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Background The COVID-19 pandemic has strained ICUs worldwide. To learn from our experience, we described the critical care response to the outbreak. Methods This is a case study of the response of the Intensive Care Department (75-bed capacity) at a tertiary-care hospital to COVID-19 pandemic, which resulted in a high number of critically ill patients. Results Between March 1 and July 31, 2020, 822 patients were admitted to the adult non-cardiac ICUs with suspected (72%)/confirmed (38%) COVID-19. At the peak of the surge, 125 critically ill patients with COVID-19 were managed on single day. To accommodate these numbers, the bed capacity of 4 ICUs was increased internally from 58 to 71 beds (+40%) by cohorting 2 patients/room in selected rooms; forty additional ICUs beds were created in 2 general wards; one cardiac ICU was converted to managed non-COVID-19 general ICU patients and one ward was used as a stepdown for COVID-19 patients. To manage respiratory failure, 53 new ICU ventilators, 90 helmets for non-invasive ventilation and 47 high-flow nasal cannula machines were added to the existing capacity. Dedicated medical teams cared for the COVID-19 patients to prevent cross-contamination. The nurse-to-patient and RT-to-patient ratio remained mostly 1:1 and 1:6, respectively. One-hundred-ten ward nurses were up-skilled to care for COVID-19 and other ICU patients using tiered staffing model. Daily executive rounds were conducted to identify patients for transfer and at least 10 beds were made available for new COVID-19 admissions/day. The consumption of PPE increased multiple fold compared with the period preceding the pandemic. Regular family visits were not allowed and families were updated daily by videoconferencing and phone calls. Conclusions Our ICU response to the COVID-19 pandemic required almost doubling ICU bed capacity and changing multiple aspects of ICU workflow to be able to care for high numbers of affected patients.

Summary Background and aims The optimal amount of protein intake in critically ill patients is unclear. The objective of this pilot trial is to assess the feasibility of a large randomized controlled trial testing higher versus lower protein intake in critically ill patients. Methods In this pilot randomized controlled trial (REPLacing Protein via Enteral Nutrition in a Stepwise ApproacH in critically ill patients: A pilot randomized controlled trial (REPLENISH pilot trial), critically ill patients underwent 2-step screening for eligibility on ICU day 1 and 5. Patients with renal disease were excluded. Eligible patients were randomized into REPLENISH group (target protein 1.8–2.2 g kg/day) and Standard group (target protein 0.8–1.0 g/kg/day) from day 6–14 after ICU admission. Dietitians adjusted caloric and protein intake throughout the study period (Day 1–14) to maintain similar caloric targets of permissive underfeeding (40–60% of estimated energy expenditure) in both study groups. Results Of 704 patients screened at 3 centers in Saudi Arabia from May 2018 to May 2019, only 63 (8.9%) were eligible and 40 (5.7% of screened) were randomized with an average of 2 patients enrolled in the trial per month. Among eligible patients, the consenting rate was high at 89%. During the intervention period, patients in the REPLENISH group (N = 21) had a modestly higher protein intake (median of 1.30 g/kg/day (Q1 Q3: 1.11, 1.57)) than those in the standard group (median of 0.77 g/kg/day (Q1 Q3: 0.57, 1.00); P = 0.0004). Only 31.4% of patients in the whole cohort had >80% of prescribed protein. The duration of daily interruption of feeding was almost 4 h in both groups. The 90-day mortality for the patient study cohort was 20.5%. Anthropometric and muscle strength measurements were performed in less than 50% of patients. Conclusions This pilot trial highlighted several areas for improvement in the study protocol before launching a large randomized controlled trial. The restrictive eligibility criteria, the complex adjustments of protein and energy and some of the outcome measurements were identified as targets for modifications, to improve enrollment and generalizability and to enhance adherence to study interventions and measurements. Trial registration: clinicaltrials.gov identifier NCT03480555.

Several approaches have been proposed to address the challenge of catheter ablation of persistent atrial fibrillation (AF). However, the optimal ablation strategy is unknown. We sought to evaluate the efficacy of pulmonary vein isolation (PVI) plus low-voltage area (LVA) ablation using contemporary high-density mapping to identify LVA in patients with persistent AF.Consecutive patients accepted for AF catheter ablation were studied. High-density bipolar voltage mapping data were acquired in sinus rhythm using multipolar catheters to detect LVA (defined as bipolar voltage0.5 mV). Semiautomated impedance-based software was used to ensure catheter contact during data collection. Patients underwent PVI + LVA ablation (if LVA present).A total of 145 patients were studied; 95 patients undergoing PVI + LVA ablation were compared with 50 controls treated with PVI only. Average age was 61 ± 10 years, and 80% were male. Baseline characteristics were comparable. Freedom from atrial tachycardia/AF at 18 months was 72% after PVI + LVA ablation vs 58% in controls (P = 0.022). Median procedure duration (273 [240, 342] vs 305 [262, 360] minutes; P = 0.019) and radiofrequency delivery (50 [43, 63] vs 55 [35, 68] minutes; P = 0.39) were longer in the PVI + LVA ablation group. Multivariable analysis showed that the ablation strategy (PVI + LVA) was the only independent predictor of freedom from atrial tachycardia/AF (hazard ratio, 0.53; 95% confidence interval, 0.29-0.96; P = 0.036). There were no adverse safety outcomes associated with LVA ablation.An individualized strategy of high-density mapping to assess the atrial substrate followed by PVI combined with LVA ablation is associated with improved outcomes. Adequately powered randomized clinical trials are needed to determine the role of PVI + LVA ablation for persistent AF.

We examined the association between surveillance for deep vein thrombosis (DVT) among medical-surgical critically ill patients by twice-weekly ultrasonography and 90-day all-cause mortality. This was a pre-planned sub-study of the Pneumatic Compression for Preventing Venous Thromboembolism (PREVENT) trial (Clinicaltrials.gov: NCT02040103) that compared addition of intermittent pneumatic compression (IPC) to pharmacologic prophylaxis versus pharmacologic prophylaxis alone. The surveillance group included enrolled patients in the trial, while the non-surveillance group included eligible non-enrolled patients. Using logistic regression and Cox proportional hazards models, we examined the association of surveillance with the primary outcome of 90-day mortality. Secondary outcomes were DVT and pulmonary embolism (PE). The surveillance group consisted of 1682 patients and the non-surveillance group included 383 patients. Using Cox proportional hazards model with bootstrapping, surveillance was associated with a decrease in 90-day mortality (adjusted HR 0.75; 95% CI 0.57, 0.98). Surveillance was associated with earlier diagnosis of DVT [(median 4 days (IQR 2, 10) vs. 20 days (IQR 16, 22)] and PE [median 4 days (IQR 2.5, 5) vs. 7.5 days (IQR 6.1, 28.9)]. There was an increase in diagnosis of DVT (adjusted HR 5.49; 95% CI 2.92, 13.02) with no change in frequency in diagnosis of PE (adjusted HR 0.56; 95% CI 0.19, 1.91). Twice-weekly surveillance ultrasonography was associated with an increase in DVT detection, reduction in diagnostic testing for non-lower limb DVT and PE, earlier diagnosis of DVT and PE, and lower 90-day mortality. The PREVENT trial is registered at ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013.

Background: Metabolic syndrome (MetS) and osteoporosis are two of the world's major healthcare issues. There are several studies which explored the association between MetS and bone mineral density (BMD), but all of them are cross-sectional. These studies cover all populations, including expatriated, which did not determine the actual problem among Saudi women. This is the first case-control study that determines the causal relationship between MetS and BMD. The objective of this study is to determine the relationship between metabolic syndrome and bone mass density among Saudi menopausal women in Eastern Province - Saudi Arabia. Methods: It’s a case-control study and 380 menopausal Saudi women were selected through simple random sampling. They were divided into 190 cases with osteoporosis and 190 without osteoporosis. Bone Mineral Density (BMD) at the total hip was determined using dual-energy X-ray absorptiometry (DEXA). T score was calculated. The association between the risk factors of MetS and bone mineral density was determined by binary logistic regression analysis using SPSS (statistical package of social science) software. Results: Among women, the prevalence of MetS was substantially higher in those with osteoporosis. The Mets is positively correlated with bone mineral density. (r=0.08, p=0.051). The occurrence of MetS was associated with increased osteoporosis among Saudi women (B=0.004; p=0.005) after adjustment of confounders. The existence of obesity was significantly associated with increased odds of Bone marrow density among women (OR 2.56; 95 % CI, 2.22-3.44; p=0.030) after adjustment of confounders. Conclusion: The incidence of MetS was associated with osteoporosis in Saudi women.

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p

Background ― Metabolic syndrome (MetS) is the world's major public health problem. Objectives ― Assessment of metabolic syndrome impact on bone mineral density (BMD) among Saudi menopausal women in Eastern Province – Saudi Arabia. Material and Methods ― It’s a case control study and 380 menopausal Saudi women were selected through stratified random sampling; they are divided into 190 cases with osteoporosis and 190 without osteoporosis. BMD at the total hip were determined using dual-energy X-ray absorptiometry (DEXA). The T score was calculated, the relationship between the risk factors of MetS and bone mineral density were analyzed by statistical methods. Results ― Prevalence of MetS was substantially higher among osteoprotic women. The MetS is significantly correlated with bone mineral density (r=0.08, P=0.05). The occurrence of MetS was associated with increased osteoporosis among Saudi women (B=0.004; 0.05) after adjustment of confounders. The presence of obesity (component of MetS) was significantly associated with increased odds of Bone marrow density among women (OR 2.56, 95% CI, 2.22–3.44, P=0.030) after adjustment of confounders. Conclusion ― MetS was significantly associated with an osteoporosis in Saudi women.

Objectives In this study, we evaluated the inflammatory response in patients with severe acute respiratory infection due to the Middle East respiratory syndrome and non-Middle East respiratory syndrome and assessed the presence of distinct inflammatory subphenotypes using latent class analysis. Design Prospective cohort study. Setting A tertiary care ICU in Riyadh, Saudi Arabia. Patients Consecutive critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Intervention None. Measurements and main results We measured cytokines on days 1, 3, 7, and 14 of ICU stay. We included 116 patients (40 with Middle East respiratory syndrome severe acute respiratory infection and 76 with non-Middle East respiratory syndrome severe acute respiratory infection). On ICU day 1, both patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection had higher levels of interleukin-3, interleukin-4, interleukin-6, interleukin-8, interleukin-17A, eotaxin, and epidermal growth factor compared with healthy controls. There were no differences in cytokines over time between patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection. Using day 1 cytokine levels, latent class analysis categorized patients into two subphenotypes: subphenotype 1 (n = 74 [64%]) and subphenotype 2 (n = 42 [36%]); the latter had significantly higher levels of interleukin-1β, interleukin-1ra, interleukin-2, interleukin-6, interleukin-7, interleukin-8, interleukin-10, interleukin-12p70, interleukin-15, interleukin-17A, inducible protein-10, monocyte chemoattractant protein-1, macrophage inflammatory protein-1α, macrophage inflammatory protein-1β, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, granulocyte-colony stimulating factor, interferon-α, and interferon-γ. Although baseline characteristics were not different between the two subphenotypes, patients in the subphenotype 2 had higher ICU mortality compared with the subphenotype 1 (18/42 [43%] vs 17/74 [23%]; p = 0.03). Conclusions One third of critically ill patients with Middle East respiratory syndrome severe acute respiratory infection and non-Middle East respiratory syndrome severe acute respiratory infection demonstrated a subphenotype characterized by increased proinflammatory cytokines, consistent with cytokine storm. Further research is needed to examine whether immunomodulators have differential effects based on inflammatory subphenotypes.

Background and Aim: Hypercholesterolemia (HC) is the major leading cause of cardiovascular disease worldwide. Such atherogenic aberration deeply impacts blood circulation. Resveratrol (R) is a polyphenol that has received attention as a hypolipidemic, antioxidant, and vascular agility advocate. Efficient blood redistribution is a key element in mammalian thermoregulation. We hypothesized that R treatment may aid in mitigating hyperthermic responses under both acute and chronic heat stress (HS) conditions in HC male rats. Materials and Methods: All rats were initially fitted with miniaturized thermologgers to measure core body temperature (Tcore). With a 2 × 2 factorial arrangement, four groups were randomly allotted, in which half of the animals ingested an HC diet (C+), while the other half ingested a control (C-) diet, throughout the whole study duration of 35 days. Seven rats from each dietary treatment, however, received R (R+; 13 mg/kg BW/day), while the rest received normal saline (R-) for 5 continuous days. All animals were maintained at thermoneutrality (TN; ambient temperature; Ta=23.15±0.04°C) for a period of 30 continuous days (days 0-29). On day 29, an acute HS (HS; Ta=35.86±0.37°C; for 9 nocturnal h) was imposed. Then, from day 29, a chronic HS protocol (Ta=32.28±1.00°C) was maintained until the past day of the trial (day 34), after which blood samples were drawn for analyses of platelet (PL) count, total antioxidant activity (TAO), total cholesterol (TC), triglycerides (TGs), and lipid peroxidation (LP). Results: Switching animals from TN to HS resulted in abrupt rises in Tcore. The HC diet induced a significant (p

Background There is limited data on the scar burden in patients with atrial fibrillation (AF). In this study, we sought to evaluate the presence and extent of an abnormal left atrial (LA) substrate in patients with paroxysmal or persistent AF. Methods Consecutive patients who underwent initial AF catheter ablation were prospectively enrolled. Endocardial voltage mapping was acquired in sinus rhythm using multipolar mapping catheters. Automated software was used to ensure homogeneous data collection. Assessment of low-voltage area (LVA) was performed by a reviewer blinded to clinical details. Results One hundred and four patients were prospectively enrolled; 69 had paroxysmal and 35 persistent AF. The mean LA volume was 159 ± 48 mL, and the average number of LA points collected was 1308 ± 1065. Atrial LVAs were present in 23 of 69 (33%) subjects with paroxysmal and 20 of 35 (57%) with persistent AF ( P = 0.02). Amongst 43 of 104 patients with scar, the average extent of LVA was 19.4 ± 21.6 cm 2 and the mean percentage area was 7.6 ± 8.8%. Univariate analysis showed that age, LA volume, and persistent AF were associated with the presence of LVA. Multivariable analysis showed that age (odds ratio [OR] 1.05; 95% confidence interval [CI] 1.00-1.11; P = 0.046) and LA volume (OR 1.02; 95% CI 1.01-1.04; P P = 0.56). Conclusions There is wide variability in the presence and extent of LVA in patients with paroxysmal or persistent AF. Age and LA volume were predictors of LVA. There was no correlation between AF classification and the presence of LVA.

To compare visual dysfunction between very preterm-born (VPB) children with no retinopathy of prematurity (no-ROP) at 6–10 years of age and age- and sex-matched full-term-born controls. This is an observational, prospective study that included 30 children, 6–10 years of age, born ≤ 32 weeks of gestation, with no-ROP, and 30 age- and sex-matched full-term-born controls, conducted from January 2015 until August 2015. All children underwent complete ophthalmic evaluation. Main outcome measures include visual functions (best corrected visual acuity (BCVA), color vision, and stereoacuity), ocular alignment, refractive errors, and the presence of amblyopia and nystagmus. Mean BCVA of the right eyes was 0.04 ± 0.08 logMAR for VPB children and 0.02 ± 0.05 logMAR for the full-term children (P = 0.075). Mean BCVA for the left eyes was 0.07 ± 0.09 logMAR for VPB children and 0.02 ± 0.05 logMAR for the full-term children (P = 0.014). Refractive errors were slightly higher though not statistically significant in VPB children compared to full-term children (P = 0.125). The incidence of myopia and hypermetropia was 16.7 and 40%, respectively, in VPB children and 10 and 23.3%, respectively, in full-term children. Anisometropia found only in VPB children with an incidence of 16.7%. Amblyopia found in 10% of VPB children compared to 3.3% in full-term children. Strabismus was found equally in 10% of each group. VPB children with no-ROP are at an increased risk of developing decreased BCVA at least in one eye and anisometropia compared to age-matched full-term controls.

Background: Early detection of acute kidney dysfunction (AKD) in cirrhotic patients is crucial. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been identified as an early marker of AKD. The aim of the study was to evaluate serial uNGAL as a marker and predictor of AKD in liver cirrhosis patients. Methods: Serial uNGAL and serum creatinine (sCr) levels were measured daily during the first 6 days of admission. Furthermore, sCr levels and the estimated glomerular filtration rate (eGFR) were measured after 3 - 6 weeks. The uNGAL levels in patients with and without abnormal sCr were compared. Results: Fifty-seven consecutive cirrhotic patients were enrolled in the study. Eight of 14 patients (57%) who developed abnormal uNGAL level also had abnormal sCr level (odds ratio (OR) = 3.4, 95% CI: 0.99 - 12.03, P = 0.05). After 6 weeks, 41% of patients exhibited an abnormal uNGAL level and abnormal sCr (OR = 6.7, 95% CI: 1.55 - 28.85, P = 0.01). Area under the curve (AUROC) and the best cut-off point for highest NGAL in 6 days were 0.64 and 72.55 ng/mL, respectively. Conclusions: There is a modest association between highest uNGAL in the first 6 days of admission and sCr at week 6 in all participants. This may indicate that in cirrhotic patients, uNGAL level during the first 6 days of admission has a potential predictability for the development of high sCr and low eGFR 6 weeks later. The AUROC of 0.64 quantifies the overall ability of uNGAL to discriminate between those individuals who will have a raised sCr levels and those who will not. J Clin Med Res. 2018;10(5):419-428 doi: https://doi.org/10.14740/jocmr3366w

Background: Cirrhosis is the irreversible fibrosis of liver, it continues to be a common cause of morbidity and mortality. It is accompanied by inflammation and malnutrition and thus can have a negative effects on bone metabolism and promote fractures accordingly. Aim of the study: to evaluate the risk of fractures among patients with cirrhosis. Methods: A systematic review of the scientific literature following PRISMA/STROBE guidelines, Medline Cochrane Library and Embase abstracts were retrieved using an algorithm comprising relevant MeSH terms from 1980 to 2017. Publications on the association of cirrhosis/bone fracture were abstracted independently by the authors and included in both gender and gender-specific meta-analyses, following recalculations of published data as appropriate. The Newcastle-Ottawa scale was used to evaluate the quality of included studies. Results: 8 studies met the inclusion criteria enrolling 988 patients (286 of which are diagnosed with alcoholic liver disease (ALD). Overall, ALD demonstrated a relative risk (RR) of 1.825, 95%CI: 1.370-2.28, P < 0.001 for the development of bone fractures. Bone mineral density (BMD) was not significantly different between the ALD and control groups, although there was a trend toward lower BMD in patients with ALD. Sensitivity analyses showed consistent results. Conclusion: in accordance to the present meta-analysis, there is a significant correlation between bone fractures and ALD independent of BMD.

Background Compliance with the clinical practice guidelines of sepsis management has been low. The objective of our study was to describe the results of implementing a multifaceted intervention including an electronic alert (e-alert) with a sepsis response team (SRT) on the outcome of patients with sepsis and septic shock presenting to the emergency department. Methods This was a pre–post two-phased implementation study that consisted of a pre-intervention phase (January 01, 2011–September 24, 2012), intervention phase I (multifaceted intervention including e-alert, from September 25, 2012–March 03, 2013) and intervention phase II when SRT was added (March 04, 2013–October 30, 2013) in a 900-bed tertiary-care academic hospital. We recorded baseline characteristics and processes of care in adult patients presenting with sepsis or septic shock. The primary outcome measures were hospital mortality. Secondary outcomes were the need for mechanical ventilation and length of stay in the intensive unit and in the hospital. Results After implementing the multifaceted intervention including e-alert and SRT, cases were identified with less severe clinical and laboratory abnormalities and the processes of care improved. When adjusted to propensity score, the interventions were associated with reduction in hospital mortality [for intervention phase II compared to pre-intervention: adjusted odds ratio (aOR) 0.71, 95% CI 0.58–0.85, p = 0.003], reduction in the need for mechanical ventilation (aOR 0.45, 95% CI 0.37–0.55, p

This study aimed to evaluate haptoglobin (Hp), serum amyloid A (SAA), and C-reactive protein (CRP) in goats following exposure to heat and transportation stressors. In the heat stress (HS) experiment (4-week period), six goats were exposed to direct solar radiation vs. six goats exposed to shade regimen. In the transportation stress experiment, six goats were transported for 2 h in a vehicle vs. a control group (n = 6). Blood samples were collected and serum concentrations of acute phase proteins (APPs) were measured. Rectal temperature, respiratory rate, heart rate, and body weight were recorded. All statistical analyses were performed using the proc General Linear Model (SPSS 19.0). Results indicated that Hp and SAA concentrations were significantly affected by HS (P

Rationale: The optimal nutritional strategy for critically ill adults at high nutritional risk is unclear.Objectives: To examine the effect of permissive underfeeding with full protein intake compared with standard feeding on 90-day mortality in patients with different baseline nutritional risk.Methods: This is a post hoc analysis of the PermiT (Permissive Underfeeding versus Target Enteral Feeding in Adult Critically Ill Patients) trial.Measurements and Main Results: Nutritional risk was categorized by the modified Nutrition Risk in Critically Ill score, with high nutritional risk defined as a score of 5–9 and low nutritional risk as a score of 0–4. Additional analyses were performed by categorizing patients by body mass index, prealbumin, transferrin, phosphate, urinary urea nitrogen, and nitrogen balance. Based on the Nutrition Risk in Critically Ill score, 378 of 894 (42.3%) patients were categorized as high nutritional risk and 516 of 894 (57.7%) as low nutritional risk. There was no association betw...

The objective of this study was to evaluate leptin, ghrelin, and leptin/ghrelin ratio in critically ill patients and association of leptin/ghrelin ratio with outcomes. This is a sub-study of the PermiT trial (ISRCTN68144998). A subset of 72 patients who were expected to stay &gt, 14 days in the Intensive care unit were enrolled. Blood samples were collected on days 1, 3, 5, 7, and 14. Samples were analyzed for leptin and active ghrelin in addition to other hormones. Baseline leptin/ghrelin ratio was calculated, and patients were stratified into low and high leptin/ghrelin ratio based on the median value of 236. There was a considerable variation in baseline leptin level: Median 5.22 ng/mL (Q1, Q3: 1.26, 17.60). Ghrelin level was generally low: 10.61 pg/mL (Q1, Q3: 8.62, 25.36). Patients with high leptin/ghrelin ratio compared to patients with low leptin/ghrelin ratio were older, had higher body mass index and more likely to be diabetic. There were no differences in leptin/ghrelin ratio between patients who received permissive underfeeding and standard feeding. Multivariable logistic regression analysis showed that age and body mass index were significant independent predictors of high leptin&ndash, ghrelin ratio. Leptin&ndash, ghrelin ratio was not associated with 90-day mortality or other outcomes. Age and body mass index are predictors of high leptin/ghrelin ratio. Leptin/ghrelin ratio is not affected by permissive underfeeding and is not associated with mortality

Background The objective of this study was to evaluate the effect of ribavirin and recombinant interferon (RBV/rIFN) therapy on the outcomes of critically ill patients with Middle East respiratory syndrome (MERS), accounting for time-varying confounders. Methods This is a retrospective cohort study of critically ill patients with laboratory-confirmed MERS from 14 hospitals in Saudi Arabia diagnosed between September 2012 and January 2018. We evaluated the association of RBV/rIFN with 90-day mortality and MERS coronavirus (MERS-CoV) RNA clearance using marginal structural modeling to account for baseline and time-varying confounders. Results Of 349 MERS patients, 144 (41.3%) patients received RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a; none received rIFN-β1b). RBV/rIFN was initiated at a median of 2 days (Q1, Q3: 1, 3 days) from intensive care unit admission. Crude 90-day mortality was higher in patients with RBV/rIFN compared to no RBV/rIFN (106/144 [73.6%] vs 126/205 [61.5%]; P = .02]. After adjusting for baseline and time-varying confounders using a marginal structural model, RBV/rIFN was not associated with changes in 90-day mortality (adjusted odds ratio, 1.03 [95% confidence interval {CI}, .73–1.44]; P = .87) or with more rapid MERS-CoV RNA clearance (adjusted hazard ratio, 0.65 [95% CI, .30–1.44]; P = .29). Conclusions In this observational study, RBV/rIFN (RBV and/or rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was commonly used in critically ill MERS patients but was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance., In this observational study accounting for baseline and time-varying confounders, ribavirin and recombinant interferon (rIFN-α2a, rIFN-α2b, or rIFN-β1a) therapy was not associated with reduction in 90-day mortality or in faster MERS-CoV RNA clearance.

Introduction Cognitive health is not only affected by age, as there is significant inter-individual variability in cognitive decline. Studies have shown that cognitive function can be affected by a number of lifestyle factors, which can either delay or expedite the process of cognitive decline. Methodology We explored this effect in our demographic in Saudi Arabia by carrying out a cross-sectional study involving 202 adults above the age of 40 from two tertiary care hospitals. Cognitive function was scored using a standardized test assessing cognitive function, known as the Mini Mental State Examination (MMSE). In addition, we used a specifically designed questionnaire in order to investigate several lifestyle components. Results The results showed that in our sample, the mean MMSE score was 23.45 ± 4.203 SD. Females (n = 94) scored on average 3 points less than males (95% CI: 2.0–4.2 points, p Conclusion Cognitive function as scored by the MMSE is not only affected by age, but shows gender variability and is strongly associated with different lifestyle factors in the studied demographic. Further research is required to establish a causal relationship and allow for generalizability.

Small ruminants (sheep and goats) play a predominant role in the economy of million people, and have provided meat, milk, skin, wool and fiber for centuries. Animals undergo various kinds of stressors, i.e. physical, nutritional, chemical, psychological and heat stress (HS). Among all, HS is the most concerning at present in the ever-changing climatic scenario. Climate change is the most serious long-term challenge faced by small ruminants’ owners worldwide. HS results in decreased growth, reproduction, production, milk quantity and quality, as well as natural immunity, making animals more vulnerable to diseases, and even death. Thus, HS results in great economic losses, emphasizing the necessity to objectively assess animal welfare. The increasing demand for animal products paralleled by the frequent hot climate is a serious threat for the agriculture sector. The ability of sheep and goats to cope with HS without harming their welfare and productive performance has been often overrated. To date, little attention has been paid to comprehensive detailed data on the adverse effect of HS on sheep and goats. Therefore, this review discusses in detail the sheep and goats’ behavioral, physiological, molecular/cellular, hematological, biochemical and immunological responses under HS conditions. In addition, this review also presents the adverse effects of HS on reproduction and fertility, milk quantity and quality, feed intake, and water consumption of sheep and goats. Finally, this review suggests various methods for HS alleviation. In conclusion, HS impairs productivity and well-being in sheep and goats. The improved understanding of the impact of HS on small ruminants will help in developing management techniques to alleviate HS and highlighting the need for future researches on HS in sheep and goats.

Efficacy testing will be challenging because of the small pool of donors with sufficiently high antibody titers., We explored the feasibility of collecting convalescent plasma for passive immunotherapy of Middle East respiratory syndrome coronavirus (MERS-CoV) infection by using ELISA to screen serum samples from 443 potential plasma donors: 196 patients with suspected or laboratory-confirmed MERS-CoV infection, 230 healthcare workers, and 17 household contacts exposed to MERS-CoV. ELISA-reactive samples were further tested by indirect fluorescent antibody and microneutralization assays. Of the 443 tested samples, 12 (2.7%) had a reactive ELISA result, and 9 of the 12 had reactive indirect fluorescent antibody and microneutralization assay titers. Undertaking clinical trials of convalescent plasma for passive immunotherapy of MERS-CoV infection may be feasible, but such trials would be challenging because of the small pool of potential donors with sufficiently high antibody titers. Alternative strategies to identify convalescent plasma donors with adequate antibody titers should be explored, including the sampling of serum from patients with more severe disease and sampling at earlier points during illness.

IntroductionVentilator-associated pneumonia (VAP) is a common healthcare-associated infection in the intensive care unit (ICU). Probiotics are defined as live microorganisms that may confer health benefits when ingested. Prior randomised trials suggest that probiotics may prevent infections such as VAP and Clostridioides difficile–associated diarrhoea (CDAD). PROSPECT (Probiotics to Prevent Severe Pneumonia and Endotracheal Colonization Trial) is a multicentre, double-blinded, randomised controlled trial comparing the efficacy of the probiotic Lactobacillus rhamnosus GG with usual care versus usual care without probiotics in preventing VAP and other clinically important outcomes in critically ill patients admitted to the ICU.Methods and analysisThe objective of E-PROSPECT is to determine the incremental cost-effectiveness of L. rhamnosus GG plus usual care versus usual care without probiotics in critically ill patients. E-PROSPECT will be performed from the public healthcare payer’s perspective over a time horizon from ICU admission to hospital discharge.We will determine probabilities of in-ICU and in-hospital events from all patients alongside PROSPECT. We will retrieve unit costs for each resource use item using jurisdiction-specific public databases, supplemented by individual site unit costs if such databases are unavailable. Direct costs will include medications, personnel costs, radiology/laboratory testing, operative/non-operative procedures and per-day hospital ‘hoteling’ costs not otherwise encompassed. The primary outcome is the incremental cost per VAP prevented between the two treatment groups. Other clinical events such as CDAD, antibiotic-associated diarrhoea and in-hospital mortality will be included as secondary outcomes. We will perform pre-specified subgroup analyses (medical/surgical/trauma; age; frailty status; antibiotic use; prevalent vs no prevalent pneumonia) and probabilistic sensitivity analyses for VAP, then generate confidence intervals using the non-parametric bootstrapping approach.Ethics and disseminationStudy approval for E-PROSPECT was granted by the Hamilton Integrated Research Ethics Board of McMaster University on 29 July 2019. Informed consent was obtained from the patient or substitute decision-maker in PROSPECT. The findings of this study will be published in peer-reviewed journals.Trial registration numberNCT01782755; Pre-results.

Objectives: The objectives of this study were to evaluate the clinical and nutritional correlates of high free fatty acids (FFAs) level in critically ill patients and the association with outcomes, and to study the effect of short-term caloric restriction (permissive underfeeding) on FFAs level during critical illness. Patients/Method: In this pre-planned sub-study of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we included critically ill patients who were expected to stay for &ge, 14 days in the intensive care unit. We measured FFAs level on day 1, 3, 5, 7, and 14 of enrollment. Of 70 enrolled patients, 23 (32.8%) patients had high FFAs level (baseline FFAs level &gt, 0.45 mmol/L in females and &gt, 0.6 mmol/L in males). Results: Patients with high FFAs level were significantly older and more likely to be females and diabetics and they had lower ratio of partial pressure of oxygen to the fraction of inspired oxygen, higher creatinine, and higher total cholesterol levels than those with normal FFAs level. During the study period, patients with high FFAs level had higher blood glucose and required more insulin. On multivariable logistic regression analysis, the predictors of high baseline FFAs level were diabetes (adjusted odds ratio (aOR): 5.36, 95% confidence interval (CI): 1.56, 18.43, p = 0.008) and baseline cholesterol level (aOR, 4.29, 95% CI: 11.64, 11.19, p = 0.003). Serial levels of FFAs did not differ with time between permissive underfeeding and standard feeding groups. FFAs level was not associated with 90-day mortality (aOR: 0.49, 95% CI: 0.09, 2.60, p = 0.40). Conclusion: We conclude that high FFAs level in critically ill patients is associated with features of metabolic syndrome and is not affected by short-term permissive underfeeding.

BackgroundDuring critical illness in humans, the effects of caloric restriction on the inflammatory response are not well understood. The aim of this study is to examine the associations of caloric restriction, inflammatory response profiles and outcomes in critically ill patients.MethodsThis is a sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998). Serum samples were collected on study days 1, 3, 5, 7 and 14 and analyzed for a panel of 29 cytokines. We used principal component analysis to convert possibly correlated variables (cytokine levels) into a limited number of linearly uncorrelated variables (principal components). We constructed repeated measures mixed linear models to assess whether permissive underfeeding compared to standard feeding was associated with difference cytokine levels over time.ResultsA total of 72 critically ill patients were enrolled in this study (permissive underfeeding n = 36 and standard feeding n = 36). Principal component analysis identified 6 components that were responsible for 78% of the total variance. When adjusted to principal components, permissive underfeeding was not associated with 90-day mortality (adjusted odds ratio 1.75, 95% confidence interval 0.44, 6.95, p = 0.43) or with incident renal replacement therapy. The cytokines did not differ with time between permissive underfeeding and standard feeding groups.ConclusionsThe association of permissive underfeeding compared to standard feeding with mortality was not influenced by the inflammatory profile. Permissive underfeeding compared to standard feeding was not associated with differences in the serum levels of cytokines in critically ill patients.

The effect of short-term caloric restriction on gene expression in critically ill patients has not been studied. In this sub-study of the PermiT trial (Permissive Underfeeding or Standard Enteral Feeding in Critically Ill Adults Trial- ISRCTN68144998), we examined gene expression patterns in peripheral white blood cells (buffy coat) associated with moderate caloric restriction (permissive underfeeding) in critically ill patients compared to standard feeding. Blood samples collected on study day 1 and 14 were subjected to total RNA extraction and gene expression using microarray analysis. We enrolled 50 patients, 25 in each group. Among 1751 tested genes, 332 genes in 12 pathways were found to be significantly upregulated or downregulated between study day 1 and 14 (global p value for the pathway ≤ 0.05). Using the heatmap, the differential expression of genes from day 1 to 14 in the permissive underfeeding group was compared to the standard feeding group. We further compared gene expression signal intensity in permissive underfeeding compared standard feeding by constructing univariate and multivariate linear regression models on individual patient data. We found differential expression of several genes with permissive underfeeding, most notably those related to metabolism, autophagy and other cellular functions, indicating that moderate differences in caloric intake trigger different cellular pathways.

Abstract The MIRACLE trial (MERS-CoV Infection tReated with A Combination of Lopinavir/ritonavir and intErferon-β1b) investigates the efficacy of a combination therapy of lopinavir/ritonavir and recombinant interferon-β1b provided with standard supportive care, compared to placebo provided with standard supportive care, in hospitalized patients with laboratory-confirmed MERS. The MIRACLE trial is designed as a recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The aim of this article is to describe the statistical analysis plan for the MIRACLE trial. The primary outcome is 90-day mortality. The primary analysis will follow the intention-to-treat principle. The MIRACLE trial is the first randomized controlled trial for MERS treatment. Trial registration ClinicalTrials.gov, NCT02845843. Registered on 27 July 2016.

Summary Background The effect of moderate caloric enteral intake in critically ill patients with hypercapnic acute respiratory failure (HCARF) is unclear. We studied the impact of permissive underfeeding (PUF) compared with standard feeding (SF) on various HCARF outcomes. Materials and methods The PermiT trial randomized 894 patients to either PUF (40–60% caloric requirement) or SF (70–100% requirement) with similar protein intake and found no difference in mortality, mechanical ventilation (MV) duration and ventilator-free days. In this post-hoc study, we restricted analysis to mechanically-ventilated patients with HCARF (PaCO2 >45 mmHg on the first two study days) and assessed the impact of trial interventions and fat-to-carbohydrate ratio on outcomes. Results One-hundred-twenty patients had HCARF (59 PUF and 61 SF, age 53.7 ± 17.8 years, body mass index 31.1 ± 11.2 kg/m2, Acute Physiology and Chronic Health Evaluation II score 21.7 ± 7.1 and day-1 PaCO2 61 ± 16 mmHg). Caloric intake was 815 ± 270 kcal/day in PUF group and 1289 ± 407 kcal/day in SF group. The two groups had similar PaCO2 levels during ICU stay. The 90-day mortality (33.9% versus 35.6%, p = 0.85), MV duration (10.7 ± 6.8 versus 11.1 ± 8.1 days, p = 0.56) and ventilator-free days (52.9 ± 38.6 versus 51.2 ± 38.0 days, p = 0.80) were also similar in PUF and SF groups, respectively. Ventilator-free days and 90-day mortality were similar when the fat-to-carbohydrate ratio was Conclusions In patients with HCARF, SF and PUF were associated with similar PaCO2, MV duration, ventilator-free days and mortality. Fat-to-carbohydrate ratio was not associated with mortality or ventilator-free days. Trial registration ISRCTN Registry: ISRCTN68144998.

Background The Pneumatic CompREssion for Preventing VENous Thromboembolism (PREVENT) trial evaluates the effect of adjunctive intermittent pneumatic compression (IPC) with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on venous thromboembolism (VTE) in critically ill adults. Methods/design In this multicenter randomized trial, critically ill patients receiving pharmacologic thromboprophylaxis will be randomized to an IPC or a no IPC (control) group. The primary outcome is “incident” proximal lower-extremity deep vein thrombosis (DVT) within 28 days after randomization. Radiologists interpreting the lower-extremity ultrasonography will be blinded to intervention allocation, whereas the patients and treating team will be unblinded. The trial has 80% power to detect a 3% absolute risk reduction in the rate of proximal DVT from 7% to 4%. Discussion Consistent with international guidelines, we have developed a detailed plan to guide the analysis of the PREVENT trial. This plan specifies the statistical methods for the evaluation of primary and secondary outcomes, and defines covariates for adjusted analyses a priori. Application of this statistical analysis plan to the PREVENT trial will facilitate unbiased analyses of clinical data. Trial registration ClinicalTrials.gov, ID: NCT02040103. Registered on 3 November 2013; Current controlled trials, ID: ISRCTN44653506. Registered on 30 October 2013. Electronic supplementary material The online version of this article (10.1186/s13063-018-2534-6) contains supplementary material, which is available to authorized users.

Background: Cognitive decline is not inevitable with age; studies have shown that it can be affected by a number of education and work related factors. We explored this association by carrying out a cross-sectional study in King Khalid University Hospital and King Abdulaziz University Hospital in Riyadh, Saudi Arabia. Methods: We enrolled 202 adults, whose ages ranged between 40 and 85 years. Data was collected using a validated Arabic translation of a standardized test assessing cognitive function, known as the Mini Mental State Examination (MMSE). Subjects were also inquired about their level of education and work status. Results: The results showed that in our subjects of adults above the age of 40, the mean MMSE score was 23.45 (SD=4.203). Females (n=94) had lower scores than their male counterparts (n=108) (mean difference: 3.11, 95% CI 2 to 4.22; p

Background It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. Methods The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. Discussion This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. Trial registration ClinicalTrials.gov, ID: NCT02845843. Registered on 27 July 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2427-0) contains supplementary material, which is available to authorized users.

Introduction The Kingdom of Saudi Arabia (KSA) is one of countries with the world's highest number of deaths per 100,000 populations from road traffic accidents (RTAs). Numerous trauma victims sustain abdomino-pelvic injuries, which are associated with considerable morbidity and mortality. The purpose of this study was to describe profile, outcomes and predictors of mortality of patients with abdomino-pelvic trauma admitted to the intensive care unit (ICU) in a tertiary care trauma centre in Riyadh, KSA. Methods This was a retrospective analysis of prospectively collected ICU database. All consecutive patients older than 14 years with abdomino-pelvic trauma from March 1999 to June 2013 were included. The followings were extracted: demographics, injury severity, mechanism and type of injury, associated injuries, use of vasopressors and mechanical ventilation, and worst laboratory results in the first 24 h. The primary outcome was hospital mortality. We compared profile and outcomes between survivors and non-survivors and reported predictors of mortality. Results Of the 11,374 trauma patients who were admitted to the hospital during the study period, 2120 (18.6%) patients had abdomino-pelvic injuries, out of which 702 (33.1%) patients were admitted to the ICU. The mean age was 30.7 (SD 14.4) years and the majority was male (89.5%). RTA was the most common cause of abdomino-pelvic trauma (70.4%). Pelvis (46.2%), liver (25.8%), and spleen (23.1%) were the most frequently injured organs; and chest (55.6%), head (41.9%), and lower extremities (27.5%) were the most commonly associated injuries. Mechanical ventilation was required in 89.6% with a mean duration of 9.1 (SD 9.2) days and emergency surgery was performed in 45.0% of the patients with prolonged ICU and hospital length of stay (10.8 [SD 10.8], 56.9 [SD 96.7] days; respectively). Of the 702 patients with abdomino-pelvic trauma, 115 (16.4%) patients did not survive. Associated head trauma and retroperitoneal haematoma, higher level of lactic acid on admission and ISS, and advanced age were potential risk factors for hospital mortality. Conclusions Abdomino-pelvic injuries are common in trauma patients, affecting mainly young male victims, and are associated with significant morbidity and mortality, and resource utilisation.

Rationale Corticosteroid therapy is commonly used among critically ill patients with the Middle East Respiratory Syndrome (MERS), but its impact on outcomes is uncertain. Analyses of observational studies often do not account for patients’ clinical condition at the time of corticosteroid therapy initiation. Objectives To investigate the association of corticosteroid therapy on mortality and on MERS coronavirus RNA clearance in critically ill patients with MERS. Methods MERS ICU patients were included from 14 Saudi Arabian centers between September 2012 and October 2015. We carried out marginal structural modeling to account for baseline and time-varying confounders. Measurements and Main Results Of 309 patients, 151 received corticosteroids. Corticosteroids were initiated at a median of 3.0 days (Quartile Q1, 3: 1.0, 7.0) from ICU admission. Patients who received corticosteroids were more likely to receive invasive ventilation (141/151 [93.4%] vs. 121/158 [76.6%], p≤0.0001) and had higher 90-day crude mortality (112/151 [74.2%] vs. 91/158 [57.6%], p=0.002). Using marginal structural modeling, corticosteroid therapy was not significantly associated with 90-day mortality (adjusted odds ratio 0.75, 95% CI 0.52, 1.07, p=0.12), but was associated with delay in MERS coronavirus RNA clearance (adjusted hazard ratio 0.35, 95% CI: 0.17, 0.72, p=0.005). Conclusions Corticosteroid therapy in patients with MERS was not associated with a difference in mortality after adjustment for time-varying confounders, but was associated with delayed MERS coronavirus RNA clearance. These findings highlight the challenges and importance of adjusting for baseline and time-varying confounders when estimating clinical effects of treatments using observational studies.

Background The demand for critical care beds is increasing out of proportion to bed availability. As a result, some critically ill patients are kept in the Emergency Department (ED boarding) awaiting bed availability. The aim of our study is to examine the impact of boarding in the ED on the outcome of patients admitted to the Intensive Care Unit(ICU). Methods This was a retrospective analysis of ICU data collected prospectively at King Abdulaziz Medical City, Riyadh from ED between January 2010 and December 2012 and all patients admitted during this time were evaluated for their duration of boarding. Patients were stratified into three groups according to the duration of boarding from ED. Those admitted less than 6 h were classified as Group I, between 6 and 24 h, Group II and more than 24 h as Group III. We carried out multivariate analysis to examine the independent association of boarding time with the outcome adjusting for variables like age, sex, APACHE, Mechanical ventilation, Creatinine, Platelets, INR. Results During the study period, 940 patients were admitted from the ED to ICU, amongst whom 227 (25%) were admitted to ICU within 6 h, 358 (39%) within 6–24 h and 355 (38%) after 24 h. Patients admitted to ICU within 6 h were younger [48.7 ± 22.2(group I) years, 50.6 ± 22.6 (group II), 58.2 ± 20.9 (group III) (P = 0.04)]with less mechanical ventilation duration[5.9 ± 8.9 days (Group I), 6.5 ± 8.1 (Group II) and 10.6 ± 10.5 (Group III), P = 0.04]. There was a significant increase in hospital mortality [51(22.5), 104(29.1), 132(37.2), P = 0.0006) and the ICU length of stay(LOS) [9.55 days (Group I), 9.8 (Group II) and 10.6 (Group III), (P = 0.002)] with increase in boarding duration. In addition, the delay in admission was an independent risk factor for ICU mortality(OR for group III vs group I is 1.90, P = 0.04) and hospital mortality(OR for group III vs Group I is 2.09, P = 0.007). Conclusion Boarding in the ED is associated with higher mortality. This data highlights the importance of this phenomenon and suggests the need for urgent measures to reduce boarding and to improve patient flow.

Objectives:To describe patient characteristics, clinical manifestations, disease course including viral replication patterns, and outcomes of critically ill patients with severe acute respiratory infection from the Middle East respiratory syndrome and to compare these features with patients with severe acute respiratory infection due to other etiologies. Design:Retrospective cohort study. Setting:Patients admitted to ICUs in 14 Saudi Arabian hospitals. Patients:Critically ill patients with laboratory-confirmed Middle East respiratory syndrome severe acute respiratory infection (n= 330) admitted between September 2012 and October 2015 were compared to consecutive critically ill patients with community-acquired severe acute respiratory infection of non–Middle East respiratory syndrome etiology (non–Middle East respiratory syndrome severe acute respiratory infection) (n= 222). Interventions:None. Measurements and Main Results:Although Middle East respiratory syndrome severe acute respiratory infection patients were younger than those with non–Middle East respiratory syndrome severe acute respiratory infection (median [quartile 1, quartile 3] 58 yr [44, 69] vs 70 [52, 78];p< 0.001), clinical presentations and comorbidities overlapped substantially. Patients with Middle East respiratory syndrome severe acute respiratory infection had more severe hypoxemic respiratory failure (PaO2/FIO2: 106 [66, 160] vs 176 [104, 252];p< 0.001) and more frequent nonrespiratory organ failure (nonrespiratory Sequential Organ Failure Assessment score: 6 [4, 9] vs 5 [3, 7];p= 0.002), thus required more frequently invasive mechanical ventilation (85.2% vs 73.0%;p< 0.001), oxygen rescue therapies (extracorporeal membrane oxygenation 5.8% vs 0.9%;p= 0.003), vasopressor support (79.4% vs 55.0%;p< 0.001), and renal replacement therapy (48.8% vs 22.1%;p< 0.001). After adjustment for potential confounding factors, Middle East respiratory syndrome was independently associated with death compared to non–Middle East respiratory syndrome severe acute respiratory infection (adjusted odds ratio, 5.87; 95% CI, 4.02–8.56;p< 0.001). Conclusions:Substantial overlap exists in the clinical presentation and comorbidities among patients with Middle East respiratory syndrome severe acute respiratory infection from other etiologies; therefore, a high index of suspicion combined with diagnostic testing is essential component of severe acute respiratory infection investigation for at-risk patients. The lack of distinguishing clinical features, the need to rely on real-time reverse transcription polymerase chain reaction from respiratory samples, variability in viral shedding duration, lack of effective therapy, and high mortality represent substantial clinical challenges and help guide ongoing clinical research efforts.

Background The optimal amount of protein intake in critically ill patients is uncertain. Objective In this post hoc analysis of the PermiT (Permissive Underfeeding vs. Target Enteral Feeding in Adult Critically Ill Patients) trial, we tested the hypothesis that higher total protein intake was associated with lower 90-d mortality and improved protein biomarkers in critically ill patients. Design In this post hoc analysis of the PermiT trial, we included patients who received enteral feeding for ≥3 consecutive days. Using the median protein intake of the cohort as a cutoff, patients were categorized into 2 groups: a higher-protein group (>0.80 g · kg-1 · d-1) and a lower-protein group (≤0.80 g · kg-1 · d-1). We developed a propensity score for receiving higher protein. Primary outcome was 90-d mortality. We also compared serial values of prealbumin, transferrin, 24-h urinary nitrogen, and 24-h nitrogen balance on days 1, 7, and 14. Results Among the 729 patients included in this analysis, the average protein intake was 0.8 ± 0.3 g · kg-1 · d-1 [1.0 ± 0.2 g · kg-1 · d-1 in the higher-protein group (n = 365) and 0.6 ± 0.2 g · kg-1 · d-1 in the lower-protein group (n = 364); P

Websites and applications that match and connect individuals for romantic purposes are commonly used in the Western world. However, there have not been many previous investigations focusing on cultural factors that affect the adoption of similar technologies in religiously conservative non-Western cultures. In this study, we examine the socio-technical and cultural factors that influence the perceptions and use of matchmaking technologies in Saudi Arabia. We report the methods and findings of interviews with 18 Saudi nationals (nine males and nine females) with diverse demographics and backgrounds. We provide qualitatively generated insights into the major themes reported by our participants related to the common approaches to matchmaking, the current role of technology, and concerns regarding matchmaking technologies in this cultural con-text. We relate these themes to specific implications for designing marital matchmaking technologies in Saudi Arabia and we outline opportunities for future investigations., Comment: 11 pages, 1 table, DIS 2017

Since September 2012, 170 confirmed infections with Middle East respiratory syndrome coronavirus (MERS-CoV) have been reported to the World Health Organization, including 72 deaths. Data on critically ill patients with MERS-CoV infection are limited.To describe the critical illness associated with MERS-CoV.Case series.3 intensive care units (ICUs) at 2 tertiary care hospitals in Saudi Arabia.12 patients with confirmed or probable MERS-CoV infection.Presenting symptoms, comorbid conditions, pulmonary and extrapulmonary manifestations, measures of severity of illness and organ failure, ICU course, and outcome are described, as are the results of surveillance of health care workers (HCWs) and patients with potential exposure.Between December 2012 and August 2013, 114 patients were tested for suspected MERS-CoV; of these, 11 ICU patients (10%) met the definition of confirmed or probable cases. Three of these patients were part of a health care-associated cluster that also included 3 HCWs. One HCW became critically ill and was the 12th patient in this case series. Median Acute Physiology and Chronic Health Evaluation II score was 28 (range, 16 to 36). All 12 patients had underlying comorbid conditions and presented with acute severe hypoxemic respiratory failure. Most patients (92%) had extrapulmonary manifestations, including shock, acute kidney injury, and thrombocytopenia. Five (42%) were alive at day 90. Of the 520 exposed HCWs, only 4 (1%) were positive.The sample size was small.MERS-CoV causes severe acute hypoxemic respiratory failure and considerable extrapulmonary organ dysfunction and is associated with high mortality. Community-acquired and health care-associated MERS-CoV infection occurs in patients with chronic comorbid conditions. The health care-associated cluster suggests that human-to-human transmission does occur with unprotected exposure.None.

Purpose: This study examined the effect of permissive underfeeding compared to target feeding and intensive insulin therapy (IIT) compared to conventional insulin therapy (CIT) on the inflammatory mediators monocyte chemoattractant protein 1 (MCP-1), soluble intercellular adhesion molecule 1 (sICAM-1), and tissue factor (TF) in critically ill patients. Methodology: This was a substudy of a 2 &times, 2 factorial design randomized controlled trial in which intensive care unit (ICU) patients were randomized into permissive underfeeding compared to target feeding groups and into IIT compared to CIT groups (ISRCTN96294863). In this substudy, we included 91 patients with almost equal numbers across randomization groups. Blood samples were collected at baseline and at days 3, 5, and 7 of an ICU stay. Linear mixed models were used to assess the differences in MCP-1, sICAM-1, and TF across randomization groups over time. Results: Baseline characteristics were balanced across randomization groups. Daily caloric intake was significantly higher in the target feeding than in the permissive underfeeding groups (P-value &lt, 0.01), and the daily insulin dose was significantly higher in the IIT than in the CIT groups (P-value &lt, 0.01). MCP-1, sICAM-1, and TF did not show any significant difference between the randomization groups, while there was a time effect for MCP-1. Baseline sequential organ failure assessment (SOFA) score and platelets had a significant effect on sICAM-1 (P-value &lt, 0.01). For TF, there was a significant association with age (P-value &lt, 0.01). Conclusions: Although it has been previously demonstrated that insulin inhibits MCP-1, sICAM-1 in critically ill patients, and TF in non-critically ill patients, our study demonstrated that IIT in critically ill patients did not affect these inflammatory mediators. Similarly, caloric intake had a negligible effect on the inflammatory mediators studied.

Aims: To measure the association between number of patient encounters and training provided to residents, as well as the residents' perceived achievement of training objectives. Settings and Design: This cross-sectional study was done on Family Medicine residents in Eastern province, Makkah and Asir regions. Materials and Methods: A questionnaire was developed by the investigator and validated by two experts. All residents, except first year residents, were included. Data were collected by the investigator through direct contact with the residents. Statistical analysis: Cronbach's alpha, analysis of variance, t-test, and univariate regression model were used. Results: Reliability of the questionnaire was found to be 75.4%. One hundred and seven residents (response rate, 83.6%) had completed the questionnaire. The mean age was 29.1 ± 2.5 years, half of the residents were male, most of them (83.2%) were married, and more than half (54.2%) of the residents had worked in primary health care (PHC) before joining the programme. Age and duration of work in PHC before joining the programme were significantly and positively associated with the outcome. In Family Medicine rotations, continuity of care, percentage of patients discussed, and number of trainers were associated with the outcome. On the other hand, percentage of patients discussed in different settings and opportunity for the residents to evaluate patients in an outpatient setting were among the factors affecting the outcome in the hospital rotations. Conclusions: Factors identified (age, duration of work in PHC, discussion, and opportunity to evaluate patients) might help residents, trainers, and decision makers in ensuring residents benefit from the different rotations. Further studies to link the effect of the identified factors on resident outcome and patient care are required.

Objectives. We compared venous thromboembolism (VTE) prophylaxis practices and incidence in critically ill cirrhotic versus noncirrhotic patients and evaluated cirrhosis as a VTE risk factor. Methods. A cohort of 798 critically ill patients followed for the development of clinically detected VTE were categorized according to the diagnosis of cirrhosis. VTE prophylaxis practices and incidence were compared. Results. Seventy-five (9.4%) patients had cirrhosis with significantly higher INR (2.2 ± 0.9 versus 1.3 ± 0.6, P<0.0001), lower platelet counts (115,000 ± 90,000 versus 258,000 ± 155,000/μL, P<0.0001), and higher creatinine compared to noncirrhotic patients. Among cirrhotics, 31 patients received only mechanical prophylaxis, 24 received pharmacologic prophylaxis, and 20 did not have any prophylaxis. Cirrhotic patients were less likely to receive pharmacologic prophylaxis (odds ratio, 0.08; 95% confidence interval (CI), 0.04–0.14). VTE occurred in only two (2.7%) cirrhotic patients compared to 7.6% in noncirrhotic patients (P=0.11). The incidence rate was 2.2 events per 1000 patient-ICU days for cirrhotic patients and 3.6 events per 1000 patient-ICU days for noncirrhotics (incidence rate ratio, 0.61; 95% CI, 0.15–2.52). On multivariate Cox regression analysis, cirrhosis was not associated with VTE risk (hazard ratio, 0.40; 95% CI, 0.10–1.67). Conclusions. In critically ill cirrhotic patients, VTE incidence did not statistically differ from that in noncirrhotic patients.

This study aimed to measure the performance of primary health care centres in Eastern province, Saudi Arabia, using the WHO/International Network of Rational Use of Drugs patient care and facility-specific drug use indicators. In a cross-sectional study, 10 health centres were selected using systematic random sampling. A total of 300 patients were interviewed while visiting the centre from January to March 2011 and 10 pharmacists from the same centres were interviewed. Average consultation time was 7.3 min (optimal > or = 30 min), percentage of drugs adequately labelled was 10% (optimal 100%) and patient's knowledge of correct dosage was 79.3% (optimal 100%). The percentage of key drugs in stock was only 59.2% (optimal 100%). An overall index of rational facility-specific drug use was calculated and applied to rank the health centres for benchmarking.

Background: Nutritional support has been recognized as an essential part of intensive care unit management. However, the appropriate caloric intake for critically ill patients remains ill defined. Objective: We examined the effect of permissive underfeeding compared with that of target feeding and of intensive insulin therapy (IIT) compared with that of conventional insulin therapy (CIT) on the outcomes of critically ill patients. Design: This study had a 2 · 2 factorial, randomized, controlled design. Eligible patients were randomly assigned to permissive underfeeding or target feeding groups (caloric goal: 60‐70% compared with 90‐100% of calculated requirement, respectively) with either IIT or CIT (target blood glucose: 4.4‐6.1 compared with 10‐11.1 mmol/L, respectively). Results: Twenty-eight-day all-cause mortality was 18.3% in the permissive underfeeding group compared with 23.3% in the target feeding group (relative risk: 0.79; 95% CI: 0.48, 1.29; P = 0.34). Hospital mortality was lower in the permissive underfeeding group than in the target group (30.0% compared with 42.5%; relative risk: 0.71; 95% CI: 0.50, 0.99; P = 0.04). No significant differences in outcomes were observed between the IIT and CIT groups. Conclusion: In critically ill patients, permissive underfeeding may be associated with lower mortality rates than target feeding. This trial was registered at controlled-trials.com as ISRCTN96294863. Am J Clin Nutr 2011;93:569‐77.

Background/Aim : To determine the mortality rate in a cohort of hospitalized patients with cirrhosis and examine their resuscitation status at admission. Materials and Methods : A retrospective chart review was conducted of patients with cirrhosis who were admitted to a tertiary care hospital in Riyadh, Saudi Arabia, from January 1, 2009, to December 31, 2009. Results: We reviewed 226 cirrhotic patients during the study period. The hospital mortality rate was 35%. A univariate analysis revealed that worse outcomes were seen in patients with advanced age or who had worse child-turcotte-pugh (CPT) scores, worse model for end-stage liver disease (MELD) scores, low albumin and high serum creatinine. Using a multivariate analysis, we found that advanced age (P=0.004) and high MELD (P=0.001) scores were independent risk factors for the mortality of cirrhotic patients. The end-of-life decision were made in 34% of cirrhotic patients, and the majority of deceased patients were "no resuscitation" status (90% vs. 4%, P

Surveillance ultrasounds in critically ill patients detect many deep venous thrombi (DVTs) that would otherwise go unnoticed. However, the impact of surveillance for DVT on mortality among critically ill patients remains unclear.We are conducting a multicenter, multinational randomized controlled trial that examines the effectiveness of adjunct intermittent pneumatic compression use with pharmacologic thromboprophylaxis compared to pharmacologic thromboprophylaxis alone on the incidence of proximal lower extremity DVT in critically ill patients (the PREVENT trial). Enrolled patients undergo twice weekly surveillance ultrasounds of the lower extremities as part of the study procedures. We plan to compare enrolled patients who have surveillance ultrasounds to patients who meet the eligibility criteria but are not enrolled (eligible non-enrolled patients) and only who will have ultrasounds performed at the clinical team's discretion. We hypothesize that twice-weekly ultrasound surveillance for DVT in critically ill patients who are receiving thromboprophylaxis will have more DVTs detected, and consequently, fewer pulmonary emboli and lower all-cause 90-day mortality.We developed a detailed a priori plan to guide the analysis of the proposed study and enhance the validity of its results.

The insecticide chlorpyrifos (CPF) is widely used in the Kingdom of Saudi Arabia (KSA) to control agricultural pests. The present work is a preliminary investigation of the effect of CPF on healing of cutaneous leishmaniasis (CL) lesions, caused by Leishmania major in farmers exposed to this insecticide, after treatment with Pentostam(®). Lesion diameters were measured and CPF concentrations in the blood plasma of farmer and non-farmer CL patients in Al-Ahsa were detected by gas chromatography/mass spectrometry/mass spectrometry before and 6 weeks after treatment with Pentostam(®). CPF concentrations in the blood of farmer patients ranged between 4.570 and 7.096 ng/μl (mean = 6.19 ± 0.881 ng/μl) before and after treatment with Pentostam(®). The mean lesion diameter in these patients decreased by a factor of 2.21 after treatment with Pentostam(®); they measured 1.85-11.75 mm, (mean = 6.165 ± 3.500 mm) before treatment and 0.22-6.10 mm (mean = 2.796 ± 2.102 mm) after treatment. Lesion diameter increased exponentially with the increase of CPF concentration in the patients' blood. CPF was not detected in the non-farmer patients before or after treatment. Their mean lesion diameter decreased by a factor of 6.86 after treatment with Pentostam(®); they measured 1.33-7.10 mm (mean = 2.882 ± 1.764 mm) before treatment and 0.11-0.92 mm (mean = 0.425 ± 0.277 mm) after treatment. The mean lesion diameter in farmer patients was much greater than that of non-farmer patients both before (2.14×) and after (6.657×) treatment with Pentostam(®). Chronic exposure to low levels of the pesticide aggravates the development and delays the healing of CL lesions due to immunotoxicity and/or peripheral neurotoxicity caused by CPF. Further detailed studies would assess CPF effect on the severity of infection with CL in agricultural workers continuously exposed to this insecticide in different areas of KSA in conformity of their finding.

Obesity has been described as a relative contraindication for percutaneous tracheostomy. The objective of our study was to examine the safety and complications of percutaneous tracheostomy in obese patients. We conducted a prospective cohort study of all consecutive patients who underwent percutaneous tracheostomy at a tertiary medical-surgical intensive care unit between May 2004 and October 2005. We compared percutaneous tracheostomy in obese patients (body mass index ≥30 kg/m2) to non-obese patients. We documented the occurrence of the following complications: aborting the procedure, accidental extubation, conversion to surgical tracheostomy, paratracheal placement, the development of pneumothorax, major bleeding (requiring blood product transfusion or surgical intervention) or death. We also documented hypoxia, minor bleeding (requiring pressure dressing or suturing), subcutaneous emphysema and transient hypotension. During the study period, 227 percutaneous tracheostomies were performed. There were 50 percutaneous tracheostomies in the obese group and 177 in the non-obese group. In 45 obese patients, percutaneous tracheostomy was performed without bronchoscopic guidance. Major complications were significantly higher in obese patients (12% vs. 2%, P=0.04), while the rate of minor complications was not significantly different between the two groups. There were no instances of death or pneumothorax, subcutaneous emphysema or need for surgical intervention during or in the postoperative period in either group. Our study suggests that percutaneous tracheostomy can be performed safely in the majority of obese patients.