The developmental consequences of early adverse care on infant macaques: A cross-fostering study.

Early life adversity/stress (ELA/ELS), particularly adverse caregiving experiences such as child maltreatment (MALT), is a main risk factor for psychopathology, including psychiatric disorders such as anxiety, depression, ADHD, and substance abuse. Yet how these alterations unfold during development and the underlying mechanisms remain poorly understood, as it is difficult to prospectively and longitudinally study early developmental phases in humans, and nearly impossible to disentangle postnatal caregiving effects from heritable traits. This study examined the specific effects of "nurture" (maternal care) versus "nature" (heritable, biological maternal factors) on nonhuman primate infant socioemotional, stress neuroendocrine, and physical development. For this we used a translational and naturalistic macaque model of infant maltreatment by the mother with randomized assignment at birth to either mothers with a history of maltreating their infants (MALT group, n = 22) or to competent mothers (Control group, n = 20). Over the first 6 months of life (roughly equivalent to 2 years in humans), we examined the development of the mother-infant relationship, as well as infants' social behavior and emotional reactivity. In parallel, we assessed hypothalamic-pituitary-adrenal (HPA) axis function longitudinally, using measures of hair cortisol accumulation, and basal morning plasma cortisol. We identified broad impairments in maternal care exhibited by MALT foster mothers, beyond maltreatment (physical abuse, rejection) events, suggesting that MALT foster mothers provide an overall lower quality of care to their infants compared to Controls. MALT infants exhibited alterations in their initiations and breaks of proximity towards their mothers, as well as heightened emotional reactivity in comparison to Controls. Most striking are the HPA axis findings, with MALT infants showing higher levels of plasma cortisol across the first 6 postnatal months as well as higher hair cortisol accumulation from birth through month 6 (a signature of chronic stress) than Controls. No caregiving effects were detected on physical growth, which ruled out confounding effects of maternal nutrition, metabolism, etc. Taken together, these results suggest that the developmental trajectory of MALT and Control infants is different, marked by heightened levels of emotional reactivity, increased HPA activity and alterations in mother-infant interactions in MALT animals. These findings appear to be due to specific effects of postnatal maternal care, and not to biological/ behavioral traits inherited from the mother, or due to prenatal programming caused by prenatal stress, as the cross-fostering design controlled for these potential factors. However, we also detected a couple of interesting biological effects suggesting heritable transmission of some phenotypes. The prolonged HPA axis activation during the first 6 postnatal months of life is expected to have long-term consequences for brain, physiological, and behavioral development in MALT offspring.

The development of an instrument to measure global dimensions of maternal care in rhesus macaques (Macaca mulatta).

One of the strongest predictors of healthy child development is the quality of maternal care. Although many measures of observation and self-report exist in humans to assess global aspects of maternal care, such qualitative measures are lacking in nonhuman primates. In this study, we developed an instrument to measure global aspects of maternal care in rhesus monkeys, with the goal of complementing the individual behavioral data collected using a well-established rhesus macaque ethogram during the first months postpartum. The 22 items of the instrument were adapted from human maternal sensitivity assessments and a maternal Q-sort instrument already published for macaques. The 22 items formed four dimensions with high levels of internal reliability that represented major constructs of maternal care: (1) Sensitivity/Responsivity, (2) Protectiveness, (3) Permissiveness, and (4) Irritability. These dimensions yielded high construct validity when correlated with mother-infant frequency and duration behavior that was collected from focal observations across the first 3 postnatal months. In addition, comparisons of two groups of mothers (Maltreating vs. Competent mothers) showed significant differences across the dimensions suggesting that this instrument has strong concurrent validity, even after controlling for focal observation variables that have been previously shown to significantly differentiate these groups. Our findings suggest that this Instrument of Macaque Maternal Care has the potential to capture global aspects of the mother-infant relationship that complement individual behaviors collected through focal observations.

Serotonin transporter gene variation, infant abuse, and responsiveness to stress in rhesus macaque mothers and infants.

A functional polymorphism in the promoter region of the serotonin transporter (5-HTTLPR) gene has been associated with variation in anxiety and hypothalamus-pituitary-adrenal (HPA) axis function in humans and rhesus macaques. Individuals carrying the short allele are at a higher risk for developmental psychopathology, and this risk is magnified in short allele carriers who have experienced early life stress. This study investigated the relationship between 5-HTTLPR allelic variation, infant abuse, and behavioral and hormonal responses to stress in rhesus macaques. Subjects were 10 abusive mothers and their infants, and 10 nonabusive mother-infant pairs. Mothers and infants were genotyped for the rh5-HTTLPR, and studied in the first 6 months of infant life. For mothers and infants, we measured social group behavior, behavioral responses to handling procedures, and plasma concentrations of ACTH and cortisol under basal conditions and in response to stress tests. The proportion of individuals carrying the short rh5-HTTLPR allele was significantly higher among abusive mothers than controls. Among mothers and infants, the short allele was associated with higher basal cortisol levels and greater hormonal stress responses in the infants. In addition, infants who carried the short rh5-HTTLPR allele had higher anxiety scores than infants homozygous for the long allele. The rh5-HTTLPR genotype also interacted with early adverse experience to impact HPA axis function in the infants. These results are consistent with those of previous studies which demonstrate associations between serotonergic activity and anxiety and stress reactivity, and add additional evidence suggesting that genetic variation in serotonergic function may contribute to the occurrence of abusive parenting in rhesus macaques and modulate emotional behavior and HPA axis function.

Interactive Methods for Teaching Action Potentials, an Example of Teaching Innovation from Neuroscience Postdoctoral Fellows in the Fellowships in Research and Science Teaching (FIRST) Program.

Acquiring a faculty position in academia is extremely competitive and now typically requires more than just solid research skills and knowledge of one's field. Recruiting institutions currently desire new faculty that can teach effectively, but few postdoctoral positions provide any training in teaching methods. Fellowships in Research and Science Teaching (FIRST) is a successful postdoctoral training program funded by the National Institutes of Health (NIH) providing training in both research and teaching methodology. The FIRST program provides fellows with outstanding interdisciplinary biomedical research training in fields such as neuroscience. The postdoctoral research experience is integrated with a teaching program which includes a How to Teach course, instruction in classroom technology and course development and mentored teaching. During their mentored teaching experiences, fellows are encouraged to explore innovative teaching methodologies and to perform science teaching research to improve classroom learning. FIRST fellows teaching neuroscience to undergraduates have observed that many of these students have difficulty with the topic of neuroscience. Therefore, we investigated the effects of interactive teaching methods for this topic. We tested two interactive teaching methodologies to determine if they would improve learning and retention of this information when compared with standard lectures. The interactive methods for teaching action potentials increased understanding and retention. Therefore, FIRST provides excellent teaching training, partly by enhancing the ability of fellows to integrate innovative teaching methods into their instruction. This training in turn provides fellows that matriculate from this program more of the characteristics that hiring institutions desire in their new faculty.

The EuroPhysiome, STEP and a roadmap for the virtual physiological human.

Biomedical science and its allied disciplines are entering a new era in which computational methods and technologies are poised to play a prevalent role in supporting collaborative investigation of the human body. Within Europe, this has its focus in the virtual physiological human (VPH), which is an evolving entity that has emerged from the EuroPhysiome initiative and the strategy for the EuroPhysiome (STEP) consortium. The VPH is intended to be a solution to common infrastructure needs for physiome projects across the globe, providing a unifying architecture that facilitates integration and prediction, ultimately creating a framework capable of describing Homo sapiens in silico. The routine reliance of the biomedical industry, biomedical research and clinical practice on information technology (IT) highlights the importance of a tailor-made and robust IT infrastructure, but numerous challenges need to be addressed if the VPH is to become a mature technological reality. Appropriate investment will reap considerable rewards, since it is anticipated that the VPH will influence all sectors of society, with implications predominantly for improved healthcare, improved competitiveness in industry and greater understanding of (patho)physiological processes. This paper considers issues pertinent to the development of the VPH, highlighted by the work of the STEP consortium.

Systematic review of the effectiveness of preventing and treating Staphylococcus aureus carriage in reducing peritoneal catheter-related infections.

OBJECTIVES: To determine the clinical effectiveness and cost-effectiveness of (1) alternative strategies for the prevention of Staphylococcus aureus carriage in patients on peritoneal dialysis (PD) and (2) alternative strategies for the eradication of S. aureus carriage in patients on PD. DATA SOURCES: Major electronic databases were searched up to December 2005 (MEDLINE Extra up to 6 January 2006). REVIEW METHODS: Electronic searches were undertaken to identify published and unpublished reports of randomised controlled trials and systematic reviews evaluating the effectiveness of preventing and treating S. aureus carriage on peritoneal catheter-related infections. The quality of the included studies was assessed and data synthesised. Where data were not sufficient for formal meta-analysis, a qualitative narrative review looking for consistency between studies was performed. RESULTS: Twenty-two relevant trials were found. These fell into several groups: the first split is between prophylactic trials, aiming to prevent carriage, and trials which aimed to eradicate carriage in those who already had it; the second split is between antiseptics and antibiotics; and the third split is between those that included patients having the catheter inserted before dialysis started and people already on dialysis. Many of the trials were small or short-term. The quality was often not good by today's standards. The body of evidence suggested a reduction in exit-site infections, but this did not seem to lead to a significant reduction in peritonitis, although to some extent this reflected insufficient power in the studies and a low incidence of peritonitis in them. The costs of interventions to prevent or treat S. aureus carriage are relatively modest. For example, the annual cost of antibiotic treatment of S. aureus carriage per identified carrier of S. aureus was estimated at 179 pounds (73 pounds screening and 106 pounds cost of antibiotic). However, without better data on the effectiveness of the interventions, it is not clear whether such costs are offset by the cost of treating infections and averting changes from peritoneal dialysis to haemodialysis. Although treatment is not expensive, the lack of convincing evidence of clinical effectiveness made cost-effectiveness analysis unrewarding at present. However, consideration was given to the factors needed in a hypothetical model describing patient pathways from methods to prevent S. aureus carriage, its detection and treatment and the detection and treatment of the consequences of S. aureus (e.g. catheter infections and peritonitis). Had data been available, the model would have compared the cost-effectiveness of alternative interventions from the perspective of the UK NHS, but as such it helped identify what future research would be needed to fill the gaps. CONCLUSIONS: The importance of peritonitis is not in doubt. It is the main cause of people having to switch from peritoneal dialysis to haemodialysis, which then leads to reduced quality of life for patients and increased costs to the NHS. Unfortunately, the present evidence base for the prevention of peritonitis is disappointing; it suggests that the interventions reduce exit-site infections, but not peritonitis, although this may be due to trials being in too small numbers for too short periods. Trials are needed with larger numbers of patients for longer durations.

Maternal care patterns and behavioral development of rhesus macaque abused infants in the first 6 months of life.

We investigated the maternal care patterns of rhesus macaque mothers who physically abuse their infants, and compared their infants' behavior to that of nonabused infants. Parametric and multidimensional scaling analyses indicated that abusive mothers have a distinct parenting style characterized by high rates of rejection and contact-breaking from their infants. Compared to control infants, abused infants exhibited signs of delayed independence from their mothers including higher rates of distress calls and anxiety, lower rates of contact-breaking, and differences in play. Several aspects of the abused infants' behavior were correlated with rates of abuse received during the first month, or with other maternal behaviors. These findings provide a more comprehensive characterization of the parenting styles of abusive mothers and the early behavioral development of their infants than previously available. Detailed knowledge of the early experience of abused infants is crucial for understanding possible pathological alterations in behavior and neuroendocrine function later in life.

Laparoscopic surgery for inguinal hernia repair: systematic review of effectiveness and economic evaluation.

OBJECTIVES: To determine whether laparoscopic methods are more effective and cost-effective than open mesh methods of inguinal hernia repair, and then whether laparoscopic transabdominal preperitoneal (TAPP) repair is more effective and cost-effective than laparoscopic totally extraperitoneal (TEP). DATA SOURCES: Electronic databases. Conference proceedings. Manufacturers' submissions to the National Institute for Clinical Excellence (NICE) were reviewed. REVIEW METHODS: Selected studies were rigorously assessed. Dichotomous outcome data were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Time to return to usual activities was described using hazard ratios derived from individual patient data reanalysis. A review of economic evaluations undertaken by NICE in 2001 was updated and an economic evaluation was performed. The estimation of cost-effectiveness focused on the comparison of laparoscopic repair with open flat mesh. A Markov model incorporating the data from the systematic review was used to estimate cost-effectiveness for a time horizon up to 25 years. RESULTS: Thirty-seven randomised control trials (RCTs) and quasi-RCTs met the inclusion criteria on effectiveness. Fourteen studies were included in the review of economic evaluations. Laparoscopic repair was associated with a faster return to usual activities and less persisting pain and numbness. There also appeared to be fewer cases of wound/superficial infection and haematoma. However, operation times are longer and there appears to be a higher rate of serious complications in respect of visceral (especially bladder) injuries. Mesh infection is very uncommon with similar rates noted between the surgical approaches. There is no apparent difference in the rate of hernia recurrence. Laparoscopic repair was more costly to the health service than open repair, with an estimated extra cost from studies conducted in the UK of about 300-350 pounds per patient. The point estimates of cost provided by the economic model also suggest that the laparoscopic techniques are more costly (approximately 100-200 pounds more per patient after 5 years). From the review of economic evaluations, the estimates of incremental cost per additional day at usual activities were between 86 pounds and 130 pounds. Where productivity costs were included, they eliminated the cost differential between laparoscopic and open repair. Additional analysis incorporating new trial evidence suggested that TEP was associated with significantly more recurrences than open mesh but these data did not greatly influence cost-effectiveness. CONCLUSIONS: For the management of unilateral hernias, the base-case analysis and most of the sensitivity analysis suggest that open flat mesh is the least costly option but provides less quality adjusted life years (QALYs) than TEP or TAPP. TEP is likely to dominate TAPP (on average TEP is estimated to be less costly and more effective). It is likely that, for management of symptomatic bilateral hernias, laparoscopic repair would be more cost-effective as differences in operation time (a key cost driver) may be reduced and differences in convalescence time are more marked (hence QALYs will increase) for laparoscopic compared with open mesh repair. When possible repair of contralateral occult hernias is taken into account, TEP repair is most likely to be considered cost-effective at threshold values for the cost per additional QALY above 20,000 pounds. The increased adoption of laparoscopic techniques may allow patients to return to usual activities faster. This may, for some people, reduce any loss of income. For the NHS, increased use of laparoscopic repair would lead to an increased requirement for training and the risk of serious complications may be higher. Chronic pain should now be addressed prospectively using standard definitions and allowing assessment of the degree of pain. More evidence is required on the loss of utility caused by persisting pain and numbness, as well as serious complications resulting from minor surgery. Prospective population-based registries of new surgical procedures may be the best way to address this, as a complement to randomised trials assessing effectiveness. Further research relating to whether the balance of advantages and disadvantages changes when hernias are recurrent or bilateral is also required as current data are limited. Methodologically sound RCTs are needed to consider the relative merits and risks of TAPP and TEP. Further methodological research is required into the complexity of laparoscopic groin hernia repair and the improvement of performance that accompanies experience.

Transabdominal pre-peritoneal (TAPP) versus totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair: a systematic review.

BACKGROUND: The choice of approach to the laparoscopic repair of inguinal hernia is controversial. There is a scarcity of data comparing the laparoscopic transabdominal preperitoneal (TAPP) approach with the laparoscopic totally extraperitoneal (TEP) approach, and questions remain about their relative merits and risks. METHODS: Electronic databases were searched to identify reports of trials comparing laparoscopic TAPP with laparoscopic TEP. In addition, selected conference proceedings were hand-searched, websites consulted, reference lists of all included papers were scanned, and experts contacted for other potentially eligible reports. All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic TAPP with laparoscopic TEP for inguinal hernia repair were eligible for inclusion. Large non-randomised prospective studies were also eligible for inclusion to provide further comparative evidence of complications and serious adverse events. Two reviewers independently extracted data and assessed study quality. Statistical analyses were performed using the fixed effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). RESULTS: The search identified one RCT which reported no statistically significant difference between TAPP and TEP when considering duration of operation, haematoma, length of stay, time to return to usual activities, and recurrence. The eight non-randomised studies suggest that TAPP is associated with higher rates of port-site hernias and visceral injuries whilst there appear to be more conversions with TEP. Vascular injuries and deep/mesh infections were rare and there was no obvious difference between the groups. No studies reporting economic evidence were identified. CONCLUSIONS: There is insufficient data to allow conclusions to be drawn about the relative effectiveness of TEP compared with TAPP. Efforts should be made to start and complete adequately-powered randomised controlled trials (RCTs), which compare the different methods of laparoscopic repair.

Genetic modifiers of the Kv beta2-null phenotype in mice.

Shaker-type potassium (K+) channels are composed of pore-forming alpha subunits associated with cytoplasmic beta subunits. Kv beta2 is the predominant Kv beta subunit in the mammalian nervous system, but its functions in vivo are not clear. Kv beta2-null mice have been previously characterized in our laboratory as having reduced lifespans, cold swim-induced tremors and occasional seizures, but no apparent defect in Kv alpha-subunit trafficking. To test whether strain differences might influence the severity of this phenotype, we analyzed Kv beta2-null mice in different strain backgrounds: 129/SvEv (129), C57BL/6J (B6) and two mixed B6/129 backgrounds. We found that strain differences significantly affected survival, body weight and thermoregulation in Kv beta2-null mice. B6 nulls had a more severe phenotype than 129 nulls in these measures; this dramatic difference did not reflect alterations in seizure thresholds but may relate to strain differences we observed in cerebellar Kv1.2 expression. To specifically test whether Kv beta1 is a genetic modifier of the Kv beta2-null phenotype, we generated Kv beta1.1-deficient mice by gene targeting and bred them to Kv beta2-null mice. Kv beta1.1/Kv beta2 double knockouts had significantly increased mortality compared with either single knockout but still maintained surface expression of Kv1.2, indicating that trafficking of this alpha subunit does not require either Kv beta subunit. Our results suggest that genetic differences between 129/SvEv and C57Bl/6J are key determinants of the severity of defects seen in Kv beta2-null mice and that Kv beta1.1 is a specific although not strain-dependent modifier.

Transabdominal pre-peritoneal (TAPP) vs totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: The choice of approach to the laparoscopic repair of inguinal hernia is controversial. There is a scarcity of data comparing the laparoscopic transabdominal preperitoneal (TAPP) approach with the laparoscopic totally extraperitoneal (TEP) approach and questions remain about their relative merits and risks. OBJECTIVES: To compare the clinical effectiveness and relative efficiency of laparoscopic TAPP and laparoscopic TEP for inguinal hernia repair. SEARCH STRATEGY: We searched Medline Extra, Embase, Biosis, Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Journals@ Ovid Full Text and the electronic version of the journal, Surgical Endoscopy. Recent conference proceedings by the following organisations were hand searched: Association of Endoscopic Surgeons of Great Britain & Ireland; International Congress of the European Association for Endoscopic Surgery; Scientific Session of the Society of American Gastrointestinal & Endoscopic Surgeons (SAGES); and the Italian Society of Endoscopic Surgery. In addition, specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials, relevant websites were searched and reference lists of the all included studies were checked for additional reports. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic TAPP with laparoscopic TEP for inguinal hernia repair were eligible for inclusion. Non-randomised prospective studies were also eligible for inclusion to provide further comparative evidence of complications and adverse events. DATA COLLECTION AND ANALYSIS: Statistical analyses were performed using the fixed effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes with 95% confidence intervals (CI). MAIN RESULTS: The search identified one RCT which reported no statistical difference between TAPP and TEP when considering duration of operation, haematoma, length of stay, time to return to usual activity and recurrence. The eight non-randomised studies suggest that TAPP is associated with higher rates of port-site hernias and visceral injuries whilst there appear to be more conversions with TEP. Vascular injuries and deep/mesh infections were rare and there was no obvious difference between the groups. No studies reporting economic evidence were identified. Very limited data were available on learning effects but these data suggest that operators become experienced at between 30 and 100 procedures. AUTHORS' CONCLUSIONS: There is insufficient data to allow conclusions to be drawn about the relative effectiveness of TEP compared with TAPP. Efforts should be made to start and complete adequately powered RCTs, which compare the different methods of laparoscopic repair.

Value of updating a systematic review in surgery using individual patient data.

BACKGROUND: Previous research has highlighted the advantages of individual patient data (IPD) meta-analyses. However, they are resource intensive and take considerable time to complete. The aim of this study was to determine whether the extra investment is justified by greater accuracy or usefulness by means of a case study in surgery. METHODS: An updated review using IPD, where possible, was compared with an earlier version based on aggregate published data to determine whether there were statistically significant changes in estimates of effectiveness for hernia recurrence and persisting pain. Differences related to the type of laparoscopic repair, the type of open repair and methodological quality were also explored. RESULTS: The results for hernia recurrence changed little. However, the IPD update led to divergent conclusions for persisting pain. The published data implied a statistically significant benefit in favour of open repair, whereas the IPD result implied a statistically significant benefit in favour of laparoscopic repair (P < 0.001). Methodological quality did not account for this difference. CONCLUSION: Updating of systematic reviews using IPD can be conducted successfully in surgery. This example led to little change in estimates of effectiveness for hernia recurrence but yielded qualitatively different estimates for persisting pain, an outcome rarely included in the published reports.

Systematic review of the clinical effectiveness and cost-effectiveness of tension-free vaginal tape for treatment of urinary stress incontinence.

OBJECTIVES: To evaluate the effectiveness and cost-effectiveness of tension-free vaginal tape (TVT) in comparison with the standard surgical interventions currently used. DATA SOURCES: Literature searches were carried out on electronic databases and websites for data covering the period 1966--2002. Other sources included references lists of relevant articles; selected experts in the field; abstracts of a limited number of conference proceedings titles; and the Internet. REVIEW METHODS: A systematic review of studies including comparisons of TVT with any of the comparators was conducted. Alternative treatments considered were abdominal retropubic colposuspension (including both open and laparoscopic colposuspension), traditional suburethral sling procedures and injectable agents (periurethral bulking agents). The identified studies were critically appraised and their results summarised. A Markov model comparing TVT with the comparators was developed using the results of the review of effectiveness and data on resource use and costs from previously conducted studies. The Markov model was used to estimate costs and quality-adjusted life-years for up to 10 years following surgery and it incorporated a probabilistic analysis and also sensitivity analysis around key assumptions of the model. RESULTS: Based on limited data from direct comparisons with TVT and from systematic reviews, laparoscopic colposuspension and traditional slings have broadly similar cure rates to TVT and open colposuspension, whereas injectable agents appear to have lower cure rates. TVT is less invasive than colposuspension and traditional sling procedures, and is also usually performed under regional or local anaesthesia. The principal operative complication is bladder perforation. There are currently no randomised controlled trial (RCT) data beyond 2 years post-surgery, and long-term effects are therefore currently not known reliably. TVT was more likely to be considered cost-effective compared with the other surgical procedures. Increasing the absolute probability of cure following TVT reduced the likelihood that TVT would be considered cost-effective. CONCLUSIONS: The long-term performance of TVT in terms of both continence and unanticipated adverse effects is not known reliably at the moment. Despite relatively few robust comparative data, it appears that in the short to medium term TVT's effectiveness approaches that of alternative procedures currently available, and is of lower cost. As TVT is a less invasive procedure, it is possible that some women who would currently be managed non-surgically will be considered eligible for TVT. Increased adoption of TVT will require additional surgeons proficient in the technique. It is likely that some of the higher rates of complications, e.g. bladder perforation, reported for TVT are associated with a 'learning curve'. Appropriate training will therefore be needed for surgeons new to the operation, in respect of both the technical aspects of the procedure and the choice of women suitable for the operation. Further research suggestions include unbiased assessments of longer term performance from follow-up of controlled trials or population-based registries; more data from methodologically sound RCTs using standard outcome measures; a surveillance system to detect longer term complications, if any, associated with the use of tape; and rigorous evaluation before extending the use of TVT to women who are currently managed non-surgically.

Inhibidores selectivos de COX-2 y analgesia / Selective COX-2 inhibitors and analgesia

No disponible

Laparoscopic techniques versus open techniques for inguinal hernia repair.

BACKGROUND: Inguinal hernia repair is the most frequently performed operation in general surgery. The standard method for inguinal hernia repair had changed little over a hundred years until the introduction of synthetic mesh. This mesh can be placed by either using an open approach or by using a minimal access laparoscopic technique. Although many studies have explored the relative merits and potential risks of laparoscopic surgery for the repair of inguinal hernia, most individual trials have been too small to show clear benefits of one type of surgical repair over another. OBJECTIVES: The objective of this review was to compare minimal access laparoscopic mesh techniques with open techniques. Comparisons of open mesh techniques versus open non-mesh techniques have been considered in a separate Cochrane review. SEARCH STRATEGY: We searched MEDLINE, EMBASE, and The Cochrane Central Controlled Trials Registry for relevant randomised controlled trials. The reference list of identified trials, journal supplements, relevant book chapters and conference proceedings were searched for further relevant trials. Through the EU Hernia Trialists Collaboration (EUHTC) communication took place with authors of identified randomised controlled trials to ask for information on any other recent and ongoing trials known to them. Specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials. The world wide web was also searched. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic groin hernia repair with open groin hernia repair were eligible for inclusion. Trials were included irrespective of the language in which they were reported. DATA COLLECTION AND ANALYSIS: Individual patient data were obtained, where possible, from the responsible trialist for all eligible studies. All reanalyses were cross-checked by the reviewers and verified by the trialists before inclusion. Where IPD were unavailable additional aggregate data were sought from trialists and published aggregate data checked and verified by the trialists. IPD were available for 25 trials, additional aggregated data for seven and published data only for nine. Where possible, time to event analysis for hernia recurrence and return to usual activities were performed on an intention to treat principle. The main analyses were based on all trials. Sensitivity analyses based on the data source and trial quality were also performed. Pre-defined subgroup analyses based on recurrent hernias, bilateral hernias and femoral hernias were also carried out. MAIN RESULTS: 41 published reports of eligible trials were included involving 7161 participants. Sample sizes ranged from 38 to 994, with follow-up from 6 weeks to 36 months. Duration of operation was longer in the laparoscopic groups (WMD 14.81 minutes, 95% CI 13.98 to 15.64; p<0001). Operative complications were uncommon for both methods but more frequent in the laparoscopic group for visceral (Overall 8/2315 versus 1/2599) and vascular (Overall 7/2498 versus 5/2758) injuries. Length of hospital stay did not differ between groups (WMD -0.04 days, 95% CI -0.08 to 0.00; p=0.05, but return to usual activity was earlier for laparoscopic groups (HR 0.56, 95%CI 0.51 to 0.61; p<0.0001 - equivalent to 7 days). The data available showed less persisting pain (Overall 290/2101 versus 459/2399; Peto OR 0.54, 95% CI 0.46 to 0.64; p<0.0001), and less persisting numbness (Overall 102/1419 versus 217/1624; Peto OR 0.38, 95% CI 0.4286 to 0.49; p<0.0001) in the laparoscopic groups. In total, 86 recurrences were reported amongst 3138 allocated laparoscopic repair and 109 amongst 3504 allocated to open repair (Peto OR 0.81, 95% CI 0.61 to 1.08; p = 0.16). The use of mesh during laparoscopic hernia repair is associated with a reduction in the risk of hernia recurrence, significantly so for the transabdominal preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus preperitoneal repair (TAPP) versus open non-mesh repair (overall 26/1440 versus 47/1119; Peto OR 0.45, 95% CI 0.28 to 0.72; p=0.0009). However, no difference was detected when comparing laparoscopic methods with open mesh methods of hernia repair. REVIEWER'S CONCLUSIONS: The use of mesh during laparoscopic hernia repair is associated with a relative reduction in the risk of hernia recurrence of around 30-50%. However, there is no apparent difference in recurrence between laparoscopic and open mesh methods of hernia repair. The data suggests less persisting pain and numbness following laparoscopic repair. Return to usual activities is faster. However, operation times are longer and there appears to be a higher risk of serious complication rate in respect of visceral (especially bladder) and vascular injuries.

Metal on metal hip resurfacing arthroplasty. An economic analysis.

This paper explores the cost utility of metal-on-metal hip resurfacing arthroplasty (MOM) as an alternative intervention to total hip replacement or 'watchful waiting' for patients with advanced hip disease. Early implant failure among younger and more active elderly patients can mean that the use of total hip replacement (THR) is delayed, with patients managed through 'watchful waiting', a combination of pain control and other non-surgical interventions. Information on costs is combined with evidence on effectiveness from a systematic review in a Markov model in order to estimate the incremental cost per quality adjusted life year (QALY) of MOM relative to THR and 'watchful waiting'.

Open mesh versus non-mesh for repair of femoral and inguinal hernia.

BACKGROUND: Inguinal hernia repair is the most frequent operation in general surgery. Until recently the standard procedure has been open musculo-aponeurotic repair using sutures under tension to close the defect but 'tension-free' repair using prosthetic mesh is becoming increasingly common in many countries. OBJECTIVES: The purpose of this review is to evaluate open mesh techniques in comparison with open non-mesh techniques for the surgical repair of groin hernia. SEARCH STRATEGY: Electronic databases were searched and further trials were sought from the reference lists of reports of known trials. Through the EU Hernia Trialists Collaboration authors of identified randomised controlled trials were asked for information on any other trials known to them. There was no language restriction. SELECTION CRITERIA: Studies were eligible for inclusion if they were randomised or quasi-randomised trials comparing either a) open mesh with open non-mesh repair of groin hernia or b) open flat mesh repair with plug and mesh repair of groin hernia. DATA COLLECTION AND ANALYSIS: For each outcome the results were derived using data from the best available source. The majority of data for this review came from individual patient data (IPD) supplied by the trialists. When these were unavailable data came from additional aggregated information or from published trial reports. All trials were analysed using the 'intention to treat' principle. MAIN RESULTS: Twenty trials comparing open mesh with open non-mesh repair were identified. Open mesh methods, on average, took 7-10 minutes less to perform than Shouldice procedures, but took 1-4 minutes longer than other non-mesh methods. There were no clear differences between mesh and non-mesh groups for haematomas, seromas or wound/superficial infections. Three serious operative complications were reported after open mesh repair and three following non-mesh repair. Overall, those in the mesh groups had a shorter length of hospital stay and quicker return to usual activities, but this pattern was not observed for all trials. There was a suggestion that persisting pain was less frequent after mesh repair than after non-mesh repair but this result was dependent on one trial and data were not available for 11 trials. There was no evidence of a difference between the groups with respect to persisting numbness. Fewer hernia recurrences were reported after mesh repair (Peto OR: 0.37, 95% CI: 0.26 to 0.51). There were too few data to reliably address differential effects for patients with recurrent, bilateral or femoral hernias. Two trials comparing flat mesh with plug and mesh were identified. There was no clear evidence of differences between the groups. REVIEWER'S CONCLUSIONS: There is evidence that the use of open mesh repair is associated with a reduction in the risk of recurrence of between 50% and 75%. Although the trials were heterogeneous there is also some evidence of quicker return to work and of lower rates of persisting pain following mesh repair.

Light therapy for seasonal affective disorder in primary care: randomised controlled trial.

BACKGROUND: Studies of light therapy have not been conducted previously in primary care. AIMS: To evaluate light therapy in primary care. METHOD: Fifty-seven participants with seasonal affective disorder were randomly allocated to 4 weeks of bright white or dim red light. Baseline expectations for treatment were assessed. Outcome was assessed with the Structured Interview Guide for the Hamilton Depression Scale, Seasonal Affective Disorder Version. RESULTS: Both groups showed decreases in symptom scores of more than 40%. There were no differences in proportions of responders in either group, regardless of the remission criteria applied, with around 60% (74% white light, 57% red light) meeting broad criteria for response and 31% (30% white light, 33% red light) meeting strict criteria. There were no differences in treatment expectations. CONCLUSIONS: Primary care patients with seasonal affective disorder improve after light therapy, but bright white light is not associated with greater improvements.