Design of the PERSPECTIVE study: PERsonalized SPEeCh Therapy for actIVE conversation in Parkinson's disease (randomized controlled trial).

OBJECTIVE: To evaluate the effectiveness of personalized and home-based speech therapy on quality of life, intelligibility, and social participation for people with Parkinson's disease (PD) who have a reduced intelligibility of speech. BACKGROUND: Speech problems in PD have a profound negative impact on social interaction and quality of life. Evidence for speech therapy in PD is growing, but more work remains needed to explore its full potential. Efficacy exists for highly intensive standardized speech treatment programs, but not all patients can comply with this rather intense intervention, especially the more severely affected ones. Here, we aim to study the effectiveness of personalized and home-based (remote) speech therapy in PD on quality of life and speech. The intervention will be supported by a dedicated speech training app. We expect that this approach will improve speech intelligibility and quality of life in patients irrespective of disease stage. METHODS: We will perform a single blind, randomized controlled trial, comparing 8 weeks of speech therapy to no intervention using a waiting list design. A total of 215 PD patients with problems in intelligibility will be recruited by 12 highly experienced speech therapists. All patients will be measured at baseline and after 8 weeks (primary endpoint). Additionally, the experimental group will be re-assessed one more time, after a wash-out period of 24 weeks. The control group will receive deferred treatment after 8 weeks, but without additional follow-up assessments. Our primary outcome is quality of life (as measured with PDQ-39). Secondary outcomes include speech and voice quality, intelligibility, severity of voice and speech complaints, and caregiver burden. RESULTS: The inclusion of participants has started on March 1, 2019, and is expected to be finalized on April 1, 2021. We expect to have the first results in January 2022. CONCLUSIONS: We will investigate the effectiveness of speech therapy in PD. Particular strengths of our study include a randomized and single-blinded design, the personalized treatment approach, the inclusion of PD patients irrespective of disease stage or severity of the speech complaint, the long-term follow-up, the adequate power, and the use of a patient-relevant primary endpoint. This will allow us to draw firm conclusions about the effectiveness of personalized and remote speech therapy for PD patients in all disease stages. TRIAL REGISTRATION: ClinicalTrials.gov NCT03963388 . Registered on May 24, 2019.

Risk of SARS-CoV-2 transmission upon return to work in RNA-positive healthcare workers.

BACKGROUND: Healthcare workers (HCWs) are at risk for coronavirus disease 2019 (COVID-19), and for spreading severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) amongst colleagues and patients. AIM: To study the presence of SARS-CoV-2 RNA and possible onward transmission by HCWs upon return to work after COVID-19, and association with disease severity and development of antibodies over time. METHODS: Unvaccinated HCWs with positive SARS-CoV-2 reverse transcriptase polymerase chain reaction (RT-PCR) were recruited prospectively. Data on symptoms were collected via telephone questionnaires on days 2, 7, 14 and 21 after a positive test. Upon return to work, repeat SARS-CoV-2 RT-PCR was performed and serum was collected. Repeat serum samples were collected at weeks 4, 8, 12 and 16 to determine antibody dynamics over time. Phylogenetic analysis was conducted to investigate possible transmission events originating from HCWs with a positive repeat RT-PCR. FINDINGS: Sixty-one (84.7%) participants with mild/moderate COVID-19 had a repeat SARS-CoV-2 RT-PCR performed upon return to work (median 13 days after symptom onset), of which 30 (49.1%) were positive with a median cycle threshold (Ct) value of 29.2 (IQR 26.9-29.9). All HCWs developed antibodies against SARS-CoV-2. No significant differences in symptomatology and presence of antibodies were found between repeat RT-PCR-positive and -negative HCWs. Eleven direct colleagues of six participants with a repeat RT-PCR Ct value <30 tested positive after the HCW returned to work. Phylogenetic and epidemiologic analysis did not indicate onward transmission through HCWs who were SARS-CoV-2 RNA positive upon return to work. CONCLUSIONS: HCWs regularly return to work with substantial SARS-CoV-2 RNA loads. However, this study found no evidence for subsequent in-hospital transmission.

[Revision of guideline on Q fever fatigue syndrome (QFS)]. / Herziene richtlijn Q-koortsvermoeidheidssyndroom (QVS).

In 2012 the multidisciplinary guideline Q fever fatigue syndrome was developed for the Netherlands. The availability of new research data and developments and experiences from daily clinical practice made it necessary to revise this guideline. The multidisciplinary working group that has revised the guideline is composed of representatives from all medical professions involved in the care of patients with QFS and representatives of the patients' association. The revised guideline incorporates a number of changes, including refinement of the QFS diagnostic criteria and updates regarding advice on support and reintegration.

Ventilator-induced central venous pressure variation can predict fluid responsiveness in post-operative cardiac surgery patients.

BACKGROUND: Ventilator-induced dynamic hemodynamic parameters such as stroke volume variation (SVV) and pulse pressure variation (PPV) have been shown to predict fluid responsiveness in contrast to static hemodynamic parameters such as central venous pressure (CVP). We hypothesized that the ventilator-induced central venous pressure variation (CVPV) could predict fluid responsiveness. METHODS: Twenty-two elective cardiac surgery patients were studied post-operatively on the intensive care unit during mechanical ventilation with tidal volumes of 6-8 ml/kg without spontaneous breathing efforts or cardiac arrhythmia. Before and after administration of 500mL hydroxyethyl starch, SVV and PPV were measured using pulse contour analysis by modified Modelflow® , while CVP was obtained from a central venous catheter positioned in the superior vena cava. CVPV was calculated as 100 × (CVPmax -CVPmin )/[(CVPmax + CVPmin) /2]. RESULTS: Nineteen patients (86%) were fluid responders defined as an increase in cardiac output of ≥ 15% after fluid administration. CVPV decreased upon fluid loading in responders, but not in non-responders. Baseline CVP values showed no correlation with a change in cardiac output in contrast to baseline SVV (r = 0.60, P = 0.003), PPV (r = 0.58, P = 0.005), and CVPV (r = 0.63, P = 0.002). Baseline values of SVV > 9% and PPV > 8% could predict fluid responsiveness with a sensitivity of 89% and 95%, respectively, both with a specificity of 100%. Baseline CVPV could identify all fluid responders and non-responders correctly at a cut-off value of 12%. There was no difference between the area under the receiver operating characteristic curves of SVV, PPV, and CVPV. CONCLUSION: The use of ventilator-induced CVPV could predict fluid responsiveness similar to SVV and PPV in post-operative cardiac surgery patients.

Left ventricular assist device for end-stage heart failure: results of the first LVAD destination program in the Netherlands.

PURPOSE: Mechanical circulatory support with a continuous-flow left ventricular assist device (LVAD) may be a valuable treatment in end-stage heart failure patients for an extended period of time. The purpose of this study was to evaluate the safety and efficacy of implantation of a continuous-flow LVAD in end-stage heart failure patients within the first destination program in the Netherlands. METHODS: A third-generation LVAD was implanted in 16 heart failure patients (age 61 ± 8; 81 % male; left ventricular ejection fraction 20 ± 6 %) as destination therapy. All patients were ineligible for heart transplant. At baseline, 3 and 6 months, New York Heart Association (NYHA) functional class, quality-of-life and exercise capacity were assessed. Clinical adverse events were registered. RESULTS: Survival at 30 days and 6 months was 88 and 75 %, respectively. In the postoperative phase, 6 (38 %) patients required continuous veno-venous haemofiltration for renal failure and 2 (13 %) patients required extracorporeal membrane oxygenation because of severe right ventricular failure. During follow-up, NYHA functional class and quality-of-life improved from 3.7 ± 0.1 to 2.3 ± 0.1 and 57 ± 5 to 23 ± 3 at 6 months (P < 0.001), respectively. The 6 min walking distance improved from 168 ± 42 m to 291 ± 29 m at 6 months (P = 0.001). CONCLUSION: Continuous-flow LVAD therapy is a promising treatment for patients with end-stage heart failure ineligible for heart transplant.

Strong association between failure of T cell homeostasis and the syncytium-inducing phenotype among HIV-1-infected men in the Amsterdam Cohort Study.

OBJECTIVE: To assess the association between T cell homeostasis and its failure and 1.) the occurrence of AIDS and 2.) the switch from the non-syncytium-inducing (NSI) to the syncytium-inducing (SI) HIV virus phenotype. METHODS: For each of 325 homosexual men in the Amsterdam Cohort Study, the slope of the CD3 T cell count versus time was determined. The timing (T cell inflection point (IP)) and magnitude of the change in slope were correlated with the time of the NSI/SI switch. RESULTS: Median T cell slopes before the IP (pre-IP) were nearly zero regardless of whether AIDS occurred; the slopes after the IP (post-IP) were associated with clinical outcomes, with a median annual decline of 17.6% among those who developed AIDS and increase of 4.6% in those remaining AIDS free. Among subjects considered to have a true IP (decline > 8.2%/year post-IP), the times of the SI switch and the IP slope were highly correlated (r = 0.65); among those with AIDS, the SI switch preceded the IP by a median of 0.63 years. CONCLUSION: These results support the concept of blind T cell homeostasis and also suggest that HIV-1 SI variants play an important role in the failure of T cell homeostasis.

Body mass index course in asymptomatic HIV-infected homosexual men and the predictive value of a decrease of body mass index for progression to AIDS.

Weight loss is a common characteristic of advanced stages of HIV infection. Weight changes during the asymptomatic stage of HIV infection have not been well documented and the possible predictive value of early weight loss for progression to AIDS is unknown. In 122 HIV seroconverters, the natural course of body mass index (BMI) following seroconversion was studied. No BMI decline was seen immediately following seroconversion. In the 56 AIDS cases, however, a steep BMI decline of 1.14 kg/m2 occurred 6 months before AIDS. This BMI decline was more pronounced in those with low CD4+ T cell counts (<100 x 10(6)/L) at the time of AIDS diagnosis (1.8 kg/m2). The relative hazard for progression to AIDS of a BMI decline of 1.14 kg/m2 per 6 months was 3.1, which remained similar after adjustment for CD4 count and p24 antigenemia. We conclude that the course of BMI in HIV-1 infection is biphasic: a relatively stable period is followed by a rapid decline in the 6 months preceding onset of AIDS. Furthermore, we found that this steep BMI decline was associated with faster progression to AIDS.

PIP: The possible predictive value of weight loss during the asymptomatic stage of HIV infection for progression to AIDS was assessed in 122 HIV seroconverters from the Netherlands. Study subjects were part of a broader cohort study initiated in 1984 of initially seronegative homosexuals from Amsterdam. The mean age of seroconverters was 35.8 years, with a mean follow-up time between seroconversion and AIDS diagnosis of 5.3 years (range, 0.6-10.8 years). The mean body mass index (BMI) was 22.2 kg/sq. mm at the first HIV-positive visit and 21.0 kg/sq. mm at AIDS diagnosis. Overall, there was no immediate decline in BMI in the immediate postseroconversion period. However, in the 56 men who progressed to AIDS, a BMI decline of 1.14 kg/sq. mm occurred 6 months before diagnosis. This decline was even more pronounced (1.8 kg/sq. mm) in those with CD4 T cell counts under 100 at the time of AIDS diagnosis. The relative hazard of progression to AIDS of a BMI decline of 1.14 kg/sq. mm per 6 months was 3.1. This rate persisted after adjustment for CD4 count and p24 antigenemia. Although the sensitivity of weight loss is only about one third, when weight loss is present, it can be considered a useful marker of progression to AIDS. It could not be established from this study whether weight loss was an early manifestation of an AIDS-defining illness or a true pre-AIDS decline. Initiation of antiretroviral therapy should be considered before the first signs of weight loss appear.

In vivo delayed-type hypersensitivity skin test anergy in human immunodeficiency virus type 1 infection is associated with T cell nonresponsiveness in vitro.

In a cross-sectional study, the prevalence of delayed-type hypersensitivity skin test anergy (DTHA) was examined in 136 asymptomatic human immunodeficiency virus-infected participants in relation to immunologic and virologic parameters. DTHA was assessed with a multitest cell-mediated immunity skin test. Of the 136 participants, with a mean CD4 T cell count of 335 x 10(6)/L, 25 were anergic (18.4%). In the stepwise forward multivariate logistic regression models, after adjustment for CD4 T cell counts, depending on whether it was analyzed continuously or after dichotomization (20th percentile), both T cell reactivity to CD2 plus CD28 antibodies or to CD3 antibodies were the most predictive markers of DTHA (odds ratio, 0.80; 95% confidence interval, 0.67-0.94; and odds ratio, 2.97; 95% confidence interval, 1.1-8.3, respectively). This study shows a strong correlation between the decreased T cell responses in vitro and DTHA. Therefore, next to DTHA testing, T cell function assays may be useful to test immune reconstitution observed during antiretroviral treatment.

Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine.

BACKGROUND: Treatment and prevention of HIV-1-related central-nervous-system disease may be dependent on penetration of antiretroviral drugs into the central nervous system. Few data are available about cerebrospinal-fluid penetration and concomitant changes of HIV-1-RNA concentrations during treatment with antiretroviral agents. We investigated these effects in HIV-1-infected people. METHODS: 28 antiretroviral-naive individuals with CD4 cell counts of 200/microL or more and plasma HIV-1-RNA concentrations of 10,000 or more copies/mL who were free of neurological symptoms were randomly assigned lamivudine plus either stavudine (n = 17) or zidovudine (n = 11). We did lumbar punctures on 28 individuals before and 22 individuals after 12 weeks of treatment to assess HIV-1-RNA and drug concentrations in cerebrospinal fluid. FINDINGS: All 28 individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid (median 4.64 log10 copies/mL and 4.20 log10 copies/mL in the lamivudine plus zidovudine and lamivudine plus stavudine groups, respectively). There was no correlation between plasma and cerebrospinal-fluid HIV-1-RNA concentrations (r = 0.18, p = 0.35). After 12 weeks of treatment none of the individuals had detectable HIV-1-RNA concentrations in the cerebrospinal fluid. The highest drug concentration in the cerebrospinal fluid was for lamivudine followed by stavudine and zidovudine. Concentrations were consistent over time, unlike plasma concentrations. Therefore, we found time-dependent cerebrospinal-fluid to plasma drug-penetration ratios, which were highest for zidovudine followed by stavudine and lamivudine. INTERPRETATION: The two drug combinations were equally effective in the decrease of cerebrospinal fluid HIV-1-RNA concentrations. All drugs penetrated the cerebrospinal fluid. Antiretroviral drugs other than zidovudine might be useful in the prevention of AIDS dementia complex.

Bilateral brachial plexus neuritis following parvovirus B19 and cytomegalovirus infection.

A man, 23 years of age, had a typical erythema infectiosum, complicated by a severe bilateral brachial plexus neuritis. Motor function recovered slowly and only partially after 6 months. An infection by human parvovirus B19 was demonstrated, with strongly positive and gradually declining IgM antibodies and viral DNA detectable in serum for more than 3 months. There was also clear evidence of a recent infection by cytomegalovirus. The interaction between these two viruses could be responsible for this rare and severe complication of common infections in this patient.

Endosonography in the clinical staging of Klatskin tumor.

Endosonography was performed preoperatively in 46 patients with carcinoma of the common hepatic duct and its bifurcation. The results of endosonography were correlated with findings during surgery and pathological examination of the resected specimen and classified according to the new (1987) TNM classification. Overall accuracy in assessing the depth of tumor infiltration was 86.0%. Endosonography was accurate in predicting the presence of lymph nodes but not accurate in defining non-metastatic changes of lymph nodes. Staging of distant metastases was not accurate due to the low penetration depth of ultrasound.