Regulatory framework of pharmaceutical compounding and actual developments of legislation in Europe

Pharmaceutical preparations are medicines that the pharmacist makes for the special needs of the patients that the pharmaceutical industry cannot comply for economic and logistic reasons. Pharmacy compounding is still an important component of pharmacy practice and a valuable therapeutical service that is an integrant part of the modern health care system, but its legislation is not harmonized among European and US countries.     

Reversed laterality of cerebral functions in a non-right-hander: neuropsychological and spect findings in a case of 'atypical' dominance.

A 54-year-old non-right-handed man with positive familial sinistrality showed a pure right hemisphere syndrome following a left hemisphere stroke. Severe right side hemineglect, transcortical motor dysprosodia, spatial dysgraphia and visuo-constructive impairments were observed. At no time were the expected left hemisphere abnormalities such as aphasia, alexia, right-left disorientation or finger agnosia noted. A left fronto-temporal subcortical lesion was documented on CT scan. A Tc-99m HM-PAO SPECT study revealed no cerebral blood flow changes in the right hemisphere while in the left hemisphere a fronto-temporo-parietal cerebral blood flow reduction was evident. This case of a complete reversed laterality of cognitive functions argues for a distinction to be made between 'anomalous' cerebral dominance and 'atypical' cerebral dominance.     

Diffusion tensor imaging and tractography to evaluate sacral nerve root abnormalities in endometriosis-related pain: A pilot study

Objective

To prospectively evaluate microstructural abnormalities in sacral nerve roots in women affected by chronic pelvic pain associated with endometriosis.

Methods

We enrolled 30 women with an ultrasound diagnosis of endometriosis and moderate-severe chronic pelvic pain; 10 age-matched healthy women comprised the control group. All subjects underwent 3 T magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI); the sacral roots were reconstructed by post-processing the DTI data with dedicated software. Mean fractional anisotropy (FA) values in the S1, S2 and S3 roots were quantified. Analysis of FA values was performed by two radiologists in order to evaluate the interobserver agreement.

Results

The sacral nerve roots in healthy subjects were clearly visualised. Most of the patients with endometriosis displayed abnormalities of S1, S2 and S3 bilaterally at tractography, including an irregular and disorganised appearance. FA values in the S1, S2 and S3 roots were significantly lower in patients than in controls (P?<?0.0001, <0.05 and <0.02, respectively) for both observers. No significant difference was found between observers.

Conclusion

DTI with tractography is a non-invasive means of detecting changes in the microarchitecture of the sacral nerve roots. It can qualitatively and quantitatively reveal sacral root abnormalities in patients with endometriosis-associated pain.

Key Points

? MRI is increasingly used for endometriosis and chronic pelvic pain (CPP). ? Magnetic resonance tractography can demonstrate microarchitectural abnormalities in sacral nerve roots. ? Tractography shows altered microstructure of sacral roots affected by endometriosis and CPP. ? S1–S3 fractional anisotropy values are lower in endometriosis than in healthy women. ? Sacral nerve root alteration may explain the nature of endometriosis-related CPP.     

Fatal self administration of tramadol and propofol: A case report

We describe a case of unintentional intoxication due to tramadol and propofol self administration, occurred in a middle aged man, healthcare provider, deceased despite advanced medical assistance an hour later the onset of severe and increasing dyspnea. Toxicological analysis performed with gas chromatography-mass spectrometry in blood sample, evidenced a lethal tramadol concentration and therapeutic level of Propofol. Quantitative determination was also performed in other specimens such as bile, tissues (liver, spleen, kidney) and pubic hair, to assess chronic exposure. Toxicological results and autopsy findings, supported by clinical and hematochemical data, suggested a myocardial damage, associated with respiratory failure.     

New targets, new drugs for metastatic bone pain: a new philosophy

Bone pain is a common symptom in bone metastases. The therapies that are currently available include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, steroids and gabapentin which have been demonstrated to improve neuropathic pain. In addition, preclinical studies indicate that agents such as transient receptor potential vanilloid 1 antagonists and cannabinoid 2 receptor agonist could be considered as adjuncts in ameliorating opioid side effects. New drugs are in the clinical phase of development, among which the most promising molecules seem to be anti-nerve growth factor (NGF) antibodies. Anti-NGF antibody therapy may be particularly effective in blocking bone cancer pain because NGF appears to be integrally involved in the upregulation, sensitization and disinhibition of multiple neurotransmitters, ion channels and receptors in the primary afferent nerve. The best way to treat bone metastases pain is to improve the control of skeletal disease burden. Recently, denosumab, a noncytotoxic IgG2 monoclonal antibody with high affinity for human RANKL, has been demonstrated to significantly prevent clinically relevant increase in pain compared with zoledronic acid across the tumor types. Based on these data, it has been suggested that denosumab has the potential to become a new standard of treatment in bone metastases management.     

Polyclonal and monoclonal B lymphocytes response in HCV‐infected patients treated with direct‐acting antiviral agents

Hepatitis C virus (HCV) chronic infection can be associated with extrahepatic manifestations such as mixed cryoglobulinaemia and lymphoproliferative disorders that are endowed with increased rates of morbidity and all‐cause mortality. In this study, we used flow cytometry to evaluate the effect of interferon‐free antiviral treatment on peripheral blood lymphocytes in HCV‐infected patients with or without associated lymphoproliferative disorders. Flow cytometry analysis of peripheral blood lymphocytes was performed at baseline and at the end of treatment. In HCV‐infected patients with lymphoproliferative disorders, we evaluated immunoglobulin (Ig) light chain κ/λ ratio variations as a measure of monoclonal B‐cell response to antiviral therapy. Healthy volunteers were enrolled as controls. A total of 29 patients were included, nine with and 20 without lymphoproliferative disorders. Sustained virological response was achieved in 29 of 29 patients. We observed a significant reduction in the B‐cell compartment (39% global reduction) in eight of nine HCV‐infected patients with lymphoproliferative disorders after viral clearance. We recognized the same trend, even if less pronounced, in HCV‐infected patients without lymphoproliferative disorders (9% global reduction). Among HCV‐infected patients with lymphoproliferative disorders, three showed an improvement/normalization of the immunoglobulin light chain ratio, whereas in the remaining six patients monoclonal B cells persisted to be clonally restricted even 1 year after the end of treatment. Our data show that DAAs treatment can be effective in reducing the frequency of pathological B cells in the peripheral blood of HCV‐infected patients affected by HCV‐associated lymphoproliferative disorders; however, monoclonal populations can persist after viral eradication.     

MRI quality control for the Italian Neuroimaging Network Initiative: moving towards big data in multiple sclerosis

Journal of Neurology - The Italian Neuroimaging Network Initiative (INNI) supports the creation of a repository, where MRI, clinical, and neuropsychological data from multiple sclerosis (MS)...     

Inhibition is impaired in children with obsessive‐compulsive symptoms but not in those with tics

Background : Impaired inhibitory control is thought to be a core deficit in psychiatric disorders where patients exhibit problems with controlling urges. These problems include the urge to perform movements typical of Tourette syndrome and the urge to execute compulsive actions typical of obsessive‐compulsive disorder. However, the picture emerging from studies that address this issue is controversial. Furthermore, most studies have only focused on reactive control (the ability of subjects to react to a stop signal), but not on proactive control (the ability of patients to shape their response strategies in anticipation of known task demands). Objectives : We assessed reactive and proactive inhibitory control in drug naïve children/adolescents affected by Tourette syndrome, obsessive‐compulsive disorder, and in those in which the 2 disorders co‐occur. Methods : Reaching version of the stop signal task and of a simple reaction time task were given to 37 unmedicated patients (mean age ± SD, 11.0 ± 2.3) and to 37 healthy age‐ and gender‐matched controls (mean age ± SD, 10.8 ± 1.6). Results : Both reactive and proactive inhibition scaled with the severity of obsessive‐compulsive symptoms, but not with those of tic symptoms (ie, inhibitory control in uncomplicated Tourette patients was comparable with that of healthy controls). Conclusions : We suggest that the cognitive mechanisms underlying tics and compulsions controls are likely to be different. Possibly the preserved ability to suppress actions in uncomplicated Tourette patients allows them to experience a greater feeling of self‐control, and this fact might play a key role in evolution of the disorder beyond adolescence. © 2018 International Parkinson and Movement Disorder Society