Primary surgical management of anterior pelvic organ prolapse: a systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP. METHODS: We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective. MAIN RESULTS: We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values. CONCLUSIONS: Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty. TWEETABLE ABSTRACT: New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse.

Management of mesh complications following surgery for stress urinary incontinence or pelvic organ prolapse: a systematic review.

BACKGROUND: Mesh surgery for stress urinary incontinence or pelvic organ prolapse can result in complications such as mesh exposure, mesh extrusion, voiding dysfunction, dyspareunia, and pain. There is limited knowledge or guidance on the effective management for mesh-related complications. OBJECTIVE: To determine the best management of mesh complications; a systematic review was conducted as part of the national clinical guideline 'Urinary incontinence (update) and pelvic organ prolapse in women: management'. SEARCH STRATEGY: Search strategies were developed for each indication for referral. SELECTION CRITERIA: Relevant interventions included complete or partial mesh removal, mesh division, and non-surgical treatments such as vaginal estrogen. DATA COLLECTION AND ANALYSIS: Characteristics and outcome data were extracted, and as a result of the heterogeneous nature of the data a narrative synthesis was conducted. MAIN RESULTS: Twenty-four studies were included; five provided comparative data and four studies stated the indication for referral. Reported outcomes (including pain, dyspareunia, satisfaction, quality of life, incontinence, mesh exposure, and recurrence) and the reported incidences of these varied widely. CONCLUSIONS: The current evidence base is limited in quantity and quality and does not permit firm recommendations to be made on the most effective management for mesh-related complications. Robust data are needed so that mesh complications can be managed effectively in the future. TWEETABLE ABSTRACT: Systematic review demonstrates that the outcomes following mesh revision surgery are highly variable.

Is there a role for the ob gene product leptin in essential hypertension?

In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean+/-SD age of 50 +/-14 years and a body mass index of 26.5+/-5.3 kg/m2; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean+/-SEM plasma leptin level in the whole population was 9.5+/-0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r = 0.422, P < .01) and nonhypertensive men (r = 0.644, P = .03) only. Plasma renin activity (r = 0.329, P = .03) and aldosterone levels (r = 0.342, P = .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weight.

Effects of alcohol on energy metabolism and body weight regulation: is alcohol a risk factor for obesity?

Some studies have suggested that drinking in moderation may be beneficial for health, but many of these studies do not address body weight. Evidence suggests that consuming moderate amounts of alcohol is a risk factor for obesity, which is a risk factor for several adverse health outcomes. Recommendations regarding alcohol intake thus should take into account a variety of factors, including baseline body weight, location of body fat, and overall diet.

Articular cartilage biomechanics: theoretical models, material properties, and biosynthetic response.

Articular cartilage has unique material properties that enable the cartilage to perform its physiological functions over a lifetime and under a wide range of loading conditions. Numerous studies have investigated the relationship between cartilage properties and composition/structure. For cartilage transplantation and regeneration, it is necessary to know how cartilage maintains its functionality and how cartilage responds to the ever-changing mechanical environment. In this review, we discuss theoretical and experimental studies on the behavior of articular cartilage to load. In the first part, the composition and structure of articular cartilage is presented. In the second part, theoretical models of the mechanical behavior of cartilage, experimental methods for the determination of cartilage properties, and material properties for normal, pathologic, and repair cartilage are summarized. In the third part, the relationship between mechanical loading of the cells and their corresponding biological responses are discussed. The goal for treating joint degeneration in the future lies in cartilage regeneration rather than prosthetic replacement. In order to achieve this goal, it has to be understood how structure and function, metabolic and biochemical properties, and biomechanical performance of articular cartilage can be restored.

Race specific altitude effects on blood pressure.

Altitude affects blood pressure (BP) depending on duration and absolute altitude of exposure. Until now changes in BP during exposure to altitude were studied only in Caucasians. It is not known whether BP is affected differently in black and white people in response to altitude. During a 6-day climb on Kilimanjaro, BP was measured in five white and four black people. All participants (mean +/- s.d.: age 31 +/- 8 years, body mass index 22 +/- 2 kg/m2, BP 125 +/- 11/84 +/- 9 mm Hg) had previous similar experience of high-altitude mountaineering. In the base camp (3040 m) systolic BP (SBP) was similar in both groups (131 +/- 9 vs 119 +/- 8 mm Hg). During ascent until 4600 m SBP increased in all whites (6.5 +/- 2.2 mm Hg) and decreased in all blacks (-7.3 +/- 4.6 mm Hg; P = 0.02, blacks vs whites). During descent SBP returned to initial values in whites, whereas it decreased further in blacks. Diastolic BP (DBP) and heart rate remained constant in all participants. During ascent body weight increased in all whites (1.0 +/- 0.8 kg) and decreased in all blacks (-1.9 +/- 1.4 kg; P = 0.02, blacks vs whites) whereas it returned approximately to initial levels during descent: +0.8 +/- 0.4 kg in blacks and -1.0 +/- 1.3 kg in whites (P = 0.03, blacks vs whites). In this study changes in SBP and body weight during exposure to high altitudes varied between whites and blacks. Fluid balance, acclimatisation, physical fitness or genetics could explain these findings.

A comparison of knee extensor strength curves obtained theoretically and experimentally.

Strength curves relate a measure of maximal voluntary force of a group of synergistic muscles, typically a resultant knee joint moment, to a measure of muscular length, typically a joint angle. In this study, it was hypothesized that the shape of strength curves is primarily determined by the force-length properties of the individual muscles within a synergistic group. This hypothesis was tested for knee extensor strength curves by comparing theoretically determined strength curves based on the force-length relations of the individual muscles with those obtained experimentally. The agreement between theoretical and experimental curves was good, suggesting that the initial hypothesis was correct. Accepting this result, it is possible to determine the contribution of individual muscles to the total force of the synergistic group. This information, in turn, may be utilized for practical applications in sports or for evaluating strength curves of patients with injuries or diseases of the musculoskeletal system.

Quantification of in vivo patellofemoral contact forces before and after ACL transection.

Altered knee loading following anterior cruciate ligament (ACL) transection is believed to play an important role in initiating cartilage degeneration. Changes of in vivo joint contact forces pre- and post-ACL transection have not been quantified to date. Consequently, it is not known how knee loading changes following ACL transection, and how it contributes to cartilage degeneration. The objective of this study was to quantify in vivo patellofemoral contact forces in the cat knee prior to and up to nine days following uni-lateral ACL transection. Patellofemoral contact forces were predicted using a planar three-force model with knee extensor forces and patellofemoral geometry as input. Patellofemoral movements were expressed as functions of external knee kinematics. Kinematics and knee extensor forces were measured in both hindlimbs before and after ACL transection during unrestrained locomotion. Following ACL transection, resultant patellofemoral contact forces were decreased by approximately 30% in the ACL-deficient hindlimbs. These results suggest that decreased loading in the ACL-deficient knees may initiate the early degenerative changes observed in cartilage of ACL-transected animals. It remains to be shown, if the general unloading of the joint also results in locally decreased contact loads and altered joint kinematics. Alterations of in vivo patellofemoral loading following ACL transection have been quantified for the first time in this study. A next step will be to quantify the dynamic in vivo cartilage stresses in intact and injured knees which may help to elucidate the effects of mechanical stimuli on cartilage metabolism.

Experimental evaluation of theoretical contact forces in the cat patellofemoral joint.

The purpose of this study was to evaluate the accuracy of patellofemoral contact forces predicted from a planar model of the patella by comparison with experimentally determined in situ contact forces. Patellofemoral contact pressures and areas were measured experimentally in an animal preparation with pressure sensitive film. Patellar tendon forces and lines of action used as input to the model were measured in the intact joint of the same preparation. Predicted and measured contact forces at different joint loads were compared at three different joint angles using linear regression analysis. r2-coefficients ranged from 0.94 to 0.95, and the slopes of the regression lines ranged from 1.64 to 2.11 for the three joint angles. The high r2-coefficients for all comparisons indicate that both methods were able to quantify the relative changes in the cat patellofemoral contact forces under different loading conditions accurately. However, the consistent finding of slopes greater than 1.0 indicates that the measured contact forces were systematically larger than the corresponding predicted forces. Analysis of the possible sources for the observed discrepancies between predicted and measured contact forces suggested that the directly measured patellar tendon forces were the most likely candidate causing the systematic differences. The results of this study suggest that a relatively simple model of the patellofemoral joint appears to be valid to quantify joint contact forces if appropriate patellar tendon force values can be provided as input to the model.

In-situ calibration of the implantable force transducer.

Recently, an implantable force transducer (IFT) has been introduced [Xu et al. (1992, J. Biomech. Engng 114, 170-177)] which can be used in tight spaces where force recordings with established transducers, such as the buckle-type transducers, are not possible because of impingement artifacts. The IFT is easily implanted in chronic animal preparations; however, calibration of the IFT in terminal experiments has produced unreliable results. The problems of IFT calibration are that minute movements of the transducer within the tendon, slight misalignments of the tendon, or slight errors in the line of pull cause dramatic changes in the IFT voltage output for a given applied calibration load. Here, we propose a method that eliminates the above calibration problems primarily because the target tendon is left in situ, the calibration loads are applied by the muscles which insert into the target tendon, and the transducer is implanted into the target tendon about two weeks prior to calibration. The theoretical and experimental approaches are demonstrated for the cat patellar tendon, but in principle can be performed with any tendon. The results are repeatable, lie within expected values, and reproduce some of the basic properties which have been observed in prior IFT testing.

In vivo knee joint loading and kinematics before and after ACL transection in an animal model.

Osteoarthritis (OA) is typically diagnosed in humans in its final stage when joint movement becomes painful. Clinical information about the onset and the mechanisms triggering the degenerative responses are virtually non-existent. However, research on animal models of experimental OA shows that joint adaptations associated with the onset of OA can be detected as early as two to four weeks following disruption of the normal joint mechanics. Transection of the anterior cruciate ligament (ACL) has been shown to cause OA-like symptoms in various animal models including the cat. However. the changes in joint loading responsible for the early tissue responses have not been quantified in vivo. Consequently, the relationship between abnormal joint loading and the onset of OA remains unknown. The purpose of this study was to quantify knee loading before and early after ACL transection in the cat. Knee mechanics were assessed by measuring patellar tendon forces, gastrocnemius forces, knee flexor and extensor EMGs, and hindlimb kinematics before and 5, 7, and 9 days following ACL transection in six experimental and two sham-operated animals. The knee mechanics were not affected by sham-surgery but the muscular forces. knee extensor EMGs, and knee range of motion were reduced following ACL transection compared to corresponding pre-intervention values. These results suggest that ACL transection causes a general unloading and changed kinematics of the knee. We speculate that the decrease in loading and the altered kinematics are responsible for the onset of biologic adaptations of the knee. Precise data about the local joint contact mechanics before and after ACL transection are now required to further relate the detailed changes in the knee mechanics to the early joint changes.

Forces exerted during spinal manipulative therapy.

Spinal manipulative therapy has been widely recognized in the medical fields as a conservative treatment modality for spinal dysfunction and pain. Spinal manipulative therapy consists of an application of a thrusting force on a specific part of the spine in a well-defined direction. The magnitude of this force has been associated with positive treatment effects, such as realigning vertebral bodies, mobilizing spinal joints, relaxing back musculature through reflex pathways, and producing a respiratory burst. However, direct force measurements during spinal manipulative therapy in a clinically relevant situation have not been performed to date. The purpose of this study was to measure the forces exerted onto patients during spinal manipulative therapy on various locations of the spinal column. Force measurements were obtained using a thin, flexible pressure mat. The results indicate that peak and preload forces are considerably smaller for spinal manipulative therapy performed on the cervical spine compared to corresponding values obtained on the thoracic spine and sacroiliac joint. Furthermore, for treatments on the thoracic spine and sacroiliac joint, a significant relation was found to exist between preload and peak forces.

A combination of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540) in the treatment of bronchogenic carcinoma.

Thirty patients with bronchogenic carcinoma were treated with an 8-week induction therapy consisting of cyclophosphamide, methotrexate, vincristine and VP 16-213 (NSC 141 540). Those who achieved objective remission of tumor stabilization were then placed on an intermittent treatment schedule with the same drugs. Of the 30 patients, 17 had an objective response, 5 remained without change, and 8 progressed. Responses were more frequent among anaplastic (13/19) than epidermoid or adenocarcinoma (4/11). The toxicity consisted mainly of leucopenia, thrombopenia, alopecia, nausea and vomiting. The implications of these findings in the planning of further chemotherapeutic programs are discussed.

Inadequate placement of osteochondral plugs may induce abnormal stress-strain distributions in articular cartilage --finite element simulations.

The transplantation of osteochondral (cartilage-bone) plugs is an alternative approach to treat local, full thickness cartilage defects in young patients. It is technically difficult to control the amount of the press fit tolerance and the position of the osteochondral (OC) plug in the recipient hole. Inadequate placement of the OC plugs may produce abnormal stress and strain distributions within the cartilage, and thus influence the regeneration of the injured cartilage site and the maintenance of opposing, healthy cartilage surfaces. In the present study, the influence of press fit tolerance and the placement of the OC plug on the joint contact mechanics was simulated using finite element methods. The joint was assumed to be axi-symmetric with a spherical femur and tibia and a cylindrical OC plug. Our simulations showed that small misplacements of the OC plug induced abnormal tension in the articular cartilage of the opposing, healthy cartilage surface. Such tension might induce unpredictable adaptations, or possibly degenerations, in the opposing cartilage layer. The contact stress profiles in the joint were predicted to change discontinuously across the plug/recipient interface, even when the plug was perfectly placed in the recipient hole, i.e., the plug's surface was aligned with the recipient surface. For a fixed coefficient of friction and a fixed fit tolerance, the maximal sliding force was predicted to vary with the size of the plug and reached a maximum at a specific plug diameter. The present simulations should be helpful for the design of instruments for osteochondral transplantation and placement of OC plugs, for understanding articular cartilage adaptation following osteochondral repair, and for providing insight into the mechanics at the transplant/recipient interface where proper integration of the plug into the joint is most problematic.

Forces required to cause cavitation during spinal manipulation of the thoracic spine.

The purpose of this study was to measure the forces exerted during spinal manipulative therapy of the thoracic spine simultaneously with corresponding cavitation signals. Forces were measured using a thin, flexible pressure mat which was placed on patients over the contact area between doctor and patient. Cavitation signals were measured using a skin mounted accelerometer on the spinous process of a vertebral body adjacent to the manipulated vertebral body. Mean forces of spinal manipulative therapy at the instant of cavitation were 364 N with a standard deviation of 106 N. These values are considerably larger than corresponding values reported for cavitation at metacarpophalangeal joints. The precise factors causing cavitation of the spinal joints could not be determined. Study designs which may allow identification of these factors are suggested.

Influence of hip and knee joint angles on excitation of knee extensor muscles.

The purpose of this study was to test if (and how) maximal excitation of the knee extensor muscles rectus femoris (RF), vastus lateralis (VL) and vastus medialis (VM) is influenced by knee and/or hip joint angles. Excitation was quantified using surface electromyography. Isometric knee extensions were performed at systematically varying knee and hip joint configurations using a strength testing machine. The results indicate that excitation of the one-joint knee extensor muscles (VL and VM) depends systematically on hip joint angles. In particular, excitation levels are higher at hip joint angles of 90 degrees (sitting) and 180 degrees (lying) compared to intermediate hip joint angles (112 degrees, 135 degrees, 157 degrees). Furthermore, it was found that excitation of all knee extensor muscles tested is higher near full knee extension (170 degrees) compared to an intermediate knee joint angle (130 degrees). Since knee extensor moments are much smaller at knee joint angles of 170 degrees compared to those at 130 degrees, it is speculated that the high excitation observed near full knee extension constitutes a neurophysiological compensation mechanism for the reduced force production ability of the muscles at this joint configuration.

Hormone and radiotherapy versus hormone or radiotherapy alone for non-metastatic prostate cancer: a systematic review with meta-analyses.

AIMS: Radiotherapy is standard treatment for localised prostate cancer and is often combined with hormone treatment to prevent androgen stimulation of prostate cancer. Hormone therapy carries significant morbidity and can only be justified in the radical treatment of localised disease if it can be balanced against a significant gain in disease control and survival. MATERIALS AND METHODS: We searched Medline, Premedline, Embase, Cochrane Library, Web of Science (SCI & SSCI) and Biomed Central for randomised controlled trials published in English comparing radiotherapy or hormone therapy alone with radiotherapy and hormone therapy in combination as first-line treatment in patients with non-metastatic prostate cancer reporting overall survival, disease-free survival, distant metastases-free survival, biochemical survival, adverse events (including cardiovascular) and/or health-related quality of life. RESULTS: Fourteen trials were included and showed that combination therapy was associated with better or similar survival and disease-free outcomes compared with single-modality treatment, and that this may particularly be the case for patients with higher risk disease. The results also suggested that combination therapy is associated with more and worse adverse events and quality of life, although this was not always the case. Some of the results are at risk of reporting bias. CONCLUSION: The published data support the use of combined treatment with androgen deprivation and radiotherapy for intermediate- and high-risk localised and locally advanced prostate cancer. Optimal timing, duration, formulation and the management of side-effects remain important questions for further research.