Design and protocol for a cluster randomised trial of enhanced diagnostics for tuberculosis screening among people living with HIV in hospital in Malawi (CASTLE study)

BACKGROUND: People living with HIV (PLHIV) have a high risk of death if hospitalised in low-income countries. Tuberculosis has long been the leading cause of admission and death, in part due to suboptimal diagnostics. Two promising new diagnostic tools are digital chest Xray with computer-aided diagnosis (DCXR-CAD) and urine testing with Fujifilm SILVAMP LAM (FujiLAM). Neither test has been rigorously evaluated among inpatients. Test characteristics may be complementary, with FujiLAM especially sensitive for disseminated tuberculosis and DCXR-CAD especially sensitive for pulmonary tuberculosis, making combined interventions of interest. DESIGN AND METHODS: An exploratory unblinded, single site, two-arm cluster randomised controlled trial, with day of admission as the unit of randomisation. A third, smaller, integrated cohort arm (4:4:1 random allocation) contributes to understanding case-mix, but not trial outcomes. Participants are adults living with HIV not currently on TB treatment. The intervention (DCXR-CAD plus urine FujiLAM plus usual care) is compared to usual care alone. The primary outcome is proportion of participants started on tuberculosis treatment by day 56, with secondary outcomes of mortality (time to event) measured to to 56 days from enrolment, proportions with undiagnosed tuberculosis at death or hospital discharge and comparing proportions with enrolment-day tuberculosis treatment initiation. DISCUSSION: Both DCXR-CAD and FujiLAM have potential clinical utility and may have complementary diagnostic performance. To our knowledge, this is the first randomised trial to evaluate these tests among hospitalised PLHIV

Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)—pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings

Background Urogenital schistosomiasis (UGS) causes inflammation and fibrosis of the urinary tract. In resource-limited settings, affordable tools for morbidity assessment in clinical care are needed. Point-of-care ultrasound has not yet been validated for UGS-related pathology. Methods We developed a protocol for Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS), assessing pathology of the bladder wall, ureters and kidneys. Following standardized training, two clinicians performed FASUS on children and adults with hematuria in Lambaréné, Gabon. Recorded ultrasound clips were remotely reviewed by two ultrasound experts as a diagnostic reference. Results In 2015 and 2016, scans were performed in 118 patients. The image quality was sufficient in 90% of bladder views and more than 97% of kidney views. UGS-compatible pathology was detected in 51/118 (43%) by the operator and in 46/107 (43%) by the experts among baseline scans of sufficient quality. Inter-rater agreement between operators and experts was very good (κ > 0.8) for hydronephrosis and good (κ > 0.6) for bladder wall thickening. Conclusions FASUS is a promising clinical, point-of-care tool for detecting UGS-related urinary tract morbidity in symptomatic patients. Based on larger validation studies, appropriate diagnostic and therapeutic algorithms for the use of FASUS should be established

Ischemic stroke as a complication of cryptococcal meningitis and immune reconstitution inflammatory syndrome: a case report.

BACKGROUND: Cryptococcal meningitis remains the leading cause of adult meningitis in Sub-Saharan Africa. Immune Reconstitution Inflammatory Syndrome (IRIS) following anti-retroviral therapy (ART) initiation is an important complication. Here we report the first documented case of a IRIS reaction presenting as an ischemic stroke. CASE PRESENTATION: A 38 year old newly diagnosed HIV-infected, ART naive Malawian male presented to a tertiary referral hospital in Blantyre, Malawi with a 2 week history of headache. A diagnosis of cryptococcal meningitis was made and the patient was started on 1200 mg fluconazole once daily and flucytosine 25 mg/kg four times daily as part of the Advancing Cryptococcal Treatment for Africa (ACTA) clinical trial. There was an initial clinical and microbiological response to anti-fungal treatment and anti-retroviral therapy was started at week 4. The patient re-presented 16 days later with recurrence of headache, fever, and a sudden onset of left sided weakness in the context of rapid immune reconstitution; peripheral CD4 count had increased from a baseline of 29 cells/μl to 198 cells/μl. Recurrence of cryptococcal meningitis was excluded through CSF examination and fungal culture. Magnetic Resonance Imaging (MRI) of the brain demonstrated multi-focal DWI (diffusion weighted imaging) positive lesions consistent with an ischemic stroke. Given the temporal relationship to ART initiation, these MRI findings in the context of sterile CSF with raised CSF protein and a rapid immune reconstitution, following an earlier favorable response to treatment is most consistent with a paradoxical Immune Reconstitution Inflammatory Syndrome. CONCLUSIONS: Stroke is an increasing cause of morbidity and mortality amongst HIV infected persons. Ischemic stroke is a recognized complication of cryptococcal meningitis in the acute phase and is thought to be mediated by an infectious vasculitis. This is the first time an ischemic stroke has been described as part of a paradoxical IRIS reaction. This report adds to the spectrum of clinical IRIS presentations recognized and highlights to clinicians the potential complications encountered at ART initiation in severely immunocompromised patients

Does the inclusion of 'professional development' teaching improve medical students' communication skills?

Background: This study investigated whether the introduction of professional development teaching in the first two years of a medical course improved students' observed communication skills with simulated patients. Students' observed communication skills were related to patient-centred attitudes, confidence in communicating with patients and performance in later clinical examinations.Methods: Eighty-two medical students from two consecutive cohorts at a UK medical school completed two videoed consultations with a simulated patient: one at the beginning of year 1 and one at the end of year 2. Group 1 (n = 35) received a traditional pre-clinical curriculum. Group 2 (n = 47) received a curriculum that included communication skills training integrated into a 'professional development' vertical module. Videoed consultations were rated using the Evans Interview Rating Scale by communication skills tutors. A subset of 27% were double-coded. Inter-rater reliability is reported.Results: Students who had received the professional development teaching achieved higher ratings for use of silence, not interrupting the patient, and keeping the discussion relevant compared to students receiving the traditional curriculum. Patient-centred attitudes were not related to observed communication. Students who were less nervous and felt they knew how to listen were rated as better communicators. Students receiving the traditional curriculum and who had been rated as better communicators when they entered medical school performed less well in the final year clinical examination.Conclusions: Students receiving the professional development training showed significant improvements in certain communication skills, but students in both cohorts improved over time. The lack of a relationship between observed communication skills and patient-centred attitudes may be a reflection of students' inexperience in working with patients, resulting in 'patient-centredness' being an abstract concept. Students in the early years of their medical course may benefit from further opportunities to practise basic communication skills on a one-to-one basis with patients

Reduction Of Phenylketones By Immobilized Baker's Yeast

Baker's yeast immobilized on chrysotile and montmorillonite stereoselectively reduced 1-phenyl-1,2-propanedione to the corresponding (1R,2S)-diol. The immobilized biocatalyst was also successfully used for asymmetric synthesis of 2-amino-1-phenylethanol and (R)- or (S)-1-phenyl-2-chloroethanol. The catalysts was reusable for more than 8 cycles. Baker's yeast immobilized on chrysotile and montmorillonite stereoselectively reduced phenylketones to the corresponding alcohols. © 1992.22191196Servi, Baker's Yeast as a Reagent in Organic Synthesis (1990) Synthesis, p. 1Csuk, Glanzer, (1991) Chem. Rev., 91, p. 49Nakamura, Inoue, Ushio, Oka, Ohmo, (1988) J. Org. Chem., 53, p. 2589Tosa, Sato, Mori, Yamamoto, Takata, Nishida, Chibata, (1979) Biotechnol. Bioeng., 21, p. 1697Naoshima, Hasegawa, Saeki, Synthesis of (R)-enantiomers of 5-hexadecanolide and 4-dodecanolide, pheromone of the oriental hornet and a defensive secretion of rove beetles, employing asymmetric reduction with immobilized baker's yeast. (1987) Agricultural and Biological Chemistry, 51, p. 3417Naoshima, Hasegawa, Synthesis of both enantiomers of phoracantholide I, a defensive secretion of the eucarypt longicorn, employing asymmetric reduction with immobilized baker's yeast. (1987) Chemistry Letters, p. 2379Kierstan, Bucke, (1977) Biotechnol. Bioeng., 19, p. 387Kawai, Tajima, Mizuno, Niimi, Sugiobka, Butsugan, Kozawa, Imai, (1988) Bull. Chem. Soc. Jpn., 61, p. 3014Nakamura, Kawai, Oka, Ohmo, (1989) Tetrahedron Lett., 30, p. 2245Thorez, (1987) Preparative Chemistry Using Supported Reagents, p. 177. , P. Laszlo, Academic Press, San DiegoStreib, (1978) Kirk-Othmer Encyclopedia of Chemical Technology, 3, p. 267. , 3rd ed., John Wiley, N. YorkLavie, Stotzky, (1986) Appl. Environ. Microbiol., 51, p. 65Kocoshis, Ghent, Gryboski, (1984) Dig. Dis. Sci., 29, p. 1148Welsh, Willisans, Veliky, (1987) Enzyme Microb. Technol., 9, p. 500Yoshii, Y.Takechi, T.Tanji, Y.Tsubone, T. Jpn. Kokai Tokkyo Koho JP 63,137,681Tarafdar, Agnihori, Chhonkar, (1988) J. Indian Soc. Soil Sci., 36, p. 553Parizotto Jr., O.Comerlato, M.H.Pedroso, P.R., Moran, P.J.S.Rodrigues, J.A.R.Carvalho, M.Joekes, I. Pat. BR, 1989, 8.903.849Brenelli, Moran, Rodrigues, Preparation of (-)-(1R, 2S)-1-Phenylpropane-1,2-Diol by Fermenting Baker's Yeast Reduction of 1-Phenyl-1,2-propanedione (1990) Synthetic Communications, 20, p. 261Chênevert, Thiboutot, Baker's yeast reduction of 1,2-diketones. Preparation of pure (S)-(-)-2-hydroxy-1-phenyl-1-propanone. (1988) Chemistry Letters, p. 1191Takeshita, Sato, Synthesis of optically active 1-phenyl-1,2-propanediol by use of baker's yeast. (1989) CHEMICAL & PHARMACEUTICAL BULLETIN, 37, p. 1085Kometani, Kitatsuji, Matsuno, Baker's yeast mediated bioreduction. A new procedure using ethanol as an energy source. (1989) Chemistry Letters, p. 1465Ohata, Ozaki, Konishi, Tsuchihashi, Reductive C2-homologation of substituted benzaldehydes by fermenting baker's yeast. (1986) Agricultural and Biological Chemistry, 50, p. 1261Bowlus, Katzenellenbogen, (1974) J. Org. Chem., 39, p. 3309Kingsbury, Cowles, (1975) J. Org. Chem., 40, p. 1302Imuta, Kawai, Ziffer, (1980) J. Org. Chem., 45, p. 3352Carvalho, Okamoto, Moran, Rodrigues, (1991) Tetrahedron, 47, p. 2073Nakamura, Kawai, Ohno, (1990) Tetrahedron Lett., 31, p. 267Further use of the IMBY was not achieved since no reduction occurred after the first reuseMacLeod, Prosser, Fikentscher, Lanyi, Mosser, (1964) Biochemistry, 3, p. 838. , Zinc sulfate has been used by some authors on the reduction of ketones. SeeMeyers, Slade, (1980) J. Org. Chem., 45, p. 2785Pratessi, Grasci, (1953) Farmaco, Ed. Sci., 8, p. 86. , Chem. Abstr. 48 1954 195