The Use of the Voice Trainer App for Vocal Control in People with a Degenerative Ataxia: A Pilot Intervention Study.

Dysarthria is disabling in persons with degenerative ataxia. There is limited evidence for speech therapy interventions. In this pilot study, we used the Voice trainer app, which was originally developed for patients with Parkinson's disease, as a feedback tool for vocal control. We hypothesized that patients with ataxic dysarthria would benefit from the Voice trainer app to better control their loudness and pitch, resulting in a lower speaking rate and better intelligibility. This intervention study consisted of five therapy sessions of 30 min within 3 weeks using the principles of the Pitch Limiting Voice Treatment. Patients received real-time visual feedback on loudness and pitch during the exercises. Besides, they were encouraged to practice at home or to use the Voice trainer in daily life. We used observer-rated and patient-rated outcome measures. The primary outcome measure was intelligibility, as measured by the Dutch sentence intelligibility test. Twenty-one out of 25 included patients with degenerative ataxia completed the therapy. We found no statistically significant improvements in intelligibility (p = .56). However, after the intervention, patients were speaking slower (p = .03) and the pause durations were longer (p < .001). The patients were satisfied about using the app. At the group level, we found no evidence for an effect of the Voice trainer app on intelligibility in degenerative ataxia. Because of the heterogeneity of ataxic dysarthria, a more tailor-made rather than generic intervention seems warranted.

Facilitators & barriers and practices of early mobilization in critically ill burn patients: A survey.

BACKGROUND: Early mobilization (EM) of intensive care (IC) patients is important but complex with facilitators and barriers. Compared to general IC patients, burn IC patients are more hyper-metabolic. They have extensive wounds, lengthy wound dressing changes, and repeated surgeries that may affect possibilities of EM. This study aimed to identify facilitators and barriers of EM in burn IC patients among all disciplines involved. Additionally, we assessed EM practices, i.e. when are which patients considered suitable for EM. METHODS: A survey was sent to 139 professionals involved in EM of burn IC patients (discipline groups: Intensivists, medical doctors, registered nurses, therapists). RESULTS: Response rate was 57 %. The majority found EM very important, yet different definitions were chosen. Perceived barriers mainly concerned patient-level factors, most frequently hemodynamic instability and excessive sedation followed by skin graft surgery, fatigue, and pain management. Most frequent barriers at the provider-level were limited staffing, safety concerns, and conflicting perceptions about the suitability of EM. At the institutional-level, we found no high barriers. Interdisciplinary variation on perceived barriers, when to initiate it, and permitted maximal activity were ascertained. CONCLUSION: Skin grafts and pain management were barriers of EM specific for burn care. Opinions on frequency, dosage and duration of EM varied widely. Improving interdisciplinary communication is key.

Integrating theory-based and data-driven methods to case conceptualization: A functional analysis approach with ecological momentary assessment.

Objective Ecological momentary assessment (EMA) and network analysis are promising empirical developments for psychotherapy research and practice, but they lack a therapeutic rationale that could guide case conceptualization and treatment planning. We developed an assessment strategy that aims to assess functional analysis with EMA. Method: The assessment strategy was applied to a series of three N-of-1 assessments in a proof-of-concept study. After selecting a personalized set of items, EMA was implemented with three measurement time points per day for a period of 30 days. The participants evaluated feasibility and acceptance. Practicing psychotherapists discussed clinical implications in a focus group. Results: The implementation of the assessment strategy seemed feasible and accepted; participants did not report any side effects. Principal component and network analyses indicated interpretable components (e.g., participant 1: hopelessness, procrastination, coping, avoidance). The focus group pointed out potentials (e.g., efficient profit of the waiting time, empowering patients) and challenges (e.g., prioritize and interpret all the information). Conclusion: The presented assessment strategy may enhance the scientific quality of case conceptualization empowering therapists' decision-making regarding treatment planning. At the same time, it is a concrete demonstration of the challenges that need to be addressed in future research.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/µL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.

OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.

Joint kinetics of the ankle and knee when running over obstacles.

AIM: When running over obstacles of increasing height, heelstrike (HS) runners switch to a forefoot (FF) landing pattern once a critical obstacle height is reached. The primary purpose of this study was to determine whether ankle or knee joint kinetic variables trigger the gait change from a HS to a FF striking pattern as obstacle height increases. METHODS: Ten subjects were filmed from the sagittal plane as they ran at their preferred running speed over a force platform during 6 obstacle height conditions ranging from 10% to 22.5% of standing height, as well as an additional baseline condition with no obstacle (0%). An inverse dynamics approach was utilized to calculate ankle and knee joint kinetics at each condition. RESULTS: Differences in joint kinetics did not occur until a height was reached at which the landing strategy changed from a HS to a FF landing pattern. Most differences occurred at the ankle joint, at which there was a greater maximum plantar flexor moment and a greater amount of energy absorbed when obstacles of sufficient height to require a FF landing pattern were negotiated. CONCLUSIONS: Although no variables were found which met all of the criteria necessary to be considered a determinant of the gait transition, there were variables which distinguished between a HS and FF strike landing pattern as obstacle height increased.

A prospective, controlled study assessing the effect of lopinavir on amprenavir concentrations boosted by ritonavir.

In a controlled, prospective study, the efficacy of ritonavir 200 mg twice daily (bid) in inhibiting the decrease of amprenavir plasma concentrations caused by co-administration of lopinavir was assessed. Twelve HIV-seropositive patients were enrolled, and nine patients completed the 28-day study. At day 14, plasma concentrations of amprenavir 600 mg bid and ritonavir 200 mg bid were determined over 12 h. At day 15, lopinavir 400 mg bid was added. At day 28, plasma concentrations of amprenavir, ritonavir and lopinavir were assessed. Co-administration of lopinavir was found to decrease the amprenavir concentration, determined as the median area under the curve over 12 h (AUC12), by 25% (AUC12 24.9 microg/h/mL vs. 18.5 microg/h/mL; P<0.01), despite the presence of ritonavir 200 mg bid. Eight participants discontinued the study regimen during the first 6 weeks because of adverse gastrointestinal events. In conclusion, gastrointestinal tolerance of a regimen containing an increased dose of ritonavir 200 mg bid was low, while the regimen did not prevent a decrease of amprenavir and possibly lopinavir plasma concentrations.

Intralimb coordination following obstacle clearance during running: the effect of obstacle height.

The purpose of this study was to investigate the different coordination strategies used following obstacle clearance during running. Ten subjects ran over a level surface and over obstacles of six different heights (10, 12.5, 15, 17.5, 20 and 22.5% of their standing height). Analysis based upon the dynamical systems theory (DST) was used and the phasing relationships between lower extremity segments were examined. The results demonstrated that the increasing obstacle height elicited behavioral changes. The foot and the leg became more independent in their actions, while the leg and the thigh strengthened their already stable relationship. The 15% obstacle height seems to be a critical height for the observed changes.

A dynamical systems investigation of lower extremity coordination during running over obstacles.

OBJECTIVE: To investigate intralimb coordination during running over a level surface and over obstacles of three different heights. DESIGN: The phasing relationships between the foot and leg motions in the frontal plane, and the shank and thigh motions in the sagittal plane were used to compare patterns of coordination. BACKGROUND: The coordinated actions of lower extremity segments are necessary to absorb the impact forces generated during running. The behavioral patterns of these segments can be studied under changing task demands using analysis techniques from the Dynamical Systems Theory. METHODS: Ten subjects ran at their self-selected pace under four conditions: over a level surface and over obstacles of different heights (5%, 10%, 15% of their standing height). A force platform was used to record impact forces during landing after obstacle clearance, while kinematics were collected using a two-camera system. RESULTS: The increases in obstacle height resulted in significant changes in impact forces (34% increase between the two extreme conditions) and more in-phase relationships between the segments during early stance. No changes were observed in the variability of the phasing relationships. CONCLUSIONS: The coordination changes observed might be compensatory strategies aimed to reduce forces and potential injury. However, since the impact forces still increased significantly, it is also possible that the observed changes might be at-risk movement patterns predisposing runners to injury.

Effects of 2,5-hexanedione on calpain-mediated degradation of human neurofilaments in vitro.

2,5-Hexanedione (2,5-HD), the neurotoxic metabolite of n-hexane, can structurally modify neurofilaments (NF) by pyrrole adduct formation and subsequent covalent cross-linking. 2,5-HD also induces accumulations of NF within the pre-terminal axon. We examined whether exposure of NF to 2,5-HD affected NF degradation. Two different models were used: (1) NF-enriched cytoskeletons isolated from human sciatic nerve were incubated with 2,5-HD in vitro and (2) differentiated human neuroblastoma cells (SK-N-SH) were exposed to 2, 5-HD in culture prior to isolation of cytoskeletal proteins. The cytoskeletal preparations were subsequently incubated with calpain II. The amount of NF-H and NF-L remaining after proteolysis was determined by SDS-PAGE and quantitative immunoblotting. NF-M proteolysis could not be quantified. Incubation of sciatic nerve cytoskeletal preparations with 2,5-HD resulted in cross-linking of all three NF proteins into high molecular weight (HMW) material with a range of molecular weights. Proteolysis of the NF-H and NF-L polypeptides was not affected by 2,5-HD-exposure. Degradation of the HMW material containing NF-H or NF-L was retarded when comparing with degradation of the NF-H and NF-L polypeptides, respectively, from control samples, but not as compared to the corresponding NF polypeptides from 2,5-HD-treated samples. Exposure of SK-N-SH cells to 2,5-HD also resulted in considerable cross-linking of NF. No differences were found between the proteolytic rates of NF-L and NF-H from exposed cells as compared with those subunits from control cells. Moreover, degradation of cross-linked NF-H was not different from monomeric NF-H. In conclusion, whether 2,5-HD affects calpain-mediated degradation of cross-linked NF proteins will depend on which model better reflects NF cross-linking as occurring in 2, 5-HD-induced axonopathy. However, with both models it was demonstrated that exposure of NF proteins to 2,5-HD without subsequent cross-linking is not adequate to inhibit NF proteolysis in vitro by added calpain.

An early onset rehabilitation program for children and adolescents after traumatic brain injury (TBI): Methods and first results.

Survived traumatic brain injuries (TBI) are one of the most serious challenges to the patient's future life. Recent literature increasingly questions the long believed protective effects of functional cerebral plasticity in children. Although TBI in children and adolescents is frequent, they are less frequently admitted to rehabilitation centers as in-patients than adults. This emphasizes the role of out-patient treatment. The progressing study described here aims to achieve a contribution to a comprehensive approach in TBI-rehabilitation for youngsters. A two-stage multimethodal program, starting with stimulation in coma while the patient is on the intensive care unit, and neuropsychological therapy after regaining consciousness is to be evaluated in a controlled, prospective and randomized study. After including nearly 50 % of the planned sample (100 persons), some preliminary results can be mentioned with all applicable caution. The effectiveness of the applied therapy can be stated here with respect to the posttraumatic development of intellectual abilities in the 6- and 12 months follow ups. Moreover, in the control group development of psychopathological alterations was found to a considerable degree and also lower ratings in a quality of life questionnaire, compared to the experimental group. It is expected to prove these differences statistically, after the total sample has been included, and thus equal distributions have been achieved in all predictive variables.

Oxidation of recombinant methionyl human granulocyte colony stimulating factor.

The oxidation of methionine residues in recombinant methionyl human granulocyte colony stimulating factor with hydrogen peroxide has been investigated. Kinetic data of the oxidation were obtained by using reversed phase-high performance liquid chromatography. The stability-indicating capability of this system was confirmed with micellar electrokinetic capillary chromatography. In the pH range 1.9-7.5, the kobs value for the oxidation process is constant. Above pH 7.5, kobs tends to increase with increasing pH. In the pH range 1.9-11.8, four oxidation products were detected in RP-HPLC. Mass spectrometric analysis revealed that one mono-, one di- and two trioxidation products were formed. Using the cyanogen bromide cleavage method the nature of the oxidation products was determined. The mono-oxidation product is the protein with Met121 oxidized, while the dioxidation product has oxidized Met121 and Met126 residues. The trioxidation products are the proteins with Met121, Met126 and Met137 or Met0, Met121 and Met126 oxidized.