ICU shift related effects on sleep, fatigue and alertness levels.

BACKGROUND: Shift work may lead to suboptimal sleep resulting in impaired alertness, and lowered performance levels, all of which can lead to medical errors. AIMS: To examine fatigue, sleepiness and behavioural alertness prospectively in a tertiary level Australian intensive care unit (ICU). METHODS: All full-time doctors providing 24-h resident cover on a 12-h day and 12-h night shift roster were invited to participate in this study. Data collected included Epworth Sleepiness Scale (ESS), sleep and awake history, Samn-Perelli Fatigue (SPF) Scale, Karolinska Sleepiness Scale (KSS) and iOS-based Psychomotor Vigilance Test (behavioural alertness). Data about medical emergency team (MET) shifts were collected separately as they were perceived to be busier shifts. RESULTS: Twenty-nine ICU doctors participated in this study for a consecutive 6-week period. At baseline the median (interquartile range (IQR)) ESS was 5 (3-9). Day shift leads to an increase in fatigue and sleepiness (both P < 0.01). Night shift leads to worsening in fatigue, sleepiness and psychomotor vigilance (all P < 0.01). MET shifts had a lower psychomotor vigilance than non-MET shifts. The difference in the psychomotor vigilance was mostly due to the difference in recorded lapses and response time. CONCLUSIONS: Shift work ICU doctors experience high levels of fatigue and sleepiness. Night shifts also lead to decreased vigilance. This is even more evident in doctors working MET shifts. These factors may lead to errors. Optimal rostering may reduce these effects and improve patient safety.

Impact of the Royal Australasian College of Physicians' clinical examination preparation on basic physician trainee assessment of jugular venous pressure.

Australian internal medicine trainees undergo intensive training in preparation for the Royal Australasian College of Physicians (RACP) clinical examination. Trainees preparing for the 2013 RACP clinical examination assessed the jugular venous pressure (JVP) of patients, with central venous pressure monitoring in the intensive care unit before and after the exam. RACP clinical examination preparation was associated with improvements of trainees' ability to identify JVP that were not elevated, although the JVP examination was performed marginally as a diagnostic test. Ongoing training might further improve this skill.

Population modeling and simulation study of the pharmacokinetics and antituberculosis pharmacodynamics of isoniazid in lungs.

Among first-line antituberculosis drugs, isoniazid (INH) displays the greatest early bactericidal activity (EBA) and is key to reducing contagiousness in treated patients. The pulmonary pharmacokinetics and pharmacodynamics of INH have not been fully characterized with modeling and simulation approaches. INH concentrations measured in plasma, epithelial lining fluid, and alveolar cells for 89 patients, including fast acetylators (FAs) and slow acetylators (SAs), were modeled by use of population pharmacokinetic modeling. Then the model was used to simulate the EBA of INH in lungs and to investigate the influences of INH dose, acetylator status, and M. tuberculosis MIC on this effect. A three-compartment model adequately described INH concentrations in plasma and lungs. With an MIC of 0.0625 mg/liter, simulations showed that the mean bactericidal effect of a standard 300-mg daily dose of INH was only 11% lower for FA subjects than for SA subjects and that dose increases had little influence on the effects in either FA or SA subjects. With an MIC value of 1 mg/liter, the mean bactericidal effect associated with a 300-mg daily dose of INH in SA subjects was 41% greater than that in FA subjects. With the same MIC, increasing the daily INH dose from 300 mg to 450 mg resulted in a 22% increase in FA subjects. These results suggest that patients infected with M. tuberculosis with low-level resistance, especially FA patients, may benefit from higher INH doses, while dose adjustment for acetylator status has no significant impact on the EBA in patients with low-MIC strains.

A randomised controlled trial of high-dose isoniazid adjuvant therapy for multidrug-resistant tuberculosis.

SETTING: Tertiary care hospital in Kanpur, India. BACKGROUND: The need for a standardised treatment protocol for multidrug-resistant tuberculosis (MDR-TB) in resource-limited countries is being increasingly recognised. OBJECTIVE: To assess the effectiveness of high-dose isoniazid (INH) (16-18 mg/kg) adjuvant to second-line therapy in documented cases of MDR-TB. DESIGN: The present study is a double blind, randomised controlled trial with three treatment arms, high-dose INH, normal-dose INH and placebo, in addition to second-line drugs. Primary outcomes of the study were time to sputum culture conversion and proportion with sputum culture negative 6 months after treatment initiation. Secondary outcomes were radiological improvement at 1 year post treatment and development of toxicity. RESULTS: After adjustment for potential confounders, subjects who received high-dose INH became sputum-negative 2.38 times (95%CI 1.45-3.91, P = 0.001) more rapidly than those who did not receive it, and had a 2.37 times (95%CI 1.46-3.84, P < 0.001) higher likelihood of being sputum-negative at 6 months. These subjects showed significantly better radiological improvement without an increased risk of INH toxicity. CONCLUSION: In low-resource scenarios where a standardised therapeutic protocol is used for MDR-TB, the protocol can be significantly improved by including high-dose INH as an adjuvant.

Use of the QuantiFERON-TB Gold In-Tube test to monitor treatment efficacy in active pulmonary tuberculosis.

SETTING: Cohort study at a tertiary care hospital. OBJECTIVE: To assess the potential use of QuantiFERON-TB Gold In-Tube (QFT-G) in monitoring clinical response to anti-tuberculosis treatment. DESIGN: We conducted a cohort study of 76 active pulmonary tuberculosis patients with serial testing by QFT-G at baseline and after 2 and 6 months of treatment. At these time points, we compared the performance of QFT-G with sputum culture status of the study subjects. RESULTS: Compared to baseline, 59 (77.6%) cases showed a decline whereas 17 (22.4%) showed persistent or stronger interferon-gamma (IFN-gamma) responses at 2 months. Using robust statistical methods, we observed that QFT-G assessment at 2 months independently and significantly predicted the likelihood of remaining sputum culture-positive at the end of the intensive phase of anti-tuberculosis treatment. A higher IFN-gamma concentration by 1 international unit (IU)/ml corresponded to a 45% (95%CI 8-97) higher likelihood of failing to convert to a negative culture, whereas a rising or persistent IFN-gamma response was associated with a 17.3 (P = 0.007) times higher likelihood of remaining culture-positive at 2 months. CONCLUSIONS: Our results suggest that QFT-G can potentially be used as a tool to monitor the efficacy of anti-tuberculosis treatment.

Correlation Of Serum Albumin And Red Cell Distribution Width (RDW) With Deep Vein Thrombosis And Pulmonary Embolism A Retrospective Study

Background:Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a severe and potentially lethal disease, with serious short and long?term complications and a potentially fatal outcome. Objective:To determine the correlation of Serum Albumin and Red cell Distribution Width( RDW),with deep vein thrombosis and pulmonary embolism.Materials & Methods: A retrospective study was carried out from the archive of patients with an event of VTE admitted in theGeneral Medicine ward, Jhalawar Medical College, Jhalawar, Rajasthan. Patients’ demographics, presenting symptoms, laboratory tests particularly RDW and Serum Albumin, medications, interventions, and outcomes were collected.Result:A total of 131 cases wereevaluated. Majority of the patients (48.8%) were in age group 45-64 years. The mean duration of hospitalization stay of venous thromboembolism (VTE) patients was 6.6 ± 1.4 days. Mean RDW (%) of the total study participants was 15.3 ± 1.4. Mean serum albumin of the total study participants was 3.3 ± 0.8.Conclusion:Majority of the patients were found with higher RDW and Low Serum Albumin.

Discordance between ROTEM® clotting time and conventional tests during unfractionated heparin-based anticoagulation in intensive care patients on extracorporeal membrane oxygenation.

We hypothesised that ROTEM® (Basel, Switzerland) INTEM® (ROTEM, Basel, Switzerland) clotting time (CT) would have good agreement with activated partial thromboplastin time (aPTT) in determining whether a dose adjustment should be made to the unfractionated heparin (UFH) infusion in patients on extracorporeal membrane oxygenation. All patients treated with extracorporeal membrane oxygenation over a five-year period were included for data analysis. Retrospective analysis was performed of prospectively collected data points, wherein aPTT, activated CT and ROTEM was performed simultaneously to monitor UFH-based anticoagulation. Two hundred data points were available for analysis. Turnaround time was shortest for activated CT followed by ROTEM and aPTT. Despite achieving therapeutic aPTT targets, the majority (>50%) of INTEM CT results were within normal limits. The aPTT and INTEM CT results correlated weakly (r=0.31, 95% confidence interval [0.17, 0.43]) and there was no agreement between the directional changes of aPTT and INTEM CT results on successive days (x² =2.33, P=0.17). Due to relative insensitivity, INTEM CT-guided UFH titration was estimated to result in a 289% increase in incidence of up-titration, over aPTT-guided titration. The INTEM CT results (r=0.36, 95% confidence interval [0.23, 0.48]) correlated weakly with UFH infusion rates. The UFH infusion rate only explained 13% variability in INTEM CT values. While haemorrhagic complications were frequent, no major clotting complications were encountered. Our results demonstrated that aPTT and INTEM CT do not provide equivalent information to guide UFH infusion rate titration during extracorporeal membrane oxygenation. Our study suggests caution regarding the use of ROTEM for guiding UFH-based anticoagulation as it may lead to excessive UFH exposure.

High prevalence of muscular ventricular septal defect in preterm neonates.

Isolated muscular ventricular septal defect was identified in 9 of 159 consecutive preterm neonates by color Doppler echocardiography, a prevalence of 56.6/1,000 live births. The neonates with ventricular septal defects appear clinically healthy, and in 87.5% of them the defect spontaneously closed within 6 to 11 months. The prevalence and rate of spontaneous closure are similar to those in full-term neonates.

Stereoselective formation of seven-coordinate titanium(IV) monomer and dimer complexes of ethylenebis(o-hydroxyphenyl)glycine.

Reactions between the antitumor agent titanocene dichloride (Cp2TiCl2) and the hexadentate ligand N,N'-ethylenebis-(o-hydroxyphenylglycine) (H4ehpg) have been investigated in aqueous solution and the solid state. The racemic ligands give crystals of the monomer [Ti(ehpg)(H2O)] x (11/3)H2O (1), while the meso ligand gives the oxo-bridged dimer [[Ti(Hehpg)(H2O)]2O] x 13H2O (2). Complex 1 crystallizes in the monoclinic space group C2/c with a = 24.149(4) A, b = 14.143(3) A, c = 19.487(3) A, beta = 105.371(13) degrees, V = 6417.7(19) A3, Z = 12, and R(F) = 0.0499 for 4,428 independent reflections having I > 2sigma(I), and contains seven-coordinate pentagonal-bipyramidal TiIV with two axial phenolate ligands (Ti-O, 1.869(2) A). The pentagonal plane contains the two N-atoms at 2.210(2) A, two carboxylate O-atoms at 2.061(2) A, and a water molecule (Ti-OH2, 2.091(3) A). Complex 2 crystallizes as an oxygen-bridged dimer in the triclinic space group P-1 with a = 12.521(6) A, b = 14.085(7) A, c = 16.635(8) A, alpha = 80.93(2) degrees beta = 69.23(2) degrees, gamma = 64.33(2) degrees , V = 2472(2) A3, Z = 4, and R(F) = 0.0580 for 5956 independent reflections having I > 2sigma(I). Each seven-coordinate, pentagonal-bipyramidal TiIV has a bridging oxide and a phenolate as axial ligands. The pentagonal plane donors are H2O, two carboxylate O-atoms, and two NH groups, which form H-bonds to O-atoms both in the same half-molecule (O...N, 2.93-3.13 A) and in the other half-molecule (O...N, 2.73-2.75 A); the second phenoxyl group of each Hehpg ligand is protonated and not coordinated to TiIV, but H-bonds to a nearby amine proton (O...N, 2.73-2.75 A) from the same ligand and to a nearby H2O (O...O, 2.68 A). In contrast to all previously reported crystalline metal-EHPG complexes containing racemic ligands, in which the N(S,S)C(R,R) or N(R,R)C(S,S) form is present, complex 1 unexpectedly contains the N(S,S)C(S,S) and N(R,R)C(R,R) forms. This is attributed to the presence of ring strain in seven-coordinate TiIV complexes. Moreover, the rac ligands selectively form crystals of monomeric 1, while the meso ligand selectively forms crystals of the dimer 2 (N(R,R)C(R,S) or N(S,S)C(S,R)). Complexes 1 and 2 exhibit phenolate-to-TiIV charge-transfer bands near 387 nm, and 2D NMR studies indicate that the structures of 1 and 2 in solution are similar to those in the solid state. Complex 1 is stable over the pH range 1.0-7.0, while 2 is stable only between pH 2.5 and pH 5.5. Cp2TiCl2 reacts with EHPG at pH* 7.0 to give complex 1 with a t 1/2 of ca. 50 min (298 K), but complex 2 was not formed at this pH* value. At pH* 3.7, the reaction is very slow: 1 forms with a half-life of ca. 2.5 d, and 2 after ca. 1 week at ambient temperature. The relevance of these data to the possible role of serum transferrin as a mediator for the delivery of TiIV to tumor cells is discussed.

Onchocerciasis in camels (Camelus dromedarius) in Saudi Arabia.

During a survey in 1980-81, 125 of 478 (26.2%) camels in Saudi Arabia were found infected with onchocerciasis. The prevalence rates in local and imported camels were 93/272 (34.2%) and 32/206 (15.5%), respectively. The disease was characterized by hard nodules in the connective tissue around the nuchal ligaments and in the subcutis. The nodules consisted of cavities containing live, degenerate or dead Onchocerca fasciata, inflammatory cells, fibrosis and calcification. The microfilariae were concentrated in the skin over the head and neck regions and often caused mild non-suppurative dermatitis.