Outcome of revision surgery for adverse local tissue reactions in patients with recalled total hip arthroplasty.

INTRODUCTION: Recalls of total hip arthroplasty (THA) implants, including metal-on-metal (MoM) THA and dual taper stems, due to increased risk of adverse local tissue reaction (ALTR), represent a challenge for both surgeons and patients. This study aims to analyze the revision surgery outcomes for ALTR in patients with recalled THA implants. METHODS: A total of 118 consecutive patients who underwent revision surgery due to ALTR with recalled THA were analyzed. Sub-group analysis was performed for recalled MoM THAs, head-neck modular stems, and dual taper neck-stems. RESULTS: At a mean follow-up of 6.6 years, the complication and reoperation rates of the recalled THAs were 32.2% and 25.4% respectively. The most common post-revision complication was dislocation (16%). Revision of modular taper corrosion THA and high-grade intraoperative tissue damage were risk factors associated with post-revision complications. CONCLUSION: This study reports high complication and reoperation rates of recalled THAs at mid-term follow-up. The high revision surgery complication rates in both groups suggest the importance of a systematic evaluation of all THA patients with at-risk implants. LEVEL OF EVIDENCE: Level III, case control retrospective analysis.

Antimicrobial resistance point-of-care testing for gonorrhoea treatment regimens: cost-effectiveness and impact on ceftriaxone use of five hypothetical strategies compared with standard care in England sexual health clinics.

BackgroundWidespread ceftriaxone antimicrobial resistance (AMR) threatens Neisseria gonorrhoeae (NG) treatment, with few alternatives available. AMR point-of-care tests (AMR POCT) may enable alternative treatments, including abandoned regimens, sparing ceftriaxone use. We assessed cost-effectiveness of five hypothetical AMR POCT strategies: A-C included a second antibiotic alongside ceftriaxone; and D and E consisted of a single antibiotic alternative, compared with standard care (SC: ceftriaxone and azithromycin).AimAssess costs and effectiveness of AMR POCT strategies that optimise NG treatment and reduce ceftriaxone use.MethodsThe five AMR POCT treatment strategies were compared using a decision tree model simulating 38,870 NG-diagnosed England sexual health clinic (SHC) attendees; A micro-costing approach, representing cost to the SHC (for 2015/16), was employed. Primary outcomes were: total costs; percentage of patients given optimal treatment (regimens curing NG, without AMR); percentage of patients given non-ceftriaxone optimal treatment; cost-effectiveness (cost per optimal treatment gained).ResultsAll strategies cost more than SC. Strategy B (azithromycin and ciprofloxacin (azithromycin preferred); dual therapy) avoided most suboptimal treatments (n = 48) but cost most to implement (GBP 4,093,844 (EUR 5,474,656)). Strategy D (azithromycin AMR POCT; monotherapy) was most cost-effective for both cost per optimal treatments gained (GBP 414.67 (EUR 554.53)) and per ceftriaxone-sparing treatment (GBP 11.29 (EUR 15.09)) but with treatment failures (n = 34) and suboptimal treatments (n = 706).ConclusionsAMR POCT may enable improved antibiotic stewardship, but require net health system investment. A small reduction in test cost would enable monotherapy AMR POCT strategies to be cost-saving.

Comparison of open and minimally invasive surgery for intradural-extramedullary spine tumors.

OBJECT Patients with symptomatic intradural-extramedullary (ID-EM) tumors may be successfully treated with resection of the lesion and decompression of associated neural structures. Studies of patients undergoing open resection of these tumors have reported high rates of gross-total resection (GTR) with minimal long-term neurological deficit. Case reports and small case series have suggested that these patients may be successfully treated with minimally invasive surgery (MIS). These studies have been limited by small patient populations. Moreover, there are no studies directly comparing perioperative outcomes between patients treated with open resection and MIS. The objective of this study was to compare perioperative outcomes in patients with ID-EM tumors treated using open resection or MIS. METHODS A retrospective review was performed using data collected from 45 consecutive patients treated by open resection or MIS for ID-EM spine tumors. These patients were treated over a 9-year period between April 2003 and October 2012 at Northwestern University and the University of Chicago. Statistical analysis was performed to compare perioperative outcomes between the two groups. RESULTS Of the 45 patients in the study, 27 were treated with the MIS approach and 18 were treated with the open approach. Operative time was similar between the two groups: 256.3 minutes in the MIS group versus 241.1 minutes in the open group (p = 0.55). Estimated blood loss was significantly lower in the MIS group (133.7 ml) compared with the open group (558.8 ml) (p < 0.01). A GTR was achieved in 94.4% of the open cases and 92.6% of the MIS cases (p = 0.81). The mean hospital stay was significantly shorter in the MIS group (3.9 days) compared with the open group (6.1 days) (p < 0.01). There was no significant difference between the complication rates (p = 0.32) and reoperation rates (p = 0.33) between the two groups. Multivariate analysis demonstrated an increased rate of complications in cervical spine tumors (OR 15, p = 0.05). CONCLUSIONS Thoracolumbar ID-EM tumors may be safely and effectively treated with either the open approach or an MIS approach, with an equivalent rate of GTR, perioperative complication rate, and operative time. Patients treated with an MIS approach may benefit from a decrease in operative blood loss and shorter hospital stays.

Cost-Effectiveness Modeling of Prostate-Specific Membrane Antigen Positron Emission Tomography with Piflufolastat F 18 for the Initial Diagnosis of Patients with Prostate Cancer in the United States.

BACKGROUND AND OBJECTIVES: Piflufolastat F 18 is a novel prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) radiotracer that is superior to standard of care (SOC) imaging for the initial staging of prostate cancer and the detection of biochemical recurrence. As piflufolastat F 18 has been approved in the United States (US) for this indication, this modeling study assessed the cost effectiveness of piflufolastat F 18 versus fluciclovine F-18, gallium68-PSMA-11 (PSMA 11), and SOC imaging (a mix of bone scans, computed tomography, and magnetic resonance imaging) for the diagnosis and staging of prostate cancer from a US healthcare system perspective. PERSPECTIVE: A US third-party payer perspective was used, which for this population reflects a mix of commercial and Medicare, considering only direct healthcare costs. SETTING: This study utilized a tertiary healthcare setting. METHODS: A decision tree was used to map the diagnostic/treatment pathway, consisting of the proportion of patients with local, regional, distant, or no disease; prostate-specific antigen (PSA) ≤ 1.0 or > 1.0; and accuracy of imaging modalities. A Markov model predicted the long-term outcomes of disease progression according to treatment decisions. Inputs to the model were informed by data from the OSPREY and CONDOR clinical trials, public data, and the literature. Treatment mix included active surveillance, radiation therapy, prostatectomy, androgen deprivation therapy (ADT), and radiation therapy + ADT, informed by expert opinion. Outcomes included life-years (LY), quality-adjusted life-years (QALY), and the incremental cost-effectiveness ratio (ICER). All costs were reported in 2021 US dollars, using the US Bureau of Labor Statistics Consumer Price Index. A willingness-to-pay (WTP) threshold of $150,000 was considered cost effective, consistent with the upper range used as the standard for price benchmarks by the Institute for Clinical and Economic Review. The robustness of the base-case results was assessed in deterministic and probabilistic sensitivity analyses. RESULTS: Over a lifetime horizon, piflufolastat F 18 had the greatest effectiveness in terms of LYs (6.80) and QALYs (5.33); for the comparators, LYs ranged from 6.58 (SOC) to 6.76 (PSMA 11) and QALYs ranged from 5.12 (SOC) and 5.30 (PSMA 11). Piflufolastat F 18 was more cost effective compared with fluciclovine F 18, PSMA 11, and SOC, with ICERs of $21,122, $55,836, and $124,330 per QALY gained, respectively. Piflufolastat F 18 was associated with the greatest net monetary benefit ($627,918) compared with the other options at a WTP threshold of $150,000. The results of the deterministic and probabilistic sensitivity analyses supported the robustness of the base-case results. CONCLUSIONS: This study suggests that piflufolastat F 18 is a cost-effective diagnostic option for men with prostate cancer in the US, with higher associated LY, QALY, and greater net monetary benefit than fluciclovine F 18, PSMA 11, and SOC imaging.

Assessing the transition from intravenous to subcutaneous delivery of rituximab: Benefits for payers, health care professionals, and patients with lymphoma.

Subcutaneous (SC) administration of rituximab provides an opportunity for reduced patient treatment burden and increased healthcare efficiencies as an alternative to intravenous (IV) rituximab. There is minimal evidence comparing costs associated with SC and IV rituximab in a US setting. This research assessed the impact of transitioning patients from IV to SC rituximab for treatment of non-Hodgkin's lymphoma (NHL) from the US payer, provider, and patient perspective. We developed a model to estimate cost differences for transitioning 20% of a patient cohort from IV to SC rituximab. We included patients with incident diffuse large B-cell lymphoma, incident and recurrent follicular lymphoma, and incident and recurrent chronic lymphocytic leukemia. In the model, each patient received the same number of doses and that there was no difference in discontinuation between cohorts due to non-inferior efficacy and a similar safety profile. Model inputs were collected from published literature and publicly available data. Scenario analyses tested the impact of availability of low-cost biosimilars. In the base case (1,000,000 covered lives), we estimated a total of 157 patients, with 769 total drug administrations. A transition of 20% of patients from IV to SC was projected to generate $153,000 in payer savings, increase provider capacity by 270 hours, and free 470 hours of patient time. Scenario analyses suggest SC administration will be cost saving for payers even with a market where biosimilars approach 50% market share. A 20% transition to SC rituximab in a single cohort of patients has the potential to generate significant US health system value in the form of payer savings, increased practice capacity, and patient time.

Reconstruction with Total Scapular Reverse Total Shoulder Endoprosthesis after Radical Tumor Excision.

Malignant musculoskeletal tumors about the shoulder girdle region involving the scapula are fairly rare, but when diagnosed, challenging and complex surgical treatment may be warranted with the primary goal of improving patient survival. These tumors are typically extensive and infiltrative at the time of presentation, requiring radical resection to achieve margins and obtain local tumor control. Historically, forequarter amputation or flail extremity were the mainstays of treatment in these cases. Presently, with recent advances in diagnostics, imaging, adjuvant therapies, and surgical treatment, many patients presenting with malignant tumors involving the scapula are candidates for limb salvage surgery. Reconstruction with endoprosthesis seems to have gained acceptance as the preferred surgical treatment for such lesions, as this intervention has resulted in improved postoperative function and cosmesis, with an acceptable complication rate. We present our experience with recent advancement in these surgical efforts in the form of shoulder girdle reconstruction with total scapular reverse total shoulder prosthesis after radical tumor excision.

Budget Impact Analysis of Comprehensive Genomic Profiling in Patients With Advanced Non-Small-Cell Lung Cancer.

PURPOSE: This study assessed the economic impact of increased use of comprehensive genomic profiling (CGP) versus conventional testing strategies among patients with advanced non-small-cell lung cancer (aNSCLC) from a US commercial health plan perspective. METHODS: A decision analytic model was developed to estimate the incremental benefits and costs across testing methodologies (CGP v non-CGP), as well as across sample types (tissue-based and liquid-based), for patients with newly diagnosed aNSCLC. Model outcomes included total direct costs, testing costs, and per member per month budget impact. Secondary model outcomes included the number of patients needed to test with CGP to add 1 life-year, and the number of patients needed to test with CGP to treat one individual with a biomarker-matched therapy. RESULTS: In a hypothetical 2,000,000-member health plan, 790 members were estimated to have incident aNSCLC; 609 underwent molecular diagnostic testing with 122 (20%) tested with CGP (109 tissue-based and 13 liquid) in the base-case. An increase in CGP from 20% to 30% (an additional 61 patients tested with CGP) was associated with 3.11 additional life-years gained and a $0.01 in US dollars per member per month budget impact. Approximately 19.6 patients would need to be tested with CGP versus non-CGP to add one life-year and 5.9 patients would need to be tested with CGP to treat at least one patient with a biomarker-matched therapy. CONCLUSION: An increase in CGP from 20% to 30% among patients with aNSCLC undergoing molecular diagnostic testing was associated with modest budget impact, most of which was attributable to prolonged survival associated with increased use of more effective treatments.

Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation.

OBJECTIVE: To estimate the impact of using the Aptima messenger RNA (mRNA) high-risk human papilloma virus (HR-HPV) assay versus a DNA HR-HPV assay in a primary HPV cervical screening programme. DESIGN: One hypothetical cohort followed for 3 years through HPV primary cervical screening. SETTING: England. PARTICIPANTS: A hypothetical cohort of women aged 25-65 years tested in the National Health Service (NHS) Cervical Screening Programme (CSP) for first call or routine recall testing. METHODS: A decision tree parameterised with data from the CSP (2017/18) and the HORIZON study. Uncertainty analyses were conducted using data from the FOCAL and GAST studies, other DNA HPV tests in addition to one-way and probabilistic sensitivity and scenarios analyses, to test the robustness of results. INTERVENTIONS: Aptima mRNA HR-HPV assay and a DNA HR-HPV assay (cobas 4800 HPV assay). MAIN OUTCOME MEASURES: Primary: total colposcopies and total costs for the cohort. Secondary: total HPV and cytology tests, number lost to follow-up. RESULTS: At baseline for a population of 2.25 million women, an estimated £15.4 million (95% credibility intervals (CI) £6.5 to 24.1 million) could be saved and 28 009 (95% CI 27 499 to 28 527) unnecessary colposcopies averted if Aptima mRNA assays are used instead of a DNA assay, with 90 605 fewer unnecessary HR-HPV and 253 477 cytology tests performed. These savings are due to a lower number of HPV positive samples in the mRNA arm. When data from other primary HPV screening trials were compared, results indicated that using the Aptima mRNA assay generated cost savings and reduced testing in every scenario. CONCLUSION: Using the Aptima mRNA assay versus a DNA assay would almost certainly yield cost savings and reduce unnecessary testing and procedures, benefiting the NHS and women in the CSP.

Structural Competency: Curriculum for Medical Students, Residents, and Interprofessional Teams on the Structural Factors That Produce Health Disparities.

Introduction: Research on disparities in health and health care has demonstrated that social, economic, and political factors are key drivers of poor health outcomes. Yet the role of such structural forces on health and health care has been incorporated unevenly into medical training. The framework of structural competency offers a paradigm for training health professionals to recognize and respond to the impact of upstream, structural factors on patient health and health care. Methods: We report on a brief, interprofessional structural competency curriculum implemented in 32 distinct instances between 2015 and 2017 throughout the San Francisco Bay Area. In consultation with medical and interprofessional education experts, we developed open-ended, written-response surveys to qualitatively evaluate this curriculum's impact on participants. Qualitative data from 15 iterations were analyzed via directed thematic analysis, coding language, and concepts to identify key themes. Results: Three core themes emerged from analysis of participants' comments. First, participants valued the curriculum's focus on the application of the structural competency framework in real-world clinical, community, and policy contexts. Second, participants with clinical experience (residents, fellows, and faculty) reported that the curriculum helped them reframe how they thought about patients. Third, participants reported feeling reconnected to their original motivations for entering the health professions. Discussion: This structural competency curriculum fills a gap in health professional education by equipping learners to understand and respond to the role that social, economic, and political structural factors play in patient and community health.

Rapid testing and treatment for sexually transmitted infections improve patient care and yield public health benefits.

A service evaluation of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) testing and result notification in patients attending a rapid testing service (Dean Street Express [DSE]) compared with those attending an existing 'standard' sexual health clinic (56 Dean Street [56DS]), and modelling the impact of the new service from 1 June 2014 to 31 May 2015. PRIMARY OUTCOME: time from patients' sample collection to notification of test results at DSE compared with 56DS. Secondary outcomes estimated using a model: number of transmissions prevented and the number of new partner visits avoided and associated cost savings achieved due to rapid testing at DSE. In 2014/15, there were a total of 81,352 visits for CT/NG testing across 56DS (21,086) and DSE (60,266). Rapid testing resulted in a reduced mean time to notification of 8.68 days: 8.95 days for 56DS (95% CI 8.91-8.99) compared to 0.27 days for DSE (95% CI 0.26-0.28). Our model estimates that rapid testing at DSE would lead to 196 CT and/or NG transmissions prevented (2.5-97.5% centile range = 6-956) and lead to annual savings attributable to reduced numbers of partner attendances of £124,283 (2.5-97.5% centile range = £4260-590,331). DSE, a rapid testing service for asymptomatic infections, delivers faster time to result notification for CT and/or NG which enables faster treatment, reduces infectious periods and leads to fewer transmissions, partner attendances and clinic costs.

Modelling-based evaluation of the costs, benefits and cost-effectiveness of multipathogen point-of-care tests for sexually transmitted infections in symptomatic genitourinary medicine clinic attendees.

OBJECTIVES: To quantify the costs, benefits and cost-effectiveness of three multipathogen point-of-care (POC) testing strategies for detecting common sexually transmitted infections (STIs) compared with standard laboratory testing. DESIGN: Modelling study. SETTING: Genitourinary medicine (GUM) services in England. POPULATION: A hypothetical cohort of 965 988 people, representing the annual number attending GUM services symptomatic of lower genitourinary tract infection. INTERVENTIONS: The decision tree model considered costs and reimbursement to GUM services associated with diagnosing and managing STIs. Three strategies using hypothetical point-of-care tests (POCTs) were compared with standard care (SC) using laboratory-based testing. The strategies were: A) dual POCT for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG); B) triplex POCT for CT-NG and Mycoplasma genitalium (MG); C) quadruplex POCT for CT-NG-MG and Trichomonas vaginalis (TV). Data came from published literature and unpublished estimates. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were total costs and benefits (quality-adjusted life years (QALYs)) for each strategy (2016 GB, £) and associated incremental cost-effectiveness ratios (ICERs) between each of the POC strategies and SC. Secondary outcomes were inappropriate treatment of STIs, onward STI transmission, pelvic inflammatory disease in women, time to cure and total attendances. RESULTS: In the base-case analysis, POC strategy C, a quadruplex POCT, was the most cost-effective relative to the other strategies, with an ICER of £36 585 per QALY gained compared with SC when using microcosting, and cost-savings of £26 451 382 when using tariff costing. POC strategy C also generated the most benefits, with 240 467 fewer clinic attendances, 808 fewer onward STI transmissions and 235 135 averted inappropriate treatments compared with SC. CONCLUSIONS: Many benefits can be achieved by using multipathogen POCTs to improve STI diagnosis and management. Further evidence is needed on the underlying prevalence of STIs and SC delivery in the UK to reduce uncertainty in economic analyses.

The "basic" approach: a single-centre experience with a cost-reducing model for paediatric cardiac extracorporeal membrane oxygenation.

Objectives: Extracorporeal membrane oxygenation (ECMO) is a lifesaving but expensive therapy in terms of financial, technical and human resources. We report our experience with a 'basic' ECMO support model, consisting of ECMO initiated and managed without the constant presence of a bedside specialist, to assess safety, clinical outcomes and financial impact on our health system. Methods: We did a retrospective single-centre study of paediatric cardiac ECMO between January 2001 and March 2014. Outcomes included postimplant complications and survival at weaning and at discharge. We used activity based costing to compare the costs of current basic ECMO with those of a 'full optional' dedicated ECMO team (hypothesis 1); ECMO with a bedside nurse and perfusionist (hypothesis 2), and ECMO with a bedside perfusionist (hypothesis 3). Results: Basic cardiac ECMO was required for 121 patients (median age 75 days, median weight 4.4 kg). A total of 107 patients (88%) had congenital heart disease; 37 had univentricular physiology. The median duration of ECMO was 7 days (interquartile range [IQR], 4-15 days). Overall survival at weaning and at 30 days in the neonatal and paediatric age groups was 58.6% and 30.6%, respectively; these results were not significantly different from Extracorporeal Life Support Organization data. Cost analysis revealed a saving of €30 366, €22 144 and €13 837 for each patient on basic ECMO for hypotheses 1, 2 and 3, respectively. Conclusions: Despite reduced human, technical and economical resources, a basic ECMO model without a bedside specialist was associated with satisfactory survival and lower costs.

Hitting the Optimal Vaccination Percentage and the Risks of Error: Why to Miss Right.

OBJECTIVE: To determine the optimal level of vaccination coverage defined as the level that minimizes total costs and explore how economic results change with marginal changes to this level of coverage. METHODS: A susceptible-infected-recovered-vaccinated model designed to represent theoretical infectious diseases was created to simulate disease spread. Parameter inputs were defined to include ranges that could represent a variety of possible vaccine-preventable conditions. Costs included vaccine costs and disease costs. Health benefits were quantified as monetized quality adjusted life years lost from disease. Primary outcomes were the number of infected people and the total costs of vaccination. Optimization methods were used to determine population vaccination coverage that achieved a minimum cost given disease and vaccine characteristics. Sensitivity analyses explored the effects of changes in reproductive rates, costs and vaccine efficacies on primary outcomes. Further analysis examined the additional cost incurred if the optimal coverage levels were not achieved. RESULTS: Results indicate that the relationship between vaccine and disease cost is the main driver of the optimal vaccination level. Under a wide range of assumptions, vaccination beyond the optimal level is less expensive compared to vaccination below the optimal level. This observation did not hold when the cost of the vaccine cost becomes approximately equal to the cost of disease. DISCUSSION AND CONCLUSION: These results suggest that vaccination below the optimal level of coverage is more costly than vaccinating beyond the optimal level. This work helps provide information for assessing the impact of changes in vaccination coverage at a societal level.

U.S. and International In-Hospital Costs of Extracorporeal Membrane Oxygenation: a Systematic Review.

CONTEXT: The in-hospital costs of extracorporeal membrane oxygenation (ECMO) have not been well established. OBJECTIVE: To evaluate the in-hospital costs of ECMO technology in both US and non-US settings for all patient types. DATA SOURCES: Systematic review of English-language articles, using the PubMed, Embase, Web of Science and EconLit databases. Searches consisted of the terms 'ECMO' AND 'health expenditures' or 'resource use' or 'costs' or 'cost analysis' or 'cost(-)effectiveness' or 'cost(-)benefit' or 'cost(-)utility' or 'economic(-)evaluation' or 'economic' or 'QALY' or 'cost per quality-adjusted life year'. STUDY SELECTION: Only full scientific research articles were included. The exclusion criteria included papers that focused on pumpless ECMO, simulation training or decision support systems; papers that did not include human subjects or were not written in English; papers that did not mention ECMO, costs, economics or resource utilization; and papers that included only outside-hospital, infrastructure capital or device capital costs. DATA EXTRACTION: Data extraction was completed by one author, using predefined criteria. RESULTS: From the database searches, 1371 results were returned, 226 records underwent a full review and 18 studies were included in the final review. Three papers studied adult populations, two studied adult and paediatric populations, five studied only paediatric populations, one studied a paediatric and neonatal population, and the remaining seven exclusively examined ECMO in neonatal populations. The sample sizes ranged from 8 to 8753 patients. ECMO for respiratory conditions was the most common diagnosis category, followed by congenital diaphragmatic hernia (CDH) and then cardiac conditions. Most papers (n = 14) used retrospective cost collection. Only eight papers stated the perspective of the cost analysis. The results show a large variation in the cost of ECMO over multiple cost categories (e.g., range of total in-hospital costs of treatment: USD 42,554-537,554 [in 2013 values]). In the U.S.A., the reported costs of ECMO were highest for CDH repair, followed by cardiac conditions, and lowest for respiratory conditions. The US charges were highest for cardiac conditions. Outside the U.S.A., the ECMO cost was highest for cardiac conditions, followed by respiratory conditions, and lowest for CDH repair. No non-US studies reported charges. CONCLUSION: The current literature shows that a large variation exists in the in-hospital cost estimates for ECMO. Further research is needed to understand how the diagnosis, setting and other factors relate to this variation in the cost of this technology. Reliable costing methodologies and cost information will be critical to inform policymakers and stakeholders wishing to maximize the value of advanced medical technologies such as ECMO.

K-Wire fracture during minimally invasive transforaminal lumbar interbody fusion: Report of six cases and recommendations for avoidance and management.

BACKGROUND: Although rare, minimally invasive spine techniques do have the risk of intraoperative device failure. Kirschner wire (K-wire) fractures during minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) have not been previously reported. This report focuses on the incidence of k-wire fractures following MI-TLIF and describes techniques to help avoid and treat these fractures when they occur. INCLUSION CRITERIA: (i) patients underwent 1, 2, or 3 level MI-TLIF over a 10-year period and (ii) had a k-wire fracture leading to a retained fragment. Exclusion criteria included: >10° coronal curves, significant sagittal malalignment, infection, and preoperative instrumentation failure. RESULTS: Of 513 patients undergoing MI-TLIF, 6 (1.2%) sustained k-wire fracture (3 males, 3 females, mean age 43 ± 13 years). Complications included k-wire fracture alone (4 patients), cerebrospinal fluid (CSF) leak (1 patient), and both ileus and revision for hardware removal (1 patient). All six patients went home postoperatively. The mean follow-up duration was 27.7 ± 37.4 months. All retained k-wire fragments were located in the vertebral bodies at the tip of the pedicle screws; none breached the anterior cortex of the vertebral bodies. None of the k-wires migrated at final follow-up 7.8 years (93.7 months) postoperatively. Furthermore, no complications were attributed to retained k-wires. CONCLUSIONS: K-wire fractures during MI-TLIF are rare (incidence of 1.2%) and retained k-wire segments led to no postoperative complications (e.g. no migration).

In situ studies of phase separation and crystallization directed by Marangoni instabilities during spin-coating.

Results of a pioneering study are presented in which for the first time, crystallization, phase separation and Marangoni instabilities occurring during the spin-coating of polymer blends are directly visualized, in real-space and real-time. The results provide exciting new insights into the process of self-assembly, taking place during spin-coating, paving the way for the rational design of processing conditions, to allow desired morphologies to be obtained.

An exploration of violence, mental health and substance abuse in post-conflict Guatemala.

Guatemala's 36-year civil war officially ended in December 1996 after some 200,000 deaths and one million refugees. Despite the ceasefire, Guatemala continues to be a violent country with one of the highest homicide rates in the world. We investigated potential associations between violence, mental health, and substance abuse in post-conflict Guatemala using a community-based survey of 86 respondents living in urban and rural Guatemala. Overall, 17.4% of our respondents had at least one, direct violent experience during the civil war. In the post-conflict period, 90.7% of respondents reported being afraid that they might be hurt by violence, 40.7% screened positive for depression, 50.0% screened positive for PTSD, and 23.3% screened positive for alcohol dependence. Potential associations between prior violent experiences during the war and indicators of PTSD and aspects of alcohol dependence were found in regression-adjusted models (p < 0.05). Certain associations between prior civil war experiences, aspects of PTSD and alcohol dependence in this cohort are remarkable, raising concerns for the health and safety of the largely indigenous populations we studied. Higher than expected rates of depression, PTSD, and substance abuse in our cohort may be related to the ongoing violence, injury and fear that have persisted since the end of the civil war. These, in turn, have implications for the growing medical and surgical resources needed to address the continuing traumatic and post-traumatic complications in the post-conflict era. Limitations of the current study are discussed. These findings are useful in beginning to understand the downstream effects of the Guatemalan civil war, although a much larger, randomly sampled survey is now needed.

Effect of immunisation against gonadotrophin releasing hormone isoforms (mammalian GnRH-I, chicken GnRH-II and lamprey GnRH-III) on murine spermatogenesis.

In mammals, the hypothalamic decapeptide, gonadotrophin releasing hormone (GnRH-I), is regarded as the major fertility regulating peptide. However, a range of isoforms also exists, varying only in the core region between amino acids 5-8. The physiological role of two of these, GnRH-II and GnRH-III, remains controversial, particularly with regard to fertility. The basis of the present study was to examine whether there is potential for GnRH-II and GnRH-III to be developed into highly specific vaccines, and to determine what the impact of their neutralisation would be on fertility. Computer modelling was used to predict how many common amino acids could be sequentially removed from the N-terminus, without loss of conformational structure. Sequences predicted to retain structure, were synthesised and conjugated to tetanus toxoid. Male mice were actively immunised, in study weeks 0, 2, 4 and 6 and peptide specific ELISA carried out. Mice immunised with TT-GnRH-I, TT-GnRH-II and TT-GnRH-III conjugates induced high antibody titres to the respective peptide. However, serum from TT-GnRH-I treated mice showed cross-reactivity to GnRH-II and GnRH-III peptides, and serum from TT-GnRH-II immunised mice showed cross-reactivity to GnRH-III. On the other hand, serum from only two of the TT-GnRH-III treated animals showed cross-reactivity to GnRH-II. Histological examination of the testes enabled comparative quantification of the disruption to spermatogenesis. Immunisation against TT-GnRH-I and TT-GnRH-III caused 66% and 68%, respectively, of seminiferous tubules viewed to show evidence of spermatogenesis, compared with 82% and 92% against TT-GnRH-II and untreated controls, respectively. Endocrine analysis revealed that only the TT-GnRH-I immunised animals showed significant reduction (p<0.05) in follicle stimulating hormone, while testosterone levels were reduced in the TT-GnRH-I and TT-GnRH-III treated animals. Taken together, our data suggests that GnRH-I and GnRH-III are implicated in spermatogenesis, unlike GnRH-II.

Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs.

A modified GnRH peptide (CHWSYGLRPG-NH(2)) was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and formulated with Quil A saponin or a sustained release injectible PLGA (poly(lactide-co-glycolide)/triacetin). For the Quil A formulations, two administrations of TT conjugate at 3-weekly intervals were followed by two booster injections with the DT conjugate in entire ram lambs. With the PLGA formulations, only two injections were administered; the first containing TT and the second DT at 6-weekly intervals. Evaluation was carried out by comparing the specific antibody levels produced in relationship to hormone profiles and testicular changes. The Quil A formulation was considered the most effective, as it caused significant reduction in testosterone and follicle stimulating hormone levels, resulting in marked suppression of spermatogenesis.

Part II: influence of dimerization of a modified GnRH-I peptide sequence on a male antifertility vaccine.

PROBLEM: In the previous paper, we described how the tetanus toxoid (TT) conjugated monomer, CHWSYGLRPG-NH2, induced high neutralizing antibody titres, which resulted in decreased levels of testosterone and subsequent antifertility. However, its counterpart HWSYGLRPGC, induced low avidity antibody titres. We wanted to know whether peptide dimerization would improve the efficacy of both peptides. METHOD OF STUDY: Male Sprague-Dawley rats were immunized with modified dimerized GnRH-I peptides (HWSYGLRPGCCGPRLGYSWH and GPRLGYSWHCCHWSYGLRPG-NH2), with or without conjugation to TT. RESULTS: The unconjugated dimers were not effective in causing castration, although the first peptide dimer did induce production of antibodies. When conjugated to TT, both dimers showed the same level of efficacy in causing castration as each other. However, there were differences in antibody binding to native GnRH. CONCLUSIONS: Dimerization and conjugation to a carrier improved the antifertility efficacy of HWSYGLRPGC, whereas the conjugated monomer CHWSYGLRPG-NH2 showed a greater level of consistent castration than its conjugated dimer.