Non-pharmaceutical interventions to reduce COVID-19 transmission in the UK: a rapid mapping review and interactive evidence gap map.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were crucial in the response to the COVID-19 pandemic, although uncertainties about their effectiveness remain. This work aimed to better understand the evidence generated during the pandemic on the effectiveness of NPIs implemented in the UK. METHODS: We conducted a rapid mapping review (search date: 1 March 2023) to identify primary studies reporting on the effectiveness of NPIs to reduce COVID-19 transmission. Included studies were displayed in an interactive evidence gap map. RESULTS: After removal of duplicates, 11 752 records were screened. Of these, 151 were included, including 100 modelling studies but only 2 randomized controlled trials and 10 longitudinal observational studies.Most studies reported on NPIs to identify and isolate those who are or may become infectious, and on NPIs to reduce the number of contacts. There was an evidence gap for hand and respiratory hygiene, ventilation and cleaning. CONCLUSIONS: Our findings show that despite the large number of studies published, there is still a lack of robust evaluations of the NPIs implemented in the UK. There is a need to build evaluation into the design and implementation of public health interventions and policies from the start of any future pandemic or other public health emergency.

Expansion of the myotonic dystrophy CTG repeat reduces expression of the flanking DMAHP gene.

Myotonic dystrophy, or dystrophia myotonica (DM), is a highly variable multisystem disease in which the classic adult-onset form displays progressive muscle wasting, cataracts, heart block, gonadal atrophy, insulin resistance and neuropsychiatric impairment. Its genetic basis is an expansion of CTG trinucleotide repeats in the DMPK protein kinase gene. Among the triplet repeat expansion disorders, DM is distinguished by the extended length of the repeat tract (5-13 kb in postmortem tissue) and its location in the 3' untranslated region of the gene that contains it. The pathophysiological mechanism for multisystem degeneration in DM is not understood. In contrast to the profound muscle wasting that characterizes advanced DM, only minor histopathological abnormalities have occurred in DMPK knockout mice or in mice that overexpress a human DMPK transgene, making it unlikely that changes in DMPK activity provide a unitary explanation for the disease. A DNAse hypersensitive site that maps 0.7 kb downstream (centromeric) from the CTG repeats is eliminated on DM chromosomes. This finding indicates that the repeat expansion may alter the adjacent chromatin structure and raises the possibility that it may also affect the expression of flanking genes. An interesting candidate flanking gene is DMAHP, a recently discovered homeodomain-encoding gene. We show here that DMAHP expression in myoblasts, muscle and myocardium is reduced by the DM mutation is cis, and the magnitude of this effect depends on the extent of CTG repeat expansion. These observations support the hypothesis that DMAHP participates in the pathophysiology of DM.

Microscope objective based 4π spectroscopic tissue scattering goniometry.

The measurement of optical scattering as a function of angle, goniometry, can provide a wealth of information about tissue. The goniometry technique described here measures the intensity profile at the pupil planes of two microscope objectives with a scattering sample between them. The maximum observable scattering angle is extended by employing off-axis illumination. This configuration permits several advantages including: i) rapid measurement of scattering into 4π sr to characterize the entire scattering phase function in isotropic tissue, ii) sensitivity to axially asymmetric scattering from anisotropic fibrous tissue, iii) selective interrogation of small regions within spatially inhomogenous tissue, iv) concurrent measurement of scattering coefficient µs , and v) measurement of wavelength dependent scattering properties via spectrally tunable source. The instrument is validated by comparing measurements of microsphere suspensions to the Mie scattering solution. Instrument capabilities are demonstrated with samples of rat brain and mouse eye tissues.

The relationship between oestrogen and executive functioning in ALS females with emerging Frontotemporal Lobar Degeneration (FTLD) supports a neuroendocrine model of FTLD attenuation.

OBJECTIVE: The prevalence of ALS cognitive or behavioural impairment (ci or bi) consistent with Frontotemporal Degeneration (FTLD) approachs 50%, while ∼5-10% progress to dementia. Our goal was to explore ci and bi differencs between bulbar and limb onset, as well as the neuroprotective potential of oestrogen in emerging FTLD. METHODS: We applied Mann Whitney U to evaluate differences in cognitive and behavioural profiles between site of onset in 78 female and 83 male non-demented ALS participants classified by current consensus criteria with ci. For females, we also examined differences by oestrogen level. FINDINGS: Between group analyses found significantly worse Letter Fluency (LF) for bulbar onset, and worse Category Fluency (CF) for bulbar females. Significantly worse performance was found for low oestrogen females for LF and Similarities, with significantly worse LF for low oestrogen bulbar onset. No significant differences were found for behavioural subgroups, while moderate-severe range traits were higher in occurrence for bulbar and low oestrogen bulbar onset. CONCLUSIONS: Findings support our previously published mesocortical pathway associated "bottom-up" model of FTLD emergence in ALSbi, extending it with a hierarchal hypothesis involving ascending cerebellar pathways in ALSci and ALSbi, further suggesting a role for oestrogen in mitigating female FTLD progression.

Performance predictors of brain-computer interfaces in patients with amyotrophic lateral sclerosis.

OBJECTIVE: Patients with amyotrophic lateral sclerosis (ALS) may benefit from brain-computer interfaces (BCI), but the utility of such devices likely will have to account for the functional, cognitive, and behavioral heterogeneity of this neurodegenerative disorder. APPROACH: In this study, a heterogeneous group of patients with ALS participated in a study on BCI based on the P300 event related potential and motor-imagery. RESULTS: The presence of cognitive impairment in these patients significantly reduced the quality of the control signals required to use these communication systems, subsequently impairing performance, regardless of progression of physical symptoms. Loss in performance among the cognitively impaired was accompanied by a decrease in the signal-to-noise ratio of task-relevant EEG band power. There was also evidence that behavioral dysfunction negatively affects P300 speller performance. Finally, older participants achieved better performance on the P300 system than the motor-imagery system, indicating a preference of BCI paradigm with age. SIGNIFICANCE: These findings highlight the importance of considering the heterogeneity of disease when designing BCI augmentative and alternative communication devices for clinical applications.

Relative stability of a minimal CTG repeat expansion in a large kindred with myotonic dystrophy.

The genetic basis for myotonic dystrophy (DM) is a CTG trinucleotide repeat expansion. The number of CTG repeats commonly increases in affected individuals of successive generations, in association with anticipation. We identified a large DM family in which multiple members had minimal CTG repeat expansions, and in which the number of CTG repeats remained in the minimally expanded range through at least three, and possibly four, generations. This relative stability of minimal CTG repeat expansions may help to maintain the DM mutation in the population.

Presentation and initial clinical course in patients with chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients without and with monoclonal gammopathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) may occur in association with a monoclonal gammopathy of undetermined significance (MGUS) or a variety of other systemic illnesses. It is not known if the clinical features of CIDP are altered by the presence of an MGUS. We compared demographic features, clinical presentation, improvement and outcome after initial treatment, and electrodiagnostic features of a group of 77 patients with idiopathic CIDP (CIDP-I, no associated systemic illness) with 26 patients with CIDP in whom an MGUS was found during evaluation of the neuropathy (CIDP-MGUS). Patients with CIDP-MGUS had, on average, a more indolent course and less severe weakness than patients with CIDP-I, despite similar motor conduction studies. CIDP-MGUS patients also demonstrated less functional impairment, more frequent sensory loss, and more abnormal sensory conduction studies than patients with CIDP-I. Because of the greater improvement of CIDP-I patients with treatment, both groups had similar outcomes from their initial episodes of weakness. Subgroup analysis of CIDP-MGUS patients did not demonstrate differences between groups with IgM and IgG or IgA gammopathies.

Quality of life in ALS is maintained as physical function declines.

OBJECTIVES: To study patients with ALS to determine how physical function, quality of life (QOL), and spirituality or religiousness change over time, and what relationship these changes have to one another. METHODS: Sixty patients with ALS were studied prospectively. They were assessed at baseline, 3 months, and 6 months, using questionnaires designed to measure general quality of life (McGill Quality of Life questionnaire), religiosity (Idler Index of Religiosity), ALS-specific health-related quality of life (SIP/ALS-19), and ALS-specific function (ALS functional rating scale). RESULTS: A two-way repeated measures multivariate analysis of variance revealed that both the passage of time and the specific QOL scales used were factors in predicting patient quality of life (F[1, 59]= 9.87, p < 0.003 and F[3, 177]= 16.90, p < 0.001) Despite a progressive decline in physical function as measured by the ALS-specific function score, the general QOL and religiosity scores changed little. In contrast, the ALS-specific health-related QOL score declined in parallel with the ALS-specific function score. CONCLUSIONS: QOL in patients with ALS appears to be independent of physical function, which agrees with a previous cross-sectional study. The ALS-specific health-related QOL score is primarily a measure of physical function. QOL instruments that assess spiritual, religious, and psychological factors produce different results than those obtained using measures of physical function alone.

Quality of life in ALS depends on factors other than strength and physical function.

OBJECTIVES: To study patients with ALS to determine the following: 1) the relationship between physical function and quality of life (QOL); 2) the instruments that best reflect patients' own ratings of QOL; and 3) whether spiritual/religious factors play a role in determining QOL. METHODS: The authors prospectively studied 96 patients with ALS using several instruments, including the McGill Quality of Life (MQOL) instrument, the Idler Index of Religiosity, the Sickness Impact Profile (SIP)/ALS-19, and several measures of strength and physical function. RESULTS: QOL as assessed by patients (MQOL single item score) did not correlate with measures of physical function and strength, but correlated with the total MQOL score (p < 0.0005), the psychological and existential subscores of MQOL (p < 0. 0005), the support subscore of MQOL (p = 0.001), and the total Idler score (p = 0.001). In contrast, correlations between SIP/ALS-19 and these measures were not significant, although SIP/ALS-19 correlated with measures of physical function and strength. CONCLUSIONS: QOL, as assessed by the patient with ALS, does not correlate with measures of strength and physical function, but appears to depend on psychological and existential factors, and thus may be measured well by the MQOL scale. Spiritual factors and support systems appear to play roles as well. SIP/ALS-19 is a good measure of physical function, but not of overall QOL.

Activation of oncogenic pathways in degenerating neurons in Alzheimer disease.

A number of recent findings have highlighted the similarities between neurogenesis during development and neurodegeneration during Alzheimer disease. In fact, neuronal populations that are known to degenerate in Alzheimer disease exhibit phenotypic changes characteristic of cells re-entering the cell division cycle. In this study, we extended these findings by investigating components of the cell cycle, known to trigger progression through G1 through activation of signal transduction cascades. Specifically, we found that proteins implicated in G1 transition, namely Cdc42/Rac, are upregulated in select neuronal populations in cases of Alzheimer disease in comparison to age-matched controls. Importantly, Cdc42/Rac shows considerable overlap with early cytoskeletal abnormalities suggesting that these changes are an extremely proximal event in the pathogenesis of the disease. Given the functional role of Cdc42/Rac in various cellular processes known to be perturbed in Alzheimer disease, namely cytoskeletal organization, oxidative balance, and oncogenic signaling, it is likely that increased neuronal Cdc42/Rac is highly significant in relation to the pathogenic process and contributes to neuronal degeneration. In fact, these findings suggest that Alzheimer disease is an oncogenic process.

Dysphagia in elderly men with myasthenia gravis.

Eight elderly men whose primary symptoms of myasthenia gravis were decreased speech and swallowing ability were seen for speech pathology evaluations and videofluoroscopic swallow studies. All patients had fatigable flaccid dysarthria and greater than expected pharyngeal phase dysphagia on videofluoroscopy; eight had decreased pharyngeal motility as demonstrated by residual material in the valleculae and pyriform sinuses bilaterally; seven had episodes of laryngeal penetration secondary to overflow of residual material; and five experienced silent aspiration despite gag reflexes and the ability to cough to command. Five patients required feeding tubes because their dysphagia responded poorly to treatment. Videofluoroscopic swallow studies revealed a common swallowing profile with pharyngeal phase dysphagia greater than expected from patient symptoms. Dysphagia did not improve at the same rate as other manifestations of myasthenia gravis.

Low diagnostic yield of sural nerve biopsy in patients with peripheral neuropathy and primary amyloidosis.

Patients with primary amyloidosis may develop peripheral neuropathy as an early feature. Sural nerve biopsy is reported to be a sensitive method for diagnosing amyloidosis in such patients. We identified nine patients, ultimately diagnosed as having amyloidosis, who were referred for peripheral neuropathy of undetermined etiology. In six, a sural nerve biopsy demonstrated no amyloid. Subsequent examination of other tissue or of the contralateral sural nerve eventually resulted in the correct diagnosis. We conclude that sural nerve biopsy may be less sensitive than previously believed for the diagnosis of amyloidosis in patients with peripheral neuropathy secondary to amyloid. When the clinical suspicion of amyloidosis is high, a nondiagnostic sural nerve biopsy should not discourage the performance of further investigative studies.

Methods for estimating the numbers of motor units in human muscles.

After the introduction by A. J. McComas of the original method for estimating the number of motor units based on manual incremental stimulation of a motor nerve, several new techniques have been developed, designed to correct for some of the errors inherent in the original technique. These methods incorporate algorithms to adjust for alternation and, to a greater or lesser extent, automate the methods, rendering the techniques less subject to operator bias and various physiological and technical errors. This review explores the advantages and drawbacks in the multiple-point stimulation (MPS), spike-triggered averaging (STA), and decomposition-enhanced STA techniques, illustrates some of the current applications of the techniques, and explores some tantalizing prospects for new studies of motor-unit physiology in the future.

Painless compressive cervical myelopathy with false localizing sensory findings.

Five patients who presented with clearly defined thoracic sensory levels were found by myelography and follow-up computed tomography (CT) to have cervical spinal cord compression. None of these patients had pain or an immediate preceding history of trauma. There is currently no satisfactory explanation for the large discrepancy between the sensory level and the level of cord compression in such patients. It is crucial that the clinician recognize the possibility of a cervical cord lesion in patients with such a presentation so that appropriate radiographic studies can be performed. Failure to appreciate this syndrome could result in failure to diagnose a treatable lesion.

Chronic inflammatory demyelinating polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy is an immune-mediated disorder which usually responds to treatment Accurate diagnosis is essential and depends on the clinician's ability to synthesize a variety of clinical, electrodiagnostic, and laboratory data. The prognosis is generally good, This review summarizes the pathogenesis, clinical presentation, evaluation, treatment, and prognosis of adults and children with CIDP with practical guidelines for selection of the most appropriate diagnostic tests and treatment modalities.

A CSF biomarker panel for identification of patients with amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with complicated pathogenesis that poses challenges with respect to diagnosis and monitoring of disease progression. OBJECTIVES: To identify a biomarker panel that elucidates ALS disease pathogenesis, distinguishes patients with ALS from neurologic disease controls, and correlates with ALS disease characteristics, and to determine the effect of HFE gene variants, a potential risk factor for sporadic ALS, on the biomarker profile. METHODS: We obtained CSF samples by lumbar puncture from 41 patients with ALS and 33 neurologic disease controls. All patients were genotyped for HFE polymorphisms. We performed a multiplex cytokine and growth factor analysis and immunoassays for iron-related analytes. Classification statistics were generated using a support vector machine algorithm. RESULTS: The groups of patients with ALS and neurologic disease controls were each associated with distinct profiles of biomarkers. Fourteen biomarkers differed between patients with ALS and the control group. The five proteins with the lowest p values differentiated patients with ALS from controls with 89.2% accuracy, 87.5% sensitivity, and 91.2% specificity. Expression of IL-8 was higher in those patients with lower levels of physical function. Expression of beta2-microglobulin was higher in subjects carrying an H63D HFE allele, while expression of several markers was higher in subjects carrying a C282Y HFE allele. CONCLUSIONS: A CSF inflammatory profile associated with amyotrophic lateral sclerosis (ALS) pathogenesis may distinguish patients with ALS from neurologic disease controls, and may serve as a biomarker panel to aid in the diagnosis of ALS pending further validation. Some of these biomarkers differ by HFE genotype.

The ALSSQOL: balancing physical and nonphysical factors in assessing quality of life in ALS.

BACKGROUND: There is no generally accepted instrument for measuring quality of life (QOL) in patients with ALS. Current instruments are either too heavily weighted toward strength and physical function or useful for the evaluation of individuals but of less utility in assessing large samples. OBJECTIVE: To develop and evaluate the psychometric properties of an ALS-specific QOL instrument (the ALSSQOL) that would reflect overall QOL as assessed by the patient and would be valid and reliable across large samples. METHODS: The ALSSQOL is based on the McGill Quality of Life Questionnaire (MQOL), modified by changes in format and by adding questions on religiousness and spirituality, items derived from interviews with ALS patients, and items identified from open-ended questions administered during the MQOL. The psychometric properties of the ALSSQOL were assessed by a prospective multicenter study in which participants completed the ALSSQOL, other instruments measuring overall QOL, and instruments assessing religiousness, spirituality, and psychological distress. RESULTS: A 59-item ALSSQOL was developed; 342 patients evaluated its psychometric properties. Completion time averaged 15 minutes. Forty-six items loaded on six factors. The ALSSQOL demonstrated concurrent, convergent, and discriminant validity for the overall instrument and convergent validity for its subscales. Analysis of individual items permitted insight into variables of clinical importance. CONCLUSIONS: This new ALS-specific quality of life instrument is a practical tool for the assessment of overall quality of life in individuals with ALS and appears to be valid and useful across large samples. Validation studies of a shortened version are now under way.

Paraproteinemia and neuropathy.

Paraprotein-associated neuropathies are a diverse group of disorders. The pathogenesis of many of them is poorly understood. Treatments have usually consisted of plasma exchange, corticosteroids, intravenous immunoglobulin, and other immunosuppressive therapies. Response to treatment has varied from good to very poor. Most recent work in this field has had two goals: achieving a better understanding of pathogenesis and developing better treatments. Such diverse entities as hepatitis C virus, vascular endothelial growth factor, and cytokines now appear to play a role in pathogenesis. More aggressive therapies such a bone marrow transplantation, interferon-alpha, and Rituximab have shown some promise.

Chronic inflammatory demyelinating polyradiculoneuropathy in children: II. Long-term follow-up, with comparison to adults.

We previously reviewed the presentation, initial clinical course, and electrodiagnostic features of children with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now report the long-term follow-up of 12 children with idiopathic CIDP, and compare these to 62 adults with idiopathic CIDP. Children often had more rapidly fluctuating courses than adults. A relapsing course was significantly more common in children than in adults. The recovery of children from each episode of deterioration was usually excellent, and better, on average, than in adults. Ventilatory support was never required for children with slowly evolving illness; only 2 children with a precipitous onset clinically resembling Guillain-Barré syndrome required ventilatory support. Prednisone, plasma exchange, and intravenous immunoglobulin (IVIg) usually were effective in children. Multiple courses of IVIg could be given with continued efficacy. Treatment often could be discontinued in children with relapsing courses. The prognosis for children was excellent. Adults demonstrated a good, but more variable, outcome.