Seven-year retrospective study understanding the latent TB infection treatment cascade of care among adults in a low incidence country.

BACKGROUND: Prevention of TB is paramount to achieving elimination targets as recommended by the World Health Organization's action framework for low incidence countries striving to eliminate TB. Although the rates of TB in Canada are low, understanding the latent TB infection (LTBI) cascade is paramount to identifying gaps in care and treatment barriers, thereby increasing the effectiveness of preventive strategies. The purpose of this study was to examine the LTBI cascade of care and identify barriers to treatment completion in adults referred from primary care to a regional tertiary care TB clinic in Ottawa, Canada. METHODS: Electronic medical records between January 2010 and December 2016 were reviewed retrospectively and an LTBI cascade of care was constructed from The Ottawa Hospital TB clinic and surrounding primary care clinics. A cohort of 2207 patients with untreated LTBI was used to ascertain the associations between demographic and clinical factors for both treatment non-initiation and non-completion using log-binomial univariable and multivariable regression models. RESULTS: Of 2207 patients with untreated LTBI who were seen in the clinic during the study period, 1771 (80.2%) were offered treatment, 1203 (67.9% of those offered) started treatment, and 795 (66.1% of those started) completed treatment. In multivariable analysis, non-initiation of treatment was associated with older age (adjusted risk ratio [aRR] 1.06 per 5-year increase, 95% CI: 1.03-1.08) and female gender (aRR 1.28, 95% CI: 1.11-1.47). Non completion of treatment was associated with referral from the TB Clinic back to the primary care team following initial consult (aRR 1.62, 95% CI: 1.35-1.94) and treatment with the standard of 9 months of Isoniazid (9H) compared to 4 months of Rifampin (4R) (aRR 1.45, 95% CI:1.20-1.74). CONCLUSIONS: LTBI treatment completion was significantly decreased among patients who were referred back to primary care from the TB clinic. The 4R regimen resulted in more people completing LTBI treatment compared to 9H in keeping with a recently published RCT. Improved education, communication, and collaboration between tertiary care TB clinics and primary care teams may improve treatment completion rates and address the TB burden in low incidence communities in Canada.

Maternal cardiac output response to colloid preload and vasopressor therapy during spinal anaesthesia for caesarean section in patients with severe pre-eclampsia: a randomised, controlled trial.

We examined the haemodynamic effects of colloid preload, and phenylephrine and ephedrine administered for spinal hypotension, during caesarean section in 42 women with severe early onset pre-eclampsia. Twenty patients with pre-delivery spinal hypotension were randomly allocated to receive an initial dose of either 50 µg phenylephrine or 7.5 mg ephedrine; the primary outcome was percentage change in cardiac index. After a 300-ml colloid preload, mean (SD) cardiac index increased from 4.9 (1.1) to 5.6 (1.2) l.min-1 .m-2 (p < 0.01), resulting from an increase in both heart rate, from 81.3 (17.2) to 86.3 (16.5) beats.min-1 (p = 0.2), and stroke volume, from 111.8 (19.0) to 119.8 (17.9) ml (p = 0.049). Fourteen (33%) and 23 (54.8%) patients exhibited a stroke volume response > 10% and > 5%, respectively; a significant negative correlation was found between heart rate and stroke volume changes. Spinal hypotension in 20 patients was associated with an increase from baseline in cardiac index of 0.6 l.min-1 .m-2 (mean difference 11.5%; p < 0.0001). After a median [range] dose of 50 [50-150] µg phenylephrine or 15 [7.5-37.5] mg ephedrine, the percentage change in cardiac index during the measurement period of 150 s was greater, and negative, in patients receiving phenylephrine vs. ephedrine, at -12.0 (7.3)% vs. 2.6 (6.0)%, respectively (p = 0.0001). The percentage change in heart rate after vasopressor was higher in patients receiving phenylephrine, at -9.1 (3.4)% vs. 5.3 (12.6)% (p = 0.0027), as was the change in systemic vascular resistance, at 22.3 (7.5) vs. -1.9 (10.5)% (p < 0.0001). Phenylephrine effectively reverses spinal anaesthesia-induced haemodynamic changes in severe pre-eclampsia, if left ventricular systolic function is preserved.

Two new species of Cylicospirura Vevers, 1922 (Nematoda: Spirocercidae) from carnivores in southern Africa, with validation of the related genera Gastronodus Singh, 1934 and Skrjabinocercina Matschulsky, 1952.

Two new species of Cylicospirura Vevers, 1922 are described from carnivores from southern Africa. Cylicospirura crocutae Junker et Mutafchiev sp. n. from Crocuta crocuta (Erxleben) in Zimbabwe is distinguished from its congeners by combinations of characters, including the presence of four cephalic and four external labial papillae, while internal labial papillae were not distinct, the presence of groups of small accessory teeth between the six large tricuspid teeth, the fifth and the sixth pairs of the caudal papillae being equidistant from the cloaca, and a large ratio of length of the muscular oesophagus to that of the glandular oesophagus. Cylicospirura pardalis Junker et Mutafchiev sp. n. from Panthera pardus (Linnaeus) in the Republic of South Africa is characterized by having tricuspid teeth with large, claw-like, abaxial cusps, four cephalic and six internal labial papillae. Based on the number of caudal papillae and the position of the vulva, the subgenera Gastronodus Singh, 1934 and Skrjabinocercina Matschulsky, 1952 are re-elevated to generic rank. Amended diagnoses are proposed for the genera Cylicospirura, Gastronodus and Skrjabinocercina. Petrowospirura lyncis Matschulsky, 1952 is recognized as valid and, together with P. petrowi Sadykhov, 1957 and P. barusi Arya, 1979, is transferred to Cylicospirura as C. lyncis (Matschulsky, 1952) Junker et Mutafchiev comb. n., C. petrowi (Sadykhov, 1957) Junker et Mutafchiev comb. n. and C. barusi (Arya, 1979) Junker et Mutafchiev comb. n., respectively.

Medicine and the Law.

Congenital high airway obstruction syndrome (CHAOS) is a rare condition that can be diagnosed antenatally by ultrasound. It is usually lethal without immediate intervention at delivery. A 24-year-old woman was diagnosed with fetal CHAOS at 27 weeks' gestation. The couple declined termination of pregnancy. A multidisciplinary team including obstetricians, geneticists, paediatric surgeons, neonatologists and anaesthetists was constituted to plan an ex utero intrapartum treatment (EXIT) procedure. After several simulations, a caesarean section was performed at 38 weeks' gestation under deep inhalational anaesthesia. The fetus was fully delivered with placenta remaining in utero to maintain perfusion. A surgical airway was established via tracheostomy in approximately 5 minutes. The operation was then completed with no maternal complications. The child remains well at 3 years of age. To our knowledge, this is the first EXIT procedure performed for CHAOS in the public sector. This procedure can be lifesaving and is possible with proper planning.

Hypoxaemia during tracheal intubation in patients with hypertensive disorders of pregnancy: analysis of data from an obstetric airway management registry.

BACKGROUND: In South Africa, hypertensive disorders of pregnancy are the leading cause of maternal mortality. More than 50% of anaesthesia-related maternal deaths are attributed to complications of airway management. We compared the prevalence and risk factors for hypoxaemia during induction of general anaesthesia in parturients with and without hypertensive disorders of pregnancy. We hypothesised that hypertensive disorders of pregnancy are associated with desaturation during tracheal intubation. METHODS: Data from 402 cases in a multicentre obstetric airway management registry were analysed. The prevalence of peri-induction hypoxaemia (SpO2 <90%) was compared in patients with and without hypertensive disorders of pregnancy. Quantile regression of SpO2 nadir was performed to identify confounding variables associated with, and mediators of, hypoxaemia. RESULTS: In the cohort of 402 cases, hypoxaemia occurred in 19% with and 9% without hypertension (estimated risk difference, 10%; 95% CI 2% to 17%; P=0.005). Quantile regression demonstrated a lower SpO2 nadir associated with hypertensive disorders of pregnancy as body mass index increased. Room-air oxygen saturation, Mallampati grade, and number of intubation attempts were associated with the relationship. CONCLUSIONS: Clinically significant oxygen desaturation during airway management occurred twice as often in patients with hypertensive disorders of pregnancy, compounded by increasing body mass index. Intermediary factors in the pathway from hypertension to hypoxaemia were also identified.

The implementation of rifapentine and isoniazid (3HP) in two remote Arctic communities with a predominantly Inuit population, the Taima TB 3HP study.

Background: The incidence of TB among Inuit is the highest in Canada. A significantly shorter latent TB infection (LTBI) treatment with rifapentine and isoniazid once weekly for 12 weeks (3HP) is now available in limited settings in Canada.Methods: A prospective open-label 2-year observational postmarketing study was conducted introducing 3HP for the first time in Canada in Iqaluit followed by a program rollout in Qikiqtarjuaq, Nunavut.Results: A total of 247 people were offered 3HP, 102 in the Iqaluit postmarketing study and 145 in the Qikiqtarjuaq program roll out. Although statistical significance was not reached, more people who started treatment completed treatment in the 3HP group (Iqaluit, 60/73 (82.2%) and Qikiqtarjuaq, 89/115 (77.4%)) than in the historical control 9INHgroup (306/420 = 72.9%) (p = 0.2). Most of the adverse events in 3HP treated patients were associated with mild discomfort but no disruption of normal daily activity. Not drinking alcohol was associated with increased 3HP completion (OR 13.33, 95% CI, 2.27-78.20) as was not taking concomitant medications (OR 7.19, 95% CI, 1.47-35.30).Conclusions: The present study supports the feasibility and safety profile of 3HP for the treatment of LTBI in Nunavut.

Laser microsurgery in cell and developmental biology.

New applications of laser microbeam irradiation to cell and developmental biology include a new instrument with a tunable wavelength (217- to 800-nanometer) laser microbeam and a wide range of energies and exposure durations (down to 25 X 10(-12) second). Laser microbeams can be used for microirradiation of selected nucleolar genetic regions and for laser microdissection of mitotic and cytoplasmic organelles. They are also used to disrupt the developing neurosensory appendages of the cricket and the imaginal discs of Drosophila.

Maternal critical care in resource-limited settings. Narrative review.

Maternal critical care reflects interdisciplinary care in any hospital area according to the severity of illness of the pregnant woman. The admission rate to intensive care units is below 1% (0.08-0.76%) of deliveries in high-income countries, and ranges from 0.13% to 4.6% in low- and middle-income countries. Mortality in these patients is high and varies from 0% to 4.9% of admissions in high-income countries, and from 2% to 43.6% in low- and middle-income countries. Obstetric haemorrhage, sepsis, preeclampsia, human immunodeficiency virus complications and tropical diseases are the main reasons for intensive care unit admission in low middle-income countries. Bedside assessment tools, such as early warning scores, may help to identify critically ill patients and those at risk of deterioration. There is a lack of uniformity in definitions, identification and treatment of critically ill pregnant patients, especially in resource-limited settings. Our aims were to (i) propose a more practical definition of maternal critical care, (ii) discuss maternal mortality in the setting of limited accessibility of critical care units, (iii) provide some accessible tools to improve identification of obstetric patients who may become critically ill, and (iv) confront challenges in providing maternal critical care in resource-limited settings. To improve maternal critical care, training programmes should embrace modern technological educational aids and incorporate new tools and technologies that assist prediction of critical illness in the pregnant patient. The goal must be improved outcomes following early interventions, early initiation of resuscitation, and early transfer to an appropriate level of care, whenever possible.

A randomised comparison of bolus phenylephrine and ephedrine for the management of spinal hypotension in patients with severe preeclampsia and fetal compromise.

BACKGROUND: Studies in healthy patients undergoing elective caesarean delivery show that, compared with phenylephrine, ephedrine used to treat spinal hypotension is associated with increased fetal acidosis. This has not been investigated prospectively in women with severe preeclampsia. METHODS: Patients with preeclampsia requiring caesarean delivery for a non-reassuring fetal heart tracing were randomised to receive either bolus ephedrine (7.5-15mg) or phenylephrine (50-100µg), to treat spinal hypotension. The primary outcome was umbilical arterial base excess. Secondary outcomes were umbilical arterial and venous pH and lactate concentration, venous base excess, and Apgar scores. RESULTS: Among 133 women, 64 who required vasopressor treatment were randomised into groups of 32 with similar patient characteristics. Pre-delivery blood pressure changes were similar. There was no difference in mean [standard deviation] umbilical artery base excess (-4.9 [3.7] vs -6.0 [4.6] mmol/L for ephedrine and phenylephrine respectively; P=0.29). Mean umbilical arterial and venous pH and lactate concentrations did not significantly differ between groups (7.25 [0.08] vs 7.22 [0.10], 7.28 [0.07] vs 7.27 [0.10], and 3.41 [2.18] vs 3.28 [2.44] mmol/L respectively). Umbilical venous oxygen tension was higher in the ephedrine group (2.8 [0.7] vs 2.4 [0.62]) kPa, P=0.02). There was no difference in 1- or 5-min Apgar scores, numbers of neonates with 1-min Apgar scores <7 or with a pH <7.2. CONCLUSIONS: In patients with severe preeclampsia and fetal compromise, fetal acid-base status is independent of the use of bolus ephedrine versus phenylephrine to treat spinal hypotension.

Risk factors for development of diabetic nephropathy and retinopathy in Jewish IDDM patients.

Risk factors associated with diabetic microvascular complications, with special reference to ethnic origin, were looked for in 231 young Jewish insulin-dependent diabetes mellitus (IDDM) patients with duration of diabetes greater than or equal to 10 yr. Median age at diagnosis of diabetes was 9.2 yr (range 0.04-26.2 yr), and median duration of the disease was 15.3 yr (range 10.0-37.2 yr). Sixty-three percent of the patients were Ashkenazi Jews, and 37% were non-Ashkenazi Jews. HbA1 was evaluated every 3 mo in the last 10 yr of follow-up, and albumin excretion rate was tested in three 24-h urine collections. Direct and indirect ophthalmoscopy was performed every year since diagnosis of diabetes, and if retinal pathology was suspected, color photographs were taken. Microalbuminuria was detected in 31% and macroalbuminuria in 7% of the patients. Nonproliferative and proliferative retinopathy was found in 44 and 12% of the patients, respectively. On logistic regression analysis, two variables were significantly and independently associated with diabetic nephropathy--non-Ashkenazi origin and mean HbA1 values over the first 5 of 10 yr of follow-up. Variables significantly and independently related to diabetic retinopathy were non-Ashkenazi origin, mean HbA1 values over the last 10 yr of follow-up, and duration of diabetes. Because non-Ashkenazi Jews in Israel are of lower socioeconomic status than Ashkenazi Jews, we stratified our patients according to their socioeconomic parameters, median HbA1 values, and duration of diabetes. Non-Ashkenazi patients were at a higher risk to develop complications in all strata.(ABSTRACT TRUNCATED AT 250 WORDS)

The protective effect of dimethyl sulfoxide in experimental ischemia of the intestine.

Experiments with two models of intestinal ischemia were performed in order to examine the protective effect of dimethyl sulfoxide (DMSO). Segmental ischemia of the small intestine for 150 minutes caused necrosis of the affected bowel in 90% of the animals. Intravenous administration of DMSO or impregnation of the peritoneum with this substance prevented the development of gangrene in 28 of 29 rats. 30 or 60 minutes of complete ischemia of the small intestine, produced by clamping of the superior mesenteric artery, resulted in partial or complete necrosis of bowel segments with a high incidence of perforation and peritonitis and a high mortality rate within the first 24 hours. Intravenous DMSO, given upon declamping of the artery, effectively protected the bowel from the ischemic damage. There were no deaths among DMSO-treated animals and at 24 h there was no evidence of ischemic damage to the intestine. Though the exact mechanism of action of DMSO is unknown, the results of these and other experiments may warrant clinical trials especially in cases of mesenteric thrombosis.

Bizarre urologic manifestations of pancreas carcinoma.

A 62-year-old patient presented with fever and abdominal pain. Urinary retention and bilateral hydronephrosis were caused by bladder malfunction due to infiltration of the bladder wall by metastases from a carcinoma of the head of the pancreas. Both ureters were free. A previous choledochoduodenostomy prevented the development of jaundice.

The watery diarrhea syndrome with hypercalcemia--a symptomatic response to phosphate buffer.

Two patients with the watery diarrhea, hypokalemia, achlorhydria syndrome are described. Both had hypercalcemia, hypophosphatemia and suppressed parathyroid hormone activity. On repeated occasions the diarrhea was controlled by oral or intravenous phosphate buffer. An exhaustive search by sophisticated non-invasive methods and by celiac arteriography failed to demonstrate a pancreatic tumor. Yet, in both cases fairly large pancreatic non-beta-cell adenomas were found at laparotomy. The removal of these tumors was followed by complete recovery.

Impairment of the postural venoarteriolar response in young type 1 diabetic patients. A study by laser doppler flowmetry.

The skin blood flow and venoarteriolar response (VAR) in the feet of the young type 1 diabetic patients were studied with laser Doppler flowmetery. The findings were correlated with diabetic microangiopathy in 24 young patients without neuropathy--14 with diabetic microangiopathy, 10 without--and 10 healthy controls. In type 1 diabetic patients and skin blood flow, after lowering of the leg, was significantly higher in the microangiopathic patients than in the healthy controls, 5.3 +/- 1.4 vs 3 +/- 1.5, (P < 0.01). The VAR index was significantly lower in both groups of diabetics as compared with controls. In conclusions laser Doppler flowmetry is an easy and reliable noninvasive technique to evaluate skin blood flow abnormalities in the the feet of young type 1 diabetic patients, including those without neuropathy. The VAR has been found abnormal in the feet of young diabetic patients with and without microangiopathy, regardless of the presence of peripheral neuropathy.

Lytic spondylolisthesis in helicopter pilots.

Trauma to the back from the force of chronic stress is thought to be an etiologic factor in isthmic spondylolisthesis (SLL). The relationship of first degree spondylolisthesis to low back pain (LBP) is controversial. We compare the prevalence of SLL in helicopter pilots who are subject to strong vibrational forces, with other airforce personnel. Helicopter pilots had more than a four times higher prevalence of SLL (4.5%) than did cadets (1.0%) and transport pilots (0.9%). Low back pain was more frequent in pilots with SLL than in those without this lesion but in no case was the pain disabling or the defect progressive. We conclude that SLL may be induced by vibrational forces and although SLL is associated with LBP, the pain was little clinical significance.

[Peritoneal equilibration test].

7 men and 3 women (mean age 62 +/- 11 years) with end-stage renal disease, who were on continuous ambulatory peritoneal dialysis, underwent a peritoneal equilibration test to determine the rate of peritoneal ultrafiltration and creatinine transfer. The test is based on glucose absorption into the plasma from the peritoneal solution and the diffusion of creatinine into the peritoneal fluid after 2-4 hours. Patients with rapid absorption of glucose have low drain water ultrafiltration volumes but higher creatinine clearances, and therefore need adjustment of the therapy plan or else should be on hemodialysis. No correlation was found between the time the patients were on treatment and glucose absorption or creatinine diffusion.

The use of uterotonic drugs during caesarean section.

The administration of oxytocic drugs during caesarean section is an important intervention to prevent uterine atony or treat established postpartum haemorrhage. Considerable past and current research has shown that these agents have a narrow therapeutic range. A detailed knowledge by anaesthetists of optimal doses and side effects is therefore required. Oxytocin remains the first line agent. In view of receptor desensitisation, second line agents may be required, namely ergot alkaloids and prostaglandins. This review examines the adverse haemodynamic and side effects, and methods for their limitation. An approach to dosing and choices of agent for the limitation of postpartum haemorrhage is suggested.

Intradermal tuberculin testing of wild African lions (Panthera leo) naturally exposed to infection with Mycobacterium bovis.

African lions in the southern half of Kruger National Park (KNP) are infected with Mycobacterium bovis. Historically, reliable detection of mycobacteriosis in lions was limited to necropsy and microbiological analysis of lesion material collected from emaciated and ailing or repeat-offender lions. We report on a method of cervical intradermal tuberculin testing of lions and its interpretation capable of identifying natural exposure to M. bovis. Infected lions (n=52/95) were identified by detailed necropsy and mycobacterial culture. A large proportion of these confirmed infected lions (45/52) showed distinct responses to bovine tuberculin purified protein derivative (PPD) while responses to avian tuberculin PPD were variable and smaller. Confirmed uninfected lions from non-infected areas (n=11) responded variably to avian tuberculin PPD only. Various non-tuberculous mycobacteria (NTM) were cultured from 45/95 lions examined, of which 21/45 were co-infected with M. bovis. Co-infection with M. bovis and NTM did not influence skin reactions to bovine tuberculin PPD. Avian tuberculin PPD skin reactions were larger in M. bovis-infected lions compared to uninfected ones. Since NTM co-infections are likely to influence the outcome of skin testing, stricter test interpretation criteria were applied. When test data of bovine tuberculin PPD tests were considered on their own, as for a single skin test, sensitivity increased (80.8-86.5%) but false positive rate for true negatives (18.75%) remained unchanged. Finally, the adapted skin test procedure was shown not to be impeded by persistent Feline Immunodeficiency Virus(Ple) co-infection.