Evaluating an app-guided self-test for influenza: lessons learned for improving the feasibility of study designs to evaluate self-tests for respiratory viruses.

BACKGROUND: Seasonal influenza leads to significant morbidity and mortality. Rapid self-tests could improve access to influenza testing in community settings. We aimed to evaluate the diagnostic accuracy of a mobile app-guided influenza rapid self-test for adults with influenza like illness (ILI), and identify optimal methods for conducting accuracy studies for home-based assays for influenza and other respiratory viruses. METHODS: This cross-sectional study recruited adults who self-reported ILI online. Participants downloaded a mobile app, which guided them through two low nasal swab self-samples. Participants tested the index swab using a lateral flow assay. Test accuracy results were compared to the reference swab tested in a research laboratory for influenza A/B using a molecular assay. RESULTS: Analysis included 739 participants, 80% were 25-64 years of age, 79% female, and 73% white. Influenza positivity was 5.9% based on the laboratory reference test. Of those who started their test, 92% reported a self-test result. The sensitivity and specificity of participants' interpretation of the test result compared to the laboratory reference standard were 14% (95%CI 5-28%) and 90% (95%CI 87-92%), respectively. CONCLUSIONS: A mobile app facilitated study procedures to determine the accuracy of a home based test for influenza, however, test sensitivity was low. Recruiting individuals outside clinical settings who self-report ILI symptoms may lead to lower rates of influenza and/or less severe disease. Earlier identification of study subjects within 48 h of symptom onset through inclusion criteria and rapid shipping of tests or pre-positioning tests is needed to allow self-testing earlier in the course of illness, when viral load is higher.

Diagnostic accuracy of an app-guided, self-administered test for influenza among individuals presenting to general practice with influenza-like illness: study protocol.

INTRODUCTION: Diagnostic tests for influenza in Australia are currently only authorised for use in clinical settings. At-home diagnostic testing for influenza could reduce the need for patient contact with healthcare services, which potentially could contribute to symptomatic improvement and reduced spread of influenza. We aim to determine the accuracy of an app-guided nasal self-swab combined with a lateral flow immunoassay for influenza conducted by individuals with influenza-like illness (ILI). METHODS AND ANALYSIS: Adults (≥18 years) presenting with ILI will be recruited by general practitioners (GP) participating in Australian Sentinel Practices Research Network. Eligible participants will have a nasal swab obtained by their GP for verification of influenza A/B status using reverse transcription polymerase chain reaction (RT-PCR) test at an accredited laboratory. Participants will receive an influenza test kit and will download an app that collects self-reported symptoms and influenza risk factors, then instructs them in obtaining a low-nasal self-swab, running a QuickVue influenza A+B lateral flow immunoassay (Quidel Corporation) and interpreting the results. Participants will also interpret an enhanced image of the test strip in the app. The primary outcome will be the accuracy of participants' test interpretation compared with the laboratory RT-PCR reference standard. Secondary analyses will include accuracy of the enhanced test strip image, accuracy of an automatic test strip reader algorithm and validation of prediction rules for influenza based on self-reported symptoms. A post-test survey will be used to obtain participant feedback on self-test procedures. ETHICS AND DISSEMINATION: The study was approved by the Human Research and Ethic Committee (HREC) at the University of Adelaide (H-2019-116). Protocol details and any amendments will be reported to https://www.tga.gov.au/. Results will be published in the peer-reviewed literature, and shared with stakeholders in the primary care and diagnostics communities. TRIAL REGISTRATION NUMBER: Australia New Zealand Clinical Trial Registry (U1111-1237-0688).

Bilateral subthalamotomy for advanced Parkinson disease.

BACKGROUND: Unilateral subthalamotomy has been reported to be effective in the treatment of rigidity, bradykinesia, and tremor of the contralateral limb. However, gait, clinical fluctuation, and postural stability are not significantly improved by unilateral lesioning of the STN in the long term. We sought to determine if bilateral surgery of the STN offers more benefits in the treatment of advanced PD. METHODS: Radiofrequency thermal coagulation was performed bilaterally in the STN in 10 patients. Under microelectrode and stereotactic guidance, surgery was directed at the dorsolateral portion of the STN in stages and followed by MRI in each patient to confirm lesion location. Patients have been followed for a median duration of 26 months as measured from the date of first surgery (range, 6-48 months) with UPDRS before and after surgery. RESULTS: Bilateral subthalamotomy demonstrated persistent benefits in bradykinesia, rigidity of the limbs, and consequently the improvement in activities of daily living, motor function, Schwab and England scales. In addition, significant improvement in axial motor features, gait, postural stability, and clinical fluctuation were present with bilateral STN surgeries. The benefits were sustained at the last evaluation period of 36 months. Tremor and drug-induced dyskinesia improved in early postoperative period, but the benefits declined over time. The reduction of daily l-dopa equivalent was 34%. No speech impairment was observed. Mild choreic movement occurred in 2 of 20 procedures that resolved spontaneously in 4 to 8 weeks. CONCLUSION: For advanced PD present with bilateral symptoms, axial motor impairment, or clinical fluctuation, staged bilateral subthalamotomy appears as a safe and effective treatment in the long term.

Network modulation by the subthalamic nucleus in the treatment of Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN DBS) has become an accepted tool for the treatment of Parkinson's disease (PD). Although the precise mechanism of action of this intervention is unknown, its effectiveness has been attributed to the modulation of pathological network activity. We examined this notion using positron emission tomography (PET) to quantify stimulation-induced changes in the expression of a PD-related covariance pattern (PDRP) of regional metabolism. These metabolic changes were also compared with those observed in a similar cohort of patients undergoing STN lesioning. We found that PDRP activity declined significantly (P < 0.02) with STN stimulation. The degree of network modulation with DBS did not differ from that measured following lesioning (P = 0.58). Statistical parametric mapping (SPM) revealed that metabolic reductions in the internal globus pallidus (GPi) and caudal midbrain were common to both STN interventions (P < 0.01), although declines in GPi were more pronounced with lesion. By contrast, elevations in posterior parietal metabolism were common to the two procedures, albeit more pronounced with stimulation. These findings indicate that suppression of abnormal network activity is a feature of both STN stimulation and lesioning. Nonetheless, these two interventions may differ metabolically at a regional level.

Evolving metabolic changes during the first postoperative year after subthalamotomy.

OBJECT: Short-term benefit from unilateral subthalamotomy for advanced Parkinson disease (PD) is associated with metabolic alterations in key targets of subthalamic nucleus (STN) and globus pallidus (GP) output. In this study positron emission tomography (PET) scanning was used to assess these changes and their relation to long-term benefits of subthalamotomy. METHODS: To determine whether the early postoperative changes persisted at longer-term follow up, the authors assessed six patients with advanced PD by using [18F]fluorodeoxyglucose-PET at 3 and 12 months postsurgery. The authors compared each of the postoperative images with baseline studies, and assessed interval changes between the short- and long-term follow-up scans. Clinical improvement at 3 and 12 months was associated with sustained metabolic decreases in the midbrain GP internus (GPi), thalamus, and pons of the lesioned side (p < 0.01). The activity of a PD-related multiregional brain network, which correlated with bradykinesia and rigidity, was reduced at both postoperative time points (p < 0.05). Comparisons of 3- and 12-month images revealed a relative metabolic increase in the GP externus (GPe) (p < 0.001), which was associated with worsening gait, postural stability, and tremor at long-term follow up. CONCLUSIONS: These findings indicate that subthalamotomy may have differential effects on each of the functional pathways that mediate parkinsonian symptomatology. Sustained relief of akinesia and rigidity is associated with suppression of a pathological network involving the GPi and its output. In contrast, the recurrence of tremor may relate to changes in the function of an STN-GPe oscillatory network.

Treatment of advanced Parkinson's disease by subthalamotomy: one-year results.

We studied effects on parkinsonian features at 6 and 12 months in 12 patients who underwent unilateral ablation of subthalamic nucleus (STN). Microelectrode mapping was used, and a lesion was created in the STN using thermal coagulation and confirmed with magnetic resonance imaging. At 6 months postoperatively, improvements were seen in several areas: 1) Unified Parkinson's Disease Rating Scales II and III (UPDRS II and III) scores, 30% in off period, 38% in on period; 2) Schwab and England Scale (S&E) score, 21%; and 3) on dyskinesia, 85%. Contralateral rigidity, bradykinesia, UPDRS II and III scores, and S&E scores remained improved at 12 months. Daily dosage of levodopa requirement was reduced by 42%. Axial motor features, gait, postural stability, off period tremor, and motor fluctuation improved at 6 and 12 months but showed a decline in benefits at 18 months. Complications include 3 cases of hemiballism, of whom 2 patients recovered spontaneously but 1 died from aspiration pneumonia. One patient had asymptomatic hematoma, and 2 suffered transient postural asymmetries. We conclude that unilateral subthalamotomy results in moderate improvement in all aspects of parkinsonian features, allows reduction in the dose of levodopa required, and ameliorates drug-induced complications throughout 12-month assessments.

Subthalamotomy for advanced Parkinson disease.

OBJECT: The aim of this study was to determine if subthalamotomy is effective in treating advanced Parkinson disease (PD). METHODS: The authors performed microelectrode mapping-guided stereotactic surgery on the subthalamic nucleus in eight patients with PD. Lesioning was performed using radiofrequency heat coagulation and confirmed with magnetic resonance imaging. Three patients who underwent unilateral and four with bilateral subthalamotomy were evaluated for up to 18 months according to the Unified PD Rating Scale (UPDRS). One patient who underwent unilateral subthalamotomy died 6 months postsurgery. At 3 months into the "off" period after surgery, there were significant improvements in contralateral bradykinesia (p < 0.0002), rigidity (p < 0.0001), tremor (p < 0.01), axial motor features (p < 0.02), gait (p < 0.03), postural stability (p < 0.03), total UPDRS scores (p < 0.03), and Schwab and England scores (p < 0.04). The benefits were sustained at 6, 12, and 18 months, except for the improvement in tremor. At 12 months into the "on" period, significant benefits were present for motor fluctuation (p < 0.04), on dyskinesia (p < 0.006), off duration (p < 0.05), total UPDRS score (p < 0.02), and contralateral tremor (p < 0.05). Benefits for motor fluctuation, off duration, and off-period tremor were lost after the 18-month follow-up period. The levodopa requirement was reduced by 66% for the unilateral and 38% for the bilaterally treated group. Bilateral subthalamotomy offered more benefits than did unilateral surgery for various parkinsonian features in both the on and off periods. Three patients suffered hemiballismus, two recovered spontaneously, and one died of aspiration pneumonia after discontinuation of levodopa. CONCLUSIONS: These findings indicate that subthalamotomy can ameliorate the cardinal symptoms of PD, reduce the dosage of levodopa, diminish complications of the drug therapy, and improve the quality of life.

Postural asymmetries following unilateral subthalomotomy for advanced Parkinson's disease.

Two cases of postural asymmetries following unilateral stereotaxic subthalamotomy were observed with head and body tilting to the side contralateral to the STN lesion, which corrected itself completely or partially with levodopa treatment. After subsequent contralateral STN surgery, the postural asymmetry disappeared in both patients. Possible mechanism is discussed.