Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter.

Previous mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context.

The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study: baseline participant profile.

OBJECTIVES: The aim of the study was to examine baseline neurocognitive impairment (NCI) prevalence and factors associated with NCI among patients enrolled in the Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study. METHODS: The NAMACO study is an ongoing, prospective, longitudinal, multicentre and multilingual (German, French and Italian) study within the Swiss HIV Cohort Study. Between 1 May 2013 and 30 November 2016, 981 patients ≥ 45 years old were enrolled in the study. All underwent standardized neuropsychological (NP) assessment by neuropsychologists. NCI was diagnosed using Frascati criteria and classified as HIV-associated or as related to other factors. Dichotomized analysis (NCI versus no NCI) and continuous analyses (based on NP test z-score means) were performed. RESULTS: Most patients (942; 96.2%) had viral loads < 50 HIV-1 RNA copies/mL. NCI was identified in 390 patients (39.8%): 263 patients (26.8%) had HIV-associated NCI [249 patients (25.4%) had asymptomatic neurocognitive impairment (ANI)] and 127 patients (13%) had NCI attributable to other factors, mainly psychiatric disorders. There was good correlation between dichotomized and continuous analyses, with NCI associated with older age, non-Caucasian ethnicity, shorter duration of education, unemployment and longer antiretroviral therapy duration. CONCLUSIONS: In this large sample of aging people living with HIV with well-controlled infection in Switzerland, baseline HIV-associated NCI prevalence, as diagnosed after formal NP assessment, was 26.8%, with most cases being ANI. The NAMACO study data will enable longitudinal analyses within this population to examine factors affecting NCI development and course.

How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well-treated HIV-positive population?

OBJECTIVES: Diagnosing neurocognitive impairment (NCI) in HIV infection requires time-consuming neuropsychological assessment. Screening tools are needed to identify when neuropsychological referral is indicated. We examined the positive and negative predictive values (PPVs and NPVs, respectively) of the three European AIDS Clinical Society (EACS) screening questions in identifying NCI. METHODS: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study recruited patients aged ≥45 years enrolled in the Swiss HIV Cohort Study between 1 May 2013 and 30 November 2016. NAMACO participants (1) answered EACS screening questions, (2) underwent standardized neuropsychological assessment and (3) completed self-report forms [Center for Epidemiologic Studies Depression Scale (CES-D)] rating mood. NCI categories were defined using Frascati criteria. PPVs and NPVs of the EACS screening questions in identifying NCI categories were calculated. RESULTS: Of 974 NAMACO participants with complete EACS screening question data, 244 (25.1%) expressed cognitive complaints in answer to at least one EACS screening question, of whom 51.3% had NCI (26.1% HIV-associated and 25.2% related to confounding factors). The PPV and NPV of the EACS screening questions in identifying HIV-associated NCI were 0.35 and 0.7, respectively. Restricting analysis to NCI with functional impairment or related to confounding factors, notably depression, the NPV was 0.90. Expressing cognitive complaints for all three EACS screening questions was significantly associated with depression (P < 0.001). CONCLUSIONS: The EACS screening questions had an NPV of 0.7 for excluding patients with HIV-associated NCI as defined by Frascati criteria. The PPV and NPV may improve if NCI diagnoses are based on new criteria.

Neglect of attention to reproductive health in women with HIV infection: contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study.

OBJECTIVES: Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate contraceptive use and unintended pregnancies in this population in Switzerland. METHODS: A self-report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database. RESULTS: Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event. CONCLUSIONS: Family planning needs in HIV-positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long-acting reversible contraceptives for women living with HIV.

Clostridium difficile infection is associated with graft loss in solid organ transplant recipients.

Clostridium difficile infection (CDI) is a leading cause of infectious diarrhea in solid organ transplant recipients (SOT). We aimed to assess incidence, risk factors, and outcome of CDI within the Swiss Transplant Cohort Study (STCS). We performed a case-control study of SOT recipients in the STCS diagnosed with CDI between May 2008 and August 2013. We matched 2 control subjects per case by age at transplantation, sex, and transplanted organ. A multivariable analysis was performed using conditional logistic regression to identify risk factors and evaluate outcome of CDI. Two thousand one hundred fifty-eight SOT recipients, comprising 87 cases of CDI and 174 matched controls were included. The overall CDI rate per 10 000 patient days was 0.47 (95% confidence interval ([CI] 0.38-0.58), with the highest rate in lung (1.48, 95% CI 0.93-2.24). In multivariable analysis, proven infections (hazard ratio [HR] 2.82, 95% CI 1.29-6.19) and antibiotic treatments (HR 4.51, 95% CI 2.03-10.0) during the preceding 3 months were independently associated with the development of CDI. Despite mild clinical presentations, recipients acquiring CDI posttransplantation had an increased risk of graft loss (HR 2.24, 95% CI 1.15-4.37; P = .02). These findings may help to improve the management of SOT recipients.

Preventive Strategies Against Cytomegalovirus and Incidence of α-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.

We assessed the impact of antiviral preventive strategies on the incidence of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections in a nationwide cohort of transplant recipients. Risk factors for the development of HSV or VZV infection were assessed by Cox proportional hazards regression. We included 2781 patients (56% kidney, 20% liver, 10% lung, 7.3% heart, 6.7% others). Overall, 1264 (45%) patients received antiviral prophylaxis (ganciclovir or valganciclovir, n = 1145; acyclovir or valacyclovir, n = 138). Incidence of HSV and VZV infections was 28.9 and 12.1 cases, respectively, per 1000 person-years. Incidence of HSV and VZV infections at 1 year after transplant was 4.6% (95% confidence interval [CI] 3.5-5.8) in patients receiving antiviral prophylaxis versus 12.3% (95% CI 10.7-14) in patients without prophylaxis; this was observed particularly for HSV infections (3% [95% CI 2.2-4] versus 9.8% [95% CI 8.4-11.4], respectively). A lower rate of HSV and VZV infections was also seen in donor or recipient cytomegalovirus-positive patients receiving ganciclovir or valganciclovir prophylaxis compared with a preemptive approach. Female sex (hazard ratio [HR] 1.663, p = 0.001), HSV seropositivity (HR 5.198, p < 0.001), previous episodes of rejection (HR 1.95, p = 0.004), and use of a preemptive approach (HR 2.841, p = 0.017) were significantly associated with a higher risk of HSV infection. Although HSV and VZV infections were common after transplantation, antiviral prophylaxis significantly reduced symptomatic HSV infections.

Viral Escape in the Central Nervous System with Multidrug-Resistant Human Immunodeficiency Virus-1.

In this study, we report the case of a patient infected with human immunodeficiency virus (HIV)-1 who developed ataxia and neurocognitive impairment due to viral escape within the central nervous system (CNS) with a multidrug-resistant HIV-1 despite long-term viral suppression in plasma. Antiretroviral therapy optimization with drugs with high CNS penetration led to viral suppression in the CSF, regression of ataxia, and improvement of neurocognitive symptoms.

Stringent adherence to a cytomegalovirus-prevention protocol is associated with reduced overall costs in the first 6 months after kidney transplantation.

BACKGROUND: We previously documented that a stringent implementation of a preemptive cytomegalovirus (CMV) prevention protocol reduced the number of CMV disease episodes after kidney transplantation, when compared with a routine preemptive protocol. The impact on overall costs was assessed. METHODS: Cost comparisons were made for inpatient and outpatient costs and overall costs, using costs provided by the financial department. Variables were analyzed using the Wilcoxon rank-sum test. A multivariable global linear model evaluated the effect of all co-variables on cost differences. In Cohort 1 (n = 84), 74% were followed with a standard CMV preemptive protocol, and 26% received prophylaxis. In Cohort 2 (n = 74), an intensified CMV surveillance protocol was applied in 74% of patients, and 26% were given prophylaxis. RESULTS: Overall, Cohort 1 had significantly higher treatment costs as compared with Cohort 2 (mean Swiss francs [CHF] 104,548 and CHF 76,983, respectively, P = 0.0005). Excluding patients who received prophylaxis reduced these costs to CHF 89,318 in Cohort 1 and CHF 73,652 in Cohort 2. Outcome between Cohort 1 and 2 was comparable. CONCLUSION: A stringent adherence to the CMV prevention protocol was associated with a significant reduction in overall costs. Whether this benefit is because of the demonstrated reduction in the rate of CMV disease needs to be assessed in a randomized trial.

Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss transplant cohort study.

BACKGROUND: The burden of enterococcal infections has increased over the last decades with vancomycin-resistant enterococci (VRE) being a major health problem. Solid organ transplantation is considered as a risk factor. However, little is known about the relevance of enterococci in solid organ transplantation recipients in areas with a low VRE prevalence. METHODS: We examined the epidemiology of enterococcal events in patients followed in the Swiss Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for infection, aminopenicillin resistance, treatment, and outcome. RESULTS: Of the 1234 patients, 255 (20.7%) suffered from 392 enterococcal events (185 [47.2%] infections, 205 [52.3%] colonizations, and 2 events with missing clinical information). Only 2 isolates were VRE. The highest infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of Enterococcus faecium. The highest colonization rates were documented in lung transplant recipients (0.33/person-year), with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic, and liver transplantation were significantly associated with infection. Previous antibiotic treatment, intensive care unit stay, and lung transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events led to an infection. Adequate treatment did not affect microbiological clearance rates. Overall mortality was 8%; no deaths were attributable to enterococcal events. CONCLUSIONS: Enterococcal colonizations and infections are frequent in transplant recipients. Progression from colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in colonization. No increased mortality because of enterococcal infection was noted.

Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients.

We assessed the impact of antiviral prophylaxis and preemptive therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective cohort of solid organ transplant recipients. Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox regression models. One thousand two hundred thirty-nine patients transplanted from May 2008 until March 2011 were included; 466 (38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively. Overall incidence of CMV disease was 6.05% and was linked to CMV serostatus (D+/R- vs. R+, hazard ratio [HR] 5.36 [95% CI 3.14-9.14], p < 0.001). No difference in the incidence of CMV disease was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR 1.16 [95% CI 0.63-2.17], p = 0.63). CMV disease was not associated with a lower graft failure-free survival (HR 1.27 [95% CI 0.64-2.53], p = 0.50). Nevertheless, patients followed by the preemptive approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63 [95% CI 1.01-2.64], p = 0.044). The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy used. However, patients on CMV prophylaxis were more likely to be free from graft failure.

A stringent preemptive protocol reduces cytomegalovirus disease in the first 6 months after kidney transplantation.

BACKGROUND: The optimal strategy to prevent cytomegalovirus (CMV) disease after kidney transplantation continues to be open to debate. The preemptive approach requires regular determination of CMV viremia and prompt initiation of therapy. METHODS: We retrospectively compared the incidence of CMV disease during two periods at our center: A first phase (P1, n = 84 kidney recipients), during which time the intensity of surveillance was determined by the responsible physician, was compared to a second phase (P2, n = 74), when a stringent protocol of CMV surveillance was required for all patients. The preemptive approach was applied for all CMV risk groups; prophylaxis was optional in the case of treatment for rejection or delayed graft function in the intermediate- and high-risk group. Follow-up was truncated at 6 months after transplant surgery. CMV syndrome was differentiated from asymptomatic replication by the presence of at least one systemic symptom, while diagnosis of CMV end-organ disease required histological confirmation. RESULTS: Immunosuppression was similar in the two periods. CMV prophylaxis was used equally (26 %) in both periods. The probability for asymptomatic viremia episodes was not different for patients in P1 and P2 regardless of the prevention strategy. For patients following the preemptive strategy, the probability for CMV disease was increased during P1 (p = 0.016), despite fewer PCR assays being performed in phase 2. Protocol violations were only observed during P1. CONCLUSIONS: The probability of CMV disease episodes (CMV syndrome and CMV end-organ disease) was substantially reduced using a very stringent protocol. This study highlights the crucial importance of a stringent protocol with optimal adherence by all caregivers if the preemptive strategy is to be successful.

Outcome of smoking cessation counselling of HIV-positive persons by HIV care physicians.

OBJECTIVES: Smoking is the most prevalent modifiable risk factor for cardiovascular diseases among HIV-positive persons. We assessed the effect on smoking cessation of training HIV care physicians in counselling. METHODS: The Swiss HIV Cohort Study (SHCS) is a multicentre prospective observational database. Our single-centre intervention at the Zurich centre included a half day of standardized training for physicians in counselling and in the pharmacotherapy of smokers, and a physicians' checklist for semi-annual documentation of their counselling. Smoking status was then compared between participants at the Zurich centre and other institutions. We used marginal logistic regression models with exchangeable correlation structure and robust standard errors to estimate the odds of smoking cessation and relapse. RESULTS: Between April 2000 and December 2010, 11 056 SHCS participants had 121 238 semi-annual visits and 64 118 person-years of follow-up. The prevalence of smoking decreased from 60 to 43%. During the intervention at the Zurich centre from November 2007 to December 2009, 1689 participants in this centre had 6068 cohort visits. These participants were more likely to stop smoking [odds ratio (OR) 1.23; 95% confidence interval (CI) 1.07-1.42; P=0.004] and had fewer relapses (OR 0.75; 95% CI 0.61-0.92; P=0.007) than participants at other SHCS institutions. The effect of the intervention was stronger than the calendar time effect (OR 1.19 vs. 1.04 per year, respectively). Middle-aged participants, injecting drug users, and participants with psychiatric problems or with higher alcohol consumption were less likely to stop smoking, whereas persons with a prior cardiovascular event were more likely to stop smoking. CONCLUSIONS: An institution-wide training programme for HIV care physicians in smoking cessation counselling led to increased smoking cessation and fewer relapses.

Hemophagocytic syndrome caused by primary herpes simplex virus 1 infection: report of a first case.

INTRODUCTION: Hemophagocytic syndrome represents a severe hyperinflammatory condition by activated macrophages. Leading viral triggering agents are Epstein-Barr virus (EBV), cytomegalovirus (CMV), and adenovirus. MATERIALS AND METHODS: We present a patient with Wegener's granulomatosis on azathioprine and prednisone medication, who developed a life-threatening hemophagocytic syndrome. Positive plasma polymerase chain reaction (PCR) with negative serology revealed a primary, disseminated infection with herpes simplex virus-1 as the triggering pathogen. After treatment with acyclovir, high-dose steroids, immunoglobulins, and etoposide, the patient recovered. CONCLUSION: Early diagnosis of potentially underlying infections of hemophagocytic syndrome influences the therapeutic approach. It is important to consider a variety of infectious agents, particularly in immunosuppressed individuals. The reported case emphasizes the importance of screening for herpes simplex virus 1.