Treatment of acute periprosthetic infections with prosthesis retention: Review of current concepts

Periprosthetic joint infection (PJI) is a devastating complication after total joint arthroplasty, occurring in approximately 1%-2% of all cases. With growing populations and increasing age, PJI will have a growing effect on health care costs. Many risk factors have been identified that increase the risk of developing PJI, including obesity, immune system deficiencies, malignancy, previous surgery of the same joint and longer operating time. Acute PJI occurs either postoperatively (4 wk to 3 mo after initial arthroplasty, depending on the classification system), or via hematogenous spreading after a period in which the prosthesis had functioned properly. Diagnosis and the choice of treatment are the cornerstones to success. Although different definitions for PJI have been used in the past, most are more or less similar and include the presence of a sinus tract, blood infection values, synovial white blood cell count, signs of infection on histopathological analysis and one or more positive culture results. Debridement, antibiotics and implant retention (DAIR) is the primary treatment for acute PJI, and should be performed as soon as possible after the development of symptoms. Success rates differ, but most studies report success rates of around 60%-80%. Whether single or multiple debridement procedures are more successful remains unclear. The use of local antibiotics in addition to the administration of systemic antibiotic agents is also subject to debate, and its pro’s and con’s should be carefully considered. Systemic treatment, based on culture results, is of importance for all PJI treatments. Additionally, rifampin should be given in Staphylococcal PJIs, unless all foreign material is removed. The most important factors contributing to treatment failure are longer duration of symptoms, a longer time after initial arthroplasty, the need for more debridement procedures, the retention of exchangeable components, and PJI caused by Staphylococcus (aureus or coagulase negative). If DAIR treatment is unsuccessful, the following treatment option should be based on the patient health status and his or her expectations. For the best functional outcome, one- or two-stage revision should be performed after DAIR failure. In conclusion, DAIR is the obvious choice for treatment of acute PJI, with good success rates in selected patients.     

Development and Implementation of National Practice Guidelines: A Prospect for Continuous Quality Improvement in Physiotherapy: Introduction to the method of guideline development

The development of national practice guidelines (NPGs) is an issue of much concern in healthcare policies world-wide to guarantee and to improve the quality and efficiency of care. The development and implementation of NPGs constitutes an important part of the quality of care policy of the Royal Dutch Physiotherapy Association (KNGF). This interest is due to pressure from society (policy-makers, healthcare managers, financiers and patients) on physiotherapists to ensure quality of care and to justify our position in the healthcare system. The development of NPGs can also be seen as a logical step in the process of professionalisation and quality assurance by physiotherapists.An NPG is described as a systematically developed statement, drafted by experts and directed at one aspect of the treatment of a health problem belonging to the domain of the profession. NPGs are based on the different stages of the physiotherapy care process, the available clinical evidence and expert consensus. Priority is given to a cost-effective approach and multidisciplinary consensus on diagnosis, treatment and primary or secondary prevention. Recommendations are based on the results of new or recorded systematic reviews or meta-analysis.NPGs are important state-of-the-art documents, which can guide professionals in their daily practice and make explicit to other relevant people what professionals can do in a certain situation or with a specific condition, and why they do it. NPGs have important functions, including supporting physiotherapists in their decision-making process; they are a frame of reference for orientation and educational purposes, they provide criteria for self-evaluation and peer review, and can initiate changes in established practice patterns.This paper describes the process and development of NPGs for physiotherapists in the Netherlands. In a companion paper the method and strategies for the implementation of NPGs and the need for evaluation of their outcome will be discussed.     

The maternal Mediterranean dietary pattern is associated with a reduced risk of spina bifida in the offspring

Objective  The objective of this study was to test the hypothesis whether a maternal dietary pattern is associated with the risk of spina bifida (SB) in the offspring.
Design  Case–control study.
Setting  Eight clinic sites in the Netherlands, 1999–2001.
Sample  A total of 50 mothers of children with SB and 81 control mothers.
Methods  Maternal food intakes were obtained by food frequency questionnaires at the standardised study moment of 14 months after the birth of the index child. Principal component factor analysis (PCA) and reduced rank regression (RRR) were used to identify dietary patterns.
Main outcome measures  Maternal biomarkers were used as response measures in the RRR analysis and composed of serum and red blood cell (RBC) folate, serum vitamin B12 and total plasma homocysteine. The strength of the use of the dietary pattern in association with SB risk was estimated by odds ratios and 95% CI with the highest quartiles of the dietary pattern as reference.
Results  A predominantly Mediterranean dietary pattern was identified by both PCA and RRR. Those dietary patterns were highly correlated ( r = 0.51, P < 0.001) and characterised by joint intakes of fruit, vegetables, vegetable oil, alcohol, fish, legumes and cereals and low intakes of potatoes and sweets. We observed a significantly increased risk of SB offspring in mothers with a weak use of the Mediterranean dietary pattern, OR 2.7 (95% CI 1.2–6.1) and OR 3.5 (95% CI 1.5–7.9). The Mediterranean dietary pattern was correlated with higher levels of serum and RBC folate, serum vitamin B12 and lower plasma homocysteine.
Conclusion  The Mediterranean dietary pattern seems to be associated with reduction in the risk of offspring being affected by SB.     

Example of somatic mosaicism in a series of de novo neurofibromatosis type 1 cases due to a maternally derived deletion

Neurofibromatosis type 1 (NF1), affecting primarily the growth of neural crest-derived tissues, is one of the most common autosomal dominant genetic disorders with an unusually high spontaneous mutation rate. In four cases of sporadic NF1, demonstrated by hemizygosity to have a deletion involving the NF1 gene, we were able to assign the deletion event to the maternally derived chromosome. One of these individuals was determined to be a somatic mosaic for NF1, as a trace of the maternally derived haplotype was detected at the NF1 locus. This indicated a postzygotic, as opposed to gametic, deletion event. It may be that somatic mosaicism is more common in NF1 than has hitherto been appreciated and may responsible in part for the high mutation rate in this disorder. In addition, it is suggested that the mechanism(s) of gene deletion is subject to a parent of origin effect, being more frequent on the maternally derived chromosome. This is in contrast to the other types of mutations which, in sporadic NF1, have been found to occur preferentially on the paternally derived chromosome. Hum Mutat 9:452–457, 1997 © 1997 Wiley-Liss, Inc.     

International variation in GP treatment strategies for subclinical hypothyroidism in older adults: a case-based survey

Background

There is limited evidence about the impact of treatment for subclinical hypothyroidism, especially among older people.

Aim

To investigate the variation in GP treatment strategies for older patients with subclinical hypothyroidism depending on country and patient characteristics.

Design and setting

Case-based survey of GPs in the Netherlands, Germany, England, Ireland, Switzerland, and New Zealand.

Method

The treatment strategy of GPs (treatment yes/no, starting-dose thyroxine) was assessed for eight cases presenting a woman with subclinical hypothyroidism. The cases differed in the patient characteristics of age (70 versus 85 years), vitality status (vital versus vulnerable), and thyroid-stimulating hormone (TSH) concentration (6 versus 15 mU/L).

Results

A total of 526 GPs participated (the Netherlands n = 129, Germany n = 61, England n = 22, Ireland n = 21, Switzerland n = 262, New Zealand n = 31; overall response 19%). Across countries, differences in treatment strategy were observed. GPs from the Netherlands (mean treatment percentage 34%), England (40%), and New Zealand (39%) were less inclined to start treatment than GPs in Germany (73%), Ireland (62%), and Switzerland (52%) (P = 0.05). Overall, GPs were less inclined to start treatment in 85-year-old than in 70-year-old females (pooled odds ratio [OR] 0.74 [95% confidence interval [CI] = 0.63 to 0.87]). Females with a TSH of 15 mU/L were more likely to get treated than those with a TSH of 6 mU/L (pooled OR 9.49 [95% CI = 5.81 to 15.5]).

Conclusion

GP treatment strategies of older people with subclinical hypothyroidism vary largely by country and patient characteristics. This variation underlines the need for a new generation of international guidelines based on the outcomes of randomised clinical trials set within primary care.     

Who Follows eHealth Interventions as Recommended? A Study of Participants' Personal Characteristics From the Experimental Arm of a Randomized Controlled Trial

Background

Computer-tailored eHealth interventions to improve health behavior have been demonstrated to be effective and cost-effective if they are used as recommended. However, different subgroups may use the Internet differently, which might also affect intervention use and effectiveness. To date, there is little research available depicting whether adherence to intervention recommendations differs according to personal characteristics.

Objective

The aim was to assess which personal characteristics are associated with using an eHealth intervention as recommended.

Methods

A randomized controlled trial was conducted among a sample of the adult Dutch population (N=1638) testing an intervention aimed at improving 5 healthy lifestyle behaviors: increasing fruit and vegetable consumption, increasing physical activity, reducing alcohol intake, and promoting smoking cessation. Participants were asked to participate in those specific online modules for which they did not meet the national guideline(s) for the respective behavior(s). Participants who started with fewer than the recommended number of modules of the intervention were defined as users who did not follow the intervention recommendation.

Results

The fewer modules recommended to participants, the better participants adhered to the intervention modules. Following the intervention recommendation increased when participants were older (χ² ₁=39.8, P<.001), female (χ² ₁=15.8, P<.001), unemployed (χ² ₁=7.9, P=.003), ill (χ² ₁=4.5, P=.02), or in a relationship (χ² ₁=7.8, P=.003). No significant relevant differences were found between groups with different levels of education, incomes, or quality of life.

Conclusion

Our findings indicate that eHealth interventions were used differently by subgroups. The more frequent as-recommended intervention use by unemployed, older, and ill participants may be an indication that these eHealth interventions are attractive to people with a greater need for health care information. Further research is necessary to make intervention use more attractive for people with unhealthy lifestyle patterns.     

Two frequent missense mutations in Pendred syndrome

Pendred syndrome is an autosomal recessive disorder characterized by early childhood deafness and goiter. A century after its recognition as a syndrome by Vaughan Pendred, the disease gene ( PDS ) was mapped to chromosome 7q22-q31.1 and, recently, found to encode a putative sulfate transporter. We performed mutation analysis of the PDS gene in patients from 14 Pendred families originating from seven countries and identified all mutations. The mutations include three single base deletions, one splice site mutation and 10 missense mutations. One missense mutation (L236P) was found in a homozygous state in two consanguineous families and in a heterozygous state in five additional non-consanguineous families. Another missense mutation (T416P) was found in a homozygous state in one family and in a heterozygous state in four families. Pendred patients in three non-consanguineous families were shown to be compound heterozygotes for L236P and T416P. In total, one or both of these mutations were found in nine of the 14 families analyzed. The identification of two frequent PDS mutations will facilitate the molecular diagnosis of Pendred syndrome.      

The human corpus luteum: reduction in macrophages during simulated maternal recognition of pregnancy

It has been shown that immune cells, particularly macrophages, accumulate in the corpus luteum during luteolysis. This study aimed to investigate the effect of maternal recognition of pregnancy on the localization and numbers of macrophages in the human corpus luteum. Corpora lutea (n = 12) were obtained from normally cycling women at the time of hysterectomy and were dated on the basis of serial urinary luteinizing hormone (LH) estimation. In addition, corpora lutea (n = 4) were collected from women who had received daily doubling doses of human chorionic gonadotrophin (HCG) to mimic the hormonal changes of early pregnancy. Macrophages were localized by immunohistochemistry using an anti-CD68 antibody. Steroidogenic cells, steroidogenic cells of thecal origin and endothelial cells were identified on serial sections by immunohistochemistry for 3beta-hydroxysteroid dehydrogenase, 17alpha-hydroxylase and von Willebrand factor, respectively. The luteal cells capable of responding directly to HCG were identified by isotopic in-situ hybridization for messenger RNA encoding LH/HCG receptors. Macrophages were localized primarily to the vascular connective tissue and theca-lutein areas of the corpus luteum, although some were found in the granulosa-lutein cell layer. Macrophage numbers increased throughout the luteal phase to a maximum in the late- luteal phase (P < 0.05). Luteal 'rescue' with HCG was associated with a marked reduction in the numbers of tissue macrophages when compared with those of the late-luteal phase (P < 0.001). One of the effects of HCG during maternal recognition of pregnancy is to prevent the normal influx of macrophages into the corpus luteum. As LH/HCG receptors localized to the steroidogenic cells, this implies a fundamental role for steroidogenic cell products in the control of macrophage influx into the human corpus luteum.      

Macrophage CD40 signaling drives experimental autoimmune encephalomyelitis

The costimulatory CD40L–CD40 dyad plays a major role in multiple sclerosis (MS). CD40 is highly expressed on MHCII⁺ B cells, dendritic cells and macrophages in human MS lesions. Here we investigated the role of the CD40 downstream signaling intermediates TNF receptor-associated factor 2 (TRAF2) and TRAF6 in MHCII⁺ cells in experimental autoimmune encephalomyelitis (EAE). Both MHCII–CD40–Traf2^−/− and MHCII–CD40–Traf6^−/− mice showed a reduction in clinical signs of EAE and prevented demyelination. However, only MHCII–CD40–Traf6^−/− mice displayed a decrease in myeloid and lymphoid cell infiltration into the CNS that was accompanied by reduced levels of TNF-α, IL-6 and IFN-γ. As CD40–TRAF6 interactions predominantly occur in macrophages, we subjected CD40^flflLysM^cre mice to EAE. This myeloid-specific deletion of CD40 resulted in a significant reduction in EAE severity, reduced CNS inflammation and demyelination. In conclusion, the CD40–TRAF6 signaling pathway in MHCII⁺ cells plays a key role in neuroinflammation and demyelination during EAE. Concomitant with the fact that CD40–TRAF6 interactions are predominant in macrophages, depletion of myeloid CD40 also reduces neuroinflammation. CD40–TRAF6 interactions thus represent a promising therapeutic target for MS. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.