Extramedullary versus intramedullary fixation of unstable trochanteric femoral fractures (AO type 31-A2): a systematic review and meta-analysis.

OBJECTIVE: The aim of this systematic review was to compare extramedullary fixation and intramedullary fixation for AO type 31-A2 trochanteric fractures in the elderly, with regard to functional outcomes, complications, surgical outcomes, and costs. METHODS: Embase, Medline, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled trials (RCTs) and observational studies. Effect estimates were pooled across studies using random effects models. Results are presented as weighted risk ratio (RR) or weighted mean difference (MD) with corresponding 95% confidence interval (95% CI). RESULTS: Fourteen RCTs (2039 patients) and 13 observational studies (22,123 patients) were included. Statistically superior results in favor of intramedullary fixation were found for Harris Hip Score (MD 4.09, 95% CI 0.91-7.26, p = 0.04), Parker mobility score (MD - 0.67 95% CI - 1.2 to - 0.17, p = 0.009), lower extremity measure (MD - 4.07 95% CI - 7.4 to - 0.8, p = 0.02), time to full weight bearing (MD 1.14 weeks CI 0.92-1.35, p < 0.001), superficial infection (RR 2.06, 95% CI 1.18-3.58, p = 0.01), nonunion (RR 3.67, 95% CI 1.03-13.10, p = 0.05), fixation failure (RR 2.26, 95% CI 1.16-4.44, p = 0.02), leg shortening (MD 2.23 mm, 95% CI 0.81-3.65, p = 0.002), time to radiological bone healing (MD 2.19 months, 95% CI 0.56-3.83, p = 0.009), surgery duration (MD 11.63 min, 95% CI 2.63-20.62, p = 0.01), operative blood loss (MD 134.5 mL, 95% CI 51-218, p = 0.002), and tip-apex distance > 25 mm (RR 1.73, 95% CI 1.10-2.74, p = 0.02). No comparable cost/costs-effectiveness data were available. CONCLUSION: Current literature shows that several functional outcomes, complications, and surgical outcomes were statistically in favor of intramedullary fixation when compared with extramedullary fixation of AO/OTA 31-A2 fractures. However, as several of the differences found appear not to be clinically relevant and for many outcomes data remains sparse or heterogeneous, complete superiority of IM fixation for AO type 31-A2 fractures remains to be confirmed in a detailed cost-effectiveness analysis.

Extramedullary versus intramedullary fixation of stable trochanteric femoral fractures: a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis compared extramedullary fixation and intramedullary fixation for stable two-part trochanteric femoral fractures (AO type 31-A1) with regards to functional outcomes, complications, and surgical outcomes. METHODS: Embase, Medline, Web of Science, Cochrane Central Register of Controlled Trials, and Google Scholar were searched for randomized controlled trials (RCTs) and observational studies. Effect estimates were pooled across studies using random effects models. Results were presented as weighted risk ratio (RR) or weighted mean difference (MD) with corresponding 95% confidence interval (95% CI). RESULTS: Five RCTs (397 patients) and 14 observational studies (21,396 patients) were included. No significant differences in functional outcomes, complications, or surgical outcomes were found between extramedullary and intramedullary fixation devices, except for a difference in duration of surgery (MD 14.1 min, CI 5.76-22.33, p < 0.001) and intra-operative blood loss (MD 92.30 mL, CI 13.49-171.12, p = 0.02), favoring intramedullary fixation. CONCLUSION: Current literature shows no meaningful differences in complications, surgical, or functional outcomes between extramedullary and intramedullary fixation of stable two-part trochanteric femoral fractures. Both treatment options result in good outcomes. This study implicates that, costs should be taken into account when considering implants or comparing fixation methods in future research.

Adherence to the emergency management of severe burns referral criteria in burn patients admitted to a hospital with or without a specialized burn center.

BACKGROUND: The primary aim was to determine to what extent referral and admission of burn patients to a hospital with or without a burn center was in line with the EMSB referral criteria. METHODS: This was a retrospective, multicenter cohort study. Burn patients admitted from 2014 to 2018 to a hospital in the Southwest Netherland trauma region and Network Emergency Care Brabant were included in this study. Outcome measures were the adherence to the EMSB referral criteria. RESULTS: A total of 1790 patients were included, of whom 951 patients were primarily presented to a non-burn center. Of these patients, 666 (70.0%) were managed according to the referral criteria; 263 (27.7%) were appropriately not referred, 403 (42.4%) were appropriately referred. Twenty (2.1%) were overtransferred, and 265 (27.9%) undertransferred. In 1213 patients treated at a burn center 1119 (92.3%) met the referral criteria. Adherence was lowest for electrical (N = 4; 14.3%) and chemical burns (N = 16; 42.1%), and was highest in 'children ≥5% total body surface area (TBSA) burned' (N = 109; 83.2%). CONCLUSION: The overall adherence to the referral criteria of patients presented to a non-burn center was fairly high. However, approximately 25% was not transferred to a burn center while meeting the criteria. Most improvement for individual criteria can be achieved in patients with electrical and chemical burns.

Choice of diffusion tensor estimation approach affects fiber tractography of the fornix in preterm brain.

BACKGROUND AND PURPOSE: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results. MATERIALS AND METHODS: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method. RESULTS: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data. CONCLUSIONS: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome.

Optimal timing of cerebral MRI in preterm infants to predict long-term neurodevelopmental outcome: a systematic review.

SUMMARY: Advances in neonatal neuroimaging have improved detection of preterm brain injury responsible for abnormal neuromotor and cognitive development. Increasingly sophisticated MR imaging setups allow scanning during early preterm life. In this review, we investigated how brain MR imaging in preterm infants should be timed to best predict long-term outcome. Given the strong evidence that structural brain abnormalities are related to long-term neurodevelopment, MR imaging should preferably be performed at term-equivalent age. Early MR imaging is promising because it can guide early intervention studies and is indispensable in research on preterm brain injury.

Acquisition guidelines and quality assessment tools for analyzing neonatal diffusion tensor MRI data.

Diffusion tensor imaging is a valuable measure in clinical settings to assess diagnosis and prognosis of neonatal brain development. However, obtaining reliable images is not straightforward because of the tissue characteristics of the neonatal brain and the high likelihood of motion artifacts. In this review, we present guidelines on how to acquire DTI data of the neonatal brain and recommend high-quality data acquisition and processing as an essential means to obtain accurate and robust parametric maps. Sudden head movements are problematic for DTI in neonates, and these may lead to incorrect values. We describe strategies to minimize the corrupting effects both in terms of acquisition (eg, more gradient directions) and postprocessing (eg, tensor estimation methods). In addition, tools are described that can help assess whether a dataset is of sufficient quality for further assessment.

Image quality assessment of the right ventricle with three different delayed enhancement sequences in patients suspected of ARVC/D.

Histopathologic findings in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) are replacement of the normal myocardium with fatty and fibrous elements with preferential involvement of the right ventricle. The right ventricular fibrosis can be visualised by post-gadolinium delayed enhancement inversion recovery imaging (DE imaging). We compared the image quality of three different gradient echo MRI sequences for short axis DE imaging of the right ventricle (RV). We retrospectively analysed MRI scans performed between February 2005 and December 2008 in 97 patients (mean age: 41.2 years, 67% men) suspected of ARVC/D. For DE imaging either a 2D Phase Sensitive (PSIR), a 2D (2D) or a 3D (3D) inversion recovery sequence was used in respectively 38, 32 and 27 MRI-examinations. The RV, divided in 10 segments, was assessed for image quality by two radiologists in random sequence. A consensus reading was performed if results differed between the two readings. Image quality was good in 24% of all segments in the 3D group, 66% in the 2D group and 79% in the PSIR group. Poor image quality was observed in 51% (3D), 10% (2D), and 2% (PSIR) of all segments. Exams were considered suitable for clinical use in 7% of exams in the 3D group, 75% of exams in the 2D group and 90% of exams of the PSIR group. Breathing-artifacts occurred in 22% (3D), 59% (2D) and 53% (PSIR). Motion-artifacts occurred in 56% (3D), 28% (2D) and 29% (PSIR). Post-gadolinium imaging using the PSIR sequence results in better and more consistent image quality of the RV compared to the 2D and 3D sequences.

The dynamics of Wuchereria bancrofti infection: a model-based analysis of longitudinal data from Pondicherry, India.

This paper presents a model-based analysis of longitudinal data describing the impact of integrated vector management on the intensity of Wuchereria bancrofti infection in Pondicherry, India. The aims of this analysis were (1) to gain insight into the dynamics of infection, with emphasis on the possible role of immunity, and (2) to develop a model that can be used to predict the effects of control. Using the LYMFASIM computer simulation program, two models with different types of immunity (anti-L3 larvae or anti-adult worm fecundity) were compared with a model without immunity. Parameters were estimated by fitting the models to data from 5071 individuals with microfilaria-density measurement before and after cessation of a 5-year vector management programme. A good fit, in particular of the convex shape of the age-prevalence curve, required inclusion of anti-L3 or anti-fecundity immunity in the model. An individual's immune-responsiveness was found to halve in approximately 10 years after cessation of boosting. Explanation of the large variation in Mf-density required considerable variation between individuals in exposure and immune responsiveness. The mean life-span of the parasite was estimated at about 10 years. For the post-control period, the models predict a further decline in Mf prevalence, which agrees well with observations made 3 and 6 years after cessation of the integrated vector management programme.

Can ivermectin mass treatments eliminate onchocerciasis in Africa?

OBJECTIVE: To elucidate the conditions in which mass treatment with ivermectin reduces the transmission of Onchocerca volvulus sufficiently to eliminate infection from an African community. METHODS: ONCHOSIM, a microsimulation model for onchocerciasis transmission, was used to explore the implications of different treatment intervals, coverage levels and precontrol endemicities for the likelihood of elimination. FINDINGS: Simulations suggested that control strategies based exclusively on ivermectin mass treatments could eliminate onchocerciasis. The duration of treatment required to eliminate infection depended heavily on the treatment programme and precontrol endemicity. In areas with medium to high levels of infection, annual mass treatments with 65% coverage for at least 25 years were necessary. Model predictions suggested that durations exceeding 35 years would be required if there were much heterogeneity in exposure to vector bites and, consequently, wide individual variation in microfilaria counts. If the treatment interval were reduced from 12 to 6 months the time for completion of the programme could be more than halved and elimination could be accomplished in areas of hyperendemicity, provided that the effects of each treatment would be the same as with annual treatments. However, it was doubtful whether high coverage levels could be sustained long enough to achieve worldwide eradication. CONCLUSION: Elimination of onchocerciasis from most endemic foci in Africa appears to be possible. However, the requirements in terms of duration, coverage, and frequency of treatment may be prohibitive in highly endemic areas.

Macrofilaricides and onchocerciasis control, mathematical modelling of the prospects for elimination.

BACKGROUND: In most endemic parts of the world, onchocerciasis (river blindness) control relies, or will soon rely, exclusively on mass treatment with the microfilaricide ivermectin. Worldwide eradication of the parasite by means of this drug is unlikely. Macrofilaricidal drugs are currently being developed for human use. METHODS: We used ONCHOSIM, a microsimulation mathematical model of the dynamics of onchocerciasis transmission, to explore the potentials of a hypothetical macrofilaricidal drug for the elimination of onchocerciasis under different epidemiological conditions, as characterized by previous intervention strategies, vectorial capacity and levels of coverage. RESULTS: With a high vector biting rate and poor coverage, a very effective macrofilaricide would appear to have a substantially higher potential for achieving elimination of the parasite than does ivermectin. CONCLUSIONS: Macrofilaricides have a substantially higher potential for achieving onchocerciasis elimination than ivermectin, but high coverage levels are still key. When these drugs become available, onchocerciasis elimination strategies should be reconsidered. In view of the impact of control efforts preceding the introduction of macrofilaricides on the success of elimination, it is important to sustain current control efforts.

Helicobacter pylori genotypes may determine gastric histopathology.

The outcome of Helicobacter pylori infection has been associated with specific virulence-associated bacterial genotypes. The present study aimed to investigate the gastric histopathology in Portuguese and Colombian patients infected with H. pylori and to assess its relationship with bacterial virulence-associated vacA, cagA, and iceA genotypes. A total of 370 patients from Portugal (n = 192) and Colombia (n = 178) were studied. Corpus and antrum biopsy specimens were collected from each individual. Histopathological features were recorded and graded according to the updated Sydney system. H. pylori vacA, cagA, and iceA genes were directly genotyped in the gastric biopsy specimens by polymerase chain reaction and reverse hybridization. Despite the significant differences between the Portuguese and Colombian patient groups, highly similar results were observed with respect to the relation between H. pylori genotypes and histopathology. H. pylori vacA s1, vacA m1, cagA+ genotypes were significantly associated with a higher H. pylori density, higher degrees of lymphocytic and neutrophilic infiltrates, atrophy, the type of intestinal metaplasia, and presence of epithelial damage. The iceA1 genotype was only associated with epithelial damage in Portuguese patients. These findings show that distinct H. pylori genotypes are strongly associated with histopathological findings in the stomach, confirming their relevance for the development of H. pylori-associated gastric pathology.

Effectiveness of annual ivermectin treatment for Wuchereria bancrofti infection.

Using estimates for the anthelmintic efficacy of a single dose of ivermectin in the treatment of lymphatic filariasis patients, Anton Plaisier, Wilma Stolk, Gerrit van Oortmarssen and Dik Habbema here present and discuss model predictions of the impact of a five-year programme of annual community treatment on the intensity of infection. They show that the effectiveness of such programmes in terms of reductions in the microfilarial density depends critically on the treatment coverage and the pattern of attendance at repeated mass administrations. Improving these factors will possibly be more important than improving the efficacy of ivermectin by increasing its dosage or by adding other drugs.

Importance of Helicobacter pylori cagA and vacA status for the efficacy of antibiotic treatment.

BACKGROUND: Virulence factors of Helicobacter pylori are associated with peptic ulcer disease and may be also associated with the efficacy of treatment. AIMS: To determine the relation between the vacA and the cagA status of H pylori, clinical disease, and treatment outcome. PATIENTS: 121 patients with H pylori infection and peptic ulcer disease or functional dyspepsia were treated by quadruple antibiotic therapy in two groups for one and two days, respectively. METHODS: DNA was isolated from gastric antral biopsy specimens, taken before and after treatment, and the vacA and cagA status was determined by polymerase chain reaction and reverse hybridisation. RESULTS: Peptic ulcer disease was significantly associated with the vacA s1 type, and cagA positivity, but not with the vacA m type. Treatment efficacy was significantly higher in patients with peptic ulcer disease, or infected with cagA+/vacA s1 strains. CONCLUSIONS: The strong association between the cagA and vacA status and peptic ulcer disease was confirmed. Cure rates seem to be higher for patients with cagA+/vacA s1 H pylori strains, which is consistent with the higher cure rate observed among ulcer patients compared with functional dyspepsia patients. Therefore, treatment studies may require stratification for presence of ulcers as well as H pylori genotypes.

Efficacy of ivermectin in the treatment of Wuchereria bancrofti infection: a model-based analysis of trial results.

Ivermectin is a promising drug for the treatment of lymphatic filariasis. A meta-analysis of trials investigating the effects of a single treatment suggested a dose-dependent effect on the production of microfilariae (mf) by adult Wuchereria bancrofti parasites. A mathematical model that describes the parasite dynamics in the human host and the impact of ivermectin treatment is presented and its outputs compared with these trials. The calculated trend in mf density after treatment appears to be particularly sensitive to the assumption about the mean life-span of mf. Adopting 0.5-2 years as a range of plausible values for this mf life-span, the model is used to estimate the impact of treatment on the parasite. It is found that irrespective of dosage, ivermectin eliminates 100% of the blood mf from a patient. Furthermore, at a dosage level of 400 micrograms/kg a single treatment irreversibly reduces the mf production of the adult parasites by at least 65%. For a dosage of 200 micrograms/kg this reduction is at least 35%. No such effect can be concluded from the results of trials using lower dosages.

Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori.

BACKGROUND & AIMS: Clinical outcome of Helicobacter pylori infection may be associated with specific virulence-associated bacterial genotypes. The aim of this study was to assess the relationships between H. pylori cagA, vacA, and iceA status and severity of disease. METHODS: Gastric biopsy specimens from 94 patients in The Netherlands were analyzed by polymerase chain reaction and reverse hybridization. RESULTS: cagA was present in 63 (67%) of 94 cases and was associated with peptic ulcer disease (P = 0.0019). vacA geno-types s1a/m1, s1b/m2, s1b/m1, s1b/m2, and s2/m2 were found in 36.2%, 23.4%, 2.1%, 5.3%, and 20.2%, respectively. Ten isolates (10.6%) contained multiple vacA genotypes. The presence of peptic ulcers was associated with type s1 strains (P = 0.0006) but not with the m type (P = 0.2035). cagA and vacA s1 were strongly associated (P < 10(-5)). iceA1 was found in 53 (56.4%) and iceA2 in 25 (26.6%) of the 94 cases. In 14 isolates (14.9%), both iceA alleles were found, and 2 (2.1%) were negative for both iceA1 and iceA2. iceA1 was also associated with peptic ulcer disease (P = 0.0042). The iceA allelic type was independent of the cagA and vacA status. CONCLUSIONS: vacA s1, cagA, and iceA1 are markers of H. pylori strains that are more likely to lead to ulcer disease.

The relationship between microfilarial load in the human host and uptake and development of Wuchereria bancrofti microfilariae by Culex quinquefasciatus: a study under natural conditions.

The uptake of Wuchereria bancrofti microfilariae (Mf) by Culex quinquefasciatus and their development in relation to human Mf density were quantified by allowing a total of 1096 wild mosquitoes to feed on 13 volunteers sleeping under partially open bed-nets. For each volunteer, each hour between 18.00 and 06.00 h the Mf density in finger-prick blood was determined and engorged mosquitoes collected. Each hourly collection of mosquitoes was kept separately. Half of them was dissected within 18 h post-feeding for the presence of ingested Mf, the other half was reared for 12 days to allow for the development of L3 larvae. About 20% of the latter mosquitoes died during these 12 days and these harboured significantly more larvae than the surviving ones, which could be an indication of excess-mortality among heavily infected mosquitoes. Assuming that variability in Mf uptake and in the number of developed L3 larvae can be described by a negative binomial distribution, a maximum-likelihood procedure was applied to estimate the relationship between human Mf density and both the arithmetic mean Mf uptake and L3 development. Both were adequately described by a saturating hyperbolic function that significantly differed from linearity. The saturation level for Mf was estimated at 29 (CI: 20-54) and for L3 larvae at 6.6 (CI: 4.3-17.0). Next, the L3 yield was related to Mf uptake indicating that the W. bancrofti-C. quinquefasciatus complex shows 'limitation', i.e. a decreasing yield for an increasing uptake. Both the number of Mf ingested and the number of L3 larvae developing per mosquito were found to be highly aggregated, with the level of aggregation decreasing in a non-linear way with human Mf density.

The LYMFASIM simulation program for modeling lymphatic filariasis and its control.

The LYMFASIM modeling framework for the transmission and control of the tropical parasitic disease lymphatic filariasis is described and its use in the context of an endemic community in north-eastern Brazil is illustrated. Lymphatic filariasis is a disease with a complex natural history with many unknowns. This complicates decision making with respect to control strategies. With LYMFASIM, a variety of hypotheses can be tested about the life history of the parasite Wuchereria bancrofti, its transmission from man to man through mosquitoes, the role of the immune system in regulating parasite numbers, the development of disease symptoms, and the effects of control measures (drug treatment or mosquito control). The implications of alternative assumptions and uncertainty about the quantification of parameters for the effectiveness of control strategies can be investigated. Thanks to the use of stochastic microsimulation, LYMFASIM is highly flexible and can be adapted and extended as new knowledge emerges.

Ivermectin for the chemotherapy of bancroftian filariasis: a meta-analysis of the effect of single treatment.

The efficacy and safety of ivermectin in the treatment of filariasis due to Wuchereria bancrofti was assessed by a meta-analysis of the results from 15 published clinical trials. Seven hundred and forty-eight microfilaraemic patients were enrolled in 7 dose-finding and 8 comparative studies. Administered as a single dose, ivermectin induced nearly complete clearance of microfilariae from the blood from the first day to 30 days post-treatment, followed by gradual recurrence of microfilaraemia and increase in its intensity. Higher doses of ivermectin showed greater clearance effects and maintained lower microfilaraemia levels for a longer time. The adverse reactions caused by the drug were flu-like, transient, generally mild and well tolerated by patients. The frequency and intensity of adverse reactions were strongly associated with pretreatment microfilaria counts in the blood, but independent of dose. The findings of the meta-analysis suggest that ivermectin given at a single annual dose of 200 micrograms/kg body weight or higher, whether or not in combination with DEC, has great potential for therapeutic strategies to control bancroftian filariasis.

Required duration of combined annual ivermectin treatment and vector control in the Onchocerciasis Control Programme in west Africa.

In the extension areas of the Onchocerciasis Control Programme in West Africa, aerial larviciding is supplemented with annual ivermectin treatment, mainly to achieve better control of morbidity. The purpose of this study is to determine whether and to what extent the addition of annual ivermectin treatment permits earlier cessation of vector control than originally recommended. The effectiveness of combined ivermectin distribution and vector control was assessed using an epidemiological model. Model predictions suggest that, dependent on the pre-control endemicity of the area and the proportion of persons treated during each ivermectin round, large-scale annual treatment permits a considerable reduction in the duration of vector control. Taking into account uncertainty about the efficacy of ivermectin, our results indicate that, provided treatment coverage is at least 65% and there is no importation of infection from elsewhere, 12 years of combined control will be sufficient to reduce the risk of recrudescence to below 1% in even the most afflicted areas.