Clinical effects of accreditation in general practice: a pragmatic randomized controlled study.

BACKGROUND: Accreditation has been implemented in general practice in many countries as a tool for quality improvement. Evidence of the effects of accreditation is, however, lacking. AIM: To investigate the clinical effects of accreditation in general practice. DESIGN AND SETTING: A mandatory national accreditation programme in Danish general practice was rolled out from 2016 to 2018. General practices were randomized to year of accreditation at the municipality level. METHODS: We conducted a pragmatic randomized controlled study with general practices randomized to accreditation in 2016 (intervention group) and 2018 (control group). Data on patients enlisted with these practices were collected at baseline in 2014 (before randomization) and at follow-up in 2017. We use linear and logistic regression models to compare differences in changes in outcomes from baseline to follow-up between the intervention and control groups. The primary outcome was the number of redeemed medications. Secondary outcomes were polypharmacy, nonsteroidal anti-inflammatory drugs (NSAIDs) without proton pump inhibitors, sleeping medicine, preventive home visits, annual controls, spirometry tests, and mortality. RESULTS: We found statistically significant effects of accreditation on the primary outcome, the number of redeemed medications, and the secondary outcome, polypharmacy. No other effects were detected. CONCLUSION: In this first randomized study exploring the effects of accreditation in a primary care context, accreditation was found to reduce the number of redeemed medications and polypharmacy. We conclude that accreditation can be effective in changing behaviour, but the identified effects are small and limited to certain outcomes. Evaluations on the cost-effectiveness of accreditation are therefore warranted.

Clinical effects of combined use of carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot.

OBJECTIVE: This study aims to analyze the clinical effects of combining carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot. METHODS: A total of 120 diabetic neuropathy patients treated at our hospital from June 2022 to November 2023 were included in the study. Patients meeting the inclusion criteria were registered, and their basic data were collected. The patients were randomly divided into two groups: the control group treated with amitriptyline and the study group treated with a combination of carbamazepine and amitriptyline. RESULTS: The study group demonstrated significantly better clinical efficacy compared to the control group (p < 0.05). There were no significant differences in psychological status and pain perception before treatment between the two groups (p > 0.05). However, post-treatment, the study group showed improved psychological status, reduced pain perception, and overall better quality of life in both physiological and psychological dimensions compared to the control group (p < 0.05). CONCLUSION: The combined use of carbamazepine and amitriptyline in the treatment of diabetic neuropathy with concurrent diabetic foot yields positive clinical outcomes. It effectively alleviates symptoms, improves psychological well-being, reduces pain sensation, and enhances overall quality of life. These findings can guide physicians in adopting a more evidence-based treatment approach and provide patients with more effective individualized treatment strategies.

Clinical effect of qingre bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease.

OBJECTIVE: To assess the clinical effect of Qingre Bawei capsules combined with budesonide in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: The retrospective study was conducted at the Baoding No.1 Central Hospital, China, and comprised data of patients with acute exacerbation of COPD admitted between June 1, 2020, and June 30, 2022. The patients were divided into two groups based on treatment methods. The group A had been treated with Qingre Bawei capsules in combination with budesonide, while the group B had been treated with budesonide alone. Both the groups had been treated for 2 consecutive weeks. The changes in blood gas indicators, inflammation indicators, and lung function indicators were compared between two groups of patients before and 24 hours after treatment. The time for clinical symptom disappearance and adverse reactions between the two groups of patients was also noted. RESULTS: Of the 120 patients, 60(50%) were in group A; 41(68.3%) males and 19(31.7%) females, with mean age 65.28±4.36 years (range: 47-78 years) and mean course of disease 31.22±4.75 hours (range: 6-65 hours). 60(50%) patients were in group B; 43(71.7%) males and 17(28.3%) females with mean age 65.31±4.31 years (range: 48-78 years) and mean course of disease 31.29±4.71 hours (range: 8-68 hours). The disappearance time of clinical symptoms in group A was better than group B (p<0.05). The levels of blood gas indicators, inflammation indicators, and lung function indicators in both groups significantly improved (p<0.05), but the degree of improvement in group A was better than group B (p<0.05); The total effective rate of group A was better than group B (p<0.05). None of the patients in either group experienced any significant adverse reaction. CONCLUSIONS: Qingre Bawei capsules combined with budesonide had a significantly better therapeutic effect on cases of acute exacerbation of chronic obstructive pulmonary disease compared to budesonide alone.

Age-stratified analysis of HTO and UKA clinical effects in cross-indicated anterior medial osteoarthritis.

PURPOSE: To compare clinical outcomes of high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) for anterior medial osteoarthritis (AMOA) as well as offer surgical recommendations through age stratification. METHODS: Between May 2019 and May 2021, 68 cross-indicated AMOA patients were analyzed. The patients were divided into HTO and UKA groups and further into two age groups of 55-60 and 60-65 years. Additionally, general data, visual analog scale (VAS) score, and Hospital for Special Surgery knee score (HSS) were analyzed. RESULTS: All the patients were followed up for 18 months. Knee joint HSS significantly improved, and VAS score decreased in both groups (P < 0.05). In the 55-60 age group, HTO showed superior knee HSS at 1 and 3 months (P < 0.05), with no significant difference at 6, 12, and 18 months. HTO had a significantly lower VAS score at one month, and the VAS scores of the two groups decreased gradually with no significant difference. In the 60-65 age group, the UKA group showed superior knee joint HSS at one month, with no significant difference at 3, 6, 12, and 18 months. The UKA group had a significantly lower VAS score at one month, and both groups' VAS scores decreased gradually with no significant difference. CONCLUSION: Both methods yield satisfactory results for AMOA cross-indications, improving knee joint function. The observed recovery trends have implications for personalized surgical recommendations, guiding interventions based on age-specific considerations for optimal outcomes in anterior medial osteoarthritis cases.

Imaging the effective networks associated with cortical function through intracranial high-frequency stimulation.

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug-resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug-resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high-frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency-domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect's network. By using standard intersubject averaging and a fine granularity HCP-MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.

Clinical and radiological evaluation of cage subsidence following oblique lumbar interbody fusion combined with anterolateral fixation.

BACKGROUND: Cage subsidence (CS) was previously reported as one of the most common complications following oblique lumbar interbody fusion (OLIF). We aimed to assess the impacts of CS on surgical results following OLIF combined with anterolateral fixation, and determine its radiological characteristics as well as related risk factors. METHODS: Two hundred and forty-two patients who underwent OLIF at L4-5 and with a minimum 12 months follow-up were reviewed. Patients were divided into three groups according to the extent of disk height (DH) decrease during follow-up: no CS (DH decrease ≤ 2 mm), mild CS (2 mm < DH decrease ≤ 4 mm) and severe CS (DH decrease > 4 mm). The clinical and radiological results were compared between groups to evaluate radiological features, clinical effects and risk factors of CS. RESULTS: CS was identified in 79 (32.6%) patients, including 48 (19.8%) with mild CS and 31 (11.8%) with severe CS. CS was mainly identified within 1 month postoperatively, it did not progress after 3 months postoperatively, and more noted in the caudal endplate (44, 55.7%). In terms of clinical results, patients in the mild CS group were significantly worse than those in the no CS group, and patients in the severe CS group were significantly worse than those in the mild CS group. There was no significant difference in fusion rate between no CS (92.6%, 151/163) and mild CS (83.3%, 40/48) groups. However, significant lower fusion rate was observed in severe CS group (64.5%, 20/31) compared to no CS group. CS related risk factors included osteoporosis (OR = 5.976), DH overdistraction (OR = 1.175), flat disk space (OR = 3.309) and endplate injury (OR = 6.135). CONCLUSION: CS following OLIF was an early postoperative complication. Higher magnitudes of CS were associated with worse clinical improvements and lower intervertebral fusion. Osteoporosis and endplate injury were significant risk factors for CS. Additionally, flat disk space and DH over-distraction were also correlated with an increased probability of CS.

The potential of training specialist oncology nurses in real-life reporting of adverse drug reactions.

Specialist oncology nurses (SONs) have the potential to play a major role in monitoring and reporting adverse drug reactions (ADRs); and reduce the level of underreporting by current healthcare professionals. The aim of this study was to investigate the long term clinical and educational effects of real-life pharmacovigilance education intervention for SONs on ADR reporting. This prospective cohort study, with a 2-year follow-up, was carried out in the three postgraduate schools in the Netherlands. In one of the schools, the prescribing qualification course was expanded to include a lecture on pharmacovigilance, an ADR reporting assignment, and group discussion of self-reported ADRs (intervention). The clinical value of the intervention was assessed by analyzing the quantity and quality of ADR-reports sent to the Netherlands Pharmacovigilance Center Lareb, up to 2 years after the course and by evaluating the competences regarding pharmacovigilance of SONs annually. Eighty-eight SONs (78% of all SONs with a prescribing qualification in the Netherlands) were included. During the study, 82 ADRs were reported by the intervention group and 0 by the control group. This made the intervention group 105 times more likely to report an ADR after the course than an average nurse in the Netherlands. This is the first study to show a significant and relevant increase in the number of well-documented ADR reports after a single educational intervention. The real-life pharmacovigilance educational intervention also resulted in a long-term increase in pharmacovigilance competence. We recommend implementing real-life, context- and problem-based pharmacovigilance learning assignments in all healthcare curricula.

Flavin-containing monooxygenase 3 (FMO3): genetic variants and their consequences for drug metabolism and disease.

The review focuses on genetic variants of human flavin-containing monooxygenase 3 (FMO3) and their impact on enzyme activity, drug metabolism and disease.The majority of FMO-mediated metabolism in adult human liver is catalyzed by FMO3. Some drugs are metabolized in human liver predominantly by FMO3, but most drug substrates of FMO3 are metabolized also by other enzymes, particularly cytochromes P-450, and the FMO3-catalyzed reaction is not the major route of metabolism.Rare variants that severely affect production or activity of FMO3 cause the disorder trimethylaminuria and impair metabolism of drug substrates of FMO3. More common variants, particularly p.[(Glu158Lys);(Glu308Gly)], can moderately affect activity of FMO3 in vitro and reduce metabolism of drug substrates in vivo, in some cases increasing drug efficacy or toxicity.Common variants of FMO3 have been associated with a number of disorders, but additional studies are needed to confirm or refute such associations.Elevated plasma concentrations of trimethylamine N-oxide, a product of an FMO3-catalyzed reaction, have been implicated in certain diseases, particularly cardiovascular disease. However, the evidence is often contradictory and additional work is required to establish whether trimethylamine N-oxide is a cause, effect or biomarker of the disease.Genetic variants of other FMOs are also briefly discussed.

Robotic, laparoscopic or open hemihepatectomy for giant liver haemangiomas over 10 cm in diameter.

BACKGROUND: To evaluate the clinical efficacy of robotic, laparoscopic, and open hemihepatectomy for giant liver haemangiomas. METHODS: From April 2011 to April 2017, consecutive patients who underwent hemihepatectomy for giant liver haemangiomas were included in this study. According to the type of operation, these patients were divided into the robotic hemihepatectomy (RH) group, the laparoscopic hemihepatectomy (LH) group, and the open hemihepatectomy (OH) group. The perioperative and short-term postoperative outcomes were compared among the three groups. The study was reported following the STROCSS criteria. RESULTS: There were no significant differences in age, sex, tumour location, body surface area (BSA), future liver remnant volume (FLR), standard liver volume (SLV), liver haemangioma volume, FLR/SLV, resected normal liver volume/resected volume, hepatic disease, rates of blood transfusion, liver function after 24 h of surgery, operative morbidity and mortality among the three groups. Compared with patients in the RH group (n = 19) and the LH group (n = 13), patients in the OH group (n = 25) had a significantly longer postoperative hospital stay (P < 0.05), time to oral intake (P < 0.05), and time to get-out-of-bed (P < 0.05); a higher VAS score after 24 h of surgery (P < 0.05); and a shorter operative time (P < 0.05). There were no significant differences in these postoperative outcomes (P>0.05) between the RH group and the LH group. When the setup time in the RH group was excluded, the operative time in the RH group was significantly shorter than that in the LH group (P<0.05). There was no significant difference in the operative time between the RH group and the OH group (P>0.05). The amount of intraoperative blood loss in the RH group was the lowest among the three groups (P<0.05), and the amount of intraoperative blood loss in the LH group was less than that in the OH group (P<0.05). CONCLUSION: Robotic and laparoscopic hemihepatectomies were associated with less intraoperative blood loss,better postoperative recovery and lower pain score. Compared with laparoscopic hemihepatectomy, robotic hemihepatectomy was associated with significantly less intraoperative blood loss and a shorter operative time.

A blinded, randomized, placebo-controlled trial of the safety of oclacitinib in cats.

BACKGROUND: Oclacitinib is a Janus kinase (JAK) 1 enzyme inhibitor and blocks JAK1-dependent cytokines and is used to control pruritus. Studies available in cats are very limited and as there is a potential role for oclacitinib in the control of pruritus in this specie, the aim of this study was to evaluate the safety and clinical effects of oral oclacitinib maleate in healthy cats. RESULTS: Thirty mixed-breed cats weighing from 2.1 to 5.3 kg each were randomly allocated to three treatment groups of 10 animals each. Cats in two groups received oclacitinib at 1 mg/kg or 2 mg/kg q 12 h orally for 28 days. Cats in the third group were given placebo tablets (cornstarch) q 12 h orally for 28 days. Oclacitinib maleate was well tolerated during the study and few adverse events were observed in treated cats. Clinical signs of toxicity were not observed in any animals treated at 1 mg/kg. Gastrointestinal clinical signs observed in the 2 mg/kg group included vomiting in two of the 10 cats and soft stools in two cats. One cat treated with placebo also exhibited soft stools. No significant differences were observed between the groups for hematologic analyses performed during the study. There was a slight increase in neutrophils and monocytes and a decrease in eosinophil mean counts in treated cats. Mean renal and liver enzymes remained normal throughout the entire study. A small, but significant increase in fructosamine levels was observed for both treated groups compared with placebo; however, values remained within the normal reference range. There were no significant difference between treated groups and the placebo group for urine specific gravity, pH, or urine protein to creatinine ratio mean values. CONCLUSIONS: Oclacitinib maleate was well tolerated by cats at 1 mg/kg and 2 mg/kg and appeared to be safe for this species when administered orally twice daily for 28 days. More studies would be needed to demonstrate if oclacitinib maleate may be a suitable alternative to treat pruritic cats.

Medical aromatherapy revisited-Basic mechanisms, critique, and a new development.

OBJECTIVE: According to a series of recent meta-analyses and systematic reviews, aromatherapy has shown to be effective in treating patients with different medical conditions. However, many of the clinical studies are of rather low methodological quality. Moreover, there is much conceptual ambiguity with regard to what aromatherapy actually constitutes. METHOD: In this paper, we discuss the conditions under which aromatherapy is most likely to be of medical value by outlining the workings of the olfactory system and the necessary requirements of odors to be therapeutic. We then introduce an aromatherapeutic inhaler that was tested in a series of studies involving 465 participants. RESULTS: This inhaler (AromaStick®) produced large to very large effects across a variety of physiological target systems (e.g., cardiovascular, endocrine, blood oxygenation, and pain), both short term and long term. DISCUSSION: Inhalation of volatile compounds from essential oils yields almost immediate, large, and clinically relevant effects as long as the scents are delivered highly concentrated from an appropriate device. The changes caused in the body seem side effect-free and can be sustained when inhalation is repeated.

Long-Term Efficacy of Deep Brain Stimulation of Bilateral Globus Pallidus Internus in Primary Meige Syndrome.

OBJECTIVE: Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) is an alternative therapy in ameliorating the clinical symptoms of primary Meige syndrome. Nevertheless, proof of its efficacy and safety is insufficient due to several case reports and small-sample clinical studies. This study aims to investigate postoperative long-term efficacy in patients undergoing DBS of the GPi for primary Meige syndrome. METHODS: We performed a retrospective study to assess the efficacy and safety of bilateral GPi stimulation in 40 patients with primary Meige syndrome who responded poorly to medical treatments or botulinum toxin injections. All participants were postoperatively followed up at the outpatient clinic, and their motor functions were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The severity of patients' dystonia was evaluated before surgery and at follow-up neurostimu-lation. RESULTS: The implanted stimulator was turned on 1 month after surgery. All 40 patients received monopolar stimulation using the following parameters: voltage 2.5-3.5 V (average: 2.6 ± 0.8 V), frequency 60-160 Hz (average: 88.0 ± 21.3 Hz), and pulse width 60-185 µS (average: 90.0 ± 21.1 µS). In 28 of 40 patients, the symptoms had signifi-cantly improved within 1 week of stimulation. Most of the patients had been followed up for 6-24 months (average: 15.0 ± 7.8 months). The clinical symptoms of all patients had significantly improved. At 6, 12, and 24 months after surgery, the BFMDRS subscores of eyes, mouth, speech, and swallowing were significantly lower, and subscores of mouth movement showed progressively decreased with prolonged stimulation time. The overall improvement rate was 83%. Five adverse events occurred in the 40 patients; all of these events resolved without permanent sequelae. CONCLUSIONS: Bilateral GPi-DBS demonstrated satisfactory long-term efficacy in the treatment of primary Meige syndrome and could serve as an effective and safe option.

[Effects of physeal bar resection in treating post-traumatic distal radius partial physeal arrest].

Objective: To evaluate the effects of treatment of post-traumatic distal radius partial physeal arrest with physeal bar resection. Methods: From February 2007 to November 2017, 11 children with distal radius physeal arrest received physeal bar resection in the Department of Pediatric Orthopedics, Beijing Jishuitan Hospital. There were 2 females and 9 males. The average age of the patients was (10.1±1.8) years (range,7-13 years). All cases had previous history of distal radius trauma. The average duration from the previous fracture to the physeal bar resection operation was (22.8±3.2) months (range,22 to 41 months). Clinical and radiological evidence of distal radius physeal arrest were suggested in all patients. A CT or MRI scan was performed preoperatively to assess the size of the physeal bridge. Inclusion criteria were patients with a physeal bridge<30% of the physeal area,and with at least 2 years of growth remaining. The physeal bar resection operation was performed with the assistance of either fluoroscopy (5 cases) or intraoperative three dimensional navigation (6 cases). After resection, the void was then filled with bone wax in all cases and distal ulnar epiphysiodesis was conducted in 5 cases. The mean follow-up duration was (3.7±1.6) years (range,1-9 years). The clinical examination data and X ray were obtained during the follow up. Results: Four cases obtained fully recovery from the operation and the deformity got fully correction. The X ray showed no bone bridge recurred. The deformity did not aggravate in 1 case. The deformity aggravated and subsequent osteotomy was conducted in the left 6 cases. Three cases in the navigation group obtained fully recovery. One case in the fluoroscopy group obtained fully recovery. Conclusions: The intraoperative three dimensional navigation can precisely locate the bone bridge. The physeal bar resection is an effective technique in some post-traumatic distal radius partial physeal arrest.

[Efficacy and safety of Anlotinib as a third-line chemotherapy for metastatic colorectal cancer].

Objective: To evaluate the efficacy and safety of Anlotinib as a third-line therapy in patients with metastatic colorectal cancer. Methods: Anlotinib was administered to patients with advanced colorectal cancer who had received ≥ second-line standardized treatment, with 12 mg daily lasting for 2 weeks and withdrawal of drugs for a week. The relevant clinical information and treatment protocols were recorded.The efficacy and safety of anlotinib were followed up. Results: A total of 26 patients were enrolled in the study group, and 24 patients could be evaluated, including 2 cases of partial response (PR) and 16 cases of stable disease (SD).The object response rate (ORR) and disease control rate (DCR) were 8.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 4.3 months (95% CI: 2.9-5.7 months) and 14.7 months (95% CI: 10.0-19.4 months), respectively. The most common adverse reactions were fatigue in 17 cases (17/26) and hand-foot skin reactions in 16 cases (16/26). Analysis of Kaplan-Meier revealed that without liver metastasis (95% CI: 11.7-32.3, P=0.011) and left-sided colonic cancer (95% CI: 11.7-46.1, P=0.014) were related to longer OS. Conclusion: Anlotinib as a third-line therapy for advanced colorectal cancer is feasible with high disease control rate and minor side effects.

[Detrusor ischemia. linical effects].

Three basic theories of the development of an overactive bladder that have experimental and clinical evidences have been described, including neurogenic, myogenic, and urothelial. Based on the results of the literature analysis, the authors suggested the existence of detrusor ischemic disease as a result of compressive impairment of its blood flow due to incomplete or short-term relaxation under overactivity or hydraulic compression of the vessels by excessive urine volume in case of hypoactive bladder.

Recreational use, analysis and toxicity of tryptamines.

UNLABELLED: The definition New psychoactive substances (NPS) refers to emerging drugs whose chemical structures are similar to other psychoactive compounds but not identical, representing a "legal" alternative to internationally controlled drugs. There are many categories of NPS, such as synthetic cannabinoids, synthetic cathinones, phenylethylamines, piperazines, ketamine derivatives and tryptamines. Tryptamines are naturally occurring compounds, which can derive from the amino acid tryptophan by several biosynthetic pathways: their structure is a combination of a benzene ring and a pyrrole ring, with the addition of a 2-carbon side chain. Tryptamines include serotonin and melatonin as well as other compounds known for their hallucinogenic properties, such as psilocybin in 'Magic mushrooms' and dimethyltryptamine (DMT) in Ayahuasca brews. AIM: To review the scientific literature regarding tryptamines and their derivatives, providing a summary of all the available information about the structure of these compounds, their effects in relationship with the routes of administration, their pharmacology and toxicity, including articles reporting cases of death related to intake of these substances. METHODS: A comprehensive review of the published scientific literature was performed, using also non peer-reviewed information sources, such as books, government publications and drug user web fora. CONCLUSIONS: Information from Internet and from published scientific literature, organized in the way we proposed in this review, provides an effective tool for specialists facing the emerging NPS threat to public health and public security, including the personnel working in Emergency Department.

Short-term persistence of oculomotor rehabilitative changes in mild traumatic brain injury (mTBI): A pilot study of clinical effects.

PRIMARY OBJECTIVE: In our earlier published studies, oculomotor therapy (OMT) was performed in 15 individuals with mild traumatic brain injury (mTBI) and over 90% of the clinical oculomotor parameters abnormal at baseline significantly improved immediately following the OMT. There was no placebo (P) effect on any of the parameters. The purpose of the present pilot study was to assess the short-term persistence of the previously obtained positive OMT findings. RESEARCH DESIGN: Upon completion of the OMT, clinical oculomotor parameters were re-assessed at 3-month and 6-month periods. No subsequent training was performed during this 6-month period. METHODS AND PROCEDURES: Clinical measures were repeated in eight of the 15 subjects who subsequently completed both the 3-month and 6-month follow-up assessments. All measures were assessed using conventional clinical testing methods. MAIN OUTCOMES AND RESULTS: Eight of the 13 (62%) clinical oculomotor parameters exhibited either persistence of, or delayed, improvement at the 3 and 6 month follow-up intervals. CONCLUSIONS: Findings demonstrate both the presence and persistence of oculomotor-based changes, suggestive of neural plasticity even in the adult, compromised brain. Further studies are warranted to confirm and extend the present pilot findings.

Congenital analbuminaemia: molecular defects and biochemical and clinical aspects.

BACKGROUND: DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA). SCOPE OF REVIEW: To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA. MAJOR CONCLUSIONS: CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases. GENERAL SIGNIFICANCE: Study of the defects in the ALB resulting in CAA allows the identification of "hot spot" regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin.

The many roles of statins in ischemic stroke.

Stroke is the third leading cause of human death. Endothelial dysfunction, thrombogenesis, inflammatory and oxidative stress damage, and angiogenesis play an important role in cerebral ischemic pathogenesis and represent a target for prevention and treatment. Statins have been found to improve endothelial function, modulate thrombogenesis, attenuate inflammatory and oxidative stress damage, and facilitate angiogenesis far beyond lowering cholesterol levels. Statins have also been proved to significantly decrease cardiovascular risk and to improve clinical outcome. Could statins be the new candidate agent for the prevention and therapy in ischemic stroke? In recent years, a vast expansion in the understanding of the pathophysiology of ischemic stroke and the pleiotropic effects of statins has occurred and clinical trials involving statins for the prevention and treatment of ischemic stroke have begun. These facts force us to revisit ischemic stroke and consider new strategies for prevention and treatment. Here, we survey the important developments in the non-lipid dependent pleiotropic effects and clinical effects of statins in ischemic stroke.

The Effect of Physical Therapy on Somatosensory Tinnitus.

Objective: The objective of this work was to assess the effect of physical therapy in patients with somatosensory tinnitus (ST) and explore the influence of physical therapy on clinical variables obtained before treatment. Methods: A total of 43 patients with ST were randomized to the immediate-start group (n = 20) and delayed-start group (n = 23). All patients received physical therapy for 1 week (seven sessions). Each session lasted 60 min. The Visual Analogue Scale (VAS), Tinnitus Handicap Inventory (THI), and numerical pain rating scale (NPRS) scores were documented at baseline and after treatment (week 1) for all patients. For subjects in the immediate-start group, the THI, VAS, and NPRS scores were measured after therapy (weeks 6, 9, and 12, respectively). Medical history characteristic functional activity scale (HCFA) scores were measured at baseline to assess the association between somatic symptoms and tinnitus. Results: At week 1, VAS, THI, and NPRS scores of patients in the immediate-start group were improved by 1.25 ± 1.59, 11.10 ± 15.10, and 0.95 ± 1.54 points, respectively, and were significantly higher than those in the delayed-start group (p < 0.05). The change in VAS, THI, and NPRS scores in the treatment group was significantly positively correlated with the scores of the HCFA before treatment (r = 0.786, p < 0.001; r = 0.680, p = 0.001; r = 0.796, p < 0.001). There was no significant difference in THI, VAS, and NPRS scores among patients in the immediate-start group between weeks 1, 6, 9, and 12 after treatment (p > 0.05). Conclusions: Although more participants were necessary in the further study, the study implies that physical therapy can reduce physical pain, improve tinnitus symptoms, and quality of life in ST patients without hearing loss, and the short-term curative effect is stable, especially for tinnitus patients with clear somatic symptoms.