Xenogeneic matrix for basal cell carcinoma reconstruction: a case report.

This case report introduces an innovative approach for tissue regeneration post-total excision of basal cell carcinoma utilizing a xenogeneic collagen matrix coupled with injectable platelet-rich fibrin. The clinical outcome underscores the efficacy and predictability of this protocol in soft tissue regeneration. While further investigation on a larger patient cohort is warranted to fully elucidate its effects and advantages, this technique holds promise in streamlining surgical procedures following excision of extraoral neoplasms. Notably, its simple handling, minimal resource requirements, and potential to mitigate donor site morbidity and patient comorbidities post-surgery signify its value in clinical practice.

Comments on energy conservation treatments for MS-related fatigue and a new proposal.

Psychological treatments of MS-related fatigue mostly depend on energy conservation programs. We argue that the evidence for energy conservation training is weak - in contrast to some reviews on this topic. The reasons for our concerns are the use of informed passive control groups allowing negative placebo effects, the lack of predefined primary outcome parameter, statistically rather than clinically significant effects, and the use of insensitive fatigue questionnaires. We propose to base psychological interventions not on a view of fatigue as a constant loss of mental energy but as a subjective representation ("feeling") of an inflammatory state, which draws away attentional capacity. This conceptualization allows to develop a three-step treatment approach: Getting short-term control on fatigue, extinction to reduce fatigue-related avoidance behavior, and a systematic increase of activities by pacing. Our proposal depends on the techniques, that can interrupt ongoing feelings of fatigue and can serve as a basis for extinction. We propose that Progressive Muscle Relaxation might be such a technique. The advantage of our model is that it shares similarities with well-established treatments for phobias and chronic pain and we discuss the shared set of assumptions. Hopefully, this will help to improve the treatment of fatigue in future.

Is recalibration more important than realignment in prism adaptation training for visuospatial neglect? A randomized controlled trial.

Prism adaptation training (PAT) as a treatment for visuospatial neglect (VSN) involves two components: recalibration and realignment. We conducted a randomized controlled trial with PAT protocols requiring different degrees of recalibration and realignment, by using a single or multi-step protocol and varying visibility of the pointing movement. Twenty-five VSN patients received an alertness treatment without prisms, followed by four PAT protocols, encompassing a multi- or single-step procedure with terminal exposure, a single-step procedure with concurrent exposure, and sham PAT, presented in random order. The primary outcome parameter was the mean response time (RT) to left-sided targets in an endogenous variant of the Posner task, and we also measured the sensorimotor aftereffect. The two protocols without visibility of most of the movement trajectory produced significant aftereffects. The single-step protocol without movement visibility resulted in shorter RTs to left-sided targets. Hence, aftereffects depended on the partial invisibility of the movement. Moreover, only allowing VSN patients to recalibrate several times and direct feedback from the pointing errors had a beneficial effect on non-motor leftward visuospatial attention. We provide preliminary evidence that maximizing the conscious experience of movement errors may be an important component for remediating VSN.Trial registration: German Clinical Trials Register identifier: DRKS00025938.

Comparing two relaxation procedures to ease fatigue in multiple sclerosis: a single-blind randomized controlled trial.

BACKGROUND: Various relaxation procedures have been proposed to reduce fatigue in multiple sclerosis (MS). However, it is unknown, which type of relaxation has the largest effect on fatigue reduction and on autonomic nervous system (ANS) activity. OBJECTIVE: We aimed to compare two biofeedback-supported relaxation exercises: a deep breathing (DB) exercise and progressive muscle relaxation (PMR), which may ameliorate MS fatigue and alter ANS activity. METHODS: We performed a single-blind randomized clinical trial, introducing MS patients (n = 34) to the DB or PMR exercise. We first tested cardiovagal integrity, reflected by changes in heart rate variability (HRV) in response to DB. Participants then performed a fatigue-inducing vigilance task, followed by the DB or PMR. State fatigue was recorded consecutively at baseline, after the vigilance task, and after the relaxation exercise, along with HRV reflecting ANS activity. RESULTS: Only patients assigned to the PMR group experienced a significant drop in fatigue, whereas both relaxation exercises changed ANS activity. MS patients showed the expected autonomic response during the cardiovagal reflex test. The vigilance task elevated short-term feelings of fatigue and significantly reduced HRV parameters of parasympathetic activity. Trait fatigue was negatively correlated with HRV during the second half of the vigilance task. CONCLUSION: PMR alleviates short-term feelings of fatigue in persons with MS. The vigilance task in combination with HRV measurements may be helpful for evaluating relaxation procedures as a treatment of fatigue. Hereby, future studies should ensure longer and more frequent relaxation exercises and focus on patients with weak to moderate fatigue. TRIAL REGISTRATION: Trial Registry: DRKS00024358.

Monocular eye patching modulates reorienting of covert attention in patients with unilateral middle cerebral artery stroke.

Unilateral brain lesions can lead to impaired contralesional attention and reduced ipsilesional and enhanced contralesional superior colliculus (SC) activity. We aimed to investigate whether modulation of SC activation via monocular eye patching can improve contralesional attention. Twenty left-hemispheric (LH) and 20 right-hemispheric (RH) patients with an acute or subacute middle cerebral artery (MCA) stroke completed an endogenous version of the Posner cueing task twice, while the left or right eye was covered with an eye patch. The LH and RH patients showed significantly slower reactions to contralesional than to ipsilesional stimuli. In addition, the eye patch modulated responses to invalidly but not those to validly cued stimuli. Post hoc analyses could not discriminate whether this effect pertained to a particular target side or eye patch position. However, exploratory analyses indicated that the observed eye patch effect might affect the RH group more than the LH group. As predicted 36 years ago, monocular eye patching modulates visuospatial attention, presumably due to differences in SC activation between the two eye patch conditions. However, this modulation seems too weak and unspecific, and therefore possibly not strong enough to be a treatment option for patients with visuospatial attention impairments.

Is recovery from left-sided neglect based on changes in automatic attention? An auditory event related potentials study.

An automatic spatial attention deficit is the primary deficit in neglect. However, the cognitive processes enabling recovery from neglect have rarely been studied. We used event-related potentials (ERP) to analyze if recovery is based on changes in automatic attention components. Twelve sub-acute patients with left visuospatial neglect were included. They received 3 weeks of intensive treatment. ERPs were recorded using two auditory paradigms: either a tone was presented randomly to the right or left ear (ATP) or as a Posner paradigm (PP) with left to right and vice versa moving cue tones and validly and invalidly cued target tones. Patients improved significantly on neuropsychological tests and neurological scales. For the ATP, no differences were observed related to the side of stimulation, but the auditory PP showed characteristic results, that is, smaller amplitudes for left-sided targets and higher amplitudes for invalid trials. Both paradigms revealed a treatment effect, but no changes were found in the amplitudes for the two target sides, which would be expected if the treatment would affect the automatic attention bias. Recovery from neglect seems not to be associated with changes in the automatic spatial attention bias, arguing that recovery might be due to higher cognitive compensatory processes.

Heart rate variability and fatigue in MS: two parallel pathways representing disseminated inflammatory processes?

BACKGROUND: Fatigue is a disabling symptom of multiple sclerosis. Its biological causes are still poorly understood. Several years ago, we proposed that fatigue might be the subjective representation of inflammatory processes. An important step for a straight-forward evaluation of our model would be to show that the level of fatigue is associated with vagal activation. The heart rate is under partial control of the vagus nerve. Using power spectrum analysis allows to separate, at least partly, sympathetic and parasympathetic impact on heart rate variability. METHODS: This narrative review summarizes the evidence for heart rate variability changes in MS patients, their relationship with fatigue and disease course. To do this, we conducted a literature search, including 45 articles relevant to the topic treated in this review. RESULTS: We illustrate that (1) inflammation leads to a change in cardiac behavior during acute and chronic phases, both in animals and in humans; (2) MS patients show changes of heart rate variability (HRV) that resemble those during acute and chronic inflammation due to multiple causes; (3) existing evidence favors a set of specific predictions about fatigue and parallel HRV changes; and (4) that MS-related brainstem lesions or neurological impairments do not completely explain HRV changes, leaving enough place for an explanatory relation between HRV and fatigue. DISCUSSION: We discuss the results of this review in relation to our model of fatigue and propose several observational and experimental studies that could be conducted to gain a better insight into whether fatigue and HRV can be interpreted as a common pathway, both reflecting activated autoimmune processes in MS patients.

Long-term results in three-dimensional, complex bone augmentation procedures with customized titanium meshes.

OBJECTIVES: Complex, three-dimensional bony defects still represent challenging situations in routine implant dentistry. The aim of this study was to evaluate implant survival in customized bone regeneration using a patient-specific titanium mesh. MATERIAL AND METHODS: Patients (n = 21, implants 36) who had obtained an augmentation procedure with patient-specific titanium mesh were examined after 5.7 ± 0.38 years. Survival rate, clinical parameters for periimplantitis (Bleeding on Probing [BOP] and suppuration), and radiographic examination were evaluated. Peri-implant marginal bone loss (MBL) was calculated by using an image assessment program. Additionally, the influence of various factors on treatment outcomes such as periodontitis, smoking, professional maintenance, or diabetes was assessed as well as the impact on quality of life applying the Oral Health Impact Profile (OHIP). RESULTS: The implant survival rate was 97%, with one implant loss in the lower jaw. At the end of the observation period, MBL showed mesial 0.13 ± 1.84 mm and distal -0.13 ± 1.73 mm. The lower jaw showed significant more MBL mesial compared with the upper jaw (p = .034, cluster-adjusted). Periodontitis was significantly associated with MBL mesial and distal (p < .05). Positive BOP (four implants) was significantly associated with MBL mesial (p = .0031) and distal (p = .0018). MBL was significantly associated with suppuration mesial (p < .0001) and distal (p < .0001). CONCLUSIONS: CBR® results in high implant survival rate and stabilized augmented marginal bone after follow-up of minimum 5 years. Periodontitis seems to play the mayor role for long-term stability indicated by BOP and suppuration.

Healthcare Providers' Knowledge of Value-Based Care in Germany: An Adapted, Mixed-Methods Approach.

BACKGROUND: Value-Based Care (VBC) is being discussed to provide better outcomes to patients, with an aim to reimburse healthcare providers (HCPs) based on the quality of care they deliver. Little is known about German HCPs' knowledge of VBC. This study aims to investigate the knowledge of HCPs of VBC and to identify potential needs for further education toward implementation of VBC in Germany. METHODS: For evidence generation, we performed a literature search and conducted an online survey among HCPs at 89 hospitals across Germany. The questionnaire was based on published evidence and co-developed with an expert panel using a mixed methods approach. RESULTS: We found HCPs to believe that VBC is more applicable in surgery than internal medicine and that well-defined cycles of care are essential for its application. HCPs believe that VBC can reduce health care costs significantly. However, they also assume that implementing VBC will be challenging. CONCLUSIONS: The concept in general is well perceived, however, HCPs do not want to participate in any financial risk sharing. Installing an authority/independent agency that measures achieved value, digital transformation, and that improves the transition between the inpatient and the outpatient sectors are top interests of HCPs.

Errorless learning and assistive technology did not improve the negative prognosis for severe dressing impairment after stroke if persisting for two weeks: A randomized controlled trial.

Following severe cerebrovascular accidents, patients are often unable to dress themselves. Little is known about the persistence and treatment of this impairment. Study 1 followed 23 patients who were (1) completely dependent on others for help with dressing (2) for two weeks continually until their discharge from the rehabilitation unit. Study 2, a randomized controlled trial of 24 patients, examined the effects of errorless learning and RehaGoal App-based dressing practice on recovery in dressing ability-impaired patients who also experienced visuospatial neglect and/or apraxia. The control and intervention groups both underwent a standard therapy in the rehab unit; the intervention group additionally received dressing training (seven sessions of 45 min). The primary outcome measure was the score on an adapted version of the Nottingham Stroke Dressing Assessment; secondary outcome measures were the Barthel Index and Functional Independence Measure. Less than one-third of the patients in Study1, showed improvement. In Study 2, the intervention produced no specific effect on patients' dressing ability. However, apraxia and neglect predicted improvement for both groups. If patients depend completely on assistance for dressing for two weeks, prospects for recovery are limited. Future studies should include additional intervention sessions and incorporate treatments for neglect or apraxia.

Can biofeedback-based training alleviate fatigue and vigilance performance in fatigued MS patients?

MS related fatigue might be related to autonomous nervous system (ANS) dysfunctions or to inflammation related vagal (hyper-) activation. Consequently, influencing ANS status may lead to relieve of fatigue. We used two opposite biofeedback interventions to either increase sympathetic ("self-alert training", SAT) or parasympathetic activation ("progressive muscle relaxation", PMR). We recorded fatigue status of patients before and after a challenging vigilance task, their behavioural performance on this task, their skin conductance response (SCR), and parameters indicating parasympathetic activity concerning heart rate variability (HRV). We repeated these recordings after the biofeedback training sessions. Patients of the SAT group were able to learn to increase their SCR voluntarily. Patients of the PMR group showed increasing parameters indicating parasympathetic modulation of the HRV. The vigilance task increased their feeling of fatigue. However, there was no effect of biofeedback training on either fatigue status or performance on the vigilance task. Our results show that MS patients can learn to change voluntarily their ANS activity using biofeedback instructions based on SCR and this can be used in future studies to test the postulated link between ANS and fatigue. However, in this experimental intervention we were unable to document a relation between ANS activity and fatigue.Trial registration: ClinicalTrials.gov identifier: NCT03268187.

The Effects of Continuous vs. Intermittent Prism Adaptation Protocols for Treating Visuospatial Neglect: A Randomized Controlled Trial.

Visuospatial neglect may interfere with activities of daily living (ADL). Prism adaptation (PA) is one treatment option and may involve two components: recalibration (more strategic) and realignment (more implicit). We examined whether recalibration or realignment is the driving force in neglect rehabilitation using PA. In a randomized controlled trial with two recruitment series and a cross-over design, 24 neglect patients were allocated to a continuous (PA-c) or intermittent (PA-i) PA procedure. During the PA-c condition, goggles were worn without doffing. In the PA-i condition, patients donned goggles twice (first series of patients) or three times (second series) during training to induce more recalibrations. Primary outcome parameters were performance (omissions) on the Apples Cancellation Test and ADL scores. To assess the efficacy of the PA treatment, we compared effect sizes of the current study with those from three groups from previous studies at the same rehabilitation unit: (1) a passive treatment with a similar intensity, (2) a placebo treatment with a similar intensity, and (3) a PA treatment with fewer therapy sessions. Treatment conditions did not significantly predict scores on primary and most secondary outcome parameters. However, the spontaneous ipsilesional body orientation improved only in patients receiving the PA-i condition and this improvement also appeared in patients showing a strong after-effect (irrespective of condition). Effect sizes for the Apples Cancellation Test and the Functional Independence Measure were larger for both PA treatment protocols than the historical control groups. We conclude that more recalibrations during an intermittent PA treatment may have a beneficial effect on spontaneous body orientation but not on other aspects of neglect or on ADL performance. Clinical Trial Registration: German Clinical Trials Register, identifier: DRKS00018813, DRKS00021539.

Audiospatial evoked potentials for the assessment of spatial attention deficits in patients with severe cerebrovascular accidents.

INTRODUCTION: Neuropsychological assessment of spatial orientation in post-acute patients with large brain lesions is often limited due to additional cognitive disorders like aphasia, apraxia, or reduced responsiveness. METHODS: To cope with these limitations, we developed a paradigm using passive audiospatial event-related potentials (pAERPs): Participants were requested to merely listen over headphones to horizontally moving tones followed by a short tone ("target"), presented either on the side to which the cue moved or on the opposite side. Two runs of 120 trials were presented and we registered AERPs with two electrodes, mounted at C3 and C4. Nine sub-acute patients with large left hemisphere (LH) or right hemisphere (RH) lesions and nine controls participated. RESULTS: Patients had no problems completing the assessment. RH patients showed a reduced N100 for left-sided targets in all conditions. LH patients showed a diminished N100 for invalid trials and contralesional targets. CONCLUSION: Measuring AERPs for moving auditory cues and with two electrodes allows investigating spatial attentional deficits in patients with large RH and LH lesions, who are often unable to perform clinical tests. Our procedure can be implemented easily in an acute and rehabilitation setting and might enable investigating spatial attentional processes even in patients with minimal conscious awareness.

Endovascular Therapy vs. Thrombolysis in Pre-stroke Dependent Patients With Large Vessel Occlusions Within the Anterior Circulation.

Background: In the past few years, several randomized trials have clearly shown that endovascular treatment (ET) in addition to intravenous thrombolysis (IVT) is superior to IVT alone in patients with proximal cerebral arterial occlusions. However, the effectiveness of ET in pre-stroke dependent patients (modified Rankin Scale ≥3) is uncertain. Methods: Using our prospectively obtained stroke database, we analyzed the impact of pre-stroke dependence on the rates of poor outcome (discharge mRS 5-6), in-hospital death, infarct sizes, and symptomatic intracranial hemorrhage (SICH) in patients with distal intracranial carotid artery M1 and M2 occlusions during two time periods. Results: From 1/2008 to 10/2012, a total of 544 patients (455 without and 89 with dependence) were treated with IVT, and from 11/2012 to 12/2019 a total of 1,061 patients (919 without and 142 with dependence) received ET (with or without IVT). Irrespective of the treatment modality, the dependent patients had significantly higher rates of poor outcome (55 vs. 32%, p < 0.001), death (24 vs. 11%; p < 0.001), or SICH (8.2 vs. 3.6%, p < 0.01) than independent patients. In dependent patients, ET significantly reduced the rates of poor outcome (49 vs. 64%, p < 0.01) and led to smaller infarcts, whereas the rates of in-hospital death (25 vs. 22%; p = 0.6) or SICH (8.5 vs. 7.9%, p = 0.9) were comparable between both treatment modalities. Conclusions: Compared with IVT, ET avoids poor outcome and leads to smaller infarcts in dependent patients. However, the overall high rates of poor outcome in this patient population stress the importance to perform decisions based on a case-by-case basis.

Repeated application of the covert shift of attention task improves endogenous but not exogenous attention in patients with unilateral visuospatial inattention.

BACKGROUND: Most neglect treatment studies focus on automatic re-orientation procedures, assuming a deficit in automatic processes. We compare an automatic- and a controlled procedure, using the endogenous and exogenous variants of Posner's covert shift of attention task. METHOD: In two experiments, neglect patients and patients with a right hemispherical stroke without neglect performed three blocks of Posner's covert shift of attention task (Posner Task) on two days. In Study 1 we used endogenous cues, in Study 2, exogenous cues. RESULTS: In the endogenous task, neglect patients improved significantly with valid left-sided cues between block 1 and 2 on Day 1, subsequently showing a plateauing. They also showed a gradual improvement on invalid trials on both days. In the exogenous condition, all participants responded only increasingly faster on trials with a long stimulus onset asynchrony. Practicing on both tasks led to fewer omissions for left-sided targets, minimally in the exogenous and clearly in the endogenous condition. CONCLUSION: In line with prior neuroanatomical studies, our study shows that practicing an endogenous, but not an exogenous, visuospatial attention task leads to significant improvements in neglect patients, especially for invalid trials, suggesting that neglect treatments based on top-down strategies should be given more attention.

Relation between cognitive fatigue and circadian or stress related cortisol levels in MS patients.

Background Cortisol levels are increased in MS patients. However, the relation between cortisol, cognitive fatigue and load is still unknown and is investigated in this study. METHOD: In 40 MS patients and 20 healthy controls, cortisol levels were assessed (in saliva) in the morning and afternoon, before and after 5 runs of a cognitively demanding divided attention task (lasting in total 25-minutes). MS patients were divided in those suffering from cognitive fatigue (MS-F) or not (MS-NF). RESULTS: MS-NF patients showed elevated cortisol levels in the morning and in the afternoon before the reaction time task compared to healthy controls. Differences in cortisol levels among the four measurements were also larger compared to healthy controls and MS-F patients. These differences could not be explained by medication, EDSS score, MS course, age or gender. MS-NF patients also produced more omissions on the attention task compared to healthy controls and MS-F patients. MS-F patients experienced more fatigue after the attention task, but they did not show a task related performance decline. CONCLUSION: MS-NF patients, and not MS-F patients, deviate in cortisol release and task performance from healthy controls and from MS-F patients. We suggest that MS-NF patients suffer from a dysregulation of their circadian cortisol level.

Population Health Management Approach: Integration of Community-Based Pharmacists into Integrated Care Systems: Reflections from the U.S., Achievements in Scotland and Discussions in Germany.

The annual amount spent on healthcare per capita is higher and expected to grow in the U.S. compared to healthier level 4 countries (e.g., United Kingdom, Canada, Germany, Australia, Japan, Sweden, Netherlands), while health outcomes continue to be suboptimal [123]. Therefore, healthcare is slowly shifting from a fee-for-service to value-based care, which addresses social determinants of health, promotes outcome-based contracting and employs more Population Health Management (PHM) activities. The root cause for this shift has been the increase in patients' out-of-pocket costs and the pervasiveness of poorer outcomes. PHM has been defined by many as a mindset and activities that support the Triple Aim Initiative (i.e., improving population health, experience of care, reducing costs) [4]. This article outlines the value of pharmacists on health outcomes in the U.S., Germany, and Scotland and innovative PHM approaches through pharmacist collaborative networks, polypharmacy management and pharmacists' integration in care models [15].