Manual therapy applied by general practitioners for nonspecific low back pain: results of the ManRück pilot-study

Abstract Background Nonspecific acute low back pain (LBP) is a common reason for accessing primary care. German guidelines recommend non-steroidal anti-inflammatory drugs and physical activity as evidence-based treatments. Manual Therapy (MT) remains controversial. To increase evidence-based treatment options for general practitioners (GPs), a Pilot-Study was set up to gather information about the required conditions and setting for an RCT. Methods The open pilot-study assesses recruitment methods for GPs and patients, timelines, data collection and outcomes of treatment immediately (T0) and 1, 6 and 12 weeks after consultation (T1, T2, T3). Inclusion criteria for GPs were: no experience of MT; for patients: adults between 18 and 50 suffering from LBP for less than 14 days. Study process: Patients’ control-group (CG) was consecutively recruited first and received standard care. After GPs received a single training session in MT lasting two and a half hours, they consecutively recruited patients with LBP to the intervention group (IG). These patients received add-on MT. Primary outcomes: (A): timelines and recruitment success, (B): assessment tools and sample size evaluation, (C) clinical findings: pain intensity change from baseline to day 3 and time till (a) analgesic use stopped and (b) 2-point pain reduction on an 11-point scale occurred. Secondary outcomes: functional capacity, referral rate, use of other therapies, sick leave, patient satisfaction. Results 14 GPs participated, recruiting 42 patients for the CG and 45 for the IG; 49% (56%) of patients were women. Average baseline pain was 5.98 points, SD: ±2.3 (5.98, SD ±1.8). For an RCT an extended timeline and enhanced recruitment procedures are required. The assessment tools seem appropriate and provided relevant findings: additional MT led to faster pain reduction. IG showed reduced analgesic use and reduced pain at T1 and improved functional capacity by T2. Conclusions Before verifying the encouraging findings that additional MT may lead to faster pain reduction and reduced analgesic use via an RCT, the setting, patients’ structure, and inclusion criteria should be considered more closely. Trial registration Number: DRKS00003240 Registry: German Clinical Trials Registry (DRKS) URL: https://www.drks.de/drks_web/. Registration date: 14.11.2011. First patient: March 2012. Funding: the Rut and Klaus Bahlsen Stiftung, Hannover

On the Limited Impact of Visualizing Encryption: Perceptions of E2E Messaging Security

Communication tools with end-to-end (E2E) encryption help users maintain their privacy. Although messengers like WhatsApp and Signal bring E2E encryption to a broad audience, past work has documented misconceptions of their security and privacy properties. Through a series of five online studies with 683 total participants, we investigated whether making an app’s E2E encryption more visible improves perceptions of trust, security, and privacy. We first investigated why participants use particular messaging tools, validating a prior finding that many users mistakenly think SMS and e-mail are more secure than E2E-encrypted messengers. We then studied the effect of making E2E encryption more visible in a messaging app. We compared six different text disclosures, three different icons, and three different animations of the encryption process. We found that simple text disclosures that messages are “encrypted” are sufficient. Surprisingly, the icons negatively impacted perceptions. While qualitative responses to the animations showed they successfully conveyed and emphasized “security” and “encryption”, the animations did not significantly impact participants’ quantitative perceptions of the overall trustworthiness, security, and privacy of E2E-encrypted messaging. We confirmed and unpacked this result through a validation study, finding that user perceptions depend more on preconceived expectations and an app’s reputation than visualizations of security mechanisms

Longitudinal Multi-omics Analyses Identify Responses of Megakaryocytes, Erythroid Cells, and Plasmablasts as Hallmarks of Severe COVID-19.

Temporal resolution of cellular features associated with a severe COVID-19 disease trajectory is needed for understanding skewed immune responses and defining predictors of outcome. Here, we performed a longitudinal multi-omics study using a two-center cohort of 14 patients. We analyzed the bulk transcriptome, bulk DNA methylome, and single-cell transcriptome (>358,000 cells, including BCR profiles) of peripheral blood samples harvested from up to 5 time points. Validation was performed in two independent cohorts of COVID-19 patients. Severe COVID-19 was characterized by an increase of proliferating, metabolically hyperactive plasmablasts. Coinciding with critical illness, we also identified an expansion of interferon-activated circulating megakaryocytes and increased erythropoiesis with features of hypoxic signaling. Megakaryocyte- and erythroid-cell-derived co-expression modules were predictive of fatal disease outcome. The study demonstrates broad cellular effects of SARS-CoV-2 infection beyond adaptive immune cells and provides an entry point toward developing biomarkers and targeted treatments of patients with COVID-19