Limited available data for dosing in obesity of the medicines used in this case are discussed, with the emphasis on ertapenem. The case illustrates the difficulties in dosing medicines to morbidly overweight patients. The number of such patients is increasing but data on adequate doses of medicines are scarce. We demonstrate that ertapenem 1,5 g i.v. once daily provided adequate drug exposure for susceptible bacteria in a 250 kg patient with normal renal function. The case suggests the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients. Vd) which could be increased due to increased lean body mass and increased adipose tissue, binding to plasma proteins, metabolism, and elimination. eGFR and tubular secretion have been reported to increase in obesity [Obesity may influence many aspects of the pharmacokinetics (PK) of medicines such as the volume of distribution ( obesity . All the obesity .Ertapenem is a highly protein-bound (>90%) and mostly renally eliminated carbapenem antibiotic with low volume of distribution, indicated for the treatment of intra-abdominal infections, community acquired pneumonia, and skin and soft tissue infections caused by susceptible bacteria . The staAlthough anticipated alterations in the PK of ertapenem could possibly lead to changes in dosing requirements, increased dosing might be associated with adverse effects. Reduced dosing of ertapenem is recommended to patients with renal failure and cases of central nervous system toxicity  have been described in this patient population , 6. Moni2. Enterobacter aerogenes  was cultivated from tracheal aspirate and treatment was started with ertapenem 1,5 g per day.A 58-year-old morbidly obese man was admitted to the ICU of Tartu University Hospital, Estonia, with bilateral bacterial pneumonia , acute respiratory failure, and sepsis. Attempt to assess the patient's body weight with ICU bed equipped with weight scales resulted in alarm that 250 kg is exceeded, while no other equipment for precise measurements of that range of weight was available. Taking his height of 178 cm, his body mass index is >85 kg/mThe dose of 1,5 g was chosen empirically. SPC recommends 1 g daily; we increased the dose arbitrarily with the assumption to somewhat increased volume distribution in this particular patient. The albumin levels and renal function were close to normal through the entire treatment period . Thanks Cmax) of ertapenem at steady state was 106.66 mg/L and through concentration (Cmin) 3.38 mg/L. According to the product information, the average Cmax and Cmin of ertapenem following a single 1 g intravenous dose in healthy young adults were 155 mg/L and 1 mg/L, respectively.The measured maximum total concentration  and clinical symptoms resolved.Vdss) than subjects with normal body weight (Vdss in adults is approximately 8 litres (0.11 litres/kg)).In this superobese patient, the maximum ertapenem serum concentration remained relatively low despite the administration of 150% of recommended daily dose. This may indicate that this subgroup of patients has somewhat higher volume of distribution  could be higher in morbidly overweight subjects  compared to classes I-II obese subjects (mean increase in V1 of approximately 40% [2). On day 2, the Vdss was 57.8 litres in patients with a 53-kg fat-free mass [Vdss of ertapenem are not clear.The literature data whether to use ideal, lean, or actual body weight for ts BMI, >0 kg/m2 cCmin of our patient might reflect lower rate of elimination, although the renal function according to eGFR was normal. Another possible explanation is the serum albumin effect, as ertapenem is highly protein-bound drug [The higher und drug . The serfT>MIC = 100%).The PK parameter most correlated to the antibacterial efficacy of ertapenem is the time plasma concentration exceeding the MIC of the infecting organism . For bacOur results suggest that the 1,5 g dose of ertapenem could provide adequate drug exposure for superobese patients with normal renal function for achieving the pharmacodynamic targets. The case also demonstrates the usefulness of therapeutic drug monitoring of antibiotics, especially in critically ill patients. However, therapeutic drug monitoring of several antibiotics is not routinely available. There are several limitations of this study. There are many factors during the intensive care treatment and patient's clinical situation that could affect the generalizability of our results and to establish cause-effect relationship. Further research is needed on the adequate dosing of ertapenem in obese critical care patients.


Oxidative stress is known as the leading factor responsible for varicocele-related infertility and for that reason, many antioxidant therapies have been proposed. Considering that, we evaluated the reproductive outcomes and fertility of varicocelized rats and the impact of chrysin within these parameters. The animals were allocated into three groups: sham (control), varicocele treated via gavage with 50 mg/kg/day of chrysin (V1), or vehicle (V2) for 56 days. Chrysin treatment prevented oxidative damage resulting from varicocele by decreasing testicular concentrations of malondialdehyde and sperm DNA fragmentation. It also improved histological aspect of the testis and maintained morphometric parameters similar to the sham group. Furthermore, there were no differences in body and reproductive organ weights, histopathological analysis of epididymis, sperm counts and morphology, testosterone levels, sexual behavior, and fertility parameters among experimental groups. Our results reinforce the idea that injuries provoked by experimental varicocele are related, at least in part, to oxidative stress. Moreover, varicocele showed bilateral deleterious effects without interfering with fertility. Chrysin administration significantly ameliorated sperm parameters, protecting the reproductive system against varicocele damages. For that reason, chrysin might be an alternative adjuvant therapy to improve sperm quality in men presenting this condition. Infertility is one of the main public health problems, and in more than 40% of these cases, male disorders are involved. In this context, varicocele is considered the leading cause of infertility once it is present in approximately 15% of the male population, 35% of men with primary infertility and 70–80% with secondary infertility . In addiEven though varicocele is known and studied for many years, the physiopathological mechanisms underlying the varicocele have not yet been fully elucidated. However, some theories that include venous stasis leading to hypoxia and testicular hyperthermia, reflux of toxic adrenal and renal metabolites, and hormonal dysfunction and increased oxidative stress (OS) have been proposed .Since men with varicocele present high levels of ROS, nitric oxide (NO), and lipid peroxidation products like malondialdehyde (MDA), as well as decrease in antioxidant defenses, it is believed that OS is a key element in the varicocele-related infertility .Usually, men are advised to submit to a surgical procedure known as varicocelectomy, which is considered efficient once it improves seminal and hormonal parameters –11. HoweChrysin, a flavonoid found in honey, propolis, and plant extracts, is a potent antioxidant that has been widely studied due to its mechanism of action that prevents conversion of testosterone to estrogen through inhibition of enzyme CYP19 , 17. ThiWistar male  and female rats  were supplied by the Central Biotherium of São Paulo State University (UNESP), Botucatu, and maintained under controlled environment with 23°C, 12/12 h light-dark cycle with free access to food and tap water. The experimental procedures were approved by the local Ethics Committee for the Use of Experimental Animals of the University of São Paulo State (protocol number 772-CEUA) and are in accordance with the Guide for the Care and Use of Laboratory Animals .n = 5–10) and varicocele groups received daily oral gavage dose of 50 mg/kg/day of chrysin  diluted in vehicle (corn oil and DMSO) or only vehicle solution  for 56 days. The treatment period was chosen based on the duration of spermatogenesis in rats, which is approximately 56 days, since it requires 4.5 cycles within 13 days each, of the seminiferous epithelium in order for the spermatogonia to become spermatozoa [In all experiments, male rats were allocated into three experimental groups: sham-operate  78–80 by partial occlusion of the left renal vein using the method described by Turner  with modn = 10; V1 n = 8; V2 n = 10) were euthanized by decapitation at the 57th day of treatment in order to assess body and reproductive organ weights, to evaluate the histological aspect of testis and epididymis, and to perform the morphometric analysis of the testis.In this experiment, Twenty-eight adult male rats  were stained with hematoxylin and eosin (HE) and examined under light microscopy. Testicular evaluation was conducted by analyzing a hundred seminiferous tubules per animal, randomly chosen, and classified as normal (organized germ cell layers in the seminiferous epithelium) or abnormal . The testicular interstitium was also evaluated but in a qualitative manner. Regarding the epididymis, the histological examination was qualitative. The entire longitudinal section was evaluated for the structure and aspect of epithelium, lumen, and interstitium.Testes and epididymides after weighted were fixed in Bouin's solution  for 24 h. The organs were immersed in paraffin wax and sectioned in 5 The diameter of the seminiferous tubules and height of germinal epithelium (stage IX of spermatogenesis) were evaluated in 10 sections of seminiferous tubules per animal.n = 8 per group) were euthanized and had their blood collected for hormonal measurements, the testis was excised for sperm count and epididymal portions were used for evaluation of sperm motility, morphology, count, and comet assay.Following the same experimental protocol as the previous step, twenty-four adult male rats  and subsequently was stored at −20°C. The concentration of testosterone (serum and intratesticular) was accessed using ImmuChem™ Double Antibody Testosterone 125I RIA Kit, and intra-assay variability for this hormone was 4.1%.The epididymis was placed in a small petri dish containing 1 mL of modified human tubal fluid (HTF) medium (Irvine Scientific) prewarmed to 34°C. The proximal cauda was perforated and sperm suspension was transferred to a Makler chamber maintained at 34°C. Through a phase-contrast microscope at 400x magnification, one hundred sperm were classified as mobile and immobile.μL of sperm solution (the same used for motility assay) was aliquoted and added to 900 μL of 10% formol saline. Then, smears were prepared on histological slides, which were left to air dry for 40 minutes and observed under a phase-contrast microscope at 400x magnification. A total of 200 spermatozoa per animal were evaluated and abnormalities were classified in two main categories: head abnormalities  and tail abnormalities  [For sperm morphology analysis, 100  bended) , 33.6 cells/mL. An aliquot (75 μL) of the solution was placed on precoated slides with 1% normal melting point agarose . The slide was first immersed in lysis buffer  containing 40 mM DTT and 2% Triton X-100 for 1 h at 4°C and subsequently in lysis buffer containing proteinase K (0.1 mg/mL), for 2.5 hrs at 37°C. The DNA was fractionated by alkaline electrophoresis  at 3 V/cm and 270 mAmps for 45 mins. Finally, the slides were washed with water, fixed in absolute ethanol, and air-dried and stored in the dark until analysis. For microscopy, the slides were stained with SYBR® Gold  and analyzed using the Comet Assay IV software . A total of 50 cells were analyzed per slide  and DNA damage was measured by analyzing the tail intensity (% of migrated DNA).Sperm DNA fragmentation was evaluated by the comet assay as previously described  with theAfter collecting the testis from both sides, these organs were decapsulated and then frozen at −20°C until the homogenization previously described by , with adOn the 57th day of treatment, twenty-six male rats were paired with adult females in order to evaluate sexual behavior and reproductive performance. After analyzing these parameters, the animals were euthanized by decapitation and had both testes and epididymides weighted and stored at −80°C for posterior lipid peroxidation assay.n = 9; V1, n = 7; V2, n = 10) were placed in boxes of polycarbonate crystal, for 5 minutes before the introduction of one sexually receptive adult female. The behavior assay started at the time that female was placed, and the following measures were recorded for the next 40 minutes: latency of the first mount, number of mounts, latency of the first intromission, number of intromissions preceding the first ejaculation, latency of first ejaculation, and number of ejaculations [Sexual behavior was performed on the 57th day of treatment for 4 hours in the dark phase of the cycle under red illumination. For this, 26 male rats . The protein content in the homogenate was determined by Bradford assay  using boμL of the obtained homogenate was added to 500 μL thiobarbituric acid (0.8%), 500 μL acetic acid buffer, 200 μL of SDS (8.1%), and 100 μL of water. These samples were then incubated for 2 hours at 95°C and allowed to cool to room temperature. The absorbance was measured at 532 nm. All of the assays were performed in duplicate, and the amount of lipid peroxidation was expressed as nmol TBARS/g protein.The level of lipid peroxidation was assessed using the TBARS assay by Draper and Hadley . Brieflyχ2 test was used for categorical dependent variables. Differences were considered significant when p ≤ 0.05. The statistical analyses were performed by the software GraphPad Prism (version 5.0).Data were expressed as mean ± standard error of mean (SEM) or median and interquartile range. Parametric variables were compared by ANOVA followed by Tukey's test, nonparametric variables were compared by Kruskal-Wallis followed by Dunn's test, and Final body weight and both relative and absolute reproductive organ weights were similar among experimental groups .Histopathological analysis of epididymis did not reveale any alterations (data not shown) among experimental groups. However, varicocele induction significantly increased the number of seminiferous tubules with abnormalities in ipsilateral testis and the treatment with chrysin decreased this parameter to similar values to sham Figures . DespiteSperm counts in the testis and epididymis of the V2 group  as well p < 0.02), and despite the treatment with chrysin had improved this parameter, no differences were documented  in ipsilateral and contralateral sides, and the treatment with chrysin improved this parameter, decreasing the percentage of tail intensity to sham levels (The comet assay showed that varicocelized rats (V2) had an extremely significant increase in sperm DNA fragmentation (m levels .p < 0.0005) and contralateral (p < 0.01) sides when compared to chrysin and sham groups  . ConsideBesides compromising the integrity of the sperm plasma membrane, ROS may also interfere in cellular mechanisms through degradation of proteins. For that reason, nuclear and mitochondrial DNA of germ cells is highly susceptible to double-strand breaks . ConsideMoreover, another factor that is involved in the impairment of sperm quality is hypoxia. Studies have demonstrated that, along with OS , testis Similar to previous reports , anotherAlthough varicocele is often associated with impaired spermatogenesis and hormonal dysfunction –66, our Regarding sperm motility, varicocele caused a significant decrease in mobile sperm in the ipsilateral side when compared to sham. This effect might be explained by hypoxia and by its sensitivity to oxidative stress . VaricocPrevious works documented, through artificial insemination  and natuIn conclusion, our data showed that a varicocele had a bilateral character, despite causing more severe damages in ipsilateral testis and reinforcing that OS is a key element in its pathophysiology once several testicular and sperm alterations, associated with high concentrations of MDA, were observed in varicocelized rats. It also contributed with new information regarding the sexual behavior and reproductive performance in this experimental model. Furthermore, chrysin proved to be a potent antioxidant agent, capable of protecting germ cells against the deleterious effects of varicocele, by decreasing testicular MDA concentrations and sperm DNA fragmentation and improving sperm quality. For that reason, the use of this compound as an adjuvant therapy should be considered in order to improve sperm quality of men presenting this condition.


Leishmania infantum was not addressed conclusively. In 2006, a country-wide collection of sand flies performed in 14 sites selected based on recent occurrence of VL cases showed that Phlebotomus neglectus was by far the most prevalent species (95.6%). Furthermore, 15% of pools made from 422 P. neglectus females tested positive for Leishmania sp. genomic DNA. In the same year, Culicoides trapping was performed for bluetongue disease surveillance in 91 sites of southern Albania, targeting livestock farms regardless recent occurrence of VL in the surveyed areas. In 35 sites where sand flies were collected along with midges, Phlebotomus perfiliewi was the most prevalent among the Phlebotomus species identified, however search for leishmanial DNA in females of this species was unsuccessful. In 2011, sand flies were trapped in 4 sites of north Albania characterized by high VL incidence, and females were dissected to search for Leishmania infections. Both P. neglectus and P. tobbi were collected at high densities. Two positive specimens were detected from a sample of 64 P. neglectus trapped in one site (3.1%). Parasites were successfully cultured from one specimen and characterized as belonging to Leishmania infantum zymodeme MON-1, the only zymodeme so far identified as the agent of human and canine leishmaniasis in the country. Altogether our studies indicate that P. neglectus is the main leishmaniasis vector in Albania.The incidence of visceral leishmaniasis (VL) in Albania is higher than in other countries of southern Europe, however the role of local sand fly species in the transmission of  Leishmania co-infection are recently increasing in adults. VL cases occur in urban settlements on the Adriatic coastal plain and the adjoining river valleys. About 80% of patients notified to the Institute of Public Health from 1995 through 2014 were from peripheral districts of Shkoder and Lezhë in the north, Tirana in the centre and Lushnjë, Fier, Berat and Vlorë in the south. The remaining cases were from rural areas in coastal or lake territories. It is likely that a proportion of VL cases occurred in remote rural areas are left undiagnosed or unreported. Although very underreported, cutaneous leishmaniasis (CL) is seen with higher rates from Lezhë, Elbasan, Krujë, Tiranë and Berat districts .Among the Mediterranean countries endemic for visceral leishmaniasis (VL), Albania is recorded as one of the most affected . Unlike Leishmania infantum. Some of them, typed by Multilocus Enzyme Electrophoresis (MLEE), were found to belong to zymodeme Montpellier (MON)-1, the commonest zymodeme agent of VL in the Mediterranean region  and canine leishmaniasis cases were obtained and identified biochemically or molecularly as n region .Phlebotomus (Larroussius) subgenus, namely Ph. neglectus, Ph. perfiliewi and Ph. tobbi, all species incriminated as L. infantum vectors elsewhere in the Mediterranean .In total, 132 sites were investigated for sand flies during 2001–2014 , of whicLeishmania infections in putative vectors by means of molecular methods. The survey included a total of 14 sites. Target areas consisted of small villages or peri-urban quarters of towns where VL cases were recently reported in resident population. Sites consisted of cow barns and chicken pens near houses. A census of potential sand fly hosts revealed communities made of humans (4–15), dogs (1–4), cats (1–6), cows (1–4), sheep (0–40), pigs (0–10), chickens (5–15) and rabbits (0–8). Altitude of sites varied between the districts, ranging 5–499 m above sea level (a.s.l.) for most of them (8 districts), and 806–1000 m for 2 mountainous districts.Between June and September 2006 sand flies were collected in 10/36 districts, representative of northern (4), central (3) and southern territories (3), with the aim of providing further information on sand fly species distribution and prevalence, and to search for Culicoides midges trapping in the frame a bluetongue disease surveillance program. A total of 91 sites in 9 counties were investigated, located in three southernmost districts of Vlorë, Gjirokastër and Korçë. Target sites were farms with presence of pigs, equines or ruminant livestock. A sampling frame based on 88 km2 sections was applied due to the cross-sectional nature of the study and the wide range of habitats present over a small geographical territory. Using Arcview9 GIS software , the sampling frame was superimposed on a map layer of the study area. A code was given to each section in order to identify that specific area and the closest village to the middle of the section was used as the sampling point. Altitudes of sites varied between the three districs, ranging from 2–702 m a.s.l. in Vlorë, 149–977 m a.s.l. in Gjirokastër and 517–1322 m a.s.l. in Korçë. Farms chosen as trapping sites satisfied specific criteria including the presence of at least 5 livestock units , location at least 2.5 km from the sea coast, and no insecticides used during the past 6 months.Between May and October 2006 sand flies were collected by taking advantage of a systematic Leishmania isolation and characterization from dissected sand fly specimens, was performed in September 2011 in rural and peri-urban sites of 4 villages of Lezhë district. The choice of representative sites for sand fly collections was based on the following: i) high cumulative incidence of VL in the population; ii) previous knowledge (from Study 1) of the endemic presence of potential L. infantum vector species, and iii) logistic considerations, such as a convenient distance from the equipped laboratory necessary for microscopy dissections and cultures to be performed in aseptic conditions.A survey designed for Culicoides as main target species. At best of our knowledge, no studies are available on the comparative effectiveness between these two types of traps for the collection of sand flies. In Studies 1 and 3, two-three CDC traps per site were set in protected habitats such as inside or close to animal pens, in courtyards adjacent to houses or under the eaves of buildings. Traps were suspended at approximately 1.5 meters above the ground and were operated from one hour before sunset until one hour after sunrise. The light traps were retrieved each morning and the collected insects taken alive to laboratory for processing.Catches were performed using two methods, standard CDC miniature light traps  worldwide used for sand flies collection, and Onderstepoort-type blacklight traps with 8 W UV-light bulbs and downdraught suction motors which have Culicoides monitoring. In each collecting site, one trap was used for one night only. The traps were positioned outdoor within 25 m from the housed livestock, 1.5–2 m above ground, and were operated overnight. The resultant insect catch was poured through a fine gauze square and then transferred to a plastic jar containing 70% alcohol for transportation.In Study 2, catches were carried out using 10 Onderstepoort-type traps for In both types of catches, phlebotomines were sorted under a binocular microscope, counted and stored in alcohol prior to their identification following standard taxonomic keys ,9.Leishmania genomic DNA in groups of females pooled by species, site and date of collection. The specimens were homogenized in 1.5 ml sterile tubes using a plastic pestle. 40 μL lysis buffer  was added and the homogenate was digested overnight at 37°C by 2 μg/μL proteinase K (Promega). Genomic DNA was extracted by phenol-chloroform and precipitated with 100% ethanol and then centrifuged for 30 min at 13,000g. The DNA pellet was resuspended in 50 μL of sterile water and stored at—20°C until use. Small-subunit ribosomal DNA was amplified by n-PCR technique by sequential amplification of gene fragments using kinetoplastid specific primers R221 and R332, and Leishmania sp. primers R223 and R333 .Ph. tobbi collected in the southernmost part of the country tested Leishmania positive by a molecular method in Study 1 in 2006, we failed to demonstrate microscopically the occurrence of natural infections in 145 Ph. tobbi specimens examined in north Albania in Study 3. In general, Ph. tobbi was found low prevalent in several Albanian sites associated to VL transmission as compared with Ph. neglectus , or parasite isolation and mass cultivation (for MLEE). DNA material left from the eight nPCR-Leishmania positive pools proved insufficient, or possibly degraded, for the PCR-RFLP amplification protocol. Furthermore, one of the two infected P. neglectus specimens had a scanty infection of promastigotes which did not grow in culture and were lost for molecular typing.The Ph. neglectus is the main vector of human leishmaniasis in Albania, as three main vector incrimination criteria  it exhibits anthropophily and also feeds on the canine reservoir host; iii) this species was found to harbour infectious stages of the Leishmania species and zymodeme causing human and canine disease in Albania.Altogether our studies reasonably indicate that iewed in ) were saS1 Video(WMV)Click here for additional data file.


BackgroundTo appraise the spectrum of small bowel complications following pelvic irradiation and to assess the clinical outcome and factors associated with adverse clinical outcome in these patients.MethodsThis descriptive clinical study was done for three years in a tertiary care center in South India. Patients managed for post-irradiation small bowel complications, irrespective of the indication for radiotherapy, were studied. Patients with associated non-gastrointestinal radiation toxicity, radiation proctitis, and radiation colitis were excluded. The parameters assessed were the range of small bowel complications, a comparison of operative and non-operative management, morbidity and mortality, the severity of complications in relation to the dose of radiotherapy, and various factors influencing the clinical outcome.ResultsA total of 50 patients were studied. Stricture and perforation peritonitis were the most common presentation . A majority of the patients  presented after six months following radiotherapy. Post-operative mortality was 16% (n=5). Age, body mass index (BMI), previous surgery, operative intervention, primary or adjuvant radiotherapy, concurrent chemoradiotherapy (CCRT), and various radiation protocols were not associated with adverse clinical outcomes with respect to overall mortality, the requirement of surgery, and operative mortality. However patients who were operated and those who received CCRT had a significantly longer mean intensive care unit (ICU) stay  as well as overall mean hospital stay  and an insignificant mortality rate .ConclusionThe present study observed that the patients who were operated and those who received CCRT had significantly longer hospitalization and relatively higher mortality. Considering the fact that many of the patients who develop post-irradiation complications may not report back to the same center, the incidence of small bowel complications could be higher in reality, which ascertains the necessity for more precision in the radiation technique and operative care in developing countries. Pelvic irradiation is one of the principal modes of treatment for both gynecological and non-gynecological malignancies. Radiation oncology has made tremendous progress in terms of newer techniques like high-precision radiotherapy, three-dimensional conformal radiotherapy, intensity modulated radiotherapy, etc. Recent advances in radiation delivery using linear accelerators with novel fractionation schemes and the use of radioprotective drugs during radiotherapy have helped in reducing the frequency and severity of radiotoxicity . In spitThe small intestine is the most susceptible organ affected by chronic radiation enteritis and accounts for significant morbidity and a fourfold increase in the mortality compared to radiation colitis or proctitis . The ranConsidering the fact that about one-third of the patients with chronic radiation enteritis will require surgical treatment ultimately, a detailed analysis of this clinical spectrum is required. Studies on the outcome of small bowel complications following pelvic radiotherapy are also sparse. Hence, this study was carried out to investigate the spectrum and clinical outcome of these complications and factors that significantly influence the outcome in a tertiary care regional cancer center.The study was a descriptive clinical study of patients who were managed for small bowel complications following pelvic radiotherapy. Patients managed for post-irradiation small bowel complications in the department of surgery for three years were assessed for outcome parameters. All patients treated for the small bowel complications following pelvic irradiation irrespective of the indication of the radiotherapy were included in the study. Indications for radiotherapy included gynecological malignancy, prostatic cancer, and carcinoma rectum. Patients with associated non-gastrointestinal radiation toxicity, radiation proctitis, and radiation colitis were excluded from the study.Written informed consent was obtained from all prospective patients. The investigation and management of the patients presenting to the surgical unit, including the decision to operate or to manage conservatively, were left to the treating surgeon per the existing protocol and depending on the patient condition. All operations were carried out by competent surgeons with reasonable expertise in emergency surgical management. Post-operatively, patients were followed for up to 30 days for outcome parameters, including surgical site infection (SSI). The clinical presentation of post-radiotherapy small bowel complication was categorized into three groups based on the time interval between the radiotherapy and the onset of small bowel complication. The presentation was termed "acute" if a complication develops within six weeks, "late" when presented between six weeks to six months, and "chronic" if more than six months.The parameters assessed were the range of early and late small bowel complications following pelvic irradiation, the proportion of patients requiring operative management, a comparison of operative and non-operative management, patients requiring more than one surgery, and the reason for the reoperation. This study also analyzed morbidity and mortality, the severity of complications in relation to the dose of radiotherapy, the time interval for the development of a complication after radiotherapy, factors influencing the severity of complications like co-morbidities, BMI, and previous abdominal surgery. The institute's ethics committee approved the study.Statistical analysisThe distribution of data on the clinical/surgical profile of complications and the outcome were expressed as frequencies and percentages. The comparison of profiles between the subgroups  was carried out using the chi-square test and Fischer’s exact test. To assess the clinical and demographical factors associated with the outcome, a logistic regression analysis was carried out at the 5% level of significance and a P value < 0.05 was considered significant. A statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) 16.0 software (IBM (SPSS) Statistics Armonk, NY).In this study, a total of 50 patients with small bowel complications following pelvic radiation for various pelvic malignancies were assessed for the outcome parameters, including the clinical and operative outcome. Out of the 50 patients, 47 patients were female (94%). The age of the patients ranged from 30-70 years with more patients in the age group of 40-60 years. However, the age and gender distribution did not show any significant difference in incidents of post-radiotherapy small bowel complications. In a majority of the patients, the indication of pelvic irradiation was carcinoma cervix representing 90% (n=45) of the study population followed by carcinoma rectum  and carcinoma prostate . A majority of the study population (90%) had normal BMI. Diabetes and hypertension were present in 28% (n=14) and 4% (n=2), respectively, and 24% (n=12) of patients had both. BMI or presence of co-morbidity did not significantly affect the clinical outcome of small bowel complications.Small bowel complications: presentation and clinical outcomePatients admitted for post- pelvic radiation small bowel complications stayed in the hospital for an average of 13.8 days. There was a significant increase in the duration of hospital stay in patients who were operated compared to those who were managed conservatively both in terms of ICU stay  as well as overall hospital stay  Patients in this study group had a wide range of small bowel complications following pelvic radiotherapy. Mortality in this study group was 16% , followed by adhesive intestinal obstruction , radiation enteritis , sub-acute intestinal obstruction , and pyoperitoneum . The time interval from the radiotherapy to the presentation of surgical small bowel complication ranged from three weeks to 13 years with a mean interval of 32 weeks. A majority of the patients  presented after six months. One patient presented early, with perforation peritonitis within six weeks of completion of radiotherapy . Twelve patients (24% of the study population) presented late, between six weeks to six months from radiotherapy. Among the patients who received conservative management, eight patients  eventually required surgical intervention.Out of 31 patients who were operated, all of them had the involvement of the ileum in the form of Ileal perforation n=21; 67%), stricture, or both . One patient (3%) had six perforations in the ileum. The most common operative procedure executed was resection and Ileostomy . Two patients underwent resection and anastomosis (6.24%). Wedge resection and primary closure were done in one patient (3.2%). Adhesiolysis was done in one patient (3.2%). Laparotomy and lavage were done for pyoperitoneum in two patients (6.24%). Surgical site infection (SSI) , postoperative pneumonia , stoma-related complications  and deep vein thrombosis  were the complications seen in the operated patients. In patients with SSI, five (16%) developed laparostoma. One patient (3.2%) developed short bowel syndrome due to extensive resection. None of the patients in the study group had fistulas or hemorrhage as a complication of radiation. Mortality among the patients who underwent various surgical procedures did not differ significantly  .Factors affecting clinical outcomeA majority of the patients  in the study group received primary radiotherapy and 10 patients (20%) received adjuvant radiotherapy following surgery. There were no significant differences in the requirement of operative intervention, overall mortality, and postoperative mortality between the two groups Table .Similarly, various clinical presentations, the requirement for operative intervention, and operative mortality did not significantly differ in patients who received various radiotherapy protocols both in carcinoma cervix and other diagnoses Table , Table 5On comparing patients who received concurrent chemoradiotherapy (CCRT) and those who received radiotherapy alone, the length of hospitalization was significantly longer  in the concurrent chemoradiotherapy group that was operated  remains high. Turina M et al. reported 1.2% to 37% incidence of intestinal complications following pelvic irradiation [The most susceptible organ for radiation injury following pelvic irradiation is the small intestine. Rapidly dividing mucosal crypt cells, which are highly radiosensitive, make the small intestine more susceptible to developing post-irradiation complications -7. An acHuscher A et al. described that the incidence of radiation injury to the bowel was more common in patients who received radiotherapy for carcinoma cervix ,4. In thOperative interventionIn the study population, 62% of the patients (n=31) had undergone emergency surgical treatment. Surgery in this scenario is challenging because of various factors like post-radiation skin changes, intestinal adhesions, fibrotic changes in mesentery and peritoneum, and intestinal fibrosis and strictures. The most common indication for surgery in this study was the perforation of the small bowel . Intestinal obstruction was the most common indication in the study by Regimbeau et al. [The most common operative finding was an ileal perforation with or without stricture n=12; 38.7%) and ). Stricture alone was seen in one patient (3.2%). The most common operative procedure carried out was the resection of the involved bowel segment and stoma. This was in contrast with other studies by Regimbeau et al. and Hatcher et al., where resection anastomosis was the frequently done surgical procedure [; 38.7% a.7% and (Resection and anastomosis were done in two of the operated patients without an anastomotic leak postoperatively (6.4%). Regimbeau et al. reported higher leak rates (10%) after resection and ileoileal anastomosis . Though Predictors of outcome in post-radiotherapy small bowel complicationsMany authors have reported a relation among age, BMI, CCRT, radiation dose, previous abdominal surgery, and co-morbidities with the occurrence and severity of radiation-induced intestinal damage ,10. Old Iraha S et al. documented that co-morbidities like diabetes mellitus, hypertension, and vascular diseases were associated with more severe radiation enteritis . In thisA majority of the patients  in this study had undergone surgery prior to the pelvic radiation. However, it did not affect the presentation or operative outcome in these patients compared to those who had no surgical procedures done earlier. Iraha et al., Hatcher et al., and many others, in their studies, showed that the severity of the complication was influenced by prior abdominal surgery ,12. MostRadiation dose, technique, and concurrent chemoradiationAll the patients in this study received a radiation dose of 45 to 50 Gy on an average, as reported by Turina et al . All theMortality and secondary cancerA secondary malignancy in the irradiated area is one of the concerns in patients undergoing pelvic irradiation. Turina et al. reported a 10% incidence of secondary cancer in their patients [Age, BMI, previous surgery, operated or conservative management, primary or adjuvant radiotherapy, CCRT, and various radiation protocols were not associated with adverse clinical outcomes with respect to overall mortality, the requirement of surgery, and operative mortality in patients who developed post-irradiation small bowel complication. However, patients who were operated and those who received CCRT had significantly longer hospitalization and relatively higher mortality. Considering the fact that many of patients who develop a complication may not report back to the same center, the incidence of small bowel complication could be higher in reality, which ascertains the necessity for more precision in radiation technique and operative care in developing countries like India.


To compare the values of central and brachial systemic blood pressure (SBP) between women and men over 60 years of age with systemic arterial hypertension. This study was a quantitative, descriptive, cross-sectional study with elderly patients admitted to and selected from spontaneous and scheduled demand at basic health units in Uberlândia, Minas Gerais, Brazil, between March 2013 and March 2014. We included 69 study participants and compared central and brachial SBP using a Sphygmocor® XCEL device . Significant differences were found in the blood pressure values of the whole population in the central versus brachial systolic blood pressure (SP) [140(21) versus 153(23) mmHg] and in the central versus brachial pulse pressure (PP) [55(18) versus 70(18) mmHg]. Additionally, females exhibited higher blood pressure levels than males . Elderly women exhibited higher blood pressure values than elderly hypertensive men. Systemic blood pressure (SBP) changes with ageing. Systolic blood pressure (SP) rises progressively, whereas diastolic blood pressure (DP) rises until the 6th decade of life and then stabilizes or gradually decreases –4.SBP levels measured indirectly through cuffs placed either on the upper limbs or at the aortic root [the central SBP levels (SBPc)] constitute independent factors for cardiovascular risk (CVR) , 6. EvidEpidemiological studies have confirmed that the physiological hormonal changes that occur in women during and after menopause affect the systemic circulation, thereby increasing SBP and consequently CVR. Additionally, CVD is the leading cause of mortality in postmenopausal women, with a prevalence equal to or higher than the prevalence in men due to low plasma oestrogen levels, among other factors –20.As good markers of CVR, central and peripheral blood pressure values could diverge in the same patient and behave differently in elderly female patients. Therefore, the objective of the present study is to compare the central and brachial SBP values between women and men over 60 years of age with systemic arterial hypertension (SAH).n = 69; (II) women: 71 ± 7 years, n = 39; and (III) men: 68 ± 6.5 years, n = 30. All patients were active, stable, and conscious.This study was a quantitative, descriptive, cross-sectional study with elderly patients ≥60 years of age who were admitted and selected from the spontaneous and scheduled demand at basic health units (BHUs) in the municipal network of Uberlândia, Minas Gerais, Brazil, from March 2013 to March 2014. The first 69 hypertensive participants were included in the study and were divided into three groups of patients as follows: (I) overall study population: 70 ± 7.3 years, This study was conducted in accordance with the attributes defined in Resolution CNS 466/12 and approved by the Ethics Committee in Research of the Federal University of Uberlândia under opinion number 224,540 and CAAE 37440114.3.0000.5152.Patients with SAH, a SBPb ≥ 140/90 mmHg, or a SBPb ≤ 140/90 mmHg with the use of one or more antihypertensive drugs (controlled) were considered.A Sphygmocor XCEL applanation tonometry device  was used to measure both SBPb and SBPc simultaneously and noninvasively. The components of the SBP surveyed were the SP, DP, PP, and mean arterial pressure (MAP) . All values are expressed in mmHg. The SBPc and SBPb measurement procedure was performed only once and was based on a previous description .t-test was applied to compare the values of the SBPc and SBPb components according to the normality of the sample. Differences were considered significant when P < 0.05. Statistical analysis was performed using Statistical Package for Social Science (SPSS) version 20 for Windows.The results for the continuous variables shown in Tables The clinical characteristics of the overall study population and the population according to sex are shown in Cross-sectional and longitudinal studies have confirmed a higher prevalence of hypertension in elderly postmenopausal women –19, 22 aIn the present study, all patients were randomly included. We observed that women presented high SPc and PPc mean values, whereas men remained within the limits considered normal , 26. We P < 0.05).Both SP and PP increase with age, mainly due to the decrease in elasticity of the large vessels as a consequence of their respective structural modifications , 4, 20. Son et al.  conducteKim et al.  also shoThe AIx@75 (heart rate-corrected augmentation index) is considered as a composite marker of reflection waves and arterial stiffness. In this sense, it was evidenced that postmenopausal women had higher arterial stiffness when compared to elderly hypertensive men  30]..30].To the best of our knowledge, Brazilian studies demonstrating and comparing the components of central and brachial SBP in postmenopausal women with elderly hypertensive men via applanation tonometry are rare. Notably, this study is a preliminary study with the inclusion of the first 69 hypertensive patients, which will help guide future research.This study is a cross-sectional study with the inherent limitations of this type of design. The study patients used several classes of antihypertensive drugs, including beta-adrenergic blockers , which do not effectively reduce central pressure levels –13, 31. Significant differences were found in both the central and brachial SP and PP values between women and men. The elderly women presented higher blood pressure values than those of the elderly hypertensive men.


Sleep disorders are often underreported to physicians by patients with allergies. This study aimed to characterize the sleep disorders associated with respiratory allergy to house dust mites (HDM) at the time of initiation of sublingual allergen immunotherapy (SLIT) in routine clinical practice.This prospective, cross-sectional, observational study was conducted between November 2014 and March 2015 at 189 French trial sites and included 1750 participants suffering from HDM allergy who were initiating SLIT. Participants aged less than 5 years old and those who had previously started an allergen immunotherapy (AIT) for HDM allergy were not enrolled in the study. Sleep disorders were assessed by self-administered questionnaires: the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI) and a modified version of the Hotel Dieu-42 (HD-42) sleep disorder questionnaire. Logistic regression models adjusted for obesity, smoking status, asthma control and nasal obstruction were used to study the relationship between allergic rhinitis (AR) classification and sleep disorders/complaints.Of the 1786 participants enrolled, 1750 (907 adults and 843 children) composed the analysis population. The majority of participants (73.5% of adults and 65.8% of children) reported that their sleep disorders had prompted them to consult their physician. The most commonly observed sleep complaints were poor-quality sleep (50.3% of adults and 37.3% of children), snoring  and nocturnal awakening . Difficulties falling asleep were reported by 27.0% of adults and 24.7% of children. Adults and children suffering from severe persistent AR experienced sleep complaints significantly more often than participants with intermittent or mild persistent AR.This study highlights the high frequency of sleep disorders and their significant impact on patients with AR induced by HDM, in particular when AR is persistent and severe. Consequently, asking allergic patients about the quality of their sleep appears to be important, especially when the patient has persistent and severe AR. Allergic rhinitis (AR) is common and is estimated to affect approximately 25% of the population in France and Canada , 2. AlleThis was a prospective, cross-sectional, observational study conducted at 189 sites in France. In total, 801 investigators were randomly selected from the records obtained in the Thalès Cegedim survey database, which contains information on physicians with “allergology” activity within the following specialties: general practice, pneumology, paediatrics, ear, nose and throat (ENT) and dermatology. Randomization was performed to achieve the highest level of representativeness of the sample based on feasibility and geographic distribution . Overall, 212 investigators (26.5%) agreed to participate in the trial. Each investigator prospectively included 6–10 participants who met the inclusion/exclusion criteria in consecutive consultations.The study was conducted in compliance with the Declaration of Helsinki, Good Epidemiological/Pharmacoepidemiological Study guidelines, good practice guidelines and local regulations.The study protocol was approved by the relevant French review boards “Comité Consultatif sur le Traitement de l’Information en matière de Recherche dans le domaine de la Santé” (CCTIRS) and “Commission Nationale de l’Informatique et des Libertés” (CNIL).Eligible participants were at least 5 years old and starting SLIT for HDM allergy. Participants who had previously started an AIT  for an HDM allergy were not enrolled in the trial. Participants were analysed according to age, i.e., 5–17 years old [children] and 18 years and more [adults]. Oral informed consent was obtained from all participants.For each participant enrolled in the study, the different variables were recorded on a paper case report form (CRF). The CRF was completed by the physician himself for each participant who met the inclusion/exclusion criteria. Each participant and/or his/her legal representative (for participants or children unable to answer on their own) also completed a self-administered questionnaire. All data were collected anonymously.Sleep disorders were assessed by reliable self-administered questionnaires commonly used in different populations: the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISI) and a modified version of the Hotel Dieu-42 (HD-42) sleep disorder questionnaire. The ESS is a subjective tool constructed and tested in the early 1990s  that hasSleep disorders were defined using the categories of items and criteria shown in Table The ISI was used to assess the severity of insomnia in the past month. The 7 items on the ISI were scored by the participant on a scale ranging from 0 to 4; the scores were then summed to obtain a total insomnia score, which was presented quantitatively and by category , 15–21: clinical insomnia (moderate), 22–28: clinical insomnia (severe).The severity of daytime sleepiness was globally assessed using the ESS scale. The 8 items on the ESS scale were scored on a scale ranging from 0 to 3, and these scores were summed to obtain a daytime sleepiness score. The total score was presented quantitatively and by category .The statistical analysis was performed using SAS version 9.2 (SAS Institute Inc. North Carolina USA).All variables collected in the CRFs and questionnaires and the derived parameters were included in the descriptive statistical analysis. Quantitative variables were analysed in terms of the mean, standard deviation, median, first quartile, third quartile, and extreme values. Binary, categorical, and ordinal parameters were analysed regarding the number and frequency within various categories.The primary objective of the MORPHEE study was to describe the nature and frequency of sleep disorders in participants with respiratory allergy to HDM for whom SLIT had been initiated. All data relating to quality of sleep in the participants’ self-administered questionnaire were described for the analysis population overall and for subgroups according to age (adult/child) and type of allergic rhinitis (AR)  were retained for the analysis.The main characteristics of the participants are summarized in Table Overall, the most common forms of allergy in the participants’ family history were rhinitis , conjunctivitis (16.8 and 21.5%) and asthma (27.0 and 40.0%). More than half of participants were polysensitized, most commonly to grass pollen , pets (44.4 and 42.7%) and tree pollen (34.3 and 33.3%).According to the Allergic Rhinitis and its Impact on Asthma (ARIA) 2010 classification , particiAdults had been diagnosed with AR for an average of 8.4 ± 9.4 years, and children, for an average of 3.0 ± 3.2 years. In patients with current asthma associated with AR, asthma was most commonly intermittent (48.8%) or mild and persistent (29.3%). According to the Global Initiative for Asthma (GINA) guidelines , asthma Allergy to HDM was most commonly confirmed using a positive skin test (1707 positives out of 1720 tested participants [99.2%]) and/or specific IgE tests (885 positives out of 891 tested participants [99.3%]).The medications most frequently prescribed within the 12 months prior to enrolment were antihistamines (90.6% of adults and 84.6% of children) and nasal corticosteroids (58.3% of adults and 53.6% of children); 3.1% of adults and 4.0% of children said that they had not received any drug prescriptions in the previous 12 months. According to the 5-item self-administered satisfaction questionnaire, 83% of adults and 75% of children were not satisfied with their current allergy treatment, mainly due to a lack of efficacy in relieving their symptoms (56.6%) and the belief that the quantity of drugs was too large (52.1%).The majority of participants (73.5% of adults and 65.8% of children) reported that their sleep problems were the main reason for their consultation, as shown in Fig. Logistics regression models adjusted for BMI, smoking status, nasal obstruction and asthma control show that adults suffering from severe persistent AR were more likely to experience difficulties falling asleep , nocturnal awakenings , poor-quality sleep  and clinical insomnia . No influence of persistent severe AR on snoring or daytime sleepiness was observed. However, obesity and overweight were shown to be highly related to the prevalence of snoring  and nasal obstruction was also related to poor-quality sleep .Similarly, logistic regression models showed that children with severe persistent AR were more likely to experience poor-quality sleep , clinical insomnia , daytime sleepiness , and snoring , but no effect of severe persistent AR on difficulty falling asleep or nocturnal awakening was observed. Nasal obstruction (moderate or severe) also had an impact on poor-quality sleep  and snoring .Furthermore, both adults and children, who suffered from severe persistent AR were more likely to become uncomfortable with their sleep, particularly regarding disturbances in their daily lives , apparent sleep difficulties , dissatisfaction with their current sleep  and concerns about their difficulties falling asleep .According to a report published in 2006 by the French Ministry of Health and Solidarity, approximately 20–30% of the French population complained of sleep disorders, 15–20% of whom had moderate insomnia; 9–10%, severe insomnia; and approximately 8%, excessive daytime sleepiness. These conditions each have direct consequences for public health . Many stThe analysis of the frequency of sleep disorders according to type of AR showed that sleep disorders were more common in severe persistent AR than in other forms of AR. These results support those of the DREAM and SOMNIAAR studies, which previously showed a positive correlation between deterioration in quality of sleep and AR severity , 8. SpecThe distribution of participants in the MORPHEE study according to AR category can be compared to those of other studies conducted among participants with AR caused by different allergens  or with AR induced by HDM (ADARA and ANTARES studies). In the ADARA study, 75.4% of asthmatic participants (adults and children) and 79.1% of non-asthmatic participants had moderate to severe persistent AR . The ANTAt the time of their consultation, nearly 80% of participants were not satisfied with their treatment before SLIT, mainly because it did not relieve their allergies (56.7%) or because the amount of drugs taken was too high (52.1%). The prescription of AIT is thus consistent with the ARIA good practice guidelines for treating respiratory allergies for patients with moderate to severe AR when symptomatic drugs and avoidance measures cannot relieve their symptoms. Unlike symptomatic treatments, AIT can significantly modify the disease in a clinically relevant way in the years following treatment and in the long term , 32.As the MORPHEE study used a cross-sectional observational design, it had certain limitations. In particular, the method used to document sleep disorders did not allow for assessments of the existence or extent of bias associated with systematic questioning. However, the frequency with which sleep disturbances were reported when questions were asked to both physicians and participants via a self-reported questionnaire clearly demonstrated that sleep disorders are highly prevalent and not always accounted for in the treatment of allergic patients.This finding highlights the importance of asking patients about the quality of their sleep during allergy consultations to better identify their problems.Furthermore, the participating physicians may have consciously or unconsciously selected participants for the study; however, this possibility was inevitable. Although the sequential nature of enrolment helped reduce this bias and minimized the potential bias related to the enrolment of more severe participants due to their more frequent consultations, it cannot be ruled out that the participants enrolled in the MORPHEE study tended to have more severe conditions and therefore more intense sleep disorders. Although less robust than clinical trials from a methodological point of view, observational studies do, nonetheless, have the advantage of allowing “real-life” data to be collected and thus reflect routine medical practice when a sufficient number of participants has been included. Finally, the characteristics of the participants in the study were very similar to those of patients with HDM allergies who are usually seen in routine practice; this similarity allowed the results to be generalized to patients starting SLIT for HDM allergy.This survey clarified the characteristics and effects of sleep disorders in a large sample of participants consulting their physician for AR caused by HDM who were considering initiating SLIT. The multivariable logistic regression models showed that subjects suffering from severe persistent AR were more likely to experience difficulty falling asleep, nocturnal awakening, clinical insomnia and poor-quality sleep than those with other types of AR.Consequently, asking patients about the quality of their sleep during consultations for respiratory allergies appears to be important, especially when they have persistent and severe AR.The results of large placebo-controlled double-blind clinical trials have shown favourable effects of an HDM SLIT tablet, and the results of the MORPHEE survey further encourage exploration of the qualitative and quantitative benefits of SLIT in improving sleep in patients with HDM allergy.


The gluteus medius (GMED) affects hip function as an abductor. We evaluated muscle volume and degeneration of the GMED by using CT-based analysis and assessed factors that affect hip abductor strength in patients with unilateral hip osteoarthritis (OA).We examined clinical and imaging findings associated with hip abductor strength in consecutive 50 patients with unilateral hip OA. Hip abductor muscle strength and Harris hip score (HHS) were assessed. Leg length discrepancy (LLD) and femoral offset were assessed using X-ray; CT assessment was employed for volumetric and qualitative GMED analysis. Volumetric analysis involved measurement of cross sectional area (CSA) and three-dimensional (3D) muscle volume. CT density was measured for the qualitative assessment of GMED degeneration with or without adjustment using a bone mineral reference phantom.Hip abductor muscle strength on the affected side was significantly lower than that on the contralateral healthy side and positively correlated with overall score and score for limping of gait of HHS, demonstrating the importance of hip abductor strength for normal hip function. A significant correlation was found between CSA and 3D muscle volume, unadjusted CT density and adjusted CT density, and hip abductor strength and these CT measurements. Multiple linear regression analysis demonstrated that 3D muscle volume, adjusted CT density, and LLD are independent factors affecting hip abduction.3D measurement of muscle volume and adjusted CT density more accurately reflect quantity and the GMED quality than do conventional assessments. Increase in muscle volume, recovery of muscle degeneration, and correction of LLD are important for improving limping in patients with hip OA. Hip abductor muscles are important determinants for hip function . AbductoComputed tomography (CT) is one of the commonly used imaging tools for the quantification of muscle volume around the hip , 5. MeasThe purposes of our study were to evaluate muscle volume and muscle degeneration of GMED using CT based analysis, and to assess the effect of hip abductor muscle strength on hip function and factors affecting hip abductor strength in patients with unilateral hip OA. For this purpose, we quantified clinical parameters, X-ray findings, and CT measurements of the GMED. CT measurements involved muscle volume quantified by CSA and 3D reconstruction and muscle degeneration by CT density with or without adjustment using bone mineral reference phantom.This prospective study was approved by our institutional review board. We enrolled 50 consecutive patients with unilateral hip OA between April 2012 and May 2014 with informed consent. Those patients suffered from symptomatic hip for an average of 9 years  before initial presentation to our hospital. For clinical assessment, the Harris hip score (HHS) was recorded. To assess hip abductor strength, isometric hip abductor strength measurements were performed on all patients using a manual isokinetic/isometric dynamometer . During the test, the participants lay on their side with the test leg up and with the dynamometer secured on the lateral side of their thigh. The pad on the dynamometer was centered over the distal lateral femur at a standardized point of 80% of the length between the greater trochanter and the lateral femoral condyle. The testing leg was positioned straight (0° of hip and knee flexion and 0° of hip rotation), whereas the non-testing leg was positioned in approximately 30° of hip flexion and 30° of knee flexion against the table for comfort and stability. During the hip abduction testing, a careful causation was given on the reproducibility of lower leg motion, especially in patients with severe hip pain. The participant was asked to perform three maximal isometric contractions for 5 s with 30 s of rest between the repetitions on each side. The peak force from the 3 trials was used for statistical analysis. Abductor muscle strength was measured by hip surgeons in our institution.All patients were scanned with a plain anterior-posterior X-ray of the hip in a standing position and computed tomography (CT) using transaxial CT scans . Scanner settings were approximately 120 kV and 300 mA, with a slice thickness of 1.5 mm. The 50 patients were examined in the supine position using a spiral CT-scanner with their pelvis in the neutral position and the lower limb placed in patient’s natural rotation. Natural rotation meant the lower leg position in relax position. Since stretch of muscle might affect the muscle volumes, we did not enforce lower legs to patella median position. Transverse images were obtained from the iliac crest to the condyles of the femur in each patient.Leg length discrepancy  and femoMuscle degeneration was quantified by calculating the mean CT density, which was measured as hounsfield units (HU). CT density was adjusted by calculating the equivalent hydroxyapatite amount in muscle area and a calibration phantom  using dedicated software that calculates adjusted HU of the muscle in the CT image based upon reference values measured in bone mineral reference phantom Fig.  14]..14].p values less than 0.2 in forced entry method . A p-value of <0.05 was considered significant.Pearson’s test was used for correlation analyses. Statistical significance of differences was determined by Student t-test or non-parametric Mann-Whitney test of data sets that were not normally distributed. To assess intra-observer and inter-observer reliabilities in measuring muscle volume of the GMED, intra-class correlation coefficients were calculated. For this purpose, 3D muscle volumes of the GMED in 12 patients were measured twice by the author with 6 months of interval period (TM) to determine intra-observer reliability, and those values in the same patients were also measured by another blinded orthopedic surgeon (HC) to determine inter-observer reliability. Multiple linear regression analysis was performed to identify the factors affecting abductor muscle strength. At first, a univariate regression analysis was performed with the following factors as explaining variables: muscle volume of the GMED, adjusted CT density, CSA of the GMED, CT density of the GMED, age, sex, BMI, LLD, femoral offset and KL grade. Secondly, all the variables were analyzed by multiple linear regression analysis (forced entry method). Thereafter, a backward selection method of multiple linear regression analysis was done with selected variables with 2  and a mean age of 62 years  were enrolled. Mean femoral offset on the affected hip was significantly lower than that on the healthy hip . Mean LLD was −10.9 mm  on the affected side and 4, 8 and 38 patients had a hip OA with KL grade 2, 3, and 4, respectively. The muscle strength of the hip abductor on the affected side was significantly lower than that on the contralateral healthy side  with an average body mass index of 23.3 kg/mTo assess the factors that affect hip abductor muscle strength among clinical and radiological findings, univariate and multiple linear regression analysis were performed. Univariate linear regression analysis determined that CSA, 3D muscle volume, CT density, adjusted CT density, sex, and BMI, were factors that affected hip abductor muscle strength on the affected side. With further investigation using multiple linear regression analysis, 3D muscle volume, adjusted CT density, and LLD were found to be the factors that affected hip abductor strength on the affected side Tables . Similarr = −0.19, p = 0.024) or LLD and adjusted CT density .Cross-sectional and 3D muscle volume of the GMED showed a strong positive correlation Fig. . Hip abdThe purposes of our study were to evaluate the effect of hip abductor muscle strength on hip function, to validate the utility of our CT-based analysis for the quantification of muscle volume and muscle degeneration of GMED, and to assess factors that affect hip abductor strength in patients with unilateral hip OA. Reduction of muscle volume and degeneration of the GMED were evident in the present study, which agrees with findings of previous reports –4. CorrePrevious studies have demonstrated an association between two-dimensional area of the GMED and hip abductor muscle strength –4; howevAtrophic changes in muscle property may also be responsible for muscle weakness in patients with gait disorder. Nevertheless, quantification of muscle degeneration has not received sufficient attention. Upon CT assessment, several studies have measured radiological density to evaluate muscle degeneration , 5, 15. No study yet has comprehensively demonstrated the effect of related factors on hip abductor muscle strength by using multilinear regression analysis. Few studies have evaluated the relevance of implant orientations, including hip center and femoral offset for hip abductor strength in total hip arthroplasty patients . PatientOne of the limitations in this study was that we only assessed the gluteus medius. Since hip motion requires complicated coordination of several muscles, assessment of other muscles is necessary for a practical understanding of functional disability in patients with hip OA. However, our volumetric and qualitative CT analysis may be useful in the assessment of other muscles and provides better information compared to CSA-based conventional analysis. The second limitation of this study was that we used a bone mineral reference phantom to adjust muscle density. The reference system, which was specifically prepared for muscle assessment, should be assessed in future CT-based studies. The third limitation was that discrepancies in strength testing may be related to hip pain, rather than true muscle weakness. During the testing, a careful causation was given on the reproducibility of lower leg motion, especially in patients with severe hip pain. However, although we tried to exclude the effect of hip pain on the testing, the severe hip pain might affect the measurement of muscle strength.In conclusion, we investigated factors that affected hip abductor muscle strength in patients with unilateral hip OA by using a novel volumetric and qualitative CT-based analysis of GMED. 3D measurement of muscle volume rather than CSA, adjusted CT density rather than unadjusted CT density, and LLD rather than femoral offset were found to be important factors that affect abductor muscle strength in patients with unilateral OA. An increase in muscle volume, recovery of muscle degeneration, and correction of LLD are important for improving gait limping in patients with hip OA.


To identify factors, available at the time of trauma admission, associated with the development of chronic pain to allow testing of preventive approaches.  In a retrospective observational cohort study, we included all patients ≥ 18 years old admitted for injury in 57 adult trauma centers in the province of Quebec (Canada) between 2004 and 2014. Chronic pain was defined as follows: treated in a chronic pain clinic, diagnosed with chronic pain, or received at least 2 prescriptions of chronic pain medications 3 to 12 months postinjury.  A total of 95,134 patients were retained for analysis. Mean age was 59.8 years (±21.7), and 52% were men. The causes of trauma were falls (63%) and motor vehicle accidents (22%). We identified 14,518 patients  who developed chronic pain. After controlling for confounding factors, the variables associated with chronic pain were spinal cord injury , disc-vertebra trauma , history of alcoholism , history of anxiety , history of depression , and being female . The area under the receiving operating characteristic curve derived from the model was 0.80.  We identified risk factors present on hospital admission that can predict trauma patients who will develop chronic pain. These factors should be prospectively validated. Traumatic injury accounts for approximately 37 million emergency department visits each year in the US . For manThe prevalence of posttraumatic chronic pain varies greatly between and within injury types: from 22 to 93% in orthopedic trauma , 26–96% Several studies have identified risk factors of chronic pain development in trauma patients , 7. DemoIf used during the acute pain phase, some therapeutic strategies  may help prevent the development of chronic pain . As primThe main objective of the present study was to identify factors, available at hospital admission, associated with the development of chronic pain for trauma patients and to develop a predictive model.A retrospective multicenter cohort study was conducted using three government population databases. All patients of 18 years and older admitted for injury to any one of 57 adult trauma centers  in the province of Quebec (Canada) between 2004 and 2014 were included in the study. Patients who died or with a follow-up period less than 1 year and those with multiple trauma episodes (difficult to identify which trauma episode was associated with chronic pain) were excluded.Quebec Trauma Registry was developed in 1993 and involves mandatory data collection for patients admitted to any provincial trauma center according to the following inclusion criteria: death following injury, hospital stay > 2 days, intensive care unit admission, or transfer from another hospital. Medical archivists extract registry data from patients' medical files, using standardized coding protocols. Anatomic injuries are coded with the Abbreviated Injury Scale (AIS) according to guidelines published by the Association for the Advancement of Automotive Medicine [The Medicine . The regMED-ECHO  is a medico administrative database managed by the Quebec Ministry of Health. It contains information on principal and secondary diagnoses and medical interventions for all hospitalizations in the province of Quebec. For each included patient, access to MED-ECHO information was granted for a time period ranging from 1 year before to 8 years after the target injury.RAMQ medical consultations and medication database of the Régie de l'Assurance Maladie du Québec is an administrative database maintained by the Quebec Ministry of Health and contains diagnostic information and specific codes for chronic pain visits for all medical consultations in the province of Quebec. It also contains information on all medication prescriptions filled for Quebec residents covered by the Quebec prescription drug insurance plan, which represent approximately 50% of all included individuals. The RAMQ database provided information on included patients for the same time period as for the MED-ECHO database.The The three databases were linked using a unique anonymous identification number provided by the “Régie de l'assurance maladie du Québec.” Access to these databases required the ethic approval of the “Commission d'accès à l'information du Québec” (CAI) and the “Responsable de l'accès à l'information et de la protection des renseignements personnels de la RAMQ” (RAI-RAMQ). The CAI and the RAI-RAMQ approved our study for cases registered in the Quebec Trauma Registry between 2004 and 2014.Chronic pain (pain experienced for at least 3 months) patients were identified using any of the following 3 criteria: (1) Patients who were referred to a specialized chronic pain clinic . (2) Patients diagnosed with chronic pain  during their entire follow-up period (up to 8 years after injury). We used the entire follow-up (from 3 months to 8 years after injury) for these chronic pain criteria since access to specialized chronic pain clinics can extend for years. (3) Patients who filled at least 2 prescriptions of opioids or at least 1 prescription of chronic pain medication  , injury severity score (ISS), abbreviated injury scale (AIS), emergency department (ED) stay duration, and history of alcoholism, depression, or anxiety 1 year prior to target injury. A score greater than 15 on the ISS was used to define major trauma or polytrauma . The firt-tests) to compare the characteristics of the included patients versus those who were excluded (died or had a follow-up less than 1 year). We randomly selected two-thirds of cases to generate a derivation sample used to create a model to predict chronic pain and the last third was used as a validation sample [t-tests) to compare the characteristics of the derivation and the validation samples. Since small differences can result in a statistically significant test in very large samples, Cohen's effect sizes are presented instead of p values. Small, medium, and large effect sizes for Chi-square are 0.1, 0.3, and 0.5, respectively, and for the t-test statistic, 0.2, 0.5, and 0.8, respectively [We used univariate statistics  were selected for multivariate analysis. We used a multivariate logistic regression analysis with backward stepwise procedure to develop the model on the derivation sample using chronic pain development as the dependent variable. Performance of the derivation sample model was assessed using Nagelkerke's On the validation sample, the logistic regression equation (derived on the derivation sample) was used to predict chronic pain. Performance and discrimination were also evaluated using the Brier score and the c-statistic, respectively.Alpha levels were set at 0.05 and all analyses were performed using SPSS version 23 . Results are reported according to the “Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis” (TRIPOD) Statement .The Québec Trauma Registry included a total of 151,189 adult patients admitted for an injury between January 1, 2004, and March 31, 2014. Of these patients, 11% were excluded for having more than one injury episode, 6.3% because they met the chronic pain criteria during the year preceding their target injury episode, and 19.8% because they died or had a follow-up shorter than a year. A total of 95,134 subjects to create the derivation and validation sample were retained .  Table The mean age of the selected sample was 59.8 years (SD ± 21.7), almost half (48.1%) were female, and the mean follow-up duration was 4.8 years (SD ± 2.4). The most common mechanism of injury was falls (63%), 17% had major trauma, and the average time spent in the ED was 17 hours. In the whole sample, 14,518 patients  developed chronic pain during the follow-up period according to our three criteria: 92% of the chronic pain patients were identified through chronic pain medication consumption, 7% had a chronic pain clinic consultation code, and 4% were diagnosed with chronic pain when subsequently hospitalized.Univariate comparisons of patients' characteristics for the derivation and the validation samples are presented in N = 62,669) are presented in p value calculated on the derivation sample was 0.01, the Nagelkerke's percentage of variance explained was 0.28, the Brier score was 0.11, and area under the ROC curve was 0.80 (95% CI: 0.79–0.81). Except for calibration (Hosmer–Lemeshow), performance (Nagelkerke's and Brier score) and discrimination (area under the ROC curve) values are within the range of an informative model.Because collinearity was strong between insurance status and age , age was removed from the multivariate analysis. Results of the multivariate logistic regression analysis using the derivation sample , the Brier score remained at 0.11 and the area under the ROC curve was estimated at 0.80 (95% CI: 0.80–0.81) which is consistent with strong discrimination [When the logistic regression equation using the same predictors was applied to the validation sample . Except for loss of consciousness, which was no longer significant, the same set of predictors with approximately the same odds ratios was associated with the development of chronic pain.In a sensitivity analysis on the derivation sample, we performed the same stepwise logistic regression using only patients covered by the Quebec prescription drug insurance plan , injury characteristics, and history of alcoholism, anxiety, or depression have all previously been identified as predictors of chronic pain , 19–22. However, our study was done on a very large sample size  from the Quebec Trauma Registry, a reliable government supervised database. For example, inclusion in the Quebec Trauma Registry is mandatory; it uses standardized coding protocols and is subject to periodic validation. Our study is also the first to focus on risk factors present on hospital admission. Furthermore, we validated our predictive model on a large distinct sample . This predictive model could allow for the prompt screening of the trauma population at risk of developing chronic pain, early testing, and implementation of preventive approaches.The discrimination power of our model is good  and is higher than a recently published study predicting chronic pain development in patients with acute low back pain . HoweverThe prevalence of chronic pain development found in the present study (15.3%) is lower than that observed in two major reviews in trauma populations (from 22% to 96%) . The chrThis study has other limitations. The majority (92%) of our chronic pain patients were identified through the use of the chronic pain medication criteria. Since almost half of our trauma population were not covered by the Quebec prescription drug insurance plan, the prevalence of chronic pain development was likely underestimated, even in the presence of the other two criteria.The definition of chronic pain in our study may introduce other biases in the estimation of chronic pain prevalence and could also affect our risk factor modelling. Since we used the following proxy—filling at least 2 pain medication prescriptions within 3 to 12 months after the target injury—to define chronic pain development, we cannot exclude that some patients filled their prescriptions but did not consume any medication, or were taking pain medication for a subsequent injury/health problem or even became addicted to the pain medication. The retrospective design of this study limited our choice of chronic pain development predictors to variables included in the Quebec Trauma Registry. For example, pain intensity level on hospital admission, which has been shown as a consistent predictor of chronic pain in a trauma population, was not available in the Quebec Trauma Registry. Finally, history of alcoholism, depression, and anxiety was limited to the year preceding the target injury. Prospective studies are needed to evaluate and improve the ability of our model to predict chronic pain development from predictors that are available at hospital admission.Despite the relatively low incidence of chronic pain in our injury cohort, we identified risk factors present on hospital admission that can reliably predict trauma patients who will develop chronic pain. These factors should be prospectively validated. Hospital admission screening of the trauma population at risk of developing chronic pain could allow for early testing and implementation of preventive approaches.