Cost-effectiveness analysis of upadacitinib as a treatment option for patients with rheumatoid arthritis in the Kingdom of Saudi Arabia.

AIM: To evaluate cost-effectiveness of upadacitinib (targeted synthetic-disease modifying anti-rheumatic drug [ts-DMARD]) as first-line (1 L) treatment versus current treatment among patients with rheumatoid arthritis (RA) in the Kingdom of Saudi Arabia (KSA), who had an inadequate response to prior conventional-synthetic (csDMARDs) and/or biologic-DMARDs (bDMARDs). METHODS: This Excel-based model included patients with moderate (Disease Activity Score [DAS28]: >3.2 to ≤5.1) or severe RA (DAS28 > 5.1). Cost-effectiveness of current treatment (1 L: adalimumab-originator/biosimilar; second-line (2 L): other bDMARDs/tofacitinib) was compared against a new treatment involving two scenarios (1 L: upadacitinib, 2 L: adalimumab-biosimilar [scenario-1]/adalimumab-originator [scenario-2]) for a 10-year time-horizon from societal perspective. Model outcomes included direct and indirect costs, quality-adjusted life-years (QALYs), hospitalization days, number of orthopedic surgeries, and incremental cost-utility ratio (ICUR) per QALY. RESULTS: With the current pathway, estimated total societal costs for 100 RA patients over 10-year period were Saudi Riyal (SAR) 50,450,354 (United States dollars [USD] 13,453,428) (moderate RA) and SAR50,013,945 (USD13,337,052) (severe RA). New pathway (scenario-1) showed that in patients with moderate-to-severe RA, upadacitinib led to higher QALY gain (+8.99 and +15.63) at lower societal cost (cost difference: -SAR2,023,522 [-USD539,606] and -SAR3,373,029 [-USD899,474], respectively). Thus, as 1 L, upadacitinib projects "dominant" ICUR per QALY over current pathway. Moreover, in alternate pathway (scenario-2), upadacitinib also projects "dominant" ICUR per QALY for patient with severe RA (QALY gain: +15.63; cost difference: -SAR 164,536 [-USD43,876]). However, moderate RA was associated with additional cost of SAR1,255,696 (USD334,852) for improved QALY (+8.99) over current pathway (ICUR per QALY: SAR139,742 [USD37,264]). Both scenarios resulted in reduced hospitalization days (scenario-1: -14.83 days; scenario-2: -11.41 days) and number of orthopedic surgeries (scenario-1: -8.36; scenario-2: -6.54) for moderate-to-severe RA over the current treatment pathway. CONCLUSION: Upadacitinib as 1 L treatment in moderate-to-severe RA can considerably reduce healthcare resource burden in KSA, majorly due to reduced drug administration/monitoring/hospitalization/surgical and indirect costs.

Arabic intensive care delirium screening checklist's validity and reliability: A multicenter study.

PURPOSE: To develop an Arabic version of Intensive Care Delirium Screening Checklist (ICDSC) and assess its validity and reliability among critically ill patients. MATERIALS AND METHODS: Multicentered study of convenience sample of adult ICU patients. Arabic translation was performed with rigorous back-to-back translation methods. Concurrent validity was established by calculating the sensitivity and specificity of two examiner assessments compared to a psychiatric evaluation. Kappa coefficients describe interrater reliability, whereas Cronbach α and composite reliability depict internal consistency. RESULTS: Three hundred critically ill patients were enrolled. Of these, validity testing was assessed in 180 patients. ICDSC screening was positive for delirium in 11% of enrolled patients. The area under the receiver operator characteristic (ROC) curve is 0.9413, with predicted sensitivity 70% (95% confidence interval [CI]: 60-81%) and specificity 99% (95% CI: 98-100%). The Arabic ICDSC showed acceptable internal consistency (Cronbach α = 0.63 and composite reliability = 0.64). Interrater agreement was excellent (Kappa coefficient [Ò¡] = 0.85). CONCLUSIONS: Arabic ICDSC is a valid and reliable delirium-screening tool among Arabic-speaking ICU population. Future studies could address whether these findings are generalizable to a higher proportion of mechanically ventilated patients, and address acceptability and reliability in other Arabic language critical care settings.

Electrocortical and Biochemical Evaluation of Antidepressant Efficacy of Formulated Nanocurcumin.

The present study aims to evaluate the antidepressant efficacy of curcumin nanoparticles on rat model of depression induced by reserpine. Rats were divided into control, the rat model of depression induced by daily i.p. injection of reserpine (0.2 mg/kg for 21 days), and the rat model of depression treated daily with the formulated CNPs (20 mg/kg for 7 and 15 days). The behavioral evaluation was assessed for all groups of animals by the forced swim test (FST). Monoamine neurotransmitters were measured in the cortex and hippocampus via fluorescence spectroscopy. The electrophysiological evaluation was carried out by recording and analyzing the electrocorticogram (ECoG) in a group of animals that served as self-control. The chronic administration of reserpine resulted in a significant decrease in the duration of the active phase in the FST; a significant decrease in the cortical and hippocampal levels of serotonin, norepinephrine, and dopamine; a significant increase in spectral power of alpha and delta waves; and a significant decrease in spectral power of theta, beta-1, and beta-2 waves with respect to control values. Administration of CNPs for 7 days has improved the performance of animals in FST indicated by the increase in the duration of the active phase. Additionally, the levels of serotonin and dopamine have been restored; however, the level of norepinephrine has been not completely recovered in both cortex and hippocampus. A significant increase in alpha and beta-2 waves, an increase in theta and beta-1, and a decrease in delta waves have been recorded after 7 days of treatment. Extending treatment with CNPs for 15 days has succeeded in restoring the active phase in FST and monoamine level in the cortex and hippocampus to control like values. In addition, ECoG waves have returned to near control like values. It could be concluded that the formulated nanocurcumin has an effective and potent antidepressant activity that was evidenced by electrical, chemical, and behavioral tests.

Advances in atomic physics: Four decades of contribution of the Cairo University - Atomic Physics Group.

In this review article, important developments in the field of atomic physics are highlighted and linked to research works the author was involved in himself as a leader of the Cairo University - Atomic Physics Group. Starting from the late 1960s - when the author first engaged in research - an overview is provided of the milestones in the fascinating landscape of atomic physics.

Influence of racing on the serum concentrations of acute-phase proteins and bone metabolism biomarkers in racing greyhounds.

This study was designed to evaluate the influence of racing on the serum concentrations of the acute-phase proteins (APPs) C-reactive protein (CRP), haptoglobin (Hp) and serum amyloid A (SAA) in 32 endurance-racing greyhounds. The study also aimed to investigate the effect of a 7 km race on the bone biomarkers osteocalcin (OC), bone-specific alkaline phosphatase (b-ALP) and pyridinoline cross-links (PYD). Total white blood cell (WBC) count, and the serum concentrations of cortisol, tumour necrosis factor-α (TNF-α), vitamin D and testosterone were also determined. Blood samples were collected 24 h prior to (T0) and within 2 h of completion of the race (T1). Compared to baseline values, WBC count did not change significantly (P = 0.2300), serum cortisol, Hp and SAA increased, while TNF-α and CRP decreased (P <0.0001 for each). There were no significant differences between the pre- and post-race serum concentrations of OC and PYD (P = 0.9500 and P = 0.2600, respectively), but serum b-ALP increased significantly (P = 0.0004). Serum concentrations of vitamin D and testosterone increased after racing (P = 0.0100 and P <0.0001, respectively). In this study, a 7 km race stimulated an acute-phase response, demonstrated by significant increases in the serum concentrations Hp and SAA in racing greyhounds. Increased serum b-ALP post-race probably indicates a change in bone metabolism and deserves further study.

Influence of stimulation by electroejaculation on myocardial function, acid-base and electrolyte status, and hematobiochemical profiles in male dromedary camels.

This study was carried out to evaluate the effect of electroejaculation (EEJ) on myocardial function, acid-base balance, and hematobiochemical profiles in male dromedary camels. Twenty sexually mature, apparently healthy male camels were assigned to EEJ. Parallel, eight naturally mated male camels were enrolled as a control group. Three blood samples were collected from each camel: just before (T0), directly after (T1), and 24 hours after (T2) EEJ or natural mating. The serum concentrations of the cardiac biomarker troponin I (cTnI), blood gas parameters, and hematobiochemical profiles were determined. Nineteen camels were ejaculated by the end of the second circuit and one by the end of the first circuit. In both groups, the mean heart and respiratory rates had increased significantly immediately after the procedure, but returned to normal values 24 hours after the procedure. The mean serum concentration of cTnI had increased significantly in all camels after EEJ, but not in controls. However, at 24 hours post-EEJ, the serum concentration of cTnI did not differ significantly compared with baseline values. The blood pH and base excess had decreased, and the PCO2 and lactic acid had increased after EEJ. The EEJ provoked decreases in hematocrit and mean corpuscular volume. In the control group, the base excess, HCO3(-), TCO2, anion gap, and lactic acid increased slightly after mating but did not reach a significant level compared with premating values. It is concluded that EEJ in camels results in a reversible myocardial injury, changes in the acid-base status, and increase the lactic acid concentration.

Clinical and ultrasonographic findings of some ocular conditions in sheep and goats.

This study was carried out to describe the ultrasonographic findings in relation to the clinical symptoms of some common ocular conditions in sheep and goats. Fifty animals (32 goats and 18 sheep) with different ocular problems were examined. Ultrasonographic examination was performed using a B-mode ocular ultrasound unit, and the structure of the globe was evaluated at a depth of 4-6 cm. Early cases (n=35, 70%) showed varying ocular conditions; hypopyon, (n=8, 16%), stromal abscesses, (n=4, 8%), and anterior uveitis (n=23, 46%). Hypopyon appeared clinically as a white or yellowish material in the anterior chamber, and ultrasonographically as a hyperechoic mass in the anterior chamber. Severe iridocyclitis was noticed in acute cases of infectious keratoconjunctivitis (IKC) accompanied by blepharospasm, photophobia, excessive tearing and eyelid margin crust formation. Ultrasonographically, the pupil appeared constricted with increased hyperechoic thickening of the ciliary body. In chronic cases of IKC, corneal pigmentation (n=5, 10%) and cataract (n=10, 20%) were seen. Ultrasonographically the type and degree of cataract were diagnosed. The present study provides an inside view of the inner ocular structures during the course of certain eye diseases where ophthalmoscopic examination is not possible. Our findings, although preliminary, are relevant for the more complete diagnosis of certain external ocular conditions in sheep and goat herds.

The cardiac biomarkers troponin I and CK-MB in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth, and goats with pregnancy toxemia.

This study was designed to establish the reference range for the cardiac biomarkers cardiac troponin I (cTnI) and creatine kinase myocardial band (CK-MB) in nonpregnant and pregnant goats, goats with normal birth, goats with prolonged birth associated with dystocia, and goats with pregnancy toxemia. Fifty-seven does, categorized into three groups (G1 to G3), were used. These groups were comprised of 20 healthy does (G1), 19 does with prolonged birth (G2), and 18 does with pregnancy toxemia (G3). Six blood samples (T0 to T5) were collected from G1. The first blood sample (T0) was taken before insemination, the second (T1) at the first trimester, the third (T2) at the second trimester, the fourth (T3) at the last trimester, the fifth (T4) within 12 h of parturition, and the sixth blood sample (T5) was taken 10 days after parturition. A sample of blood was obtained from G2 and G3 upon admission to the hospital. At T0 to T3, no cTnI was detected in any of the 20 does in G1. At parturition (T4), seven of the 20 goats (35%) exhibited slightly elevated cTnI concentrations (range, 0.01 to 0.04 ng/mL). Ten days after parturition (T5), cTnI was not detected in any of the 20 goats. In 10 of the 19 goats (53%) with prolonged birth (G2), the cTnI was significantly elevated to a mean value of 0.094 ± 0.155 ng/mL, with a maximum value of 0.61 ng/mL. In 16 of the 18 goats (89%) with pregnancy toxemia (G3), the cTnI was significantly elevated to a value of 0.852 ± 1.472 ng/mL, with a maximum value of 5.219 ng/mL. Comparing the values of CK-MB in G1 (T0 to T5), G2 and G3 revealed nonsignificant differences. Only a slight elevation in the CK-MB levels in goats with prolonged birth (G2) was noted. We concluded that in healthy does, the cardiac biomarker cTnI is not elevated during normal pregnancy. The serum cTnI concentration may be elevated in a number of goats at normal vaginal or cesarean delivery. Finally, cTnI is significantly elevated in does with pregnancy toxemia and could be used as a prognostic indicator in such cases. The cardiac biomarker CK-MB is not a good indicator of parturition stress in does. Serum cTnI is elevated in goats with pregnancy toxemia, indicating some degree of cardiac dysfunction.

Ultrasonography as a diagnostic and prognostic approach in cattle and buffaloes with fatty infiltration of the liver.

The aim of the present study was to determine whether ultrasonographic evaluation of the hepatic parenchyma could be used as a diagnostic and prognostic approach in cows and buffaloes with hepatic lipidosis. For this purpose, cows (n=16) and buffaloes (n=10) with fatty infiltration of the liver were examined by ultrasonography. Treated cows and buffaloes were monitored for hepatic changes ultrasonographically, biochemically and histologically. Clinical findings were non-specific and included anorexia, recumbency, muzzle necrosis, and icteric mucosal membranes. Laboratory data revealed neutrophilia, hyper gamma-globulinemia, elevated activities of aspartate aminotransferase, gamma-glutamyl transpeptidase, creatine kinase and lactate dehydrogenase, and high concentrations of insulin, total bilirubin, non-esterified fatty acids and beta-hydroxyl butyric acid. Laboratory results 7, and 21 days after treatment showed progressive improvement in the chemistry profile. On admission, ultrasonographic examination of the hepatic parenchyma in cows and buffaloes revealed either increased or decreased hepatic echogenicity; histologic examination revealed marked fatty infiltration of the hepatocytes. One week after treatment, the hepatic parenchyma was visualized easily, liver boundaries were clearly imaged, and histologic examination of hepatic specimen showed a moderate degree of fatty infiltration. Three weeks after treatment, the hepatic parenchyma was almost similar to normal, the hepatic and portal blood vessels could be easily imaged, and the histologic picture had greatly improved where the liver resembled the normal organ. Six cows and seven buffaloes made a full recovery while the remaining ten cows and three buffaloes were slaughtered and thoroughly examined postmortem. Ultrasonography showed a good correlation with histologic and laboratory findings.

The diagnostic criteria used in bovine bacterial endocarditis: a meta-analysis of 460 published cases from 1973 to 2011.

Bacterial endocarditis (BE) is the most common valvular disease in cattle but diagnosis in the living animal remains a challenge for clinicians. The objective of the study was to report evidence-based veterinary medicine data concerning the clinical presentation and results of ancillary tests of necropsy-confirmed cases of bovine BE. A systematic review and subsequent meta-analysis was performed using Medline and CAB abstracts of every article on bovine BE published in English, Japanese, German and French. The clinical criteria that were specifically assessed for diagnosis of BE were: tachycardia, heart murmur, signs of congestive heart failure, presence of fever, evidence of lameness/polyarthritis, one or more positive blood cultures and positive echocardiograms for BE. A total of 34 studies (460 cases of BE) satisfied the inclusion criteria for the systematic review. The sensitivity (Se), specificity (Sp) and 95% confidence interval (CI) were obtained using a random-effect meta-analysis for studies reporting five or more cases. The Se (95% CI) were 86.9% (39.1-98.6%) for positive haemoculture, 84.3% (60.4-95.0%) for echocardiography, 79.7% (70.1-86.8%) for the presence of tachycardia, 60.3% (51.8-68.3%) for the presence of a murmur, 45.7% (32.5-59.5%) for the presence of fever, 43.5% (25.6-63.3%) for the presence of lameness/polyarthritis, and 37.3% (21.6-57.0%) for the presence of clinical signs of heart failure. The Sp (95% CI) was 95.3% (93.3-96.8%) for lameness, 72.6% (45.8-89.2%) for the presence of a murmur, 67.0% (55.5-76.7%) for the presence of fever, and 27.1% (14.3-45.2%) for the presence of tachycardia. This meta-analysis confirmed that the diagnosis of BE is a difficult process. Echocardiography seems to be a sensitive diagnostic tool despite the absence of any consensus on the ultrasonographic definition of the disease. However, from these results, it was impossible to determine whether multiple positive findings or clinical tests increase the sensitivity for the diagnosis of bovine BE.

DNA damage in peripheral blood mononuclear cells and neutrophils of dairy cows during the transition period.

This study was designed to investigate the apoptotic process in peripheral blood mononuclear cells (PBMC) and polymorphonuclear neutrophil leukocytes (PMN) in dairy cattle during the transition period. Blood samples were collected from 4 dairy cattle at 3 weeks before the expected parturition (wk -3), parturition (wk 0) and 3 weeks after parturition (wk +3). The DNA damage of PBMC and PMN was evaluated based on the comet assay using visual scoring (arbitrary units). Undamaged DNA remained within the core (score 0) and the broken DNA migrated from the core towards the anode forming the tail of a comet (scores 1-4). Significantly higher scores in PBMC at wk 0 and wk +3 were observed compared with those in PMN although there were no significant changes of scores in either cell type during the experimental period. It is suggested that the apoptotic rate of PBMC is accelerated compared with that of PMC during the transition period.

Ovarian hydrobursitis in female camels (Camelus dromedaries): biochemical, bacterial and protozoal evaluation.

The aim of this study was to evaluate female camels affected with ovarian hydrobursitis (n = 31) for hematological and biochemical findings and for bacterial and protozoal infections. Blood samples were obtained and surgical ablation of the affected bursa was performed. Bursal fluid, follicular fluid, and serum were subjected to hormonal and biochemical analyses. Bursal fluids were cultured and colonies were identified using BioMérieux Vitek two compact system. Passive haemagglutination test was used for detection of Trypanosoma evansi. Indirect ELISA technique was carried out for detection of anti-Hydatid cysts anti-bodies. Neutrophilia was found in the affected animals (P = 0.01) with tendencies for monocytosis (P = 0.06) and eosinophelia (P = 0.05). Bursal fluid had a tendency for high estradiol-17ß concentration compared to blood serum (P = 0.07). Progesterone and cholesterol concentrations were similar in bursal fluid, follicular fluid and serum. Total protein, phosphorus, and magnesium concentrations were greater (P < 0.05) in the bursal fluid than in serum. Oligella urethralis, Alloiococcus otitis, Granulicatella adicens, Escherichia coli, Sphingobacterium thalpophilum, Streptococcus sanguinis, Aeromonas salmonicida, Pseudomonas stutzeri, Staphylococcus warneri, Staphylococcus hominis, and Rhizobium radiobacter were isolated from 46.7% of bursal fluids. T. evansi was positive in 9.7% of cases. None were positive for hydatid cyst. Accordingly, we suggest that the ovarian hydrobursitis syndrome is initially an inflammatory process and the accumulated bursal fluid is partially originated from follicular fluid.

Hormonal, biochemical, and hematological profiles in female camels (Camelus dromedarius) affected with reproductive disorders.

The aim of this study was to assess the blood profiles in female camels affected with common reproductive disorders. Estradiol-17beta (E(2)), progesterone (P(4)), thyroxin (T(4)), zinc (Zn), copper (Cu), calcium (Ca), phosphorus (P), magnesium (Mg), cholesterol, glucose, triglycerides, total protein, albumin, globulin, hematocrite, and total and differential white blood cell counts (WBC) were determined in blood of female camels affected with endometritis (n=15), vaginal adhesions (n=15), and ovarian cysts (n=15). Normal cyclic animals were used as controls (n=15). Diagnosis of reproductive disorders was based on transrectal palpation, ultrasonographic examination, and exploration of the vagina. Increased WBC counts (P=0.03) and a tendency for neutrophelia (P=0.05) were noted in female camels with vaginal adhesions. These animals were also characterized by having higher concentration of serum P(4) (P=0.0001), T(4) (P=0.001) and total protein (P=0.007), in comparison with female camels with endometritis, ovarian cysts, or controls. Animals having ovarian cysts with thin walls and homogenous hypoechogenic contents had greater serum E(2) (P=0.001) and P(4) (P=0.0001) than those having ovarian cysts with thick walls and non-homogenous echogenic contents. Animals with endometritis, vaginal adhesions, and ovarian cysts revealed lower serum Zn concentration than that of control group (P=0.003). Other blood parameters did not differ significantly compared to controls. In conclusion, this is the first report characterizing blood constituents in female camels with various reproductive disorders. These profiles may be valuable in clarifying the etio-pathogenesis of these disorders.

Causes of blindness and needs of the blind in Mansoura, Egypt.

A study of 113 blind people in Mansoura, Egypt highlighted the causes and risk factors for blindness, and health and social care needs of the blind. In two-thirds of cases, blindness occurred before 10 years of age. Risk factors for blindness were reported by more than half the study population. Congenital causes accounted for almost half the cases. The commonest causes of bilateral blindness were corneal opacities, cataract and glaucoma. Almost three-quarters of causes were avoidable. Health and social care for this group was inadequate and more than half would benefit from further management. Legislation for keratoplasty, a registry of blind people, and a nationwide community survey on the epidemiology of blindness are needed urgently.

Causes of blindness and needs of the blind in Mansoura, Egypt

A study of 113 blind people in Mansoura, Egypt highlighted the causes and risk factors for blindness, and health and social care needs of the blind. In two-thirds of cases, blindness occurred before 10 years of age. Risk factors for blindness were reported by more than half the study population. Congenital causes accounted for almost half the cases. The commonest causes of bilateral blindness were corneal opacities, cataract and glaucoma. Almost three-quarters of causes were avoidable. Health and social care for this group was inadequate and more than half would benefit from further management. Legislation for keratoplasty, a registry of blind people, and a nationwide community survey on the epidemiology of blindness are needed urgently

Effects of industrial formulations of Bacillus thuringiensis on the biology of Musca domestica L. (Diptera : Muscidae).

The effects of two industrial formulations of Bacillus thuringiensis (Bactimos and Vectobac) on larval and adult stages of Musca domestica L. were assessed in the laboratory. Biocides concentrations of 0.4% to 2% were tested on larvae, while the concentrations of 1% and 2% were tested on adults and were given to the flies in their diet. Larval mortality ranged between 38% and 53% and between 55% and 71% for bactimos and Vectobac respectively. Pupation rates decreased from 91% in the control group down to 47% and 29% for Bactimos and Vectobac respectively. Moreover, adult emergence rates decreased 3-4 folds in groups treated with the highest biocide concentrations. The effect on adult mortality was relatively lower, as control adults showed 4% mortality whereas those treated with Bactimos and Vectobac experienced 17-28% and 32-44% mortality respectively. In addition, biocides treatment induced a dramatic decrease in female fecundity from 273 eggs/female in the control to 118-180 eggs/female treated siblings. These findings indicate that Bactimos and Vectobac possess both direct and indirect harmful effects on Musca domestica.