Prevalence of symptomatic pelvic organ prolapse in a Swedish population

Our aim was to estimate the prevalence of symptomatic pelvic organ prolapse (POP) in a Swedish urban female population. The cross-sectional study design included 8,000 randomly selected female residents in Stockholm, 30–79-year old. A postal questionnaire enquired about symptomatic POP, using a validated set of five questions, and about urinary incontinence and demographic data. Of 5,489 women providing adequate information, 454 (8.3%, 95% confidence interval 7.3–9.1%) were classified as having symptomatic POP. The prevalence rose with increasing age but leveled off after age 60. In a logistic regression model that disentangled the independent effects, parity emerged as a considerably stronger risk factor than age. There was a ten-fold gradient in prevalence odds of POP with parity, the steepest slope (four-fold) being between nulliparous and primiparous women. The prevalence of frequent stress urinary incontinence was 8.9% and that of frequent urge incontinence 5.9%. Out of the 454 women with prolapse, 37.4% had either or both types of incontinence.     

Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre.

BACKGROUND: Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients. METHODS: The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics. RESULTS: At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/V(urea), peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan-Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients. CONCLUSION: Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.     

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from nephrotic rats and from patients with nephrotic syndrome activate the epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells and in Xenopus laevis oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a urinary serine protease by matrix-assisted laser desorption/ionization time of-flight mass spectrometry. Purified plasmin activated ENaC currents, and inhibitors of plasmin abolished urinary protease activity and the ability to activate ENaC. In nephrotic syndrome, tubular urokinase-type plasminogen activator likely converts filtered plasminogen to plasmin. Consistent with this, the combined application of urokinase-type plasminogen activator and plasminogen stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC γ subunit ectodomain. These data suggest that a defective glomerular filtration barrier allows passage of proteolytic enzymes that have the ability to activate ENaC.Nephrotic syndrome is characterized by proteinuria, sodium retention, and edema. Increased renal sodium reabsorption occurs in the cortical collecting duct (CCD),^1,2 where a rate-limiting step in transepithelial sodium transport is the epithelial sodium channel (ENaC), which is composed of the three homologous subunits: α, β, γ.³ENaC activity is regulated by hormones, such as aldosterone and vasopressin (AVP)^4,5; however, adrenalectomized rats and AVP-deficient Brattleboro rats are capable of developing nephrotic syndrome,^1,6 and nephrotic patients do not consistently display elevated levels of sodium-retaining hormones,^7,8 suggesting that renal sodium hyper-reabsorption is independent of systemic factors. Consistent with this, sodium retention is confined to the proteinuric kidney in the unilateral puromycin aminonucleoside (PAN) nephrotic model.^2,9,10There is evidence that proteases contribute to ENaC activation by cleaving the extracellular loops of the α- and γ-subunits.^11–13 Proteolytic activation of ENaC by extracellular proteases critically involves the cleavage of the γ subunit,^14–16 which probably leads to the release of a 43-residue inhibitory peptide from the ectodomain.¹⁷ Both cleaved and noncleaved channels are present in the plasma membrane,^18,19 allowing proteases such as channel activating protease 1 (CAP1/prostasin),²⁰ trypsin,²⁰ chymotrypsin,²¹ and neutrophil elastase²² to activate noncleaved channels from the extracellular side.^23,24 We hypothesized that the defective glomerular filtration barrier in nephrotic syndrome allows the filtration of ENaC-activating proteins into the tubular fluid, leading to stimulation of ENaC. The hypothesis was tested in the PAN nephrotic model in rats and with urine from patients with nephrotic syndrome.     

The economic cost of low back pain in Sweden in 2001

BACKGROUND: Low back pain (LBP) is a common cause of lost work days and disability. In 2001, expenditure for back pain represented 11% of the total costs for short-term sick leave in Sweden, and about 13% of all early retirement pensions were granted for back problems, of which LBP is the most important symptom. The magnitude of LBP as a health problem justifies a closer look at its burden of illness to society. MATERIALS AND METHODS: We assessed the costs of LBP to society in Sweden in 2001. The study was conducted in a cost-of-illness framework, measuring both the direct costs of providing health care to LBP patients, and the indirect costs as the value of the production that is lost because people are too ill to work. The costs were estimated by a prevalence and top-down approach. RESULTS: The total cost of LBP was 1860 million EUR in Sweden in 2001. The indirect costs due to lost productivity accounted for 84% of the total cost. INTERPRETATION: The cost of illness due to low back pain was substantial, but does not appear to have risen during the last 10-15 years.     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Valgus intertrochanteric osteotomy for malunion and nonunion of trochanteric fractures

OBJECTIVE: To evaluate the results of valgus intertrochanteric osteotomy for varus nonunion and malunion of trochanteric fractures. SETTING: University hospital. DESIGN: Retrospective clinical study. PATIENTS: Fifteen patients (age range 29-84 years) with varus malunion (11 cases) or varus nonunion (4 cases). Indication for surgery was nonunion or varus malunion with limb shortening greater than 2 cm associated with limp, abductor muscle insufficiency, hip pain, and back pain. INTERVENTION: The patients were treated by a valgus intertrochanteric osteotomy fixed with a 120 degrees double-angled blade plate. RESULTS: Average follow-up was 5.5 years (range 2-10 years). Fourteen patients healed without complications: 12 patients within 4 months; 2 delayed unions within 6 months. One patient required revision surgery for a loss of fixation due to a fall 6 weeks after surgery. This osteotomy also healed. Average lengthening achieved by osteotomy was 2 cm (range 1-5 cm). In all patients, the resulting range of flexion in the hip joint was greater than 90 degrees, Harris hip score before surgery was 73 points (range 61-83), and after surgery 92 points (range 76-98). Osteoarthritis or avascular necrosis of the femoral head did not develop in any of the cases. CONCLUSION: Valgus intertrochanteric osteotomy is an effective procedure that reliably restores hip function in trochanteric malunion or nonunion.     

The reverse epidemiology of plasma total homocysteine as a mortality risk factor is related to the impact of wasting and inflammation.

BACKGROUND: The reason(s) for the apparently paradoxical 'reverse' association in end-stage renal disease (ESRD) patients in whom a low, rather than a high, total plasma total homocysteine (tHcy) level is an indicator of poor outcome remains unclear. The aim of this study was to examine whether the inverse association maintains, mitigates or reverses after comprehensive multivariate adjustment for the presence of wasting and inflammation as well as other potential confounders. METHODS: We studied 317 ESRD patients starting dialysis therapy. Fasting blood samples were taken for the analyses of tHcy, serum albumin, C-reactive protein (CRP), serum creatinine and plasma folate. Nutritional status was assessed by subjective global assessment (SGA). Survival was followed for up to 66 months; 105 patients died. RESULTS: Using Kaplan-Meier analysis, a low tHcy concentration (< or =30 micromol/l) was associated with higher all-cause and cardiovascular (CV) mortality (P < 0.05). Using Cox proportional analysis adjusting for age, gender, glomerular filtration rate = GFR, cardiovascular disease = CVD, plasma folate, total cholesterol and diabetes mellitus, the all-cause and CV mortality still tended to be high for patients with low tHcy. Adding nutritional and inflammation markers (Body mass index = BMI, SGA, serum creatinine, serum albumin and CRP), a low tHcy level was no longer associated with higher mortality but a trend for high tHcy was observed. CONCLUSIONS: The link between wasting inflammation and a low tHcy appears to be responsible for the reverse association between plasma tHcy and clinical outcome in ESRD patients. After adjustment for confounders including nutritional and inflammation markers, a trend towards increased death risk for high, rather than low, tHcy levels was apparent after adjustment.     

Is distal locking with IMHN necessary in every pertrochanteric fracture?

Two groups of patients were treated for pertrochanteric fractures (AO/ASIF 31A1+A2) with an intramedullary hip nail. In the first group of 44 patients distal dynamic locking was used, and in the second group of 74 patients the nail was not distally locked. Comparison of the two groups of patients did not show any difference in terms of the period of fracture healing, radiological and functional results or frequency of complications. In the group with a distally locked nail the surgery took 40.4 minutes, while in the group without distal locking only 34.4 minutes. In total, we recorded only seven complications, none of which were caused by absence of distal locking of the nail. This study has shown that distal locking of IMHN is unnecessary in most pertrochanteric fractures (AO/ASIF 31A1+2). The only exceptions are comminution of the lateral wall of the greater trochanter, secondary diaphyseal fracture line, large posteromedial fragment extended distally below the level of the lesser trochanter and broad intramedullary canal.     

No effect of risedronate on femoral periprosthetic bone loss following total hip arthroplasty: A 4-year follow-up of 61 patients in a double-blind,randomized placebo-controlled trial

Background and purpose

We have previously shown that during the first 2 years after total hip arthroplasty (THA), periprosthetic bone resorption can be prevented by 6 months of risedronate therapy. This follow-up study investigated this effect at 4 years.

Patients and methods

A single-center, double-blind, randomized placebo-controlled trial was carried out from 2006 to 2010 in 73 patients with osteoarthritis of the hip who were scheduled to undergo THA. The patients were randomly assigned to receive either 35 mg risedronate or placebo orally, once a week, for 6 months postoperatively. The primary outcome was the percentage change in bone mineral density (BMD) in Gruen zones 1 and 7 in the proximal part of the femur at follow-up. Secondary outcomes included migration of the femoral stem and clinical outcome scores.

Results

61 of the 73 patients participated in this 4-year (3.9- to 4.1-year) follow-up study. BMD was similar in the risedronate group (n = 30) and the placebo group (n = 31). The mean difference was −1.8% in zone 1 and 0.5% in zone 7. Migration of the femoral stem, the clinical outcome, and the frequency of adverse events were similar in the 2 groups.

Interpretation

Although risedronate prevents periprosthetic bone loss postoperatively, a decrease in periprosthetic BMD accelerates when therapy is discontinued, and no effect is seen at 4 years. We do not recommend the use of risedronate following THA for osteoarthritis of the hip.Adaptive bone remodeling around the femoral stem following total hip arthroplasty (THA) results in regional loss of bone mass, especially in proximal parts of the femur—most of which takes place within the first postoperative year (Bodén et al. 2006, Sköldenberg et al. 2006). Periprosthetic bone loss may predispose to periprosthetic fracture, aseptic loosening, and difficulties at revision surgery (Lindahl 2007, Streit et al. 2011, Sköldenberg et al. 2014).The bisphosphonate (BP) risedronate has been used successfully to prevent osteoporotic fractures, mainly in the hip and vertebrae, by inhibiting osteoclast activity (McClung et al. 2001). In recent years, the possible use of BPs to prevent or ameliorate periprosthetic adaptive bone resorption, osteolysis, and implant migration has been investigated thoroughly in animal models and humans. The short-term results of several studies showing the effects of postoperative BP treatment in reducing periprosthetic bone loss up to a year after the arthroplasty have already been published (Venesmaa et al. 2001, Wilkinson et al. 2001, Hennigs et al. 2002, Wilkinson et al. 2005, Arabmotlagh et al. 2006).We have previously found that risedronate given once a week for 6 months after THA reduces periprosthetic bone resorption around an uncemented femoral stem in the first and second postoperative year (Sköldenberg et al. 2011). We now report the 4-year outcome in the same cohort.     

Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors: A Possible Explanation for the Train-of-four Fade

Background: Nondepolarizing neuromuscular blocking agents (NMBAs) are extensively used in the practice of anesthesia and intensive care medicine. Their primary site of action is at the postsynaptic nicotinic acetylcholine receptor (nAChR) in the neuromuscular junction, but their action on neuronal nAChRs have not been fully evaluated. Furthermore, observed adverse effects of nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. The aim of this study was to examine the effect of clinically used nondepolarizing NMBAs on muscle and neuronal nAChR subtypes.

Methods: Xenopus laevis oocytes were injected with messenger RNA encoding for the subunits included in the human [alpha]1[beta]1[varepsilon][delta], [alpha]3[beta]2, [alpha]3[beta]4, [alpha]4[beta]2, and [alpha]7 nAChR subtypes. The interactions between each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, mivacurium, pancuronium, rocuronium, and vecuronium were studied using an eight-channel two-electrode voltage clamp setup. Responses were measured as peak current and net charge.

Results: All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. The neuronal nAChRs were reversibly and concentration-dependently inhibited in the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) of the block at the neuronal nAChRs was dependent both on subtype and the NMBA tested. The authors did not observe activation of the nAChR subtypes by any of the NMBAs tested.