Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review.

The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug-drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods: We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results: Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions: Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.

A real-world experience of SARS-CoV-2 infection in a tertiary referral centre of Montréal: Unexpected low prevalence and low mortality.

BACKGROUND: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with chronic liver disease (CLD) and liver transplant (LT) recipients remains a concern. The aim of this study was to report the impact of coronavirus disease 2019 (COVID-19) infection among patients at the tertiary health care centre Centre hospitalier de l'Université de Montréal (CHUM) during the first wave of the SARS-CoV-2 pandemic. METHODS: This real-world, retrospective cohort included all patients admitted to our liver unit and/or seen as an outpatient with CLD with or without cirrhosis and/or LT recipients who tested positive to SARS-CoV-2 infection. Cases were considered positive as defined by the detection of SARS-CoV-2 by reverse-transcription polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. RESULTS: Between April 1 and July 31, 2020, 5,637 were admitted to our liver unit and/or seen as outpatient. Among them, 42 were positive for SARS-CoV-2. Twenty-two patients had CLD without cirrhosis while 16 patients had cirrhosis at the time of the infection (13, 2, and 1 with Child-Pugh A, B, and C scores, respectively). Four were LT recipients. Overall, 15 of 42 patients (35.7%) were hospitalized; among them, 7 of 42 (16.7%) required respiratory support and 4 of 42 (9.5%) were transferred to the intensive care unit. Only 4 of 42 (9.5%) patients died: 2 with CLD without cirrhosis and 2 with CLD with cirrhosis. Overall survival was 90.5%. CONCLUSION: This real-world study demonstrates an unexpectedly low prevalence and low mortality in the context of SARS-CoV-2 infection among patients with CLD with or without cirrhosis and LT recipients.

Risks of hepatitis C virus reactivation in a real-life population of oncology patients treated in an academic center.

BACKGROUND: Chemotherapy has been associated with a theoretical risk of hepatitis C virus (HCV) reactivation. However, little is known about the amplitude of viral replication and the incidence of subsequent hepatic exacerbation. METHOD: We aimed to describe the occurrence of hepatitis flare and HCV reactivation at our center. We included, over a period of 5 years, adult patients with chronic HCV receiving intravenous chemotherapy. We excluded patients with undetectable HCV RNA, hepatocellular carcinoma, liver metastases or other etiologies of hepatic disease. The primary objective was to identify hepatic flares (elevation of alanine aminotransferase 3 times above the upper limit of normal). Secondary objectives were to assess viral reactivation (HCVr, HCV-RNA ≥1 log10 IU/mL when compared to baseline value), hepatic decompensation, mortality and the impact on the chemotherapy. Descriptive statistics were used. RESULTS: A total of 11 patients with chronic HCV were identified among the 5761 oncology patients. Five patients experienced a hepatic flare with median maximal ALT value of 139 U/L (IQR 133-237). Only 2 patients met criteria for HCVr with a median RNA increase of 1.16 log IU/mL (IQR 1.1-1.2). One patient presented with both HCVr and a hepatic flare. Only one patient required chemotherapy discontinuation following hepatic flare. No hepatic decompensation or related mortality were observed. CONCLUSION: We identified a very small number of HCV cases among our population. We observed HCVr and hepatic flares, but only one consequence on cancer treatment. Nonetheless, HCV screening is encouraged among patients undergoing chemotherapy to allow close follow-up of hepatic function.

Exercise Interventions for Community-Dwelling Older Adults Following an Emergency Department Consultation for a Minor Injury.

This study compared effects of exercise-based interventions with usual care on functional decline, physical performance, and health-related quality of life (12-item Short-Form health survey) at 3 and 6 months after minor injuries, in older adults discharged from emergency departments. Participants were randomized either to the intervention or control groups. The interventions consisted of 12-week exercise programs available in their communities. Groups were compared on cumulative incidences of functional decline, physical performances, and 12-item Short-Form health survey scores at all time points. Functional decline incidences were: intervention, 4.8% versus control, 15.4% (p = .11) at 3 months, and 5.3% versus 17.0% (p = .06) at 6 months. While the control group remained stable, the intervention group improved in Five Times Sit-To-Stand Test (3.0 ± 4.5 s, p < .01). The 12-item Short-Form health survey role physical score improvement was twice as high following intervention compared with control. Early exercises improved leg strength and reduced self-perceived limitations following a minor injury.

The usefulness of muscle architecture assessed with ultrasound to identify hospitalized older adults with physical decline.

BACKGROUND: Muscle mass and strength decline are known to be key factors in the development of physical incapacities in later life. These structural and functional declines are even more significant in older people during hospitalizations, increasing risk of falls, fractures, and loss of quality of life. In clinical daily practice, functional and muscular decline are assessed using the validated Short Physical Performance Battery (SPPB). Nevertheless, psychological conditions (pain, demotivation, depression) and temporary physical incapacities (e.g: hip fracture) during hospitalization can be significant barriers to evaluate these patients. Skeletal muscle ultrasound assessment could be an alternative in clinical daily practice since muscle architecture (MA) is related to poor muscle function. However, this potential objective and clinical tool is not yet implemented in geriatric setting during hospitalization. Our study aimed at: 1) comparing MA, muscle mass and strength measurements in hospitalized older adults with different functional levels, 2) evaluating the association between these measurements. METHODS: Forty-four hospitalized older adults were divided in 2 groups: 21 Pre-Disabled (PDis (SPPBscore: 6-9): 81 ±â€¯7 years old, SPPBscore:7.6 ±â€¯1.1) and 23 Disabled (Dis (SPPBscore:<6): 83 ±â€¯7 years old, SPPBscore:3.6 ±â€¯1.6). SPPB, body mass (BM) and composition (bio-impedance), handgrip strength (HS, dynamometer) and MA (Pennation angle (PA), muscle thickness (MT); ultrasound) were evaluated. RESULTS: Relative muscle strength (HS/BM: 0.28 ±â€¯0.08 vs 0.34 ±â€¯0.09 kg/kg), PA (10.6 ±â€¯1.8 vs 12.3 ±â€¯1.9°), and MT (16.4 ±â€¯0.4 vs 19.2 0.4 mm) but not lean body mass were significantly different between Dis and PDis, respectively. Significant associations between PA and the SPPBscore (r2 = 0.37) or walking speed (r2 = 0.38); between SCF and walking speed (r2 = -0.36); as well as between MT and SPPBscore (r2 = 0.29), walking speed (r2 = 0.30), LBM (r2 = 0.382) or MMI (r2 = 0.361) were observed. CONCLUSION: Muscle architecture (proxy of muscle quality) and functional capacities/status of hospitalized older adults are related. Thus, ultrasound seems to be a potential useful and objective screening tool for clinicians to assess/prevent physical decline during hospitalization. Larger and/or longitudinal studies are needed to confirm our findings from a pilot pragmatic study.

Feasibility and Effects of a Physical Activity Program Using Gerontechnology in Assisted Living Communities for Older Adults.

BACKGROUND: The number of older adults residing in assisted living communities is increasing. Despite the benefits of physical activity (PA) on physical and cognitive capacities, and the opportunities for being active offered in these living environments, this population is highly sedentary and more at risk of physical decline. This study aimed to assess the feasibility, the acceptability, and the effects of PA intervention using gerontechnology in assisted living communities. METHODS: Forty-two older adults in 4 assisted living communities were recruited and randomly assigned to an exercise intervention group (EX) or a control group (CON) using a 2:1 ratio. The EX group followed a 12-week PA program (2 sessions per week) using gerontechnology. Body composition, health status, quality of life, and functional capacities were evaluated at baseline, 12 weeks, and 24 weeks after baseline. RESULTS: Differences between groups were observed in the number of reported comorbidities (EX: 3.1 ± 1.6 vs CON: 5.0 ± 1.8; P = .007), SF-36 total score (EX: 80% ± 10% vs CON: 66% ± 15%; P = .004), and Short Physical Performance Battery (SPPB) total score (EX: 9.1 ± 1.8 vs CON: 7.5 ± 1.4; P = .006) at baseline. The EX group completed 89% ± 17% of the 24 prescribed sessions and realized 67% ± 13% of them in autonomy, reaching a quality level of 87% ± 6%. Of the EX participants, 93.8% enjoyed the exercises a lot or well, and 92.8% of them rated the exercises as being either easy or a little difficult. Changes between baseline and follow-up were statistically different between groups for walking speed (EX: +0.10 ± 0.20 vs CON: -0.04 ± 0.16 m/s; P = .04) and the SPPB score (EX: +1.1 ± 2.0 vs CON: -0.4 ± 1.6; P = .03). CONCLUSION: We found that PA intervention using gerontechnology in assisted living communities for older adults was feasible and acceptable, but more importantly induced improvement in functional capacities and walking speed, which is the main predictor of mortality in the elderly population.

Overexpression of Toll-like receptor 4 amplifies the host response to lipopolysaccharide and provides a survival advantage in transgenic mice.

Toll-like receptors are transmembrane proteins that are involved in the innate immune recognition of microbial constituents. Among them, Toll-like receptor 4 (Tlr4) is a crucial signal transducer for LPS, the major component of Gram-negative bacteria outer cell membrane. The contribution of Tlr4 to the host response to LPS and to infection with virulent Salmonella typhimurium was studied in four transgenic (Tg) strains including three overexpressing Tlr4. There was a good correlation between the level of Tlr4 mRNA expression and the sensitivity to LPS both in vitro and in vivo: Tg mice possessing the highest number of Tlr4 copies respond the most to LPS. Overexpression of Tlr4 by itself appears to have a survival advantage in Tg mice early during infection: animals possessing more than two copies of the gene survived longer and in a greater percentage to Salmonella infection. The beneficial effect of Tlr4 overexpression is greatly enhanced when the mice present a wild-type allele at natural resistance-associated macrophage protein 1, another critical innate immune gene involved in resistance to infection with Salmonella. Tlr4 and natural resistance-associated macrophage protein 1 exhibit functional epistatic interaction to improve the capacity of the host to control bacterial replication. However, this early improvement in disease resistance is not conducted later during infection, because mice overexpressing Tlr4 developed an excessive inflammatory response detrimental to the host.