The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind randomized controlled trial

BACKGROUND:The efficacy of dietary supplements in chronic fatigue syndrome (CFS) is uncertain, with conflicting evidence. Aim: To assess the effect of a polynutrient supplement on fatigue and physical activity of patients with CFS. DESIGN:Prospective randomized placebo-controlled, double-blind trial. METHODS:Fifty-three patients (16 males, 37 females) fulfilling the CDC criteria of CFS. The entry criteria were a score on the Checklist Individual Strength subscale fatigue severity (CIS fatigue) >or=40 and a weighted sum score of >or=750 for the eight subscales of the Sickness Impact Profile (SIP8) and no use of nutritional supplements in the 4 weeks prior to entry. The exclusion criteria were pregnancy and lactose intolerance. The intervention-a polynutrient supplement containing several vitamins, minerals and (co)enzymes, or placebo, twice daily for 10 weeks-was preceded by 2 weeks of baseline measurements. Outcome measurements took place in week 9 and 10 of the intervention. Five participants dropped out (4 supplement, 1 placebo). The main outcome measures were CIS fatigue score, number of CDC symptoms and SIP8 score. Efficacy analyses were performed on an intention-to-treat basis. RESULTS:No significant differences were found between the placebo and the treated group on any of the outcome measures: CIS fatigue +2.16 (95%CI -4.3 to +4.39, p=0.984); CDC symptoms +0.42 (95%CI -0.61 to +1.46, p=0.417); SIP8 +182 (95%CI -165 to +529, p=0.297). No patient reported full recovery. DISCUSSION:The findings do not support the use of a broad-spectrum nutritional supplement in treating CFS-related symptoms.     

Less severe retinopathy of prematurity induced by surfactant replacement therapy

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.     

Studies on a second and third ring cyclization in anthracycline biosynthesis

This paper focuses on study of second and third ring cyclization in anthracycline biosynthesis by a heterologous gene expression. Firstly, anthracycline non-producing Streptomyces peucetius mutant, D2 was heterologously complemented to produce daunomycins with plasmids pSgs44 and pSYE66, which contain putative cyclase genes of S. galilaeus and S. nogalater, respectively. A point mutation in the cyclase gene dpsY of D2 has changed glycine to serine resulting inactivation of the enzyme. Secondly, the putative cyclase gene snoaM from S. nogalater, was expressed in a gene cassette in S. lividans TK24 and S. coelicolor CH999 to study the influence of the cyclase gene on auramycinone production and the impact of endogenous genes on production profiles. The results obtained confirms that a cyclase closing the second and third ring of a polyketide is essential in anthracycline biosynthesis.     

What Are the Interobserver and Intraobserver Variability of Gap and Stepoff Measurements in Acetabular Fractures?

BackgroundGap and stepoff values in the treatment of acetabular fractures are correlated with clinical outcomes. However, the interobserver and intraobserver variability of gap and stepoff measurements for all imaging modalities in the preoperative, intraoperative, and postoperative phase of treatment is unknown. Recently, a standardized CT-based measurement method was introduced, which provided the opportunity to assess the level of variability.Questions/purposes(1) In patients with acetabular fractures, what is the interobserver variability in the measurement of the fracture gaps and articular stepoffs determined by each observer to be the maximum one in the weightbearing dome, as measured on pre- and postoperative pelvic radiographs, intraoperative fluoroscopy, and pre- and postoperative CT scans? (2) What is the intraobserver variability in these measurements?MethodsSixty patients with a complete subset of pre-, intra- and postoperative high-quality images (CT slices of < 2 mm), representing a variety of fracture types with small and large gaps and/or stepoffs, were included. A total of 196 patients with nonoperative treatment (n = 117), inadequate available imaging (n = 60), skeletal immaturity (n = 16), bilateral fractures (n = 2) or a primary THA (n = 1) were excluded. The maximum gap and stepoff values in the weightbearing dome were digitally measured on pelvic radiographs and CT images by five independent observers. Observers were free to decide which gap and/or stepoff they considered the maximum and then measure these before and after surgery. The observers were two trauma surgeons with more than 5 years of experience in pelvic surgery, two trauma surgeons with less than 5 years of experience in pelvic surgery, and one surgical resident. Additionally, the final intraoperative fluoroscopy images were assessed for the presence of a gap or stepoff in the weightbearing dome. All observers used the same standardized measurement technique and each observer measured the first five patients together with the responsible researcher. For 10 randomly selected patients, all measurements were repeated by all observers, at least 2 weeks after the initial measurements. The intraclass correlation coefficient (ICC) for pelvic radiographs and CT images and the kappa value for intraoperative fluoroscopy measurements were calculated to determine the inter- and intraobserver variability. Interobserver variability was defined as the difference in the measurements between observers. Intraobserver variability was defined as the difference in repeated measurements by the same observer.ResultsPreoperatively, the interobserver ICC was 0.4 (gap and stepoff) on radiographs and 0.4 (gap) and 0.3 (stepoff) on CT images. The observers agreed on the indication for surgery in 40% (gap) and 30% (stepoff) on pelvic radiographs. For CT scans the observers agreed in 95% (gap) and 70% (stepoff) of images. Postoperatively, the interobserver ICC was 0.4 (gap) and 0.2 (stepoff) on radiographs. The observers agreed on whether the reduction was acceptable or not in 60% (gap) and 40% (stepoff). On CT images the ICC was 0.3 (gap) and 0.4 (stepoff). The observers agreed on whether the reduction was acceptable in 35% (gap) and 38% (stepoff). The preoperative intraobserver ICC was 0.6 (gap and stepoff) on pelvic radiographs and 0.4 (gap) and 0.6 (stepoff) for CT scans. Postoperatively, the intraobserver ICC was 0.7 (gap) and 0.1 (stepoff) on pelvic radiographs. On CT the intraobserver ICC was 0.5 (gap) and 0.3 (stepoff). There was no agreement between the observers on the presence of a gap or stepoff on intraoperative fluoroscopy images (kappa -0.1 to 0.2).ConclusionsWe found an insufficient interobserver and intraobserver agreement on measuring gaps and stepoffs for supporting clinical decisions in acetabular fracture surgery. If observers cannot agree on the size of the gap and stepoff, it will be challenging to decide when to perform surgery and study the results of acetabular fracture surgery.Level of EvidenceLevel III, diagnostic study.     

The incidence of negative intraoperative findings after unsuccessful hydrostatic reduction of ileocolic intussusception in children: A retrospective analysis

Background

There is a lack of studies addressing the occurrence of negative intraoperative findings (that is the absence of intussusception) after an unsuccessful hydrostatic reduction of an ileocolic intussusception. The aim of this study is to determine the incidence of negative intraoperative findings after unsuccessful hydrostatic reduction of ileocolic intussusception.

Validation of the Patient Health Questionnaire-9 for Major Depressive Disorder in the Occupational Health Setting

Purpose Because of the increased risk of long-term sickness leave for employees with a major depressive disorder (MDD), it is important for occupational health professionals to recognize depression in a timely manner. The Patient Health Questionnaire-9 (PHQ-9) has proven to be a reliable and valid instrument for screening MDD, but has not been validated in the occupational health setting. The aim of this study was to validate the PHQ-9 for MDD within a population of employees on sickness leave by using the MINI-International Neuropsychiatric Interview (MINI) as a gold standard. Methods Participants were recruited in collaboration with the occupational health service. The study sample consisted of 170 employees on sickness leave between 4 and 26 weeks who completed the PHQ-9 and were evaluated with the MINI by telephone. Sensitivity, specificity, positive and negative predictive value, efficiency and 95 % confidence intervals (95 % CIs) were calculated for all possible cut-off values. A receiver operator characteristics (ROC) analysis was computed for PHQ-9 score versus the MINI. Results The optimal cut-off value of the PHQ-9 was 10. This resulted in a sensitivity of 86.1 % [95 % CI (69.7–94.8)] and a specificity of 78.4 % [95 % CI (70.2–84.8)]. Based on the ROC analysis, the area under the curve for the PHQ-9 was 0.90 [SE = 0.02; 95 % CI (0.85–0.94)]. Conclusion The PHQ-9 shows good sensitivity and specificity as a screener for MDD within a population of employees on sickness leave.     

Randomized and double-blinded pilot clinical study of the safety and anti-diabetic efficacy of the Rauvolfia-Citrus tea, as used in Nigerian traditional medicine

Aim of the study

The aim of this randomized and double blinded pilot clinical trial was to investigate the anti-diabetic efficacy of the Rauvolfia-Citrus (RC) tea in humans. We have earlier shown that a combination of calorie-restriction and chronic administration of the RC tea to the genetic diabetic (BKS-db) mice resulted in the normalization of blood sugar, reduction in lipid accumulated in the mice eyes and prevention of the degeneration of the otherwise brittle BKS-db pancreas. The tea is made by boiling foliage of Rauvolfia vomitoria and fruits of Citrus aurantium and is used to treat diabetes in Nigerian folk medicine.

Materials and methods

The RC tea was produced using the Nigerian traditional recipe and tested in the traditional dosage on 23 Danish type 2 diabetes (T2D) patients. The participants were divided into two equivalent groups after stratification by sex, age and BMI, in a 4-month double-blinded, placebo-controlled and randomized clinical trial. Most of the study subjects (19/23) were using oral anti-diabetic agents (OADs). Mean disease duration was 6 ± 4.6 years, mean age was 64 ± 7 years and mean BMI was 28.7 ± 3.8 kg/m². Prior to starting the treatment, the participants received individual dietician consultations.

Results

At the end of the 4-month treatment period, the treated group showed an 11% decrease in 2-h postprandial plasma glucose relative to the 3% increase in the placebo group (p = 0.004). The improvement in blood glucose clearance with RC tea treatment was reflected in a 6% reduction in HbA_1c (p = 0.02) and in a 10% reduction in fasting plasma glucose (p = 0.02), when comparing the post 4-month treatment to pre-treatment baseline values. Though the basal levels of phosphorylated acetyl CoA carboxylase enzyme in skeletal muscle were significantly reduced in the treated group (p = 0.04), as compared to the placebo, only the pattern of reductions in the tissue fatty acids (FAs) differed in the two groups. While all types of FAs were reduced in placebo, only saturated (SFA) and monounsaturated (MUFA) FAs were reduced with treatment. Interestingly, a modest increase in the polyunsaturated FAs fraction was observed in the RC treated group. In addition, the reduction in SFA and MUFA with RC tea treatment came solely from the triglyceride fractions, as there was an increase in the skeletal muscle phospholipids.

Conclusions

Chronic administration of the RC tea to overweight T2D on OADs caused significant improvements in markers of glycaemic control and modifications to the fatty acid profile of skeletal muscle, without adverse effects or hypoglycaemia. Further exploration of the anti-diabetic effects of the RC tea is warranted.     

Is a long leg a risk for hip or knee osteoarthritis?

Background and purpose — 7% of the asymptomatic population has leg-length inequality (LLI) greater than 12?mm. It has been proposed that LLI of >5?mm can be associated with an increased risk of osteoarthritis (OA) of the knee and hip. We studied a possible association between LLI and OA of the knee and hip joint.

Patients and methods — We followed 193 individuals (97 women, 96 men) for 29 years. The initial mean age of the participants was 43 (34–54) years, and they had no clinical histories or signs of leg symptoms. The initial standing radiographs of their hips were re-examined and measured for LLI and signs of OA. None had any signs of OA. At the follow-up, data on performed hip or knee arthroplasties were obtained.

Results — 24 (12%) of the subjects had no discernible leg-length difference, 62 (32%), had LLIs of 1–4?mm, 74 (38%) of 5–8?mm, 21 (11%) of 9–12?mm, and 12 (6%) of over 12?mm. 16 (8%) of the subjects had undergone arthroplasty for primary OA during follow-up, and of those, 8 for both hip and knee OA. 10 individuals had undergone an arthroplasty of the longer leg and only 3 of the shorter leg. In the group of equal leg length, 3 had had an arthroplasty of hip or knee.

Interpretation — We noted that hip or knee arthroplasty due to primary OA had been done 3 times more often to the longer leg than to the shorter.     

A common challenge in older adults: Classification,overlap, and therapy of depression and dementia

Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field.     

Patient satisfaction after knee arthroplasty: A report on 27,372 knees operated on between 1981 and 1995 in Sweden

During a validation process of the Swedish Knee Arthroplasty Register (SKAR), living registered patients were sent a questionnaire to ask if they had been reoperated on. This gave an opportunity to pose a simple four-point question with respect to patient satisfaction which 95% of patients answered. We analyzed the answers of patients operated on between 1981 and 1995 and found that only 8% of the patients were dissatisfied regarding their knee arthroplasty 2-17 years postoperatively. The satisfaction rate was constant, regardless of when the operation had been performed during the 15-year period. The proportion of satisfied patients was affected by the preoperative diagnosis, patients operated on for a long-standing disease more often being satisfied than those with a short disease-duration. There was no difference in proportions of satisfied patients, whether they had primarily been operated on with a total knee arthroplasty (TKA) or a medial unicompartmental arthroplasty (UKA). For TKAs performed with primary patellar resurfacing, there was a higher ratio of satisfied patients than for TKAs not resurfaced, but this increased ratio diminished with time passed since the primary operation. Unrevised knees had a higher proportion of satisfied patients than knees that had been subject to revision, and among patients revised for medial UKA, the proportion of satisfied patients was higher than among patients revised for TKA. We conclude that satisfaction after knee arthroplasty is stable and long-lasting in unrevised cases and that even after revision most patients are satisfied.