A registry based analysis of the patient reported outcome after surgery for trapeziometacarpal joint osteoarthritis.

BACKGROUND: The aim of the study was to evaluate patient reported outcome measures (PROM) before and after trapeziectomy with or without ligament reconstruction and tendon interposition for trapeziometacarpal joint arthritis with special focus on possible differences due to gender, age and surgical method. METHODS: Data from the Swedish quality registry for hand surgery (HAKIR) was analyzed preoperatively, 3 months and 1 year postoperatively for 1850 patients (mean age 63 years, 79% women). RESULTS: One year postoperatively, mean pain at rest was reduced from 50 to 12 of maximum 100. However, pain on load and weakness had not abated to the same extent (mean 30 and 34 of 100, respectively). The mean improvement in PROM did not differ between age groups or gender. The result was similar after trapeziectomy with ligament reconstruction and tendon interposition (86% of the patients) and simple trapeziectomy but few patients were operated with the latter method. CONCLUSION: Pain on load and weakness remains to some extent 1 year after surgery for trapeziometacarpal joint arthritis. The result is similar after trapeziectomy with or without ligament reconstruction and tendon interposition and the same improvement can be expected after surgery regardless of age and gender.

A clinical and microbiological study on the enantiomers of delmopinol.

Objective The clinical part of this study aimed to investigate whether the racemate of delmopinol [(±)-delmopinol] is equivalent to its two enantiomers [(+)-delmopinol and (-)-delmopinol] with respect to efficiency and to determine and compare their pharmacokinetic properties. The purpose of the pre-clinical part was to elucidate possible differences in antimicrobial efficiency. Materials and methods The compounds were tested clinically in a double-blind, randomized, cross-over study comprising three treatment periods of 4 days each. The antimicrobial efficacy of the enantiomers was compared in vitro with respect to planktonic and biofilm bacteria of different species. Results No statistically significant differences in prevention of plaque formation were observed. Except for a somewhat higher systemic exposure in terms of AUC and Cmax indicated for (-)-delmopinol compared to (+)-delmopinol, the pharmacokinetic properties were similar. The most common adverse event was a transient anaesthetic feeling in the mouth. This event was reported with the same frequency for all three test solutions. The enantiomers showed similar antimicrobial effects on planktonic bacteria and their biofilms. Conclusions The enantiomers were found to be equally effective with respect to inhibition of plaque development and only minor differences were observed with respect to their pharmacokinetic properties. No differences could be observed in the adverse events reports. There is, therefore, no reason to use one of the enantiomers of delmopinol instead of the racemate. This was further supported by the antimicrobial tests. It is suggested that the combined action of cationic and neutral delmopinol is important for its effect on biofilms.

Effects of probiotic supplementation on testosterone levels in healthy ageing men: A 12-week double-blind, placebo-controlled randomized clinical trial.

Levels of the male sex hormone testosterone are generally stable in the age interval 20-70 years, but several studies indicate an earlier, age-dependent decline. Testosterone deficiency is often underdiagnosed and under-treated, but replacement therapy has nonetheless increased during the last couple of years. Owing to possible negative side effects, alternative treatments have been investigated, including different supplementation protocols. The aim of this study was to investigate the effect of probiotic supplementation on the testosterone level in healthy men aged between 55 and 65. Hence, 12 weeks randomized, double-blinded, placebo-controlled trial was conducted to investigate the effect on testosterone levels following supplementation of the recognized probiotic Limosilactobacillus reuteri ATCC PTA 6475 on testosterone levels, using high-, low- or placebo treatment. Venous blood samples were collected at baseline, 6 and 12 weeks, for analysis of bloodwork, lipid profile, hormones, and electrolytes. Subjects were also asked to complete a questionnaire. The supplementation had no effect on testosterone levels, neither using high- or low dose, nor placebo. However, a significant decrease of triglyceride levels was observed in the high-dose group. No other parameters showed any significant change. The present study does not support the hypothesis that a probiotic supplementation can increase testosterone levels in ageing men.

Reduced Use of Antibiotics and Nasal Decongestants During Treatment with a Mouthwash Containing Delmopinol.

PURPOSE: To evaluate the use of concomitant medication in combination with a mouthwash of delmopinol HCl 0.2% based on data from 8 phase III efficacy studies on the mouthwash. MATERIALS AND METHODS: Clinical data obtained from 8 previously performed phase III studies, carried out to document the clinical efficacy of a mouthwash of delmopinol HCl 0.2% with respect plaque and gingivitis, were used to analyse the use of concomitant medication. In these 8 randomised double-blind clinical phase III studies the patients were - in addition to their normal oral hygiene measures - treated for 2-6 months with mouthwashes containing delmopinol HCl 0.2%, delmopinol HCl 0.1%, chlorhexidine digluconate 0.2% or placebo. The number of visits in each study was three. Each time the patients visited the dentist for efficacy determinations, other data were also recorded. One of these was whether the patient had used any other medication during the study. In this paper, the number of treatments of different types of concomitant medication (antibiotics, nasal decongestants and others) was used as a basis for statistical comparisons between the different test groups. RESULTS: For antibiotics (all indications), a 27% lower number of treatments was obtained in the delmopinol 0.2% group in comparison with the placebo group, and a 41% decrease was observed for treatments with antibiotics for respiratory infections. For nasal decongestants, the number of treatments was 53% lower in the delmopinol 0.2% group. CONCLUSIONS: The delmopinol HCl 0.2% solution in patients with gingivitis provided a statistically significant reduction of concomitant use of antibiotics and nasal decongestants.

Engineered bacteria to accelerate wound healing: an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial.

Background: Impaired wound healing is a growing medical problem and very few approved drugs with documented clinical efficacy are available. CXCL12-expressing lactic acid bacteria, Limosilactobacillus reuteri (ILP100-Topical), has been demonstrated to accelerate wound healing in controlled preclinical models. In this first-in-human study, the primary objective was to determine safety and tolerability of the drug candidate ILP100-Topical, while secondary objectives included assessments of clinical and biologic effects on wound healing by traditionally accepted methods and explorative and traceable assessments. Methods: SITU-SAFE is an adaptive, randomised, double-blind, placebo-controlled, first-in-human phase 1 trial (EudraCT 2019-000680-24) consisting of a single (SAD) and a multiple ascending dose (MAD) part of three dose cohorts each. The study was performed at the Phase 1 Unit, Uppsala University Hospital, Uppsala, Sweden. Data in this article were collected between Sep 20th, 2019 and Oct 20th 2021. In total 240 wounds were induced on the upper arms in 36 healthy volunteers. SAD: 12 participants, 4 wounds (2/arm), MAD: 24 participants, 8 wounds (4/arm). Wounds in each participant were randomised to treatment with placebo/saline or ILP100-Topical. Findings: In all individuals and doses, ILP100-Topical was safe and well-tolerated with no systemic exposure. A combined cohort analysis showed a significantly larger proportion of healed wounds (p = 0.020) on Day 32 by multi-dosing of ILP100-Topical when compared to saline/placebo (76% (73/96) and 59% (57/96) healed wounds, respectively). In addition, time to first registered healing was shortened by 6 days on average, and by 10 days at highest dose. ILP100-Topical increased the density of CXCL12+ cells in the wounds and local wound blood perfusion. Interpretation: The favourable safety profile and observed effects on wound healing support continued clinical development of ILP100-Topical for the treatment of complicated wounds in patients. Funding: Ilya Pharma AB (Sponsor), H2020 SME Instrument Phase II (#804438), Knut and Alice Wallenberg foundation.

Effectiveness of psychotropic medications in the maintenance phase of bipolar disorder: a meta-analysis of randomized controlled trials.

The purpose of this meta-analysis was to examine the efficacy of maintenance treatments for bipolar disorder. Placebo-controlled or active comparator bipolar maintenance clinical trials of ≥6 months' duration with at least 15 patients/treatment group were identified using Medline, EMBASE, clinicaltrials.gov, and Cochrane databases (1993 to July 2010). The main outcome measure was relative risk for relapse for patients in remission. Twenty trials (5,364 patients) were identified. Overall, lithium and quetiapine were the most studied agents (eight and five trials, respectively). The majority of studies included patients who had previously responded to treatment for an acute episode. All interventions, with the exception of perphenazine+mood stabilizer, showed a relative risk for manic/mixed or depressive relapse below 1.0, although there was variation in the statistical significance of the findings vs. placebo. No monotherapy was associated with a significantly reduced risk for both manic/mixed and depressed relapse. Of the combination treatments, only quetiapine+lithium/divalproex, was associated with a significantly reduced risk vs. comparator (placebo+lithium/valproate) for relapse at both the manic/mixed and depressed poles of bipolar illness. Limitations for the analysis include differences in study durations and definitions of relapse. In conclusion, available maintenance therapies show considerable variation in efficacy. The efficacy of lithium and divalproex has been confirmed, but newer therapies, such as a number of atypical antipsychotics were also shown to be effective in bipolar disorder. Efficacy of all maintenance interventions needs to be balanced against the safety and tolerability profiles of individual agents.

Pharmacokinetics and clinical efficacy of delmopinol in an open rinse time study in healthy volunteers.

PURPOSE: To compare three different rinse times with delmopinol (15, 30 and 60 seconds) with respect to inhibition of plaque growth and to determine the pharmacokinetic parameters of delmopinol for these rinse times. METHODS: This open and randomized study with a cross-over design was performed in healthy male volunteers and consisted of four treatment periods of 1 week separated by washout periods of at least 6 days. The first test period started with staining of the teeth followed by planimetric recordings before and after professional cleaning. Adverse records were also obtained. The volunteers, randomly assigned to a rinsing time sequence, were instructed to cease all oral hygiene measures except for the mouthrinse with placebo or delmopinol solutions. The rinses were performed without supervision twice daily for 7 days for each rinsing time. On Day 7, plaque % index and planimetric registrations were obtained, adverse effects recorded and the teeth were cleaned professionally. Plasma samples for the pharmacokinetic evaluation were also taken. The remaining test periods were performed in the same way, except that no baseline planimetric recordings were made. During the washout periods the volunteers returned to their normal oral hygiene behavior. Venous blood samples were drawn from all volunteers into sodium heparin-containing tubes. RESULTS: A significant time-response was obtained with respect to the planimetric results. The mean areas of the teeth covered with plaque after the test periods (placebo, 15, 30 and 60 seconds) were 41%, 29%, 23% and 18%, respectively. Statistical analysis showed that rinsing with delmopinol for 30 or 60 seconds differed significantly (P < 0.05) from placebo. There was also a significant difference between rinsing for 15 and 60 seconds. From the plaque % index data it was found that all three rinsing times differed significantly from placebo. However, between the three rinse times with active solution, no significant difference in plaque % index occurred. Statistical analysis of the systemic exposure, in terms of the pharmacokinetic parameters AUC(12h) and C(max) showed a significant treatment effect. The exposure increased with increasing rinse time, although the increase (AUC(12h) and C(max)) was less than proportional to the rinse time.

An Open, Uncontrolled Pilot Study on 12-Week Use of VagiVital for Treatment of Vulvovaginal Atrophy in Breast Cancer Patients Undergoing Adjuvant Aromatase-Inhibitor Therapy.

PURPOSE: This pilot study assessed the efficacy of 12 weeks of daily treatment with a vaginal gel based on a water-based cellulose gel in reducing the severity of moderate-severe symptoms of vulvovaginal atrophy (VVA) and followed adverse events in female breast cancer patients undergoing treatment with adjuvant aromatase- inhibitor therapy. METHODS: In this open, uncontrolled pilot study, the efficacy and safety of the gel during a treatment period of 12 weeks (daily 1×1 mL) were evaluated (n=28). The gel is made of water and hypromellose, a hydropropylmetyl cellulose, which works by coating the vagina, and was developed to treat moderate-severe symptoms of VVA. The primary efficacy variable was the most bothersome symptom (MBS; among vulvovaginal irritation and itching, vaginal dryness, dysuria, or dyspareunia) self-identified at baseline on a four-point scale. RESULTS: A total of 28 patients fulfilled all entry criteria and had data available after the start of treatment. Treatment with the gel reduced MBS scores from baseline (n=28, mean 2.71) to week 12 (n=27, mean 1.33, mean reduction 1.37; p=0), and reduced the overall total scores for VVA symptoms from a mean of 5.39 at baseline to 2.25 at week 12 (p=0). Eleven subjects (39%) reported 19 AEs. CONCLUSION: A 12-week treatment with the gel significantly reduced the severity of MBSs and VVA symptoms, improved quality of life, and was safe to use in women with breast cancer undergoing adjuvant aromatase-inhibitor therapy. In view of the beneficial effects of nonhormonal treatments, for cancer patients in particular, the water-based cellulose gel VagiVital is a suitable candidate for first-choice treatment of VVA symptoms in breast cancer patients and in women predisposed to cancer.

Construct validity, floor and ceiling effects, data completeness and magnitude of change for the eight-item HAKIR questionnaire: a patient-reported outcome in the Swedish National Healthcare Quality Registry for hand surgery.

Introduction: The aim of this study was to evaluate the construct validity, floor and ceiling effects, data completeness and magnitude of change over time for the eight-item patient questionnaire (HQ-8) in the Swedish Healthcare Quality Registry for hand surgery (HAKIR). Methods: Construct validity was investigated through predefined hypotheses and correlation statistics between the single items in HQ-8 (pain on load, pain on motion without load, pain at rest, stiffness, weakness, numbness, cold sensitivity and ability to perform daily activities) and QuickDASH. Floor and ceiling effects and data completeness were analysed at preoperative (n = 13,197), three months (n =10,702) and one year (n = 9,986) responses from hand surgery patients. Effect sizes were calculated for pre- and postoperative change scores in elective conditions and postoperative scores for acute conditions. Results: Correlation coefficients at pre, 3 and 12 months ranged from 0.44 to 0.79 in the total group. No ceiling effect occurred, but a floor effect for the total group was noted for all items at all follow-ups. Missing responses were < 2.6% except for cold sensitivity. The effect sizes varied from small to large for individual items in elective diagnoses. For acute injuries, small effect sizes were found. Discussion: This study provides evidence of construct validity of HQ-8, lack of ceiling effect, expected floor effect, good data completeness and an ability to detect changes over time. The results indicate that HQ-8 measures unique aspects of disability. The HQ-8 could complement the Quick-DASH in describing patient-reported outcomes after hand surgery.

Potential Virus Involvement in Alzheimer's Disease: Results from a Phase IIa Trial Evaluating Apovir, an Antiviral Drug Combination.

BACKGROUND: Accumulating data suggest infectious agents are involved in Alzheimer's disease (AD). The two primary aims of this trial were to assess safety and efficacy of an antiviral drug combination on AD progression. OBJECTIVE: The trial evaluated whether Apovir, a combination of two antiviral agents, pleconaril (active on enteroviruses) and ribavirin (active on several viruses), could slow AD progression. METHODS: Sixty-nine patients 60-85 years were treated with Apovir or placebo for 9 months and followed until 12 months after end of treatment. Cognitive tests, safety, biomarkers, drug plasma, and cerebrospinal fluid concentrations were assessed. RESULTS: The tolerability of Apovir was compromised as demonstrated by the large drop-out rate and increased frequency and severity of adverse events. The primary endpoint, demonstrating a difference in change from baseline to 9 months between groups in ADAS-cog total score, was not met (p = 0.1809). However, there were observations indicating potential effects on both ADAS-cog and CDR-SB but these effects need to be verified. Also, there was a decrease in cerebrospinal fluid amyloid-ß in Apovir at 9 months (p = 0.0330) but no change in placebo. CONCLUSION: This was the first randomized, placebo controlled clinical trial exploring antiviral treatment on AD progression. The trial is considered inconclusive due to the large drop-out rate. New trials are needed to verify if the indications of effect observed can be confirmed and which component(s) in Apovir contributed to such effects. Pleconaril alone may be studied to improve the tolerability and to verify if enterovirus is involved in the disease process.

Treatment options for bipolar depression: a systematic review of randomized, controlled trials.

This meta-analysis examined the effectiveness of treatments of bipolar depression. Trials were identified using the MEDLINE, EMBASE, http://www.clinicaltrials.gov, and Cochrane databases (1993 to July 2008). The outcome measures included mean change in Montgomery-Asberg Depression Rating Scale (MADRS) or Hamilton Depression Rating Scale (HAM-D) total scores, and rates of response and remission. Overall, 19 publications were included. Medications included quetiapine, lamotrigine, paroxetine, lithium, olanzapine, aripiprazole, phenelzine, and divalproex. The most trials were identified for quetiapine (5) and lamotrigine (6). Not all medications were associated with symptomatic improvement (significant reduction in MADRS/HAM-D total scores vs placebo), with lamotrigine, paroxetine, aripiprazole, and lithium not being different from placebo. Highest reductions in MADRS scores versus placebo were reported for the olanzapine-fluoxetine combination (1 trial: -6.6; 95% confidence interval [CI], -9.59 to -3.61; P = 0.000) and quetiapine monotherapy (5 trials: for 300 mg/d, -4.8; 95% CI, -6.18 to -3.49; P = 0.000; for 600 mg/d, -4.8; 95% CI, -6.22 to -3.28; P = 0.000), with quetiapine monotherapy also showing the highest reduction in HAM-D scores (4 trials: -4.0; 95% CI, -5.0 to -2.9; P = 0.000). All medications except paroxetine, lithium, aripiprazole, and phenelzine significantly improved the ratio of probabilities of response (overall rate, 1.31; 95% CI, 1.22-1.40) and remission (1.32; 95% CI, 1.20-1.45) versus placebo. Variability in efficacy exists between treatments of bipolar depression. Quetiapine and the olanzapine-fluoxetine combination showed the greatest symptomatic improvement. Efficacy considerations will need to be balanced against safety and tolerability of the individual agents.

The Influence of Implant Surface on Maintenance of Marginal Bone Levels for Three Premium Implant Brands: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this meta-analysis was to evaluate the short- and long-term outcomes for marginal bone level changes around implants that benefit from one of three commercially available implant surface preparations: Astra Tech OsseoSpeed (ATO), Straumann SLA/SLActive (SLA), and Nobel Biocare TiUnite (NBT). MATERIALS AND METHODS: A MEDLINE (full text) search was conducted in July 2019 using the search terms "dental implant," "prospective," "bone level," and either implant surface/brand "TiUnite," "Nobel," "Nobel Biocare" (Nobel Biocare); or "OsseoSpeed," "Astra Tech" (Astra Tech); "Dentsply" or "SLA"; "SLActive" or "Straumann," in different combinations. Additionally, searches in Google Scholar, Elsevier, and Wiley publisher homepages were made. The abstracts were screened for eligibility, according to predefined inclusion and exclusion criteria. Initial screening resulted in 588, 813, and 616 publications for ATO, SLA, and NBT, respectively. The principal outcome measure was change in marginal bone levels at the 1- and 5-year follow-ups. A weighted mean value for the marginal bone level changes (MBLCw) based on the number of implants analyzed in each of the studies and a standard error mean for the MBLCw were calculated (SEMw). A test of the null hypotheses that the MBLC was equal in each pair of the three groups was carried out for all data available at the implant level, using both the Student t test and Wilcoxon rank sum test. A P value below 5% was considered statistically significant. RESULTS: After a full-text analysis and screening, a total of 37 ATO, 23 SLA, and 53 NBT publications qualified for inclusion in the meta-analysis for both the 1- and 5-year data. At the 1-year follow-up, data were available for 2,586 implants for ATO, compared with 1,490 and 3,948 implants for SLA and NBT, respectively. A weighted analysis revealed that mean MBLCw was -0.29 mm (SEMw: 0.0005 mm, SD: ± 0.42 mm) for ATO, compared with -0.83 mm (SEMw: 0.0025 mm, SD: ± 0.36 mm) for SLA and -0.87 mm (SEMw: 0.0006 mm, SD: ± 0.56 mm) for NBT. There was a statistically significant difference between ATO vs SLA (P < .0001), ATO vs NBT (P = .0012), and SLA vs NBT (P = .0488). Data at the 5-year follow-up were available for 1,168, 202, and 1,683 implants from the ATO, SLA, and NBT groups, respectively. Analysis revealed that mean MBLCw was -0.35 mm (SEMw: 0.0038 mm, SD: ± 0.66 mm) for ATO compared with -0.74 mm (SEMw: 0.0154 mm, SD: ± 0.45 mm) for SLA and -1.19 mm (SEMw: 0.0107 mm, SD: ± 0.61 mm) for NBT. There was a statistically significant difference between ATO vs SLA (P = .0024) and ATO vs NBT (P = .0240). The difference between SLA and NBT did not reach statistical significance (P = .0769). CONCLUSION: Based on the current meta-analysis, the null hypotheses could be rejected, and even if all groups demonstrated only a small mean amount of change in marginal bone levels at the 1- and 5-year follow-ups, there was a statistically significant difference between the three implant surface preparations, with the ATO surface showing superior marginal bone maintenance.

Safety and Efficacy of an Oxytocin Gel and an Equivalent Gel but Without Hormonal Ingredients (Vagivital® Gel) in Postmenopausal Women with Symptoms of Vulvovaginal Atrophy: A Randomized, Double-Blind Controlled Study.

PURPOSE: The primary objective was to compare the efficacy of 12 weeks of daily treatment with Aqueous Hypromellose-based vaginal (Vagivital®) gel versus Aqueous Hypromellose-based vaginal gel plus 400 IU oxytocin gel in reducing the severity of the most bothersome vulvovaginal atrophy symptoms (MBS: itching, dysuria, bleeding, and pain/discomfort during vaginal sexual activity) observed at baseline. The secondary objectives were to evaluate the other vulvovaginal atrophy symptoms, vaginal pH, superficial squamous cells, and the safety and tolerability of both gels. PATIENTS AND METHODS: This double-blind, randomized study evaluated the safety and efficacy of subjects randomly assigned to 12 weeks of daily intravaginal oxytocin gel (n=79) or Aqueous Hypromellose-based vaginal gel (n=78). The efficacy evaluation was performed using data from all included subjects who fulfilled entry criteria. RESULTS: Both treatments induced statistically significant reductions in the severity of the MBS from baseline until 4 weeks (Vagivital mean reduction 0.90, p=0.0000; Oxytocin mean reduction 0.82, p=0.0000) and 12 weeks post baseline (Vagivital mean reduction 1.28, p=0.0000; Oxytocin mean reduction 1.16, p=0.0000), but the reduction of MBS severity was not significantly different between the treatment groups at either time point. No serious adverse events were reported in the Aqueous Hypromellose-based vaginal gel group during the treatment period, but one (breast cancer) was reported in the oxytocin gel group (assessed as unlikely related to the study compound). CONCLUSION: Significant reductions in the severity of the MBS were seen in both the Aqueous Hypromellose-based vaginal gel and the oxytocin gel groups, but with no significant differences in severity reduction seen between the groups. Both gels were safe and well tolerated. Given the benefits of avoiding the use of hormones, Aqueous Hypromellose-based vaginal gel is an attractive first choice in the treatment of postmenopausal women with vulvovaginal atrophy symptoms.

The nature stroke study; NASTRU: A randomized controlled trial of nature-based post-stroke fatigue rehabilitation.

OBJECTIVE: To determine whether nature-based rehabilitation, as an add-on to standard care, has a long-term influence on post-stroke fatigue, perceived value of everyday occupations, disability, health-related quality of life, anxiety, and depression at follow-up 8 and 14 months after randomization. DESIGN: Single-blinded, 2-armed, randomized controlled trial. METHODS: Stroke survivors, identified through routine 3-month follow-up visit (sub-acute) or medical records (chronic stroke > 1 year previously), were randomized to standard care + nature-based rehabilitation (intervention group) or standard care alone (control group). Blinded evaluations were conducted at follow-up 8 and 14 months after randomization, for the following outcomes: post-stroke fatigue (Mental Fatigue Scale; MFS), perceived value of everyday occupations (Occupational value instrument with pre-defined items), disability (modified Rankin Scale; mRS), health-related quality of life (Euro-QoL-5 Demension Questionnaire), anxiety (Hospital Anxiety and Depression Scale; HAD) and depression (HAD). RESULTS: Approximately one-quarter of the screened patients were eligible for inclusion in the study; of these, half agreed to participate; a final total of 101 patients were randomized (mean age 67 years, 60% female). The patients with sub-acute stroke were highly compliant with the intervention. The participants in both the intervention and control groups improved, However, no statistically significant differences in improvement were found between the intervention and control groups for any of the outcome measures. Fatigue decreased to a value below the suggested cut-off for mental fatigue (< 10.5) in the intervention group, but not in the control group. CONCLUSION: Nature-based rehabilitation is feasible and well tolerated. A larger randomized controlled trial is warranted.

Open carpal tunnel release and diabetes: a retrospective study using PROMs and national quality registries.

OBJECTIVES: To study patient-reported outcome after open carpal tunnel release (OCTR) for carpal tunnel syndrome (CTS) in patients with or without diabetes using national healthcare quality registries. DESIGN: Retrospective cohort study. SETTING: Data from the Swedish National Quality Registry for Hand Surgery (HAKIR; www.hakir.se) were linked to data from the Swedish National Diabetes Register (NDR; www.ndr.nu). PARTICIPANTS: We identified 9049 patients (10 770 hands) operated for CTS during the inclusion period (2010-2016). PRIMARY OUTCOME MEASURES: Patient-reported outcome measures were analysed before surgery and at 3 and 12 months postoperatively using the QuickDASH as well as the HAKIR questionnaire with eight questions on hand symptoms and disability. RESULTS: Patients with diabetes (n=1508; 14%) scored higher in the QuickDASH both preoperatively and postoperatively than patients without diabetes, but the total score change between preoperative and postoperative QuickDASH was equal between patients with and without diabetes. The results did not differ between patients with type 1 or type 2 diabetes. Patients with diabetic retinopathy scored higher in QuickDASH at 3 months postoperatively than patients with diabetes without retinopathy. In the regression analysis, diabetes was associated with more residual symptoms at 3 and 12 months postoperatively. CONCLUSIONS: Patients with diabetes experience more symptoms both before and after OCTR, but can expect the same relative improvement from surgery as patients without diabetes . Patients with retinopathy, as a proxy for neuropathy, may need longer time for symptoms to resolve after OCTR. Smoking, older age, higher HbA1c levels and receiving a diabetes diagnosis after surgery were associated with more residual symptoms following OCTR.

F2-isoprostane, inflammation, cardiac function and oxygenation in the endotoxaemic pig.

Prostaglandins are profoundly involved in endotoxaemic shock. Twenty pigs were given endotoxin at various doses (0.063-16 microg kg(-1) h(-1)). Three non-endotoxaemic pigs served as controls. Two eicosanoids were measured in plasma (8-iso-PGF(2alpha), a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF(2alpha) a major metabolite of COX activity) and evaluated against the pathophysiological responses that occur during endotoxaemic shock. Endotoxin mediates an increase in both 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha). An increase in the endotoxin dose induced significant log-linear responses in 8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha). Oxidative injury correlated to the TNF-alpha, IL-6, reductions in cardiac performance and to oxygen delivery and utilisation. COX-mediated inflammatory responses correlated to TNF-alpha, IL-6 and to reductions in arterial oxygen tension. Thus, oxidative injury and COX-mediated inflammation play a central role in the manifestation of endotoxaemic shock. Furthermore, formation of these eicosanoids on endotoxin-mediated alterations in pulmonary hypertension, oxygen delivery and oxygen utilisation seems to be independent of the administered endotoxin dose.

Methodological considerations in a pilot study on the effects of a berry enriched smoothie on children's performance in school.

Berries contain bioactive compounds that may affect children's cognitive function positively, while hunger and thirst during lessons before lunch affect academic performance negatively. This pilot study addresses methodological challenges in studying if a berry smoothie, offered to schoolchildren as a mid-morning beverage, affects academic performance. The objective was to investigate if a cross-over design can be used to study these effects in a school setting. Therefore, in order to investigate assay sensitivity, 236 Swedish children aged 10-12 years were administered either a berry smoothie (active) or a fruit-based control beverage after their mid-morning break. Both beverages provided 5% of child daily energy intake. In total, 91% of participants completed the study. Academic performance was assessed using the d2 test of attention. Statistical analyses were performed using the Wilcoxon signed rank test in StatXact v 10.3. The results showed that the children consumed less of the active berry smoothie than the control (154 g vs. 246 g). Both beverages increased attention span and concentration significantly (p = 0.000). However, as there was no significant difference (p = 0.938) in the magnitude of this effect between the active and control beverages, the assay sensitivity of the study design was not proven. The effect of the beverages on academic performance was attributed the supplementation of water and energy. Despite careful design, the active smoothie was less accepted than the control. This could be explained by un-familiar sensory characteristics and peer influence, stressing the importance of sensory similarity and challenges to perform a study in school settings. The employed cross-over design did not reveal any effects of bioactive compound consumption on academic performance. In future studies, the experimental set up should be modified or replaced by e.g. the parallel study design, in order to provide conclusive results.

The new orally active immunoregulator laquinimod (ABR-215062) effectively inhibits development and relapses of experimental autoimmune encephalomyelitis.

A new orally active drug, laquinimod (ABR-215062), was shown to completely inhibit the development of murine acute experimental autoimmune encephalomyelitis (EAE). Furthermore, leukocyte infiltration into the central nervous system (CNS) was abolished in the laquinimod-treated animals. By direct comparison based on dose and total exposure, laquinimod was approximately 20 times more potent than the immunomodulator roquinimex. Laquinimod also had clear therapeutic effect when given after clinical onset in a chronic relapsing EAE model. It therefore represents a new orally active immunoregulatory drug without general immunosuppressive properties for the treatment of the autoimmune disease multiple sclerosis.

Linomide inhibits insulitis and modulates cytokine production in pancreatic islets in the nonobese diabetic mouse.

Linomide is an immunomodulator which has been shown to potently inhibit autoimmunity in several animal models for human autoimmune diseases, including type I diabetes in the nonobese diabetic (NOD) mouse. In this study, we investigate the basis for Linomide's protective effects in the NOD mouse by immunohistochemical and RT-PCR analysis of the phenotype and cytokine expression by cells infiltrating the islets of Langerhans in the pancreas. Linomide treatment was found to reduce the infiltration of T cells, B cells, dendritic cells (DC) and MHC class II(+) cells into the islets, but did not reduce macrophage (MPhi) infiltration. This was seen following Linomide treatment at 3-5, 4-8 and 14-24 weeks of age and thus appears to be independent of the stage of the autoreactive process and the extent of insulitis. The reduced insulitis may be due to reduced expression of adhesion molecules since decreased numbers of islet-associated blood vessels expressing CD106 and MAdCAM-1 were detected following Linomide treatment. Furthermore, short term Linomide treatment (3 or 7 days), which did not alter the number of infiltrating cells, was found to inhibit the production of TNF-alpha which is known to induce the expression of CD106 and MAdCAM-1. These results suggest that the reduced insulitis observed in Linomide-treated animals is secondary to a functional modulation of infiltrating cells.

A failed 6-week,randomized, double-blind, placebo-controlled study of once-daily extended release quetiapine fumarate in patients with acute schizophrenia: lessons learned.

OBJECTIVE: To demonstrate the efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in adults with acute exacerbation of schizophrenia. METHODS: A 6-week, double-blind, randomized, placebo-controlled study. In- or out-patients with a DSM-IV diagnosis of schizophrenia were randomized to fixed-dose quetiapine XR 400, 600, or 800 mg/day, quetiapine immediate release (IR) 800 mg/day, or placebo. Primary endpoint was change from baseline in Positive and Negative Syndrome Scale (PANSS) total score at Week 6. Other efficacy assessments included Clinical Global Impressions (CGI) of Severity (CGI-S) and of Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures. RESULTS: 565 patients were randomized; 333 (58.9%) completed the study. Greater numeric improvements in PANSS total score were seen for quetiapine XR (all doses) and quetiapine IR versus placebo at Week 6; the differences were not statistically significant. Secondary efficacy endpoint results were similar. There was not a high placebo response in this study, but rather an attenuation of drug effect. In general, quetiapine XR was well tolerated over 6-weeks' treatment; there were no unexpected AEs. CONCLUSION: The efficacy of quetiapine XR (400, 600, and 800 mg/day) was not established at Week 6. Quetiapine IR, an agent with established efficacy in schizophrenia, also did not separate from placebo at endpoint. Therefore, this is considered a failed study and possible reasons for this are discussed. Quetiapine XR was generally well tolerated and its safety profile was consistent with the known profile of quetiapine.