Human Studies

Large-scale procedural safety data on pterygopalatine fossa nerve blocks (PPFB) using a suprazygomatic, ultrasound-guided approach are lacking, leading to hesitancy surrounding this technique. The aim of this study was to characterize the safety of PPFB.

Defined by dysfunction or degeneration of Aδ and C fibers, small fiber neuropathies (SFNs) entail a relevant health burden. In 50% of cases, the underlying cause cannot be identified or treated. In 100 individuals (70% female individuals; mean age: 44.8 years) with an idiopathic, skin biopsy-confirmed SFN, we characterized the symptomatic spectrum and measured markers of oxidative stress (vitamin C, selenium, and glutathione) and inflammation (transforming growth factor beta, tumor necrosis factor alpha), as well as neurotoxic 1-deoxy-sphingolipids. Neuropathic pain was the most abundant symptom (95%) and cause of daily life impairment (72%). Despite the common use of pain killers (64%), the painDETECT questionnaire revealed scores above 13 points in 80% of patients. In the quantitative sensory testing (QST), a dysfunction of Aδ fibers was observed in 70% and of C fibers in 44%, affecting the face, hands, or feet. Despite normal nerve conduction studies, QST revealed Aβ fiber involvement in 46% of patients' test areas. Despite absence of diabetes mellitus or mutations in SPTLC1 or SPTLC2, plasma 1-deoxy-sphingolipids were significantly higher in the sensory loss patient cluster when compared with those in patients with thermal hyperalgesia (P < 0.01) or those in the healthy category (P < 0.1), correlating inversely with the intraepidermal nerve fiber density (1-deoxy-SA: P < 0.05, 1-deoxy-SO: P < 0.01). Patients with arterial hypertension, overweight (body mass index > 25 kg/m2), or hyperlipidemia showed significantly lower L-serine (arterial hypertension: P < 0.01) and higher 1-deoxy-sphingolipid levels (arterial hypertension: P < 0.001, overweight: P < 0.001, hyperlipidemia: P < 0.01). Lower vitamin C levels correlated with functional Aβ involvement (P < 0.05). Reduced glutathione was lower in patients with Aδ dysfunction (P < 0.05). Idiopathic SFNs are heterogeneous. As a new pathomechanism, plasma 1-deoxy-sphingolipids might link the metabolic syndrome with small fiber degeneration.

Conservative treatments for early osteoarthritis (OA) of the knee included the use of non-steroid anti-inflammatory drugs (NSAIDs) and intra-articular hyaluronic acid (HA) injection. Recently, several animal studies reported that extracorporeal shockwave therapy (ESWT) demonstrated chondroprotective effects on knee OA. The present study compared the efficacy of oral NSAIDs, HA injection, and noninvasive ESWT for early OA of the knee. Forty-five patients with early knee OA were randomized into three groups. NSAIDs group received celecoxib 200 mg daily for 3 weeks. HA group received intra-articular injection of HA once a week for 3 weeks. ESWT group received ESWT for 3 sessions at bi-weekly interval. All patients were followed up for one year. Evaluations included the visual analogue scale (VAS) score, serum enzyme-linked immunosorbent assay (ELISA), plain radiography, dual-energy X-ray absorptiometry (DEXA), and magnetic resonance imaging (MRI). In addition, the functional scores were performed including, WOMAC (Western Ontario and McMaster Universities Arthritis Index) score, KOOS (knee injury and osteoarthritis outcome) score, and IKDC (International Knee Documentation Committee) score. All three groups showed significant improvement in VAS and functional scores as well as in the collected one-year follow-up data after treatments. ESWT group had better pain relief than NSAIDs and HA groups. ESWT group had better therapeutic effects in the functional scores than NSAIDs and HA groups. The bone mineral density (BMD) of proximal tibia is significantly increased after ESWT than others. In the serum ELISA, ESWT inhibited the expression of COMP in knee OA patients as compared with NSAIDs and HA groups. The parameters of MRI showed no significant differences between three groups after treatments. ESWT and intra-articular HA injection showed comparable results than NSAIDs. ESWT was superior in pain relief than HA and NSAIDs. The results demonstrated that ESWT was an effective and alternative therapy than HA and NSAIDs for early osteoarthritis of the knees.

The objective of this study was to describe patterns in monthly migraine days (MMD) and tablet utilization, and to estimate health-related quality of life (HRQoL) measures in patients treated as needed (PRN) with rimegepant 75 mg over 52-weeks.

Intravenous immunoglobulin treatment for chronic inflammatory demyelinating polyneuropathy usually starts with a 2.0 g/kg induction dose followed by 1.0 g/kg maintenance doses every 3 weeks. No dose-ranging studies with intravenous immunoglobulin maintenance therapy have been published. The Progress in Chronic Inflammatory Demyelinating polyneuropathy (ProCID) study was a prospective, double-blind, randomised, parallel-group, multicentre, phase III study investigating the efficacy and safety of 10% liquid intravenous immunoglobulin (panzyga®) in patients with active chronic inflammatory demyelinating polyneuropathy. Patients were randomised 1:2:1 to receive the standard intravenous immunoglobulin induction dose and then either 0.5, 1.0 or 2.0 g/kg maintenance doses every 3 weeks. The primary endpoint was the response rate in the 1.0 g/kg group, defined as an improvement ≥ 1 point in adjusted Inflammatory Neuropathy Cause and Treatment score at Week 6 versus baseline and maintained at Week 24. Secondary endpoints included dose response and safety. This trial was registered with EudraCT (Number 2015-005443-14) and clinicaltrials.gov (NCT02638207). Between August 2017 and September 2019, the study enrolled 142 patients. All 142 were included in the safety analyses. As no post infusion data were available for three patients, 139 were included in the efficacy analyses, of whom 121 were previously on corticosteroids. The response rate was 80% (55/69 patients) (95% confidence interval: 69-88%) in the 1.0 g/kg group, 65% (22/34; confidence interval: 48-79%) in the 0.5 g/kg group, and 92% (33/36; confidence interval 78-97%) in the 2.0 g/kg group. While the proportion of responders was higher with higher maintenance doses, logistic regression analysis showed that the effect on response rate was driven by a significant difference between the 0.5 and 2.0 g/kg groups, whereas the response rates in the 0.5 and 2.0 g/kg groups did not differ significantly from the 1.0 g/kg group. Fifty-six percent of all patients had an adjusted Inflammatory Neuropathy Cause and Treatment score improvement 3 weeks after the induction dose alone. Treatment-related adverse events were reported in 16 (45.7%), 32 (46.4%) and 20 (52.6%) patients in the 0.5, 1.0 and 2.0 g/kg dose groups, respectively. The most common adverse reaction was headache. There were no treatment-related deaths. Intravenous immunoglobulin 1.0 g/kg was efficacious and well tolerated as maintenance treatment for patients with chronic inflammatory demyelinating polyneuropathy. Further studies of different maintenance doses of intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy are warranted.