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Background People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. Methods In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. Results We included 536 cases with a first CAD event (2000–2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300–7995] vs 5900 [4910–7200]; P < .01), but leukocytosis (>11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63–3.15) and multivariable adjusted CAD-OR = 1.59 (1.09–2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29–1.93), 2.19 (1.59–3.03), and 1.73 (1.37–2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. Conclusions PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors.

Aging, a time-dependent loss of physiological function, and its drivers are turning into a significant topic of research as the population's mean age increases. Epigenetic alterations, telomere shortening or dysfunction, mitogenic stress, oxidative stress, or accumulation of DNA damage can drive the cell to senescence: a permanent cell cycle arrest sometimes associated with a secretory phenotype and inflammatory consequences in the surrounding tissue. The amount of senescent cells grows over time in older organisms and may induce tissue inflammation and threaten overall tissue homeostasis, favoring aging. Senolytic and senomorphic therapeutics are an emerging approach to eliminate senescent cells or to block their secretory phenotypes respectively. Given that people living with HIV suffer non-AIDS comorbidities in a higher prevalence than the general population, aging is accentuated among them. Inflammation biomarkers may be helpful to assess prognosis or act as surrogate endpoints for studies of strategies focused on reversal of HIV-associated accelerated aging. This review summarizes the latest findings in aging and its major drivers, under the light of HIV infection. Since the number of older PLWH is currently rising, it will be of great importance to address and treat their age-related conditions, as well as to better decipher their biological mechanisms.

Objectives Dolutegravir is widely prescribed owing to its potent antiviral activity, high genetic barrier and good tolerability. The aim of this study was to characterize dolutegravir’s pharmacokinetic profile and variability in a real-life setting and to identify individual factors and co-medications affecting dolutegravir disposition. Methods A population pharmacokinetic model was developed using NONMEM®. Relevant demographic factors, clinical factors and co-medications were tested as potential covariates. Simulations based on the final model served to compare expected dolutegravir concentrations under standard and alternative dosage regimens in the case of drug–drug interactions. Results A total of 620 dolutegravir plasma concentrations were collected from 521 HIV-infected individuals under steady-state conditions. A one-compartment model with first-order absorption and elimination best characterized dolutegravir pharmacokinetics. Typical dolutegravir apparent clearance (CL/F) was 0.93 L/h with 32% between-subject variability, the apparent volume of distribution was 20.2 L and the absorption rate constant was fixed to 2.24 h−1. Older age, higher body weight and current smoking were associated with higher CL/F. Atazanavir co-administration decreased dolutegravir CL/F by 38%, while darunavir modestly increased CL/F by 14%. Rifampicin co-administration showed the largest impact on CL/F. Simulations suggest that average dolutegravir trough concentrations are 63% lower after 50 mg/12h with rifampicin compared with a standard dosage of 50 mg/24h without rifampicin. Average trough concentrations after 100 mg/24h and 100 mg/12h with rifampicin are 92% and 25% lower than the standard dosage without rifampicin, respectively. Conclusions Patients co-treated with dolutegravir and rifampicin might benefit from therapeutic drug monitoring and individualized dosage increase, up to 100 mg/12 h in some cases.

Importance Despite guidelines endorsing oral rehydration therapy, intravenous fluids are commonly administered to children with acute gastroenteritis in high-income countries. Objective To identify factors associated with intravenous fluid administration and hospitalization in children with acute gastroenteritis. Design, setting, and participants This study is a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) probiotic trials. Participants include children aged 3 to 48 months with 3 or more watery stools in 24 hours between November 5, 2013, and April 7, 2017, for the PERC study and July 8, 2014, and June 23, 2017, for the PECARN Study. Children were from 16 pediatric emergency departments throughout Canada (6) and the US (10). Data were analyzed from November 2, 2018, to March 16, 2021. Exposures Sex, age, preceding health care visit, distance between home and hospital, country (US vs Canada), frequency and duration of vomiting and diarrhea, presence of fever, Clinical Dehydration Scale score, oral ondansetron followed by oral rehydration therapy, and infectious agent. Main outcomes and measures Intravenous fluid administration and hospitalization. Results This secondary analysis of 2 randomized clinical trials included 1846 children (mean [SD] age, 19.1 [11.4] months; 1007 boys [54.6%]), of whom 534 of 1846 (28.9%) received oral ondansetron, 240 of 1846 (13.0%) received intravenous rehydration, and 67 of 1846 (3.6%) were hospitalized. The following were independently associated with intravenous rehydration: higher Clinical Dehydration Scale score (mild to moderate vs none, odds ratio [OR], 8.73; 95% CI, 5.81-13.13; and severe vs none, OR, 34.15; 95% CI, 13.45-86.73); country (US vs Canada, OR, 6.76; 95% CI, 3.15-14.49); prior health care visit with intravenous fluids (OR, 4.55; 95% CI, 1.32-15.72); and frequency of vomiting (per 5 episodes, OR, 1.66; 95% CI, 1.39-1.99). The following were independently associated with hospitalization: higher Clinical Dehydration Scale score (mild to moderate vs none, OR, 11.10; 95% CI, 5.05-24.38; and severe vs none, OR, 23.55; 95% CI, 7.09-78.25) and country (US vs Canada, OR, 3.37; 95% CI, 1.36-8.40). Oral ondansetron was associated with reduced odds of intravenous rehydration (OR, 0.21; 95% CI, 0.13-0.32) and hospitalization (OR, 0.44; 95% CI, 0.21-0.89). Conclusions and relevance Intravenous rehydration and hospitalization were associated with clinical evidence of dehydration and lack of an oral ondansetron-supported oral rehydration period. Strategies focusing on oral ondansetron administration followed by oral rehydration therapy in children with dehydration may reduce the reliance on intravenous rehydration and hospitalization. Trial registration ClinicalTrials.gov Identifiers: NCT01853124 (PERC) and NCT01773967 (PECARN).

Limiting antibiotic use is urgent due to increasing antibiotic resistance and the long-term implications of a disturbed microbiome. Data on antibiotic use of physicians integrating conventional and complementary medicine show that a significant reduction of antibiotic use in primary care is possible. In the setting of non-complicated infections in out-patient medicine, open dialogue with the patient, recognizing the importance of fever and reducing antipyretic use are general measures that can help reduce patients' concerns, and increase their trust in a well-functioning immune system and a treatment approach without antibiotics. Accumulating evidence suggests that complementary medicine strategies are useful in the management of common infections without antibiotics.Vu l’augmentation de la résistance aux antibiotiques et les conséquences qu’implique, à long terme, un microbiote perturbé, il est urgent de limiter leur consommation. Les données obtenues chez les médecins intégrant médecines conventionnelle et complémentaire montrent un recours aux antibiotiques diminué dans les soins primaires. Une communication adaptée, la compréhension de l’importance de la fièvre et la diminution de la prise d’antipyrétiques sont autant d’étapes clés pouvant aider les patients à surmonter leurs craintes, à renforcer leur confiance en leur système immunitaire et en un traitement sans antibiotiques en cas d’infections simples. Un nombre croissant d’études démontre ainsi que les outils de la médecine complémentaire peuvent contribuer à la gestion des infections courantes sans antibiotiques.

Ziel dieses Artikels ist es aufzuzeigen, wie die Streptokokken-Angina auch in der Schweiz meist ohne Antibiotika erfolgreich behandelt werden kann.

Background Although oral rehydration therapy is recommended for children with acute gastroenteritis (AGE) with none to some dehydration, intravenous (IV) rehydration is still commonly administered to these children in high-income countries. IV rehydration is associated with pain, anxiety, and emergency department (ED) revisits in children with AGE. Objectives We sought to better understand the factors associated with IV rehydration in children with AGE in order to inform knowledge translation strategies. Design/Methods This was a planned secondary analysis of the Pediatric Emergency Research Canada (PERC) and Pediatric Emergency Care Applied Research Network (PECARN) randomized, controlled trials of oral probiotics in children with AGE-associated diarrhea. Eligible children were aged 3–48 months and reported >3 watery stools in a 24-hour period. The primary outcome was administration of IV rehydration at the index ED visit. We used mixed-effects logistic regression model to explore univariable and multivariable relationships between IV rehydration and a prioririsk factors. Results From the parent study sample of 1848 participants, 1846 had data available for analysis: mean (SD) age of 19.1 ± 11.4 months, 45.4% females. 70.2% (1292/1840) vomited within 24 hours of the index ED visit and 34.1% (629/1846) received ondansetron in the ED. 13.0% (240/1846) were administered IV rehydration at the index ED visit, and 3.6% (67/1842) were hospitalized. Multivariable predictors of IV rehydration were Clinical Dehydration Scale (CDS) score [compared to none: mild to moderate (OR: 8.1, CI: 5.5–11.8); severe (OR: 45.9, 95% CI: 20.1–104.7), P Conclusion Higher CDS scores, antiemetic use, previous healthcare visits and country were independent predictors of IV rehydration which was also associated with increased ED revisits. Knowledge translation focused on optimizing the use of antiemetics (i.e. for those with dehydration) and reducing the geographic variation in IV rehydration use may improve the ED experience and reduce ED-revisits.

Background Hypercholesterolemia is a well established risk factor for coronary heart disease and is highly prevalent among human immunodeficiency virus (HIV)-positive persons. Antiretroviral therapy (ART) can both directly modify total cholesterol and have drug-drug interactions with statins. This makes investigating modifiable behavioral predictors of total cholesterol a pertinent task. Methods To explore the association between diet and physical activity with cross-sectionally measured total cholesterol, we administered a validated Food-Frequency-Questionnaire to participants of the Swiss HIV Cohort Study ≥45 years old. Linear mixed-effects models were applied to explore the associations between dietary patterns and physical activity with total cholesterol, after adjustment for clinical and demographic covariates. Results In total, 395 patients were included. Forty percent (158 of 395) had elevated total cholesterol (>5.2 mmol/L), and 41% (164 of 395) were not regularly physically active. In multivariable analysis, 2 factors were positively associated with total cholesterol; female sex (β = 0.562; 95% confidence interval [CI], 0.229–0.896) and the combined consumption of meat, refined/milled grains, carbonated beverages, and coffee (β = 0.243; 95% CI, 0.047–0.439). On the other hand, regular physical activity (β = −0.381; 95% CI, −0.626 to −0.136), lipid-lowering drugs (β = −0.443; 95% CI −0.691 to −0.196), ART containing tenofovir (β = −0.336; 95% CI −0.554 to −0.118), and black ethnicity (β = −0.967; 95% CI −1.524 to −0.410) exhibited a negative association. Conclusions We found independent associations between certain dietary patterns and physical activity with total cholesterol. Increasing physical activity might achieve cardiovascular and other health benefits in HIV-positive individuals. The clinical relevance of the identified dietary patterns requires further investigation in prospective cohort studies and randomized controlled trials.

Most countries exclude human immunodeficiency virus (HIV)-positive patients from organ donation because of concerns regarding donor-derived HIV transmission. The Swiss Federal Act on Transplantation has allowed organ transplantation between HIV-positive donors and recipients since 2007. We report the successful liver transplantation from an HIV-positive donor to an HIV-positive recipient. Both donor and recipient had been treated for many years with antiretroviral therapy and harbored multidrug-resistant viruses. Five months after transplantation, HIV viremia remains undetectable. This observation supports the inclusion of appropriate HIV-positive donors for transplants specifically allocated to HIV-positive recipients.

Im Spital werden teils komplexe HWI-Situationen behandelt, die Keime sind haufiger antibiotikaresistent. Eine positive Urinkultur ohne Symptome und Pyurie ist vor allem bei alteren Personen haufig; dieses Symptom soll nicht antibiotisch behandelt werden, ausser in der Schwangerschaft und vor urologischem Eingriff.

Akute Blasenentzundungen sind bei Frauen weit haufiger als bei Mannern. Wenn die Diagnose klinisch klar ist, dann bringt ein positiver Urinstreifentest keine zusatzliche Information; umgekehrt haben bis zu 30% der Frauen mit HWI einen negativen Streifentest.

The introduction of polymerase chain reaction (PCR)-based DNA amplification in the early nineties has revolutionized diagnosis of infectious diseases and has provided many fundamental insights regarding their epidemiology and clinical presentation. Compared to serology, PCR-based diagnosis may be more specific and sensitive, and may allow earlier diagnosis. Adequate patient specimens are important. Depending on the clinical setting, PCR amplification can be performed on blood samples, other clinical specimens or directly on histopathologic specimens. PCR detection of pathogen DNA is used to confirm serologic screening tests and to diagnose infections due to pathogens that are difficult to grow in culture. With chronically persistent agents, PCR may allow differentiation between clinically irrelevant and relevant infection. Suppression of viral DNA or RNA is a standard read-out of the efficacy of antiviral agents used to treat chronic hepatitis B, C, or HIV infection. Infectious disease consultation may be useful for interpretation of results. Genetic testing is increasingly being performed for antimicrobial susceptibility testing (MRSA, antitubercular treatment) and may in the future contribute to prediction of the host response to infectious disease and of antiretroviral toxicity. Increased future use of PCR-based diagnosis of infectious diseases is likely, based on increasingly automated and multiplex PCR technology.

BACKGROUND: Morbidity and mortality of individuals co-infected with HIV and hepatitis C virus (HCV) is often determined by the course of their HCV infection. Only a selected proportion of those in need of HCV treatment are studied in randomized controlled trials (RCTs). We analysed the prevalence of HCV infection in a large cohort, the number of individuals requiring treatment, the eligibility for HCV treatment, and the outcome of the combination therapy with pegylated interferon-a and ribavirin in routine practice. METHODS: We analysed prescription patterns of HCV treatment and treatment outcomes among participants from the Swiss HIV Cohort Study with detectable hepatitis C viraemia (between January 2001 and October 2004). Efficacy was measured by the number of patients with undetectable HCV RNA at the end of therapy (EOTR) and at 6 months after treatment termination (SVR). Intention-to-continue-treatment principles were used. RESULTS: A total of 2150 of 7048 (30.5%) participants were coinfected with HCV; HCV RNA was detected in 60%, and not assessed in 26% of HCV-antibody-positive individuals. One hundred and sixty (12.5%) of HCV-RNA-positive patients started treatment. In patients infected with HCV genotypes 1/4 or 2/3, EOTR was achieved in 43.3% and 81.2% of patients, respectively, and SVR rates were 28.4% and 51.8%, respectively. More than 50% of the HCV-treated patients would have been excluded from two large published RCTs due to demographic, clinical and laboratory criteria. CONCLUSIONS: Despite clinical and psychosocial obstacles encountered in clinical practice, HCV treatment in HIV-coinfected individuals is feasible with results similar to those obtained in RCTs.

SummaryStudies on the incidence of bactericidal antibodies to a Hemophilus influenzae, Type B, and an unencapsulated H. influenzae were carried out on sera from 130 healthy individuals, ranging in age from 13 to 78, and from 19 chronic bronchitics. Of the 130 sera from normal people only 2 (1.5%) lacked bactericidal antibodies to the H. influenzae, Type B, whereas 21 (16%) lacked bactericidal antibodies to the unencapsulated H. influenzae. All of the 19 sera from the chronic bronchitics were bactericidal for both Hemophilus isolates. All five sera from agammaglobulinemic patients who were on gamma globulin replacement therapy demonstrated bactericidal activity against the H. influenzae, Type B isolate.Utilizing the indirect fluorescent antibody technique, no correlation was apparent between the presence or absence of bactericidal antibodies and antibody levels as measured by immunofluorescence.