Impact and benefit-cost ratio of a program for the management of latent tuberculosis infection among refugees in a region of Canada.

INTRODUCTION: The identification and treatment of latent tuberculosis infection (LTBI) among immigrants from high-incidence regions who move to low-incidence countries is generally considered an ineffective strategy because only ≈14% of them comply with the multiple steps of the 'cascade of care' and complete treatment. In the Estrie region of Canada, a refugee clinic was opened in 2009. One of its goals is LTBI management. METHODS: Key components of this intervention included: close collaboration with community organizations, integration within a comprehensive package of medical care for the whole family, timely delivery following arrival, shorter treatment through preferential use of rifampin, and risk-based selection of patients to be treated. Between 2009-2020, 5131 refugees were evaluated. To determine the efficacy and benefit-cost ratio of this intervention, records of refugees seen in 2010-14 (n = 1906) and 2018-19 (n = 1638) were reviewed. Cases of tuberculosis (TB) among our foreign-born population occurring before (1997-2008) and after (2009-2020) setting up the clinic were identified. All costs associated with TB or LTBI were measured. RESULTS: Out of 441 patients offered LTBI treatment, 374 (85%) were compliant. Adding other losses, overall compliance was 69%. To prevent one case of TB, 95.1 individuals had to be screened and 11.9 treated, at a cost of $16,056. After discounting, each case of TB averted represented $32,631, for a benefit-cost ratio of 2.03. Among nationals of the 20 countries where refugees came from, incidence of TB decreased from 68.2 (1997-2008) to 26.3 per 100,000 person-years (2009-2020). Incidence among foreign-born persons from all other countries not targeted by the intervention did not change. CONCLUSIONS: Among refugees settling in our region, 69% completed the LTBI cascade of care, leading to a 61% reduction in TB incidence. This intervention was cost-beneficial. Current defeatism towards LTBI management among immigrants and refugees is misguided. Compliance can be enhanced through simple measures.

Primary infectious costochondritis due to Prevotella nigrescens in an immunocompetent patient: clinical and imaging findings.

Infection of costal cartilage is a rare observation. We report the case of a 43-year-old male patient without relevant history who presented with a progressive painful swelling of the left chest wall since 4 months. Computed tomography (CT) and magnetic resonance imaging (MRI) demonstrated an abscess within the left ninth costal cartilage with surrounding reactive changes. A CT-guided biopsy was performed and the culture of the sample revealed the presence of Prevotella nigrescens. Musculoskeletal infections by Prevotella are rarely described in the literature, Prevotella oralis and Prevotella bivia being the most frequently observed pathogens. These infections usually originate from a hematogenous spread after thoracic surgery or dental procedure. In our patient, conservative treatment was chosen. A clinical improvement was noted after 1-month antibiotherapy, confirmed by short-term and 6-month imaging follow-up showing the complete disappearance of all previously observed abnormalities.

Focus on increased serum angiotensin-converting enzyme level: From granulomatous diseases to genetic mutations.

Angiotensin I-converting enzyme (ACE) is a well-known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and degrades bradykinin, a powerful vasodilator, and as such plays a key role in the regulation of vascular tone and cardiac function. Increased circulating ACE (cACE) activity has been reported in multiple diseases, including but not limited to granulomatous disorders. Since 2001, genetic mutations leading to cACE elevation have also been described. This review takes advantage of the identification of a novel ACE mutation (25-IVS25 + 1G > A) in two Belgian pedigrees to summarize current knowledge about the differential diagnosis of cACE elevation, based on literature review and the experience of our centre. Furthermore, we propose a practical approach for the evaluation and management of patients with elevated cACE and discuss in which cases search for genetic mutations should be considered.

An unusual cause of epidemic thyrotoxicosis.

We describe the case of four patients consulting for headache and tachycardia of brutal onset. Their biological data were compatible with primary hyperthyroidism with low TSH and high T4 serum levels. Serum thyroglobulin level was low and Tc-scintigraphy showed decreased uptake with a homogenous pattern. These results allowed to conclude a thyrotoxicosis caused by thyroid hormones intake. History taking revealed consumption of beef neck meat containing all or parts of the bovine thyroid gland. Evolution was favourable with beta-blockers. A literature review of « hamburger thyrotoxicosis ¼ is presented.

A strange oculomotor palsy with eosinophilia.

A 75-year-old man was admitted to the Department of internal medicine because of a 2-month history of neurological deterioration. During the previous year, he complained of recurrent sinusitis, asthma, arthralgias, myalgias and asthenia. Later on, an oculomotor palsy, weakness and disturbance of the sensibility of the right upper limb appeared. Blood sample showed 6510 eosinophils per microlitre. The cerebral magnetic resonance demonstrated bilateral frontal and left parietal subcortical lesions from which the most voluminous presented large haemorrhagic areas. A cerebral biopsy showed small vessel's vasculitis, fibrinoid necrosis and extravascular eosinophilic encroachment. A diagnosis of oculomotor palsy secondary to eosinophilic granulomatosis with polyangeitis was then made, which was successfully treated with corticosteroids and cyclophosphamide.

A novel splice-site mutation in angiotensin I-converting enzyme (ACE) gene, c.3691+1G>A (IVS25+1G>A), causes a dramatic increase in circulating ACE through deletion of the transmembrane anchor.

BACKGROUND: Angiotensin-converting enzyme (ACE) (EC 4.15.1) metabolizes many biologically active peptides and plays a key role in blood pressure regulation and vascular remodeling. Elevated ACE levels are associated with different cardiovascular and respiratory diseases. METHODS AND RESULTS: Two Belgian families with a 8-16-fold increase in blood ACE level were incidentally identified. A novel heterozygous splice site mutation of intron 25 - IVS25+1G>A (c.3691+1G>A) - cosegregating with elevated plasma ACE was identified in both pedigrees. Messenger RNA analysis revealed that the mutation led to the retention of intron 25 and Premature Termination Codon generation. Subjects harboring the mutation were mostly normotensive, had no left ventricular hypertrophy or cardiovascular disease. The levels of renin-angiotensin-aldosterone system components in the mutated cases and wild-type controls were similar, both at baseline and after 50 mg captopril. Compared with non-affected members, quantification of ACE surface expression and shedding using flow cytometry assay of dendritic cells derived from peripheral blood monocytes of affected members, demonstrated a 50% decrease and 3-fold increase, respectively. Together with a dramatic increase in circulating ACE levels, these findings argue in favor of deletion of transmembrane anchor, leading to direct secretion of ACE out of cells. CONCLUSIONS: We describe a novel mutation of the ACE gene associated with a major familial elevation of circulating ACE, without evidence of activation of the renin-angiotensin system, target organ damage or cardiovascular complications. These data are consistent with the hypothesis that membrane-bound ACE, rather than circulating ACE, is responsible for Angiotensin II generation and its cardiovascular consequences.

Similar immunogenicity of the A/H1N1 2009 pandemic influenza strain when used as a monovalent or a trivalent vaccine.

BACKGROUND: The WHO recommended including the A (H1N1) 2009 pandemic strain in the influenza vaccines for use in the 2010-2011 northern hemisphere (NH) influenza season. The immunogenicity and safety of the trivalent split inactivated vaccine (Vaxigrip®) NH 2010-2011 formulation was compared to that observed for the corresponding non-adjuvanted monovalent A (H1N1) pandemic vaccine (Panenza®), when tested in similar populations of adult and elderly volunteers. METHODS: The monovalent vaccine was evaluated in two clinical trials, conducted respectively in both adult and elderly subjects and in a population of adults. The trivalent vaccine was evaluated in a clinical study that enrolled both adult and elderly subjects. Antibody titers were measured in serum samples drawn at day 0 (before vaccination) and 21 days after one vaccine injection using the same hemagglutination inhibition (HI) assay method. The occurrence of adverse events was reported up to 21 days after vaccination. RESULTS: Before immunization in the three studies, most of the volunteers had antibody titers below seroprotective levels against the pandemic A(H1N1) 2009 virus. After vaccination, in each trial and in each age group, high seroprotection rates, GMT ratios and seroconversion rates were observed. Seroprotection rates after administration of the monovalent vaccine reached 93% and 98% in the adult groups, and 83.7% in the elderly group. After administration of the trivalent vaccine, seroprotection rates of 92.2% and 81.3% were obtained respectively in the adult and the elderly groups. No related serious adverse events and no safety signals were detected either with the monovalent or trivalent vaccine. CONCLUSION: Comparable immunogenicity profiles were observed in three clinical trials of the pandemic A(H1N1) 2009 strain when formulated either as a monovalent or as a component of a seasonal trivalent vaccine.

Efficacy of the combination of amlodipine and valsartan in patients with hypertension uncontrolled with previous monotherapy: the Exforge in Failure after Single Therapy (EX-FAST) study.

In this randomized, double-blind, multicenter study, patients whose blood pressure (BP) was uncontrolled by monotherapy were switched directly to amlodipine/valsartan 5/160 mg (n=443) or 10/160 mg (n=451). After 16 weeks, BP control (levels <140/90 mm Hg or <130/80 mm Hg for diabetics) was achieved in 72.7% (95% confidence interval [CI], 68.6-76.9) of patients receiving amlodipine/valsartan 5/160 mg and in 74.8% (95% CI, 70.8-78.9) receiving amlodipine/valsartan 10/160 mg. Incremental reductions from baseline in mean sitting systolic and diastolic BP were significantly greater with the higher dose (20.0+/-0.7 vs 17.5+/-0.7 mm Hg; P=.0003 and 11.6+/-0.4 vs 10.4+/-0.4 mm Hg; P=.0046). Incremental BP reductions were also achieved with both regimens irrespective of previous monotherapy, hypertension severity, diabetic status, body mass index, and age. Peripheral edema was the most frequent adverse event. These results provide support for the BP-lowering benefits of complementary antihypertensive therapy with amlodipine and valsartan in patients with hypertension uncontrolled by previous monotherapy.

Impaired osmoregulation in anorexia nervosa: a case-control study.

BACKGROUND: Anorexia nervosa (AN) has been associated with abnormal osmoregulation and impaired urinary concentrating capacity. Conflicting results suggest that the disorder may be related to hypothalamic dysfunction and/or a primary renal defect. The role of antidepressants, which are increasingly prescribed in AN patients, has not been evaluated. METHODS: We analysed renal function as well as electrolyte disturbances and osmoregulation parameters at baseline and following a water deprivation test in 12 well-defined AN patients (all females, 10 taking antidepressants) vs 12 age-matched controls and 11 young female patients taking antidepressants. RESULTS: In comparison with matched controls, patients with AN were characterized by a significant alteration of osmoregulation both at baseline [lower plasma sodium and osmolality, abnormally high levels of antidiuretic hormone (ADH) and tendency towards more concentrated urine] and after water deprivation (impaired ADH reaction and lower urinary concentrating ability). The AN patients had no electrolyte abnormalities. The two patients with the shortest duration of AN showed a normal urinary concentrating ability. Patients taking antidepressants showed similar but less marked changes than AN patients, including a lower urinary concentrating ability. CONCLUSIONS: These results show that AN patients are characterized by abnormal osmoregulation at baseline and a lack of reactivity of ADH with a significant urinary concentrating defect after water deprivation. The origin of these defects in AN patients is probably multifactorial, but the duration of the disease and the prescription of antidepressants could play a role.