Synthesis of polyurethanes by polycondensation of active biscarbonates of diols with hexamethylenediamine and its derivatives

A new synthesis pathway to polyurethanes (PURs) by polycondensation of active carbonates of diols with hexamethylenediamine was investigated in detail including model studies. It has been shown that high-molecular-weight PURs (η_red ≤ 3,8 dL/g) can be obtained under optimum reaction conditions. Salts of the diamine and its N,N′-trimethyl-silylated derivative were also used for the synthesis of film- and fiber-forming PURs.     

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention – 2022 update

BackgroundA previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments.MethodsThe guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided.ResultsWe found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts’ opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives.ConclusionMonoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-022-01431-x.     

The relationship between headache-attributed disability and lost productivity: 2. Empirical evidence from population-based studies in nine disparate countries

BackgroundHeadache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity.MethodsWe used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses.ResultsFor migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R² (0–0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R² (0.04–0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16–56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant.ConclusionRelief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving.     

Headache associated with ischemic cerebrovascular disease

Headache often accompanies acute ischemic stroke. Observational studies indicate that 15 to 40% of patients with acute ischemic stroke report headache in close temporal relation to the event. The onset headache is more often seen in posterior circulation strokes than in strokes in other vascular territories. Transient ischemic attacks (TIA) can also lead to headache. The pathophysiology of headache associated with acute ischemic stroke includes edema, hemorrhagic transformation, and changes in the trigeminovascular system.     

Patient-conducted anodal transcranial direct current stimulation of the motor cortex alleviates pain in trigeminal neuralgia

Background

Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing.

Methods

Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS.

Results

Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported.

Conclusion

Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.     

The methodology of population surveys of headache prevalence,burden and cost: Principles and recommendations from the Global Campaign against Headache

The global burden of headache is very large, but knowledge of it is far from complete and needs still to be gathered. Published population-based studies have used variable methodology, which has influenced findings and made comparisons difficult. Among the initiatives of the Global Campaign against Headache to improve and standardize methods in use for cross-sectional studies, the most important is the production of consensus-based methodological guidelines. This report describes the development of detailed principles and recommendations. For this purpose we brought together an expert consensus group to include experience and competence in headache epidemiology and/or epidemiology in general and drawn from all six WHO world regions. The recommendations presented are for anyone, of whatever background, with interests in designing, performing, understanding or assessing studies that measure or describe the burden of headache in populations. While aimed principally at researchers whose main interests are in the field of headache, they should also be useful, at least in parts, to those who are expert in public health or epidemiology and wish to extend their interest into the field of headache disorders. Most of all, these recommendations seek to encourage collaborations between specialists in headache disorders and epidemiologists. The focus is on migraine, tension-type headache and medication-overuse headache, but they are not intended to be exclusive to these. The burdens arising from secondary headaches are, in the majority of cases, more correctly attributed to the underlying disorders. Nevertheless, the principles outlined here are relevant for epidemiological studies on secondary headaches, provided that adequate definitions can be not only given but also applied in questionnaires or other survey instruments.     

Influences of smoking and caffeine consumption on trigeminal pain processing

Background

Many human and animal studies have shown the influence of nicotine and caffeine on pain perception and processing. This study aims to investigate whether smoking or caffeine consumption influences trigeminal pain processing.

Methods

Sixty healthy subjects were investigated using simultaneous recordings of the nociceptive blink reflex (nBR) and pain related evoked potentials (PREP) following nociceptive electrical stimulation on both sides of the forehead (V1). Thirty subjects were investigated before and after smoking a cigarette, as well as before and after taking a tablet of 400 mg caffeine.

Results

After smoking PREP showed decreased N2 and P2 latencies indicating central facilitation at supraspinal (thalamic or cortical) level. PREP amplitudes were not changed. NBR showed a decreased area under the curve (AUC) indicating central inhibition at brainstem level. After caffeine intake no significant changes were observed comparing nBR and PREP results before consumption.

Conclusions

Smoking influences trigeminal pain processing on supraspinal and brainstem level. In the investigated setting, caffeine consumption does not significantly alter trigeminal pain processing. This observation might help in the further understanding of the pathophysiology of pain disorders that are associated with excessive smoking habits such as cluster headache. Previous smoking has to be taken into account when performing electrophysiological studies to avoid bias of study results.     

Prevalence of cluster headache in the Republic of Georgia: results of a population-based study and methodological considerations

We present a study of the general-population prevalence of cluster headache in the Republic of Georgia and discuss the advantages and challenges of different methodological approaches. In a community-based survey, specially trained medical residents visited 500 adjacent households in the capital city, Tbilisi, and 300 households in the eastern rural area of Kakheti. They interviewed all ( n  = 1145) biologically unrelated adult occupants using a previously validated questionnaire. The household responses rates were 92% in Tbilisi and 100% in Kakheti. The survey identified 32 persons with possible cluster headache, who were then personally interviewed by one of two headache-experienced neurologists. Cluster headache was confirmed in one subject. The prevalence of cluster headache was therefore estimated to be 87/100 000 (95% confidence interval < 258/100 000). We used a conservative approach, which has an obvious advantage of high-quality data collection, but is very demanding of manpower and time.     

A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds

Healing of poorly vascularized and venous stasis ulcers is often refractory to therapy, particularly when they are infected. Systemic antibiotic therapy may be of little benefit in this setting because of poor penetration of the antibiotic into the wound and the frequent associated emergence of bacterial strains resistant to common antimicrobial agents. Given the clinical significance of these problems, there is a need to explore alternative management approaches for these difficult-to-treat wounds. PhagoBioDerm is a novel wound-healing preparation consisting of a biodegradable polymer impregnated with an antibiotic and lytic bacteriophages, which was recently licensed for sale in the Republic of Georgia (one of the former Soviet Union republics). In 1999-2000, in Tbilisi, Georgia, 107 patients who had ulcers that had failed to respond to conventional therapy were treated with PhagoBioDerm alone or in combination with other interventions. The wounds/ulcers healed completely in 67 (70%) of 96 patients for whom follow-up data were available. In 22 cases in which microbiologic data were available, healing was associated with the concomitant elimination of, or a reduction in, specific pathogenic bacteria in the ulcers. Our findings suggest that this slow-release biopolymer is safe and of possible benefit in the management of refractory wounds, and they support the apparent utility of bacteriophages in this setting. Further studies, including carefully designed clinical trials, will be required to rigorously evaluate the efficacy of this novel wound dressing preparation.