1 (446.3 to 784.0) for 25(OH)D3 (study-1) and 282.2 (111.2 to 453.3) and 431.2 (179.3 to 683.2) nmol.d/L for 25(OH)D2 (study-2), respectively. There were significant correlations between day-28 changes in 25(OH)D2 and 25(OH)D3 levels in study-1 (rho = - 0.79, p < 0.001) and study-2 (rho = - 0.36, p = 0.01), and between day-28 changes in 25(OH)D2 level and baseline 25(OH)D level in study-2 (rho = - 0.42, p = 0.003). CONCLUSIONS: Compared to placebo, D3 treatment is associated with a decrease in 25(OH)D2 level similar in magnitude to D2-treatment associated decrease in 25(OH)D3 level; however, the D3-placebo difference in 25(OH)D2 level is shorter-lasting. Changes in 25(OH)D2 and 25(OH)D3 levels are correlated with each other and with baseline 25 (OH) D levels, suggesting a common regulatory mechanism. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT03035084 (registered January 27, 2017).

Drug*placebo interaction effect may bias clinical trials interpretation: hybrid balanced placebo and randomized placebo-controlled design.

BACKGROUND: Conventional randomized placebo-controlled study design assumes the absence of drug*placebo interaction. We hypothesized the presence of such an interaction and that conventionally estimated drug effect might be biased. The objectives of the study were to determine the drug*placebo interaction effect (main) and compare conventionally estimated and interaction model-estimated drug effects (secondary). METHODS: We used a hybrid of balanced placebo and randomized placebo-controlled designs. Four hundred eighty healthy volunteers were randomized to three groups. The first received hydroxyzine (25 mg) described as hydroxyzine or placebo, the second received placebo described as hydroxyzine or placebo, and the third received hydroxyzine and placebo described as unknown; each in a randomized crossover design. Seven participants failed to crossover. Group assignment was concealed from participants and study coordinators. Coordinators were blinded to group and intervention assignment. Participants and coordinators were deceived as to study objectives. Main outcomes were mean area-under-the-curve of drowsiness (therapeutic outcome) and mouth-dryness (adverse outcome), self-reported on 100 mm visual analog scale over 7 h. Drug, placebo, placebo + interaction, and total effects were estimated using analysis of covariance by comparing received hydroxyzine/told placebo to received placebo/told placebo, received placebo/told hydroxyzine to received placebo/told placebo, received hydroxyzine/told hydroxyzine to received hydroxyzine/told placebo, and received hydroxyzine/told hydroxyzine to received placebo/told placebo, respectively. Drug effect was also conventionally estimated in the third group. RESULTS: Mean (SD) age was 31.4 (6.6) years, 65% were males. There was significant difference between placebo + interaction effect and placebo effect for both drowsiness and mouth-dryness with a mean difference (95% confidence interval) of 35.1 (5.6 to 64.6) and 23.8 (2.4 to 45.2) mm*hr, respectively. Total effect was larger than the sum of drug and placebo effects for drowsiness (139.7 (109.8 to 169.6) vs. 99.1 (68.2 to 130.0) mm*hr) and mouth-dryness (63.6 (41.1 to 86.1) vs. 34.7 (11.1 to 58.4) mm*hr). Conventionally estimated drug effect was larger than interaction model-estimated drug effect for drowsiness (69.2 (45.5 to 92.8) vs. (58.3 (31.6 to 85.0) mm*hr) and mouth-dryness (19.9 (5.3 to 34.5) vs. 9.5 (-9.2 to 28.1) mm*hr). CONCLUSIONS: There is significant and important drug*placebo interaction effect that may bias conventionally estimated drug effect. TRIAL REGISTRATION: ClinicalTrial.gov identifier: NCT01501591 (registered December 25, 2011).

Typology of end-of-life priorities in Saudi females: averaging analysis and Q-methodology.

BACKGROUND: Understanding culture-and sex-related end-of-life preferences is essential to provide quality end-of-life care. We have previously explored end-of-life choices in Saudi males and found important culture-related differences and that Q-methodology is useful in identifying intraculture, opinion-based groups. Here, we explore Saudi females' end-of-life choices. METHODS: A volunteer sample of 68 females rank-ordered 47 opinion statements on end-of-life issues into a nine-category symmetrical distribution. The ranking scores of the statements were analyzed by averaging analysis and Q-methodology. RESULTS: The mean age of the females in the sample was 30.3 years (range, 19-55 years). Among them, 51% reported average religiosity, 78% reported very good health, 79% reported very good life quality, and 100% reported high-school education or more. The extreme five overall priorities were to be able to say the statement of faith, be at peace with God, die without having the body exposed, maintain dignity, and resolve all conflicts. The extreme five overall dis-priorities were to die in the hospital, die well dressed, be informed about impending death by family/friends rather than doctor, die at peak of life, and not know if one has a fatal illness. Q-methodology identified five opinion-based groups with qualitatively different characteristics: "physical and emotional privacy concerned, family caring" (younger, lower religiosity), "whole person" (higher religiosity), "pain and informational privacy concerned" (lower life quality), "decisional privacy concerned" (older, higher life quality), and "life quantity concerned, family dependent" (high life quality, low life satisfaction). Out of the extreme 14 priorities/dis-priorities for each group, 21%-50% were not represented among the extreme 20 priorities/dis-priorities for the entire sample. CONCLUSION: Consistent with the previously reported findings in Saudi males, transcendence and dying in the hospital were the extreme end-of-life priority and dis-priority, respectively, in Saudi females. Body modesty was a major overall concern; however, concerns about pain, various types of privacy, and life quantity were variably emphasized by the five opinion-based groups but masked by averaging analysis.

Vitamin D deficiency plays an important role in cardiac disease and affects patient outcome: Still a myth or a fact that needs exploration?

There is increasing evidence that a low vitamin D status may be an important and hitherto neglected factor of cardiovascular disease. This review is an overview of the current body of literature, and presents evidence of the mechanisms through which vitamin D deficiency affects the cardiovascular system in general and the heart in particular. Available data indicate that the majority of congestive heart failure patients have 25-hydroxyvitamin D deficiency. Furthermore, the low serum 25-hydroxyvitamin D level has a higher impact on hypertension, coronary artery disease an on the occurrence of relevant cardiac events. A serum 25-hydroxyvitamin D level below 75 nmol/l (30 ng/l) is generally regarded as vitamin D insufficiency in both adults and children, while a level below 50 nmol/l (20 ng/l) is considered deficiency. Levels below 50 nmol/l (20 ng/l) are linked independently to cardiovascular morbidity and mortality.

Exploring end of life priorities in Saudi males: usefulness of Q-methodology.

BACKGROUND: Quality end-of-life care depends on understanding patients' end-of-life choices. Individuals and cultures may hold end-of-life priorities at different hierarchy. Forced ranking rather than independent rating, and by-person factor analysis rather than averaging may reveal otherwise masked typologies. METHODS: We explored Saudi males' forced-ranked, end-of-life priorities and dis-priorities. Respondents (n = 120) rank-ordered 47 opinion statements on end-of-life care following a 9-category symmetrical distribution. Statements' scores were analyzed by averaging analysis and factor analysis (Q-methodology). RESULTS: Respondents' mean age was 32.1 years (range, 18-65); 52% reported average religiosity, 88 and 83% ≥ very good health and life-quality, respectively, and 100% ≥ high school education. Averaging analysis revealed that the extreme five end-of-life priorities were to, be at peace with God, be able to say the statement of faith, maintain dignity, resolve conflicts, and have religious death rituals respected, respectively. The extreme five dis-priorities were to, die in the hospital, not receive intensive care if in coma, die at peak of life, be informed about impending death by family/friends rather than doctor, and keep medical status confidential from family/friends, respectively. Q-methodology classified 67% of respondents into five highly transcendent opinion types. Type-I (rituals-averse, family-caring, monitoring-coping, life-quality-concerned) and Type-V (rituals-apt, family-centered, neutral-coping, life-quantity-concerned) reported the lowest and highest religiosity, respectively. Type-II (rituals-apt, family-dependent, monitoring-coping, life-quantity-concerned) and Type-III (rituals-silent, self/family-neutral, avoidance-coping, life-quality & quantity-concerned) reported the best and worst life-quality, respectively. Type-I respondents were the oldest with the lowest general health, in contrast to Type-IV (rituals-apt, self-centered, monitoring-coping, life-quality/quantity-neutral). Of the extreme 14 priorities/dis-priorities for the five types, 29, 14, 14, 50, and 36%, respectively, were not among the extreme 20 priorities/dis-priorities identified by averaging analysis for the entire cohort. CONCLUSIONS: 1) Transcendence was the extreme end-of-life priority, and dying in the hospital was the extreme dis-priority. 2) Quality of life was conceptualized differently with less emphasize on its physiological aspects. 3) Disclosure of terminal illness to family/close friends was preferred as long it is through the patient. 4) Q-methodology identified five types of constellations of end-of-life priorities and dis-priorities that may be related to respondents' demographics and are partially masked by averaging analysis.

The Effects of Right Ventricular Apical Pacing Frequency on Left Ventricle Function and Pulmonary Artery Pressure.

OBJECTIVE: We studied the effect of the frequency of right ventricular (HV) pacing on left ventricle (LV) function pulmonary hypertension. BACKGROUND: The incidence of new or worsening pulmonary hypertension after permanent pacemaker (PPM) or implantable cardioverter defibrillator (lCD) lead placement has not been well investigated. METHODS: We reviewed the charts of all patients undergoing PPM or ICD lead placement in our electrophysiology laboratory from December 2007 to December 2012. RESULTS: Two hundred and six patients (120 with PPM and 86 with ICD) had baseline echocardiography within six months before, and a follow up study at least six months after lead insertion. The mean age was 74 ± 14 years; 56 percent were men. The follow-up period was 29 ± 19 months. RV pacing was associated with a worsening of left ventricular ejection fraction (LVEF) in patients with high frequency of RV (55 ± 16 vs. 44 ± 18; P = 0.001), but not with those with low frequency pacing (55 ± 16 vs. 54 ± 17; P = 0.87). Similarly, RV pacing was associated with a worsening in both right ventricular systolic pressure (RVSP) (42 ± 14 vs. 48 ± 15; P = 0.01) and Pulmonary Artery Systolic Pressure (PASP) (50 ± 17 vs. 56 ± 18; P = 0.005) in patients with high frequency RV, but not in those with low frequency RV pacing [RVSP (43 ± 12 vs. 46 ± 13; P = 0.06) and PASP (51 ± 15 vs. 54 ± 16; P = 0.11)]. ONCLUSION: PPM or IICD lead implantation worsens LV function and pulmonary hypertension in patients with high frequency of RV pacing frequency. This is probably caused by the mechanical dyssynchrony induced by RV pacing.

The effects of right ventricular apical pacing with transvenous pacemaker and implantable cardioverter defibrillator on mitral and tricuspid regurgitation.

BACKGROUND: The incidence of new or worsening tricuspid regurgitation (TR) or mitral regurgitation (MR) after permanent pacemaker (PPM) or implantable cardioverter defibrillator (ICD) lead placement has not been well investigated. We studied the effect of transvenous leads implantation and right ventricular (RV) pacing on tricuspid and mitral valve regurgitations. METHODS: We reviewed the charts of all patients undergoing PPM or ICD lead placement in our electrophysiology laboratory from December 2001 to December 2006. RESULTS: A total of 206 patients (120 with PPM and 86 with ICD) had baseline echocardiography within 6months before, and a follow up study at least 6months after lead insertion. The mean age was 74±14years; 56% were men. The follow-up period was 29±19months. TR worsened by at least one grade after lead insertion in 44.7% patients (P<0.001). Pre- and post-implant changes in TR severity did not differ with respect to lead type (ICD vs. PPM) or degree of RV pacing dependence. As for MR; patients with high frequency of RV pacing (>40%) had a higher incidence of worsening MR when compared to those with low frequency of RV pacing (44% vs. 19%; P<0.001). CONCLUSION: PPM or ICD lead implantation worsens TR; that effect is probably induced by mechanical interferences with the TV closure and was consistent regardless the lead type or degree of RV Pacing. MR was noted to increase in patients with high frequency of RV pacing frequency; this is probably caused by the mechanical dyssynchrony induced by RV pacing.

Using The Descending Aortic Wall Thickness Measured In Transesophageal Echocardiography As A Risk Marker For Aortic Dissection.

OBJECTIVE: The aim of this study is to estimate whether aortic wall thickness is increased in patients with Aortic dissection (AD) compared to low risk control group and can be used in addition to aortic diameter as a risk marker of AD. BACKGROUND: AD occurs due to pathologies that may increase thickness of the aortic wall. Transesophageal echocardiography (TEE) has the ability to visualize both the thoracic aortic wall and lumen. Aortic diameter has been used to predict aortic dissection and timing of surgery, but it is not always predictive of that risk. METHODS: In 48 patients with AD who underwent TEE were examined retrospectively and compared to 48 control patients with patent foramen ovale (PFO). We measured aortic diameter at different levels, intimal/medial thickness (IMT) and complete wall thickness (CMT). Demographic data and cardiovascular risk factors were reviewed. The data was analyzed using ANOVA and student t test. RESULTS: (AD) patients were older [mean age 66 AD vs. 51 PFO], had more hypertension, diabetes, hyperlipidemia and Coronary artery disease. Both IMT and CMT in the descending aorta were increased in AD group [(1.85 vs. 1.43 mm; P=0.03 and 2.93 vs. 2.46 mm; p=0.01). As expected the diameter of ascending aorta was also greater in AD (4.61 vs. 2.92 cm; P=0.004). CONCLUSIONS: CMT and IMT in the descending aorta detected by TEE is greater in patients with AD when compared to control and may add prognostic data to that of aortic diameter.