The objective of this study was to determine the clinical presentation, systemic risk factors, source of infective microorganism, treatment outcomes, and prognostic indicators of endogenous endophthalmitis at a main tertiary referral hospital for uveitis in Malaysia. A retrospective review of medical records of 120 patients (143 eyes) with endogenous endophthalmitis over a period of 9 years between January 2007 and December 2015 was undertaken.Klebsiella pneumonia was the most common organism isolated (32.5%). Sixty-nine eyes (48.6%) were managed medically, and 73 eyes (51.4%) underwent vitrectomy. Final visual acuity of counting fingers (CF) or better was achieved in 100 eyes (73.0%). Presenting visual acuity of CF or better was significantly associated with a better final acuity of CF or better (p = 0.001).Identifiable systemic risk factors were present in 79.2%, with the majority related to diabetes mellitus (60.0%). The most common source of bacteremia was urinary tract infection (17.5%). A positive culture from ocular fluid or other body fluids was obtained in 82 patients (68.9%), and the blood was the highest source among all culture-positive results (42.0%). Gram-negative organisms accounted 42 cases (50.6%) of which Klebsiella pneumonia were the most common organisms isolated. Urinary tract infection was the main source of infection. Poor presenting visual acuity was significantly associated with grave visual outcomes. A high index of suspicion, early diagnosis, and treatment are crucial to salvage useful vision.The visual prognosis of endogenous endophthalmitis is often poor, leading to blindness. As expected, gram-negative organisms specifically  Streptococcus species, Staphylococcus aureus, and other gram-positive bacteria account for two thirds of bacterial endogenous endophthalmitis cases and gram-negative isolates are found in only 32% of cases [Klebsiella species accounting for 80 to 90% of positive cultures [Endogenous endophthalmitis (EE) occurs when infectious agents are hematogenously disseminated into the eye from a remote focus of infection. Even though this entity is relatively rare and accounts for approximately 2–15% of all cases of endophthalmitis , it is aof cases . In contcultures , 5.The outcome of endogenous endophthalmitis is often dismal. Sharma et al. reported that 60% of the eyes had a final visual acuity of hand motions or worse and as many as 29% required removals [To the best of our knowledge, there is no large case series on endogenous endophthalmitis being reported yet from Malaysia. The current study was performed to determine the clinical profile of EE at a tertiary hospital while focusing on the clinical presentation, predisposing risk factors, source of infective microorganism, treatment outcomes and prognostic indicators.A retrospective observational study was conducted in Selayang Hospital which was the main national tertiary referral center for uveitis in Malaysia. We reviewed the medical records of patients with endogenous endophthalmitis who were seen or referred to our hospital over a period of 9 years between January 2007 and December 2015. The diagnosis of endogenous endophthalmitis was defined as the presence of iritis and vitritis on ophthalmic examination and one or more of the following: (1) constitutional symptoms and systemic infection; (2) positive cultures of vitreous, blood, or other body fluids; (3) presence of loculation, vitreous debris, or membranous debris on ultrasound; (4) lack of ocular trauma or ocular surgery within 1 year from onset of infection or evidence of primary external ocular infection such as infectious keratitis or filtering bleb infection.Demographic details such as age, gender and race, presenting complaints, preexisting medical illnesses, predisposing risk factors, source of infection, laterality, visual acuity, ophthalmologic examination, ultrasound findings, microbiologic profiles, treatment modalities, and final visual outcomes were collected from medical records.The study was done according to Malaysian Good Clinical Practice (MGCP) 2nd edition January 2004 and registered in National Medical Research Register (NMRR).P value of < 0.05 was considered to be significant.Data was analyzed using the Statistical Package for Social Science (SPSS) version 22.0. Descriptive data was expressed as mean ± standard deviation (SD) for numerical data, and categorical variables were presented in frequencies and percentages. Logistic regression analysis was used to determine the factors associated with good visual outcomes. The association between presenting and final visual acuity was also analyzed using the Pearson correlation coefficient, and visual acuities were converted to logarithm of the minimal angle of resolution (logMAR) scale. For visual acuity less than counting finger (CF), the following scales were used: CF = 2.00 LogMAR units, hand motion = 2.30 LogMAR units, light perception = 2.60 LogMAR units, and no light perception = 2.90 LogMAR units. A A total of 143 eyes of 120 patients were included in this study. The age of patients ranged from 7 to 81 years, and the mean age at presentation was 52.6 ± 15.1 years. The racial distribution reflected the multiracial population in our country with 72 Malays (60.0%), 33 Chinese (27.5%), 13 Indian (10.8%), and 2 others (1.7%). There was a slight female predominance  compared to males .At least one underlying medical illness was identified in 95 patients (79.2%). Diabetes mellitus was the most common medical illness , followed by renal failure , and 15 patients (12.5%) had solid organ tumor or hematologic malignancy. Six patients (5.0%) had liver disease and 3 patients (2.5%) were pregnant. Five patients (4.2%) were on systemic corticosteroids for underlying autoimmune diseases, and 1 was on systemic immunosuppressants.A primary source of infection was identified in 90 patients (75.0%). Urinary tract infection 21, 17.5%) was the most common source of bacteremia followed by pulmonary infection , skin or soft tissue infection , and hepatobiliary infection . However, the source of infection could not be identified in 30 patients (25.0%), despite extensive systemic work-up and investigations , and involvement of the left eye  was more common. Blurring of vision , eye redness , eye pain or discomfort , and floaters  were ocular symptoms at presentation. The blurring of vision  was the most common presenting complaint, followed by eye redness  and eye pain or discomfort .The interval between the onset of ocular symptoms and the first presentation to an ophthalmologist was less than 1 week in 62 eyes (47.3%), 1 to 2 weeks in 40 eyes (30.5%), more than 2 weeks to 1 month in 10 eyes (14.5%), and more than 1 month in 10 eyes (7.6%). The interval was not available in 12 eyes which were from patients with no recorded ocular symptoms due to poor general medical condition or no documentation obtained from the medical records . This data was not available in 36 patients (30.0%). The interval between the onset of systemic symptoms and the onset of ocular symptoms was identified in 101 eyes. The interval was less than 1 week in 26 eyes (25.7%), between 1 and 2 weeks in 25 eyes (24.8%), more than 2 weeks to 1 month in 12 eyes (11.9%), and more than 1 month in 38 eyes (37.6%) , the proportion of the eyes with anterior chamber cells better than grade 3 and grade 3 or worse was similar with 67 eyes (49.6%) and 68 eyes (50.4%) respectively. Twenty-seven eyes (19.0%) had hypopyon, and 42 eyes (29.6%) had fibrin. The fundal view was present in 64 out of 143 eyes (44.8%). Among this, 32 eyes (50.0%) had choroiditis or choroidal abscess, 11 eyes (17.2%) had retinitis, 6 (9.4%) had vasculitis, and 4 (6.3%) had optic disc swelling. Six eyes had a combination of choroiditis or choroidal abscess and retinitis and 2 eyes had choroiditis or choroidal abscess, vasculitis, and optic disc swelling.Ultrasound findings were documented in 97 eyes. Fifty-five eyes (56.7%) had vitreous loculation, whereas subretinal or vitreous abscess and retinal detachment were found in 6 (6.2%) and 8 (8.2%) eyes respectively.A positive culture from ocular fluid or other body fluids was obtained in 82 patients (68.9%). The culture result of 1 patient was not available as he had it done elsewhere.The blood was the highest source among all culture-positive results 50, 42.0%). Gram-negative organisms were more common  than gram-positive organisms . Four patients (8.0%) had a positive fungal culture from the blood  had at least one positive culture from other body fluids. Other body fluid cultures yielded gram-positive organisms in 11 patients 23.9%), gram-negative in 28 patients (23.3%), and fungal in 7 patients (15.2%). Nineteen patients (41.3%) had a positive urine culture; 14 (30.4%) had positive cultures from infected catheter, skin, soft tissue, or joint; 8 (17.4%) had positive sputum cultures; 5 (10.9%) had positive culture from liver abscess; 3 (6.5%) had positive high vaginal swab; and 1 patient (2.1%) had positive cerebrospinal fluid . Of these, 22 eyes (81.4%) had bacterial and 5 eyes (18.5%) had fungal isolates. Among bacterial isolates, 10 (37.0%) were gram-positive and 12 (44.4%) were gram-negative . Systemic steroids were not used in any of the patients. In addition, 126 eyes (88.7%) received intravitreal antibiotics (vancomycin and ceftazidime or amikacin) or antifungal (amphotericin B) injections or both. The injections were repeated in 75 eyes (59.5%). Intravitreal injection was not given in 16 cases (11.3%), and 10 of them (62.5%) had relatively good presenting visual acuity of 6/24 or better and mild vitritis. They were treated with systemic antibiotics or antifungals with close monitoring. No intravitreal injection of steroids was given to any eye. Overall, 69 eyes (48.6%) were managed medically either with systemic or intravitreal antibiotics or antifungals or both.All patients were treated with systemic antibiotics or antifungal agents aimed at the source of infection and presumed causative organism. One hundred nineteen cases (85.6%) were on systemic antibiotics, and more than half (55.1%) were treated with ciprofloxacin either as monotherapy or in combination with other antibiotics. There was no statistically significant correlation between systemic ciprofloxacin and final visual outcomes  underwent vitrectomy. Early vitrectomy was performed within 2 weeks from diagnosis in 38 eyes (52.1%). Silicone oil was injected in 35 eyes (47.9%), gas in 3 eyes (4.1%), air in 19 eyes (26.0%), and no intraocular tamponade was used in 16 eyes (21.9%).The most common presenting visual acuity was between 6/60 and counting finger (CF) , followed by hand motion  and perception of light . Only 16 eyes (11.3%) and 14 eyes (9.9%) had presented visual acuity between 6/6 to 6/18 and 6/24 to 6/36 respectively. Overall, 56% had vision of CF or better at presentation. Vision was not available in 2 patients (1.4%) who could not cooperate during a vision test. Final visual acuity was available in 138 eyes (96.5%). Three patients were transferred to their original hospitals for the continuation of treatment and follow-up. One patient defaulted follow-up, and another patient passed away due to sepsis and multiorgan failure.After treatment, 100 eyes (73.0%) achieved final visual acuity of CF or better. Ten eyes developed panophthalmitis, and 6 eyes required evisceration. Table r = 0.564, p < 0.001  and presence of fundus view at presentation . In the multivariate logistic regression analysis, elevated risk for good visual outcome was observed only in good presenting visual acuity . We also found a moderate correlation between presenting visual acuity and final visual acuity  . SimilarIn a case series by Lim et al., the most common presenting complaint was decreased vision 68.8%) followed by ocular discomfort (44%), red eye (20.8%), and ocular pain (17.4%) . Ratra e.8% folloRatra et al. in their case series demonstrated that all eyes had severe diffuse endophthalmitis involving the posterior pole. Diffuse vitreous exudates were seen in 47 eyes (77%). Retina could be visualized in 13 eyes (21.3%), and 3 (4.9%) had retinal detachment. None had panophthalmitis . In anotThe diagnosis of endogenous endophthamitis is typically made following microbiologic evidence of infection from intraocular samples (aqueous or vitreous). Positive cultures from the blood, cerebrospinal fluid, or any extraocular site can be highly suggestive. In our series, the organism causing endophthalmitis was identified by a positive culture from at least one body fluid source in 82 patients (68.9%). Blood culture positivity rate varies widely, from 33 to 94% . PreviouKlebsiella was found to be responsible for approximately 90% of all endogenous bacteria endophthalmitis cases [Klebsiella was the most common causative agent [K. pneumonia which is predominant in East Asia may be due to the high incidence of cholangiohepatitis. Therefore, the East Asian population is more prone to have liver abscess than Caucasians [K. pneumonia was the most common organism isolated . Interestingly, in contrast to several East Asian studies, urinary tract infection including renal abscess  was the most common source of infection caused by K. pneumonia followed by lung infection  in our series. Liver abscess was identified in 7 patients (25.9%). Necrotizing fasciitis, infected wound breakdown, and acute gastroenteritis (AGE) were noted in one patient each. Apart from that, there was a relatively higher frequency of gram-positive cocci and fungal infection in our study, 32.5% and 16.9% respectively.Causative organisms vary geographically. Studies from the western population revealed that fungal infection was the main source in predisposed states, such as intravenous drug abusers and immunocompromised patients , 19, 21.is cases . Studiesve agent , 17. A sve agent . K. pneuucasians . We founMost systemically administered antimicrobials that have been used in the therapy of endophthalmitis do not penetrate well into the non-inflamed vitreous humor. However, the penetration of several antibiotics into the eye may be increased by inflammation which occurs following surgery, trauma, or infection. Kowalski and colleagues compared the minimum inhibitory concentration (MIC) of bacterial isolates from 66 patients with endophthalmitis and found that all of the gram-negative isolates would have been inhibited by levels of ciprofloxacin achievable following systemic administration .In endogenous endophthalmitis, the rationale for use of intravitreal injections as an adjunct to intravenous therapy is also because of reduced permeability of the retinal-pigmented epithelium to systemically administered drugs . YonekawKlebsiella endophthalmitis. However, they suggested early vitrectomy should be considered in patients whose anterior chamber inflammation did not respond well to intravitreal antibiotics [Klebsiella endogenous endophthalmitis, 50% achieved a vision of CF or better after 6 months [p = 0.327).Vitrectomy serves as a diagnostic and therapeutic option. It is indicated in cases with severe vitreous opacities, diffuse retinal infiltration, and poor presenting visual acuity and when there is no clinical improvement with systemic and intravitreal therapy. However, the role and timing of vitrectomy remain unclear in patients with endogenous endophthalmitis. Sheu et al. reported no significant relationship between vitrectomy and visual outcome in ibiotics . On the 6 months . Early v6 months . In othe6 months , 17. In Generally, the visual outcome of endogenous endophthalmitis is poor due to early and extensive retinal involvement. Virulent causative organisms, poor host defense, misdiagnosis leading to delayed treatment, inadequate treatment, inappropriate therapy, and occurrence of complications such as panophthalmitis are associated with poor prognosis. Wu et al. reported that the eyes with bacterial endogenous endophthalmitis had a worse outcome compared to patients with fungal endophthalmitis . Lim et Klebsiella endophthalmitis has been poor despite treatment with a combination of systemic and intravitreal antibiotics [K. pneumonia showed that visual acuity achieved was CF or better in 34.0% of eyes, and 16.0% had evisceration or enucleation [Klebsiella [Klebsiella endogenous endophthalmitis, only 18 eyes (25.4%) achieved final visual acuity of CF or better, which is comparable with other studies. Ten eyes were complicated with panophthalmitis, and 5 of them were due to Klebsiella pneumonia.Visual outcomes in ibiotics , 13. Cascleation . Sheu etcleation . ConnellIn our series, a good presenting visual acuity was the only prognostic factor associated with good visual outcomes of CF or better. Lim et al., Nishida et al., and Binder et al. in their case series also described that a good presenting visual acuity was significantly associated with good final visual acuity , 16, 20.This study is limited by the retrospective design. As the data was collected retrospectively, some of the information was not available. Apart from that, patients with culture-negative result were also included in this study which may have included those with non-infectious uveitis. In the future, we may need to use other methods such as polymerase chain reaction (PCR) with higher sensitivity and specificity. Lack of uniform guidelines and treatment protocol is another limitation. Observational and prospective case series are needed in the future to assess long-term outcomes.Klebsiella pneumonia were the most common organisms isolated. Urinary tract infection was the main source of infection. Poor presenting visual acuity was significantly associated with poor visual outcomes.The visual prognosis of endogenous endophthalmitis (EE) is poor. Gram-negative organisms specifically


Tuberculosis remains a major public health threat throughout the world particularly in developing countries. Evaluating the treatment outcome of tuberculosis and identifying the associated factors should be an integral part of tuberculosis treatment. The aim of this study was to assess the treatment outcome of tuberculosis and its associated factors among TB patients in the TB clinics of Harar public hospitals, Eastern Ethiopia, 2017. A retrospective document review was conducted in two public hospitals of Harar town, located 516 km east of Addis Ababa. A systematic random sampling technique was used to select the document of TB patients who were registered in the hospitals from 1st of January, 2011, to 30th of December, 2015. The data were collected using a pretested structured data extraction format. SPSS Version 21 for window was used for data processing. Bivariate and multivariate analysis with 95% confidence interval was employed in order to infer the associations between TB treatment outcome and potential predictor variables. One thousand two hundred thirty-six registered TB patients' documents were reviewed. Of these, 59.8% were male, 94.2% were urban dwellers, 97% were new cases, 61.2% were presented with pulmonary TB, and 22.8% were HIV positive. Regarding the treatment outcome, 30.4% were cured, 62.1% completed their treatment, 3.9% died, 2.4% were defaulted, and the remaining 1.2% had failed treatment. The overall rate of the treatment success among the patients was 92.5%. In the present study, being female , having pretreatment weight of 20 – 29 kg , being HIV negative , and being new TB patient (AOR = 3.22 95% CI: 1.10 - 9.47) were factors independently associated with successful treatment outcome. On the other hand, being in the age group 54 – 64 years  and age greater than 65 years  was associated with unsuccessful TB treatment outcome. In the current study, the rate of successful TB treatment outcome was acceptable. This rate should be maintained and further improved by designing appropriate monitoring strategies. Tuberculosis  remains According to WHO TB report, 20 countries share 85% of all estimated TB cases worldwide and Ethiopia falls under this category indicating high TB burden in the country .TB epidemiology is closely connected with social and economic conditions which make its prevention, care, and control more challenging , 5. ManyStudies conducted in various parts of Ethiopia reported different success rates of the treatment and the associated factors. For instance, a study conducted in the Northern part of the country reported 89.2% , but anoUndoubtedly, the success rate of TB treatment outcome and the associated factors vary from setting to setting. Routine monitoring of the extent of the outcome and its determinants is important, but studies that have focused on TB treatment outcome and associated factors are lacking in Eastern Part of Ethiopia. Therefore, the aim of this study was to assess TB treatment outcome and factors associated among TB patients in Public Hospitals of Harar town, Eastern Ethiopia.The objective of the study is to assess TB treatment outcome and associated factors among TB patients in Public Hospitals of Harar town, Eastern Ethiopia, 2017.This study was conducted in two public hospitals  in Harar town. The data were collected from April 24 to 29, 2017.A retrospective document review was conducted to assess the treatment outcome of TB patients and the associated factors from TB patients' documents registered from January 1, 2011, to December 31, 2015, at Public hospitals in Harar town.The documents of all the TB patients who were registered in the two public hospitals from 1st of January, 2011, to December 31st, 2015, were the source population.The documents of the randomly selected TB patients who were registered in the two public hospitals from 1st of January, 2011, to December 31st, 2015, were the study population.The documents of all the registered TB patients at two public hospitals were included in this study.However, registries in which treatment outcomes were missing and patients were transferred to other districts were excluded from the study. n= sample size for each group α/2= the desired level of statistical significance: 95% => 1.96 ZZβ = the desired power: 80% power => 0.84 1= proportions of good/poor treatment outcome among the nonexposed  P2= proportions of good/poor treatment outcome among the exposed  P1 − p2 = the difference in proportions of good/poor treatment outcome among the nonexposed and exposed p The sample size was determined by using double population proportions formula.cure rate among HIV negative and HIV positive TB patients By using the above formulaα=95%  Zβ= 80%, r=1, P1=85. %, P2=55.7%  n=74(2) cure rate among male and female TB patientsZα=95%  Zβ= 80%, r=2, P1=4.3% P2=8.6%  n=1026(3) Cure rate among male and female TB patientsZα=95%  Zβ= 80%, r=2, P1=3.6 % P2=7.2 %  n=1236Z From the above options, the largest sample size (1236) was selected .Totally 3329 TB patients registered during the review period, from January 1st, 2011, to December 31st, 2015, in two public hospitals .The sample size (1236) was distributed to each clinic using a proportionate allocation. Therefore, a total sample size for each TB clinic was The data were collected by using a pretested structured data extraction format. The standard TB registry, laboratory findings, and monthly cohort follow-up form were reviewed to generate the required data. The standardized checklist used included all important sociodemographic data, clinical characteristics , laboratory findings, and follow-up data. Data was collected by four BSc. nurses who have had training on comprehensive TB care and experience in data collection.Data were entered, cleaned, and analyzed using SPSS Version 21 for windows. Appropriate descriptive statistics such as mean (with standard deviation), median (with inter quartile range [IQR]), and frequencies (with percentages) were used to describe the study population in relation to relevant variables.Bivariate and multivariate analysis with 95% confidence interval was employed to infer associations between the independent and dependent variables. P value≤ 0.2 in the bivariate analyses were included in the final multivariable logistic model in order to identify the independent predictors of TB treatment outcome. A P value < 0.05 was considered statistically significant. Assumption on fitness of goodness of the final model was checked by Hosmer and Lemeshow test and was found fit.Binary logistic regression was used to calculate the crude odds ratio (COR) with 95% confidence interval. Each variable was entered into a logistic regression model so as to determine the presence of statistical significant association with the outcome variable. Multicollinearity among selected independent variables was checked through variance inflation factor (VIF) and none was found. All the explanatory variables with aEthical approval was obtained from research review technical committee of Harar health Science College. A legal authorization letter was written from Harar health Science College to study settings to get permission before data collection. The information obtained was made anonymous and deidentified prior to analysis to ensure confidentiality.In this study, treatment outcomes are categorized into successful and unsuccessful treatment outcomes.Successful treatment outcome included “cured” and “treatment completed” cases.” and patients who “died.”Unsuccessful treatment outcome included “treatment failure” cases, “defaulter,According to the WHO, Treatment Outcomes Were Categorized into the following.Successful outcome: if the TB patients were cured (negative smear microscopy at the end of the treatment and on at least one previous follow-up test) or completed treatment with resolution of symptoms. Unsuccessful outcome: if the treatment resulted in treatment failure (remaining smear positive after 5 months of treatment), patients are defaulted (patients who interrupted their treatment for two consecutive months or more after registration), or patients died. Cured: if the patients had finished treatment with negative bacteriological result at the end of the treatment. Treatment completed: if the patients had finished treatment, but without bacteriological result at the end of the treatment. Treatment failure: a patient who, while on treatment, remained smeary positive or became again smear positive at the end of the five months or later, after commencing treatment or a patient who was PTB-negative at the beginning and turned out smear positive at the end of the intensive phase. Defaulter: a patient who had been on treatment for at least 4 weeks and whose treatment was interrupted for 8 or more consecutive weeks. Died: if the patient died from any cause during the course of the treatment. New case: a patient who had never had treatment for TB or had been on anti-TB treatment for less than four weeks.  According to the standard definitions of the National Tuberculosis and Leprosy Control Program guidelines of Ethiopia (NTLCP), the folSmear positive pulmonary TB (PTB+): a patient who had at least 2 initial smear examinations positive for AFB by direct microscopy or one initial smear examination positive and culture positive or one initial smear positive and radiographic abnormalities consistent with TB. Smear negative pulmonary TB (PTB-): a patient who had three initial smear examinations negative for AFB and no response to course of broad-spectrum chemotherapy and again 3 smear examinations negative by direct microscopy and radiographic abnormalities consistent with PTB and three initial smear examinations negative by direct microscopy but positive by culture and decision by a clinician to treat with anti-TB Extra-pulmonary TB (EPTB): a patient who had TB in organs other than the lungs proven by one culture-positive specimen from extra-pulmonary site or histopathological evidence from a biopsy or TB based on strong clinical evidence with active EPTB and decision by a physician to treat with anti-TB.  Three types of TB were considered in this study. These were smear positive pulmonary TB (PTB+), smear negative pulmonary TB (PTB-), and extra-pulmonary TB (EPTB).The documents of 1236 TB patients were reviewed in this study. More than half of these TB patients (59.8%) were male, with male-to-female ratio of 1.5 to 1. Their age ranged from 1 to 95 years, with a median of 29 years (IQR: 22 - 40 years). About 363 (29.4%) of the participants were in the age range of 25 – 34 years and 355 (28.7%) were in the age range between 15 and 24 years. The weight of the TB patients ranged from 6 to 89 kg with mean (± SD) weight of 48.9 (±11.3) kg. More than half (59.7%) weighed 38 – 54 kg .Most of the attendants (97%) were new TB cases. Seven hundred fifty-six (61.2%) of the patients were presented with pulmonary TB of whom 400 (52.9%) were smear positive. Significant number of the patients 282 (22.8%) were found to be HIV positive of whom 250 (88.7%) and 258 (91.5%) were on ART and Cotrimoxazole Preventive Treatment (CPT), respectively.Among smear positive PTB patients at the beginning of the treatment, 10 (2.5%), 7 (1.75%), and 14 (3.56%) were smear positive at second, fifth, and seventh months of the treatment, respectively. Most of the (97%) patients were treated with Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol (RHZE) in intensive phase and 86.4% were on Rifampicin and Isoniazid (RH) during the continuation phase .Concerning the trend of all forms of TB, the proportion of extra-pulmonary TB slightly increased from 31.1% in 2011 to 43.3% in 2015 whereas the proportion of smear positive pulmonary TB decreased in the first three years from 40.1% in 2011 to 21.3% in 2013 .Among the TB patients included in this study, 376 (30.4%) were cured, 767 (62.1%) had completed their treatment, 48 (3.9%) were dead, 30 (2.4%) were defaulted, and the remaining 15 (1.2%) had failed treatment.The cure rate was high in the year 2011 (38.1%) and low in the year 2013 (19.8%). The default rate showed slight increment during the review period, 1.3% in the year 2011 to 3.4% in the year 2015. However, the death rate showed a reduction in the first three years (2011 – 2013) from 6.1 % to 2.0% and then started to increase in the final two years of the study period (2014 and 2015) from 3.3 % to 4.4% .P value =0.429). The treatment success rates were 94.3%, 90.7%, and 92.3% among the PTB+, PTB-, and EPTB patients, respectively. In the bivariate analysis, variables with P value of < 0.2 were sex, age, pretreatment weight, HIV status, patient category, and type of TB  in this study was 92.5%. The rate of treatment success was higher among females (93.8%) than males (91.6%) and patients from rural setting (94.4%) than urban setting (92.4%). The proportion of TB patients with treatment success steadily decreased since 2012 (94.8%), 2013 (93.9%), 2014 (93.0%), and 2015 (90.8%); however, the difference was not statistically significant  compared to the male. The HIV negative patients had 6.50 times higher odds of  having treatment success than the HIV positive. Similarly, the odds of treatment success were 3.22 (AOR = 3.222 95%CI: 1.096 - 9.472) times higher among new TB patients than retreatment TB cases . This finding was consistent with previous studies conducted in different areas of Ethiopia (Gimbi (59.3%) , Debre TThe age of the TB patients in this study ranged from 1 to 95 years, with the median age of 29 years and this is also similar to the findings of previous studies , 18, 19.In the present study, 3% of the patients were in the retreatment category. Similar findings were reported in studies conducted in Enfranz (2.4%) , Sidama The prevalence of HIV among the patients in this study was 22.8%, which is comparable with the reports from Gambella 26%) , Gimbi  were presented with extra-pulmonary TB. This finding was comparable with studies from Gimbi (36%) , WesternIn the current study, the overall rate of the treatment success of the TB patients was 92.5%, and this is similar to the findings reported from Tigray Region (89%) , Dabat (TB associated death rate in present study was 3.9%. This figure was in line with report from Dilla (3.4%) , Addis ADefaulting from Anti-TB treatment clinic is one of the main challenges of TB controlling program. The defaulting rate of TB patients from their treatment in this study was 2.4%, which is in line with the finding in Debre Tabor. However, the majority of previous studies reported that defaulting from TB treatment ranged from 2.8% in Dabat to 30.8% in South West Nigeria , 28, 32.The other main problem of TB controlling program is treatment failure. In our study, 1.2% of the TB patients were identified as treatment failure. This figure is lower than the reports from Ibadan Nigeria (8.1%) , Egypt (Identification of factors associated with treatment outcome of TB patients is very crucial in order to tackle those factors leading to poor treatment outcome. The present study revealed that being female; age greater than 55 years, having pretreatment weight of 20 – 29 kg and 38 – 54 kg, being HIV negative, and being new TB patient were independently significantly associated with successful treatment outcome.As reported by many studies , 27, 33,The HIV status of the TB patients was one of the factors that were associated with the treatment outcome. Not surprisingly, in this study, the HIV negative patients had bigger chance of successful TB treatment than the HIV positive ones. This finding is consistent with several previous studies , 27, 28.The treatment outcome of the TB patients who received TB treatment at the study area was satisfactory and in line with the WHO target. The treatment outcome was significantly associated with gender, age, pretreatment weight, HIV status, and TB category. Moreover, it was not significantly affected by place of residence, year of treatment, and types of TB.Based on the findings of this study, we recommend that frequent supportive supervision and health education programs for patients with a high risk of unsuccessful treatment outcome should be carried out. In addition, further prospective studies are needed to identify other potential sociodemographic and behavioral factors that could affect the treatment outcomes of TB patients.


Cimex lectularius), a nocturnal blood-feeding ectoparasite, is considered an urban pest with public health importance in human environments. We aimed to determine the repellency effect of oregano essential oil, Origanum vulgare, against this pest under laboratory conditions.The common bed bug (meta-toluamide (DEET).The essential oil was prepared from dried leaves using hydro-distillation method. A gas chromatography-mass spectrometer (GC-MS) was used for analysis and identification of oregano essential oil compounds. Treated surface method in Petri dish was carried out to evaluate repellency potential of the oil using 4th and 5th instar nymphs and adults. The concentration-repellency response of oregano essential oil was calculated and compared with a commercial insect repellent stick containing 33% N, N-diethyl-50 and EC99 of oregano oil (effective concentrations causing 50% and 90% repellency of bed bugs) were 1.61 and 6.57mg/cm2 at 9h after application, respectively. The 40% oregano essential oil exhibited 100% repellency against bed bug at 3, 5, 9 and 24h after application while the repellency index of DEET 33% was 100% at 3 and 5h and it decreased to 80% and 27% at 9 and 24 hours.The oregano essential oil consisted of 158 compounds with terpineol (22.85%) and α–terpinene (20.60%) being the major components by volume. The ECOregano oil 40% exhibited more repellency compared to commercial insect repellent stick containing 33% DEET. Further studies are warranted to confirm the effectiveness of oregano essential oil in personal protecting against bed bug biting. Cimex lectularius Linnaeus), is a nocturnal blood-feeding ectoparasite considered as urban, common and nuisance pest in the recent past  produced in 1954  on bed bugs in comparison with DEET against bed bugs (C. lectularius).The aim of this study was to determine the repellency activity of oregano essential oil  with folded papers as harborage and kept at 26±1 °C, 50±5% relative humidity (RH), photoperiod of 12:12 (L: D)  , 27. TheInsect repellent stick (33% DEET) as commercial formulation was purchased from Reyhan Naghsh Jahan Pharmaceutical Cosmetic and Hygienic Company. It is used widely in Iran on blood-sucking insects such as mosquitoes, sand flies, ticks and bed bugs.O. vulgare) was collected from its natural habitat from Yazd Province, central part of Iran (latitudes 54.20257 and longitudes 32. 00315). Collected Oregano specimens were identified by the Department of Pharmacognosy, Ahvaz Jundishapur University of Medical Sciences. Firstly, fresh leaves dried with air, and next 200gr of oregano was mixed with 400ml of distilled water and placed in a 1L flask. In the following the essential oil oregano used in the assay was isolated from dried fresh leaves by the hydrodistillation method using a Clevenger-type apparatus  at 90±5 for 5 hours. We extracted 0.9cc pure (about 100%) essential oil of 100gr of dried leaves of O. vulgare. Sodium sulfate was used for dehydration. The extracted essential oils were stored at 4 °C in dark glass vials for further experiment (Oregano plant (periment .Gas-chromatography-mass spectrometer (GC-MS) was used for the analysis and identification of oregano essential oil compounds . It is equipped with HP–5MS column (30m× 0.25mm× 0.25 μm). The initial temperature used was 40 °C for 1min and was later raised to 220 °C at a rate of 3 °C/min and finally raised to 270 °C for 5min at a rate of 20 °C/min. Other parameters of the GC-MC machine included carrier gas Helium (99/999%), injector temperature (260 °C), detector temperature , splitless mode, ionization potential of 70eV, scan rate of 1 scan/sec, the scan range of m/z 40–48 was used for all analysis. The essential oil constituents were identified by comparing their retention indices, mass spectra fragmentation with those in a stored Wiley 7n.1 mass computer library and those of National Institute of Standards and Technology (NIST) .2 for drawing dose-response curve. Plastic Petri dishes of 8cm diameter by 1.5cm height were used in this experiment. Ethanol was used as solvent for essential oil. White filter papers were divided into two equal halves and inserted into the bottom part of the Petri dishes. A piece of folded filter paper was placed in the middle as bed bug harborage  for each treatment group were released into the center of each Petri dish  were evaluated against the laboratory-reared bed bugs in plastic Petri dishes and compared with DEET (33%). Moreover, the concentrations were calculated as doses of 0.1, 0.21, 0.43, 0.86, 1.72, 3.45, 6.9mg/cmarborage . This paarborage . In the tri dish . The num50 and EC99). Repellency indices were calculated using: repellency =(C–T)/C×100, where C is the mean number of bed bugs located on the treated filter paper in all control plastic Petri dishes, and T is the number of bed bugs located in half part of the treated filter paper at unfixed concentration test in the plastic Petri dishes  in 2 of the surface. The data obtained from 9h exposure time was important because this time represents the typical time period when people are in bed and exposure to common bed bug biting. They were 1.61 and 6.57mg/cm2 for EC50 and EC99 at 9h after exposure, respectively with slope (±SE) = 0.469±0.073 and Chi-square (df)= 17.17 and P< 0.904. Calculated dose-response curve for Oregano essential oil after 9h is shown in The results of dose-response test are showed with the calculation of repelling effective concentration as mg essential oil per cmC. lectularius are shown in Repellency indices of oregano essential oil and 33% DEET on At 9h after exposure, significant differences were observed between repellency of 0.625%, 1.25%, 2.5%, and 5% concentrations of Oregano essential oil and 33% DEET (P< 0.001), while the differences between 10%, 20%, and 40% oregano essential oil and 33% DEET were not significant (P=0.21) .O. vulgare collected from Mazandaran was 1.018%  was the most abundant chemical component of oregano essential oil followed by α-terpinene with 20.6% (v/v). The component of α-terpinene in s 1.018% . The plas 1.018% . The ches 1.018% . In addi pipiens . In our The aim of using repellant compound towards hematophagous pest is to reduce the frequency of biting in endemic areas and prevent bites in areas where allergic reactions to biting insects are common . Very feSupella longipalpa) after the same time (10 and LC30) of oregano essential oil had an average repellency of 22.8% and 49.8% against the diamondback moth (Plutella xylustella) respectively  and bed bug patrol  as botanical repellents did not exhibit detectable repellency against bed bug in the presence of carbon dioxide source .Triathoma rubida using small restrained rats. No long-range repellency was observed. Only citronella oil was able to stop all probing and feeding of T. rubida and appears to be a promising potential repellent to prevent sleeping people from being bitten by kissing bugs (DEET, picaridin, tea tree oil, peppermint oil, and citronella oil were tested for repellency activity on ing bugs . The effing bugs .99 dose should be estimated to determine the protection time against blood-sucking insects. 6.57mg/cm2 had 99% repellency against C. lectularius in treated surface after 9 hours. Further studies are recommended to determine the protection time and repellency of oregano essential oil using EC99 on animal and human hosts.Preferably, the EC


Aims: This study aimed to describe risk reduction behaviors regarding ambient particulate matter with a diameter of 2.5 μm or less (PM2.5) among outdoor exercisers and to explore potential factors influencing those behaviors in the urban area of Nanjing, China. Method: A cross-sectional convenience sample survey was conducted among 302 outdoor exercisers in May 2015. Descriptive analysis was used to describe demographics, outdoor physical activity patterns, knowledge of PM2.5 and risk reduction behaviors. Multivariate logistic regression analysis was then used to explore factors that influence the adoption of risk reduction behaviors. Results: The most common behavior to reduce PM2.5 exposure was minimizing the times for opening windows on hazy days (75.5%), and the least common one was using air purifiers (19.3%). Two thirds of respondents indicated that they wore face masks when going outside in the haze (59.5%), but only 13.6% of them would wear professional antismog face masks. Participants adopting risk reduction behaviors regarding PM2.5 exposure tended to be females, 50–60 year-olds, those with higher levels of knowledge about PM2.5 and those who had children. Conclusions: These findings indicate the importance of improving knowledge about PM2.5 among outdoor exercisers. Educational interventions should also be necessary to guide the public to take appropriate precautionary measures when undertaking outdoor exercise in high PM2.5 pollution areas. Nanjing, the capital city of Jiangsu Province, located in eastern China, is one of the most developed and fastest growing urbanized areas. With rapid social and economic development, Nanjing has been facing the challenges of severe air pollution ,32,33,342.5 exposure and the potential factors that influence the behavior adoption. We conducted the survey during the morning and evening hours, where a high proportion of outdoor exercisers were found in the pilot study. According to data from the local meteorological department, the daily average PM2.5 concentration was 51.23 ± 21.63 µg m−3 over the survey month in Nanjing, with five days less than 30 µg m−3 and only one day peaking at 111 µg m−3. Convenience sampling was used to recruit participants at outdoor parks. Two districts, Gulou and Xuanwu, were initially selected, as they are main residential areas representing 23.4% population in the central metropolitan Nanjing [2.5 levels were relatively lower than other local districts. Secondly, four parks  in these two districts were selected to recruit participants, since they were identified as dominant exercise locations based on the pilot study ; and (4) risk reduction behaviors taken to reduce outdoor air pollution exposure including adjusting physical exercise time/frequency according to the AQI, adjusting physical exercise styles/amounts according to the AQI, the wearing of face masks when going outside in the haze, the cleaning of mouths and noses after outdoor activities, opening windows, and using air purifiers.The questionnaire design was guided by the COM-B framework. The COM-B framework is a ‘behavior system’ (B) involving three essential conditions, viz. capability (C), opportunity (O), and motivation (M), developed from the existing theories of behavior change ,38. ‘Cap2.5 [2.5 exposure and their potential influencing factors. Twenty participants, randomly selected from the study area, took part in the pilot study in early March 2015. Based on the results, questions that were unclear or problematic were revised.After preliminary research and a pilot study, behavioral questions were designed based on the relatively common six risk reduction behaviors regarding PM2.5 ,21,22,232.5 was measured by a 5-point Likert scale, ranging from 1 (very unfamiliar) to 5 (very familiar). The risk reduction behavior items were also measured by 5-point Likert scale, ranging from 1 (never) to 5 (very often). The total scores of items regarding knowledge of PM2.5 were then calculated and classified into four levels, from ‘very high’ (scores from 21 to 25), to ‘very low’ (scores from 5 to 10). We created a binary variable using mean value as a cutting point for further analysis. The variable was coded as ‘0’ representing ‘lower-level’ of risk reduction behavior , while the code ‘1’ represented ‘higher-level’ of risk reduction behavior . The mean score of 19 was selected as the final cutting point in the final model.The participants’ knowledge about PM2.5 and the extent of knowledge of PM2.5. A multivariate logistic analysis was used to investigate the predictors of participants’ risk reduction behaviors. Predictor variables were socio-demographic characteristics, including age group, gender, occupation; whether or not household with children and self-reported the extent of knowledge about PM2.5. Dummy variables were created to represent different attributes of each independent variable, with reference set based on the method of Indicator  during the regression analysis. Significance was defined as p < 0.05.The collected data were double-entered into a database using EpiData 3.1 . All analyses were performed using SPSS version 18.0 . Descriptive statistics were firstly used to illustrate the demographic characteristics and the percentages of categorical variables. Then, the total scores were calculated for describing respondents’ overall risk reduction behavior regarding PMOf the 302 respondents, 52.3% (158) were males. The mean age of the respondents was 60.8 ± 12.2 years-old, with a range from 26 to 86 years old. 22.5% (68) respondents had college diplomas or above. 27.5% (82) of the respondents reported that their individual income per month was less than RMB 3000, whilst 33.5% (100) indicated that they had monthly incomes more than RMB 5000. Around half of the respondents  suffered from chronic illnesses, including respiratory diseases (3.3%), cardiovascular and cerebrovascular diseases (41.7%), tumors (0.7%) and other chronic diseases (7.3%). 14.8% (44) of them had children in their household, and 49.3% (148) had a family member with chronic illness see .2.5 is shown in 2.5. Approximately one third  of them were ‘very familiar’ or ‘familiar’ with the sources and hazards of PM2.5 respectively. Almost one fifth (60) respondents indicated that they were ‘very familiar’ or ‘familiar’ with the connotation of AQI. Only 8.7% (26) were ‘very familiar’ or ‘familiar’ with the components of PM2.5.The knowledge of respondents regarding PM2.5 was 13.57 (SD = 4.2). Overall, 5.5% (16) of the respondents were classified into the group with ‘very high’ knowledge about PM2.5, and 22.6% (66) of them were classified into group with ‘very low’ knowledge about PM2.5.The average comprehensive score of respondent’s knowledge about PM2.5 exposure from outside. More than half of the respondents  adjusted time of day or frequency that the physical exercise was done “often” or “very often” according to the AQI. 56.7% (170) of respondents adjusted their physical exercise styles or amounts in relation to the AQI “often” or “very often” whilst 14.7% (44) of them ‘never’ did it. Approximately one third of respondents  wore face masks “very often” or “often” when going outside in the haze. Specifically, among those who wore face masks, nearly half of the respondents  would wear medical one-off masks, 36.4% (64) would wear cotton or gauze face masks, and only 13.6% (24) would wear professional antismog face masks.As shown in 2.5 exposure was minimizing times for window opened and the least common one was using air purifiers.Furthermore, 48.3% (146) of respondents indicated that they would clean their mouths and noses after outdoor activities ‘very often’ or ‘often’ whilst only 19.3% (58) of them would use air purifiers ‘very often’ or ‘often’ when airing the room. 2.5. Compared to males, females were more likely to adopt risk reduction behavior against PM2.5 risks . Respondents between the age of 50 to 60 years old were also more likely adopt risk reduction behavior than those who were younger than 50 years old . However, elderly people over 70 years old were also found to be less likely to adopt such behavior, although it is not statistically significant (p > 0.05). Compared to respondents with no children in their household, those who had children were 2.56 times more likely to adopt risk reduction behavior . In addition, the levels of knowledge about PM2.5 was found to be a significant predictor of having a ‘higher-level’ risk reduction behavior in response to PM2.5 risks .2.5 exposure among outdoor exercisers in Nanjing metropolitan area and identified the factors that are associated with those behaviors. In brief, the level of risk reduction behavior was significantly associated with gender, age, knowledge of PM2.5, and whether or not household with children.This study described six major risk reduction behaviors regarding PM2.5, their knowledge of the component of PM2.5 was limited. This may be attributed to the government’s lack of publicity on this issue. It is easier for people to access the real-time concentration of atmospheric PM2.5 via media. The health hazard of PM2.5 is mainly caused by chemicals on particulates [2.5 and the impact of mass concentration were rarely mentioned. Understanding the characteristics of PM2.5 compositions may encourage local residents to take targeted protective measures of preventing risks from PM2.5 exposure. Therefore, it is important for the government and healthcare providers to strengthen educative publicity in this area.Our study found that although respondents had a good understanding of the risks relating to PMiculates ,40. Howe2.5 exposure. The current studies showed that air purifiers could result in significant reduction in indoor PM2.5 concentration and improve human health in some areas with ambient particulate air pollution [We found avoiding opening windows was the most common risk reduction behavior. This could be explained by people’s risk perceptions of air pollution. People will take actions when they are aware of the risks to their health in the fog and haze from a variety of media sources . Avoidinollution ,45. Two ollution ,45. Howe2.5 exposure [2.5 in many previous studies [In China, AQI has been updated daily to the general public through different medias, including television, radio, newspapers, broadcast telephone messages, and the Internet, as well as the health advice about how to reduce PMexposure . Therefoexposure . Wearing studies ,26. In t studies ,24. Howe studies ,26. Henc2.5 and preventive actions during hazy days found that women were more willing to reduce their amount of outdoor activities and more willing to wear a mask than males [2.5 risk reduction behavior. Since the elderly are more sensitive to air pollution and pay more attention to their health and safety than the youth, they were found to be more likely to adopt risk reduction behaviors. Nonetheless, contrasting findings has been reported in another Chinese study that reported participants aged 18–44 were more likely to wear face masks than other older age groups [In this study, females were more likely to adopt risk reduction behaviors than males. This finding is somewhat consistent with previous studies. A study comparing Chinese residents’ perceived risks on PMan males . Age is e groups . No signe groups . The dis2.5 was found to be a strong predictor of having higher-level risk reduction behavior in this study. This can be partly explained by the COM-B framework which suggested an integrated ‘behavior system’ (B) involving capability (C), opportunity (O), and motivation (M) [In addition, knowledge of PMtion (M) ,38. In ttion (M) . Other rtion (M) .2.5. According to the COM-B framework, ‘reflective motivation’ includes the beliefs that air pollution can have negative health impact, and it is also regarded as perceived severity [2.5 threat and thereby they may take more protect measures in daily life.Households with children were found to be another potential predictor for high-level risk reduction behavior of PMseverity ,38. Simiseverity . In this2.5 among outdoor exercisers in a Chinese setting. It provides valuable information to encourage local health-related authorities to take into account the importance of reducing PM2.5 exposure on a daily basis at the individual-level and to set up appropriate intervention strategies.This study is the first study to describe multiple risk reduction behavior of PM2.5 were self-reported, which is, by definition, subjective. Thirdly, given that respondents recalled some of their behavior  instead of common behavioral habits to adverting PM2.5, the potential for recall bias was possible. Hence, objective measurements on knowledge extent regarding PM2.5 will be applied in future work. Moreover, predictors of each specific risk reduction behavior will be further investigated to expand the present findings.Several limitations to the current study should be acknowledged. Firstly, the study was conducted on convenience sample. Therefore, selection bias and underrepresentation were inevitable. Secondly, responses about the risk reduction behavior and knowledge towards PM2.5 exposure among outdoor exercisers in the Nanjing metropolitan area. It also reports on how people’s demographic characteristics and knowledge of PM2.5 affect their risk reduction behavior. Educational interventions to promote PM2.5 protective behavior should target males, aged younger than 50 or even over 71 years old, and households with no children. Our findings also draw attention to the importance of increasing public knowledge of PM2.5, as a potential strategy in reducing PM2.5 exposure. In brief, this study can be used for policy-makers and healthcare providers to ascertain a clear understanding of individual self-protection strategies to minimize exposure to air pollution, as well as their influencing factors, to improve community awareness in haze polluted areas.The present study described the multiple risk reduction behaviors regarding PM


Background and purpose — There is some concern regarding the revision rate of the Vanguard CR TKA in 1 registry, and the literature is ambiguous about the efficacy of patient-specific positioning guides (PSPGs). The objective of this study was to investigate the stability of the cemented Vanguard CR Total Knee using 2 different surgical techniques. Our hypothesis was that there is no difference in migration when implanting the Vanguard CR with either PSPGs or conventional technique. We hereby present a randomized controlled trial of 2-year follow-up with radiostereometric analysis (RSA).Patients and methods — 40 TKAs were performed between 2011 and 2013 with either PSPGs or the conventional technique and 22 of these were investigated with RSA.Results — The PSPG (8 knees) and the conventional (14 knees) groups had a mean maximum total point motion (MTPM) (95% CI) of 0.83 (0.48–1.18) vs. 0.70 (0.43–0.97) mm, 1.03 (0.60–1.43) vs. 0.86 (0.53–1.19), and 1.46 (1.07–1.85) vs. 0.80 (0.52–1.43) at 3, 12, and 24 months respectively (p = 0.1). 5 implants had either an MTPM >1.6 mm at 12 months and/or a migration of more than 0.2 mm between 1- and 2-year follow-ups. 2 of these also had a peripheral subsidence of more than 0.6 mm at 2 years.Interpretation — 5 implants (3 in the PSPG group) were found to be at risk of later aseptic loosening. The PSPG group continuously migrated between 12 and 24 months. The conventional group had an initial high migration between postoperative and 3 months, but seemed more stable after 1 year. Although the difference was not statistically significant, we think the migration in the PSPG group is of some concern. Not all patients are satisfied after total knee arthroplasty (TKA); in several studies up to 25% of patients have persistent pain and dysfunction  Total Knee  was introduced in 2003. In some registries  the prosthesis has showed promising results. Yet in another (SKAR), the Vanguard CR had a significantly higher relative risk of revision compared with other implants.The implant can be inserted by conventional surgical technique or with patient-specific positioning guides (PSPGs). PSPGs are customized and manufactured from preoperative CT or MRI data to improve postoperative alignment  in Oslo and Skien, Norway, which compared clinical and radiological but no radiostereometric analysis (RSA) results of the PSPG technique  with the conventional technique for TKA. The exclusion criteria were published in that study  were inserted in the tibia. All patients followed the same standardized postoperative rehabilitation protocol.Implant migration was evaluated using RSA. The first examination took place within a week postoperatively, then after 3, 12, and 24 months. They were all performed in the supine position by the same radiographers at each time point. We used calibration cage number 43  and ceiling mounted X-ray tubes .MB-RSA 3.40  software was used for the migration analysis. The migration was described both as segment motion of all 6 degrees of freedom (translations and rotations) and maximum total point motion (MTPM), the latter being primary outcome. In addition, we analyzed the point motion from fictive points added to the computer aided design (CAD) model of the tibial component. We had the following 7 fictive points: stem tip, anterior, posterior, posteromedial, posterolateral, medial, and lateral . All theOur upper limit for CN was 100, and for RBE 0.50 mm. 1 patient exceeded 0.5 mm RBE at 2 years and was excluded from the RSA examination at this time point. The rest had RBE of less than 0.35mm. Precision was assessed by double RSA examinations of all patients at all time points, and reported as absolute mean difference of double examinations ±1.96 x standard deviation (SD).For clinical assessment we used the Knee injury and Osteoarthritis Outcome Score (KOOS)  over the entire follow-up period and to control for repeated measurements. The fixed effects were time, group, and time-by-group interaction. The model included a random slope. As the KOOS scores were not normally distributed, the Wilcoxon signed-rank test was used to evaluate difference from preoperative to 2 years. Further, patients were divided into high- and low-risk group according their migration data , if not stated otherwise.All statistical calculations were performed using the IBM SPSS Statistics version 23 .The study was approved by the Regional Committee for Medical and Health Research Ethics, West-Norway  and the institutional review board at Oslo University Hospital (2011/7613), and registered at clinicaltrials.gov (NCT01696552). All patients were included with written consent. No financial funding from companies has been received for this study, and the authors declare that there are no conflicts of interest.See Supplementary data) and Supplementary data, The mean MTPM, and relevant point motions, translations, and rotations are shown in Tables 2 and 3 , 0.01 mm for X translation (95% CI –0.12 to 0.14), 0.01 mm for Y translation (95% CI –0.07 to 0.08), 0.03mm for Z translation (95% CI –0.25 to 0.32), 0.05° for X rotation (95% CI –0.28 to 0.37), 0.04° for Y rotation (95% CI –0.65 to 0.72), and 0.00° for Z rotation (95% CI –0.14 to 0.15).Supplementary data).We found a statistically significant improvement of all the KOOS subscales from preoperative through 2 years in the whole cohort. We could not see any difference in clinical performance for implants with migration at risk or PSPG and conventional groups (Mann–Whitney U test) .Neither could we demonstrate any other subgroup to explain the inferior stability of the high-risk group .5 complications occurred: 1 deep hematoma that was evacuated, 1 stiff knee requiring mobilization under anaesthesia, 2 superficial hematomas, and 1 superficial infection. The latter was in the PSPG group, the others in the conventional group. None of the complications required reoperation. Except for the aforementioned high-risk patient, they had good clinical scores after 2 years.Our main finding was that the implants in the PSPG group had continuous migration between 12 and 24 months. The implants in the conventional group showed migration between postoperatively and 3 months; thereafter the mean migration abated and the implant stabilized. The difference in MTPM and subsidence between the two groups, however, was not statistically significant.Several studies have discussed threshold levels for increased risk of aseptic loosening. Ryd et al.  showed tA limitation of our study is the sample size. Ideally, we would have liked between 25 and 30 participants in each group, yet several other RSA studies have suboptimal sample sizes for various reasons , the latter with only a few hundred patients reaching 10 years, and with no information regarding surgical technique. Several clinical studies also show excellent results (Kievit et al. In summary we found that the cemented Vanguard CR had a higher initial mean migration than expected at 12 months, but from 12–24 months the conventional group stabilized. The PSPG group also had continuous migration at this point. None of the implants in our study rotated more than recommended, and only 2 implants had a total peripheral subsidence above that recommended, 1 in each group. Although the PSPG group did not have a statistically different MTPM from the conventional group, we think that the findings of the migration pattern of this technique are of some concern and call for longer follow-up.http://dx.doi.org/10.1080/17453674.2018.1470866Tables 2, 3, and 5 and Figure 7 are available in the online version of this article, FDØ analysed parts of the data and wrote the manuscript. MT analysed parts of the data and critically reviewed the manuscript. JvL and SMR designed the study and critically reviewed the manuscript.The authors would like to thank the radiographers Mona Risdal, Silje Clausen, and Alexis Hinojosa, statistician Cathrine Brunborg and the study coordinators Marte Traae Magnusson and Anette Simonsen for their contributions to the study.Acta thanks Bart G Pijls and Nikolaj Sebastian Winther for help with peer review of this study.


Determine TB-LAM Ag (LAM) is a point of care test developed to diagnose tuberculosis (TB). The aim of this study was to evaluate the diagnostic performance of LAM in people living with HIV using Brazilian public health network algorithm for TB diagnosis.3 (in the Alere PIMA CD4 assay at study screening), patients coughing for at least 2 weeks or presenting a chest radiography suggestive of TB. LAM, in conjunction with sputum smear microscopy or Xpert MTB/RIF (Xpert) as compared to Mycobacterium tuberculosis culture, which was used as a reference standard. TB prevalence was 24.6%. Overall accuracy of LAM was 79.9% (73.8%-84.9%), positive and negative predictive values were 62.2% (46.1%-75.9%) and 84% (77.5%-88.8%), respectively. The overall LAM sensitivity was 46.9% (33.7%-60.6%) and specificity was 90.7% (84.9%-94.4%). The best performance of LAM was observed among patients with CD4 counts ≤50 cells/mm3 (sensitivity = 70.4% and specificity = 85.9%). When 2 respiratory smears were used in conjunction with LAM, sensitivity increased 22%, as compared to just 2 smears. Furthermore, LAM when used in conjunction with two respiratory smears, was as sensitive as compared to a single one. However, no improvement in TB diagnosis occurred when LAM was used with Xpert as compared to Xpert alone. Among 14 LAM false positive tests, Non-Tuberculosis Mycobacteria were isolated in three cases.A cross-sectional study design was used to enroll 199 adult patients in two sites in Rio de Janeiro and two in São Paulo. The study enrolled HIV-infected patients with CD4 counts ≤200 cells/mmLAM is a point of care test that increased TB diagnosis in immunosuppressed HIV-infected patients when used in conjunction with smear microscopy, but not when used with Xpert in Brazilian public health network sites. Use of LAM test should be considered in settings where immunosuppressed HIV patients need rapid TB diagnosis. Mycobacterium tuberculosis (Mtb) culture is slow to grow.Tuberculosis (TB) diagnosis continues to be a challenge in people living with HIV (PLHIV) since immunosuppression results in atypical images on the chest X-ray ,2 and paBrazil used a TB diagnostic algorithm based on smear microscopy and Mycobacterial culture until 2014 , when it3 or in those seriously ill if CD4 cell counts are unavailable [Determine TB LAM Ag (LAM) detects lipoarabinomannam, a glycolipid from Mycobacteria wall that is eliminated in the patient’s urine. The overall sensitivity is low ,8, but tvailable .3, when used in conjunction with smear microscopy or Xpert, compared to Mtb culture to determine if LAM should be incorporated into the Brazilian TB diagnosis algorithm for PLHIV in the public health system.The aim of this study was to evaluate the diagnostic performance of LAM in PLHIV with CD4 counts ≤200 cell/mmCAAE number 439.001).This study was approved by the following Institutional Review Boards: National Institute of Infectious Diseases Evandro Chagas, Center for Reference and Training STD/AIDS, Nova Iguaçu General Hospital and Institute of Infectious Disease Emilio Ribas and by National Research Ethics Committee  and 2 sites in São Paulo (Institute of Infectious Disease Emilio Ribas and Center for Reference and Training STD/AIDS). All four sites are public HIV reference health units.Patients were initially screened to detect signs and symptoms of TB and HIV. Chest X-ray was requested for those without a previous exam in the last 15 days before enrollment. Participants were also submitted to a rapid CD4 cell count through Alere PIMA Analyzer. At least one respiratory sample was provided to perform smear microscopy and Mycobacterial culture. Hemoculture and other specimens cultures were done according to patients’ signs and symptoms. During this study, Xpert was incorporated into Brazilian TB diagnosis algorithm and was included in the protocol after an amendment to the original one.3. Patients were excluded if they were pregnant, did not provide urine, failed to provide at least one respiratory sample or had initiated TB treatment 30 days before study entry.Patients were enrolled if they were 18 years old or more, HIV-positive, signed an informed consent, had cough for at least 2 weeks or presented a chest radiography suspected of TB and had CD4 counts ≤200 cells/mmAll enrolled participants provided a fresh urine sample for LAM detection. The results were independently read by two nurses and photos were taken for future comparisons.Chest X-rays showing upper lobe opacity, lower lobe upper segment opacity, milliary pattern, mediastinal adenopathy, pleural effusion or cavitation were considered suggestive of TB.TB diagnostic tests were performed by a certified public bacteriology laboratory for each site involved. Respiratory samples, as well as other suspected site samples, were processed following their own standardized practices. Laboratories staffs were blinded to patient’s clinical data and LAM results. Acid fast stain were done using Ziehl-Neelsen method and Mycobacteria load was reported as negative, scarce bacilli, +, ++ and +++ according to Brazilian TB Guidelines . At the A patient was considered with TB diagnosis if any culture (LJ or MGIT) of any respiratory or no respiratory sample resulted in Mtb isolation.All clinical and laboratorial data were recorded through Research Electronic Data Capture and data was analyzed using R-project, version 3.4.3. Descriptive analyzes were used for socio-demographic and clinical characteristics. Diagnostic accuracy measurements of sensitivity, specificity and predictive values were estimated with 95% confidence interval in overall population and stratified by CD4 cell counts , with Mtb culture as the reference standard. The tests combinations were conducted in parallel, which means subjects were classified as positive when at least one of them was positive, even if one of the tests was absent.Since there was little information regarding TB diagnosis when adding LAM to existing testing algorithms, the sample size for the study was based on several considerations. Since smear sensitivity was expected to be between 50% and 60% an increase of sensitivity between 20% and 40% was expected when adding LAM to smear. At a parsimonia situation, a non-overlapping 95% binomial confidence interval could be observed when a sensitivity increases from 55% to 85% and tested with a sample size of 40. As the inclusion strategy was to be consecutive, and TB prevalence was expected to be between 30% and 40% at the lower CD4 strata, a reasonable sample size would be between 100 and 133.Although Xpert was unavailable at Brazil in the beginning of the study, its’ design allowed the analyses of this test in TB diagnosis algorithm.3, one could not provide urine, six did not provide a respiratory sample and one used TB drugs previously  had a CD4 count ≤50 cells/mm3 . Positive and negative predictive values were 62.2% (46.1%-75.9%) and 84% (77.5%-88.8%), respectively. The overall sensitivity and specificity of LAM was 46.9% (33.7%-60.6%) and 90.7% (84.9%-94.4%), respectively .3, where sensitivity was 70.4% (51.5%-84.1%) and specificity was 85.9% (76.9%-91.7%). When two smears microscopy were combined with LAM, sensitivity was increased by 22% when compared to two smears alone, achieving a sensitivity close to Xpert. Furthermore, LAM combined with two smears was as sensitive as when combined to a single smear. LAM did not add sensitivity when combined to Xpert when compared to Xpert alone  result.(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S1 File(DOCX)Click here for additional data file.S2 File(CSV)Click here for additional data file.S3 File(ZIP)Click here for additional data file.S4 File(TXT)Click here for additional data file.


Extra-uterine pregnancy (EUP) is frequent in Cameroon but little is known about its clinical features.To describe the epidemiological, diagnostic, therapeutic and prognostic features of extra-uterine EUPs at the Yaounde Central Hospital in Cameroon.We carried out a cross-sectional study from the 1 st of January 2015 till January 31 st 2016 at the maternity of the Yaounde Central Hospital. All patients admitted for EUP were included. Data was analysed with Epi info 3.5.4 and SPSS 2.0.In this study, EUPs were diagnosed between 7 and 11 weeks of amenorrhoea including 148 cases(3.14%) out of 4707 deliveries.The mean age of patients was 28.54 ± 5.85 years and participants were mainly single (80.4%), self-employed (48.7%) and for most living in town (80.4%). Half of the patients (50.0%) had history of sexually transmitted infections and 56.8% have had a voluntary abortion. Male condom was the most frequently used contraceptive (54.7%) and EUP was iterative in 8.8% of cases. Most EUPs were ruptured (85%) and some presented haemorrhagic shock (67.5%) with nearly all (93.7%) requiring management by laprotomic salpingectomy. Death occurred in 1.3% (2/148) of cases.In Yaounde - Cameroon, diagnosis and medical care of EUP takes place with a cosiderable delay leading to high risk complications. Salpingectomy via laparotomy remains the mainstay for management of EUP. Extra-uterine pregnancy (EUP) is the main cause of first trimester maternal mortality . BesidesWe conducted a descriptive cross-sectional study at the maternity of the Yaounde Central Hospital. The study was carried out from January 1 st , 2015 till January 31 st , 2016. The population studied consisted of pregnant women consulting at maternity services at the beginning of pregnancy. Those diagnosed with ectopic pregnancies were included after informed consent. A minimum sample size of 63 participants was determined by the Lorentz’s formula.Data was collected from all patients participating in this study and included sociodemographic  and obstetrical characteristics , medical history , clinical parameters  and modality of treatment.Data management was done with Epi info version 3.5.4 and SPSS 2.0. Quantitative data were presented as mean and qualitative data percentages.Ethical clearance was obtained from the institutional ethical board of the faculty of Medicine of the University of Douala. We also obtained an administrative clearance from the executives of the Yaounde Central hospital. Prior to their inclusion, all participants signed an informed consent form.A total of 148 EUPs were recorded over a total of 4707 deliveries (3.1%). The mean age for EUPs was 28.5 ± 5.9 years. Most patients (81.8%) were aged between 20 and 34 years old. There was a predominance of married women among (80.4%) and a vast majority of these patients living in urban areas. Approximately half (48.7%) of our patients were self-employed. More than half (52.7%) of these patients were either nullipara (27.7%) or primipara (25.0%) while grand multipara (Gravida 5 and above) accounted for 8.1% (12/148). Eighty (54%) patients didn’t know their HIV status. Forty one patients (27.7%) had no contraceptive method. Rupture occurred between 7 and 12 weeks in 68.4% of patients. History of induced abortion was the most frequent risk factor (56.8%) followed by pelvic inflammatory disease (50.0%). Only 8 patients (5.4%) had previously undergone pelvic surgery. Tobacco consumption (smoking) was found in 13 patients (8.8 %). The sociodemographic and obstetrical parameters of participants are summarized in Tables In patients presenting EUPs, abrupt ruptures happened in 128 (86.4%) of them. These patients had amenorrhea out of which 99 (67.5%) of them reported pelvic pain. One hundred (67.5%) patients presented with hemodynamic shock due to the EUP. In our series, EUPs were implanted in the fallopian tube in 142 (95.9%) patients and implantation in the ampulla was the most common site of implantation (115 cases). The clinical features presented in this section are summarized in The technique for management of UPSs was surgical laparotomy in 139 (93.9%) patients. In the practice, the following procedures were carried out: total salpingectomy in 133 (93.7%) cases; tubal conservation after milking in 4 (2.8%) cases and partial salpingectomy in 5 (3.5%) cases. Management was medical (intramuscular methotrexate) in 9 cases of which 6 were successful. Blood transfusion was carried out for 125 (84.5%) patients. Two deaths were registered (1.3%).An overall EUP rate of 3.1% was found in Yaounde. This figure is similar to those reported in different locations in Cameroun a decade ago: 2.3% in Bafoussam , 3.4% inFurthermore, in our study, the mean gestational age at the time of EUP diagnosis was similar to those commonly reported in the literature . The mosLike in other hospitals, if laparoscopy is not available, surgical management was done via laparotomy for salpingectomy interventions . RuptureIn conclusion, the observed EUP rate in Yaounde is high. Single and young women with few or no children are the most affected. Most women diagnosed with EUP have history of sexually transmitted infection and induced abortion. Late diagnosis hinders non-surgical management of EUP as it is most often discovered after rupture and haemorrhagic shock. In view of reducing this burden, women should be sensibilized to start antenatal consultations early and to seek medical care at the onset of symptoms.


Hydatidosis is a zoonotic infection and treatment is mandatory to avoid complications. Surgery remains the first choice in the treatment especially for CE2-CE3b cysts. Open or laparoscopic approaches are available. However, comparative studies are limited. Data of patients who underwent cystotomy/partial cystectomy for liver hydatidosis between January 2012 and September 2016 (n=77) were evaluated retrospectively. Recurrent cases and the patients with previous hepatobiliary surgery were excluded. 23 patients were operated upon laparoscopically and named as Group 1. 48 patients operated conventionally named as Group 2. Demographics, cyst characteristics, operative time, length of hospital stay, recurrences, and surgery related complications were evaluated. Groups were similar in terms of demographics, cyst characteristics, and operative time. The length of hospital stay was 3.4 days in Group 1 and 4.7 days in Group 2 . The mean follow-up period was 17.8 months and 21.7 months, respectively (p=0.170). Overall complication rates were similar in two groups (p=0.764). Three conversion cases occurred (13%). One mortality was seen in Group 2. Four recurrences occurred in each group  (p=0.258). Laparoscopy is a safe and feasible approach for surgical treatment of liver hydatidosis. Recurrence may be prevented by selection of appropriate cases in which exposure of cysts does not pose an intraoperative difficulty. Hydatidosis is a zoonotic infection caused by a parasite Echinococcus granulosus and endemic mainly in the Mediterranean area, the Middle East, China, and the Far East , 2. AlthTreatment options are medical therapy, percutaneous interventions, and surgery. Surgery remains the gold standard in the treatment of hydatid cyst especially in CE2-CE3b cysts , 10. SurLaparoscopic treatment of hepatic hydatidosis was first reported in 1992 and became popular in recent years . MinimalComparative studies of laparoscopic and open approaches in the treatment of liver hydatidosis have been limited in literature. Controversies about the role of laparoscopy such as patient selection and the differences in surgical techniques have not yet been resolved. This study was aimed at comparing the results of laparoscopic and conventional open approaches to liver hydatidosis.After obtaining institutional board review approval, data of patients who underwent cystotomy/partial cystectomy for liver hydatidosis between January 2012 and September 2016 (n=77) were evaluated retrospectively. Diagnosis was made by conventional imaging  and serology. Recurrent cases (n=4) and the patients with previous hepatobiliary surgery (n=2) were excluded. Therefore, a total of 71 patients were included in this study. All patients were treated with albendazole  two to three weeks prior to the operation and three to six months following the operation. Appropriate antibiotic prophylaxis was performed 30 minutes prior to the operation for all patients. 23 patients who were operated upon via laparoscopic approach were named as Group 1. 48 patients who were operated upon via conventional open approach were named as Group 2. A total of five different surgeons performed the operations. Three of them were specialized in hepatopancreatobiliary surgery and the remaining two were practicing as general surgeons. Demographic data , imaging characteristics  of hydatid cysts, length of hospital stay, recurrences and surgery related complications , and mortality were evaluated. Primary end point of this study was defined as the development of surgery related complications. U test. P values lower than 0.05 were considered as statistically significant.Data were analyzed via using SPSS v20 software. Categorical variables were evaluated with Pearson chi square test. Other quantitative parameters were evaluated with Mann-Whitneyth hours. Drain was removed after 48 hours if there is no apparent bile. The patients were in follow-up period scheduled to three to six-month interval with imaging, liver function tests, and serology if necessary.Four ports were inserted: supraumbilical 10 mm port with 30 degree telescope, 10 mm epigastric port, and additional two ports that were depending mainly on the cyst location for each patient. Pneumoperitoneum were set at 12 mmHg. Gauzes soaked with 20% hypertonic saline were placed around the cysts . The cysA right subcostal or upper median incision was preferred due to cyst localization. Surgical technique was similar to laparoscopic surgery. 20% hypertonic saline was used as scolicidal agent. An open aspirator and surgical spoon were used for suction and clearance of the cyst cavity. Postoperative follow-up procedure was similar to in the laparoscopic group.There were 23 patients with mean age of 39.4 ± 19.1 years in Group 1. Male to female ratio was 11/12. Group 2 included 48 patients with a mean age of 41 ± 15.4 years. Male to female ratio was 25/23. There was no statistically significant difference between two groups in terms of gender and age . Cyst characteristics were presented in The mean operative time was 150 ± 63 minutes in Group 1 and 113 ± 63 minutes in Group 2 .The length of hospital stay was 3.4 ± 1.4 days in Group 1 and 4.7 ± 2.2 days in Group 2. Length of hospital stay was significantly longer in Group 2 (p=0.007).The duration of follow-up period was 17.8 ± 9.3 months and 21.7 ± 11.1 months in Groups 1 and 2, respectively (p=0.170). In this period, seven patients (30%) in Group 1 and 13 patients (27%) in Group 2 suffered from complications (p=0.764). Details of the complications were presented in In group 1, laparoscopic hemoclip was used in one patient and suture ligation was used in three patients to control the suspected bile leak. In Group 2, suture ligation was performed in ten patients to control the bile leak. Biliary leakage following surgery was detected 13% (3/23) and 15% (7/48) in the laparoscopy (Group 1) and open surgery (Group 2) groups, respectively (p=0.861). However, persistent bile fistula was seen in one patient in Group 1 and four in Group 2; all patients underwent endoscopic interventions, and all resolved.Although there was no mortality in Group 1, one mortality was seen in Group 2 due to postoperative hepatic encephalopathy. Four recurrences were seen in Group 1 (17%) and Group 2 (8.3%) (p=0.258).Hydatid disease is a major health problem in endemic areas. The liver is commonly affected organ that accounts 70% of the cases and most commonly the right lobe is implicated –5, 10. TSurgical strategies may vary from conservative methods such as cystotomy plus drainage and partial cystectomy to more radical methods such as lobectomy and hepatectomy. Although open procedures have usually been performed for the surgical treatment of hydatid disease, laparoscopic approaches have become popular in recent years.Laparoscopic surgery for the hydatid disease obtains the advantages of minimal invasiveness such as lesser incisional complications, faster surgery, shortened hospital stay, and good cosmetic results , 13–15. Conversion rates in laparoscopic surgery for liver hydatidosis have been reported as 4-30% in previous reports , 18–20. Another intraoperative complication of liver hydatidosis is the development of biliary fistulous tract between the cyst cavity and the biliary system that has been reported as 3-17% in the literature . TherefoLength of hospital stay may vary according to the preferred surgical modality. Shortened hospital stay has been reported in laparoscopic liver hydatidosis surgery when compared to open techniques in the literature , 14, 22.Mortality rates have been reported as 0-6.5% for hydatid disease surgery , 25. In Recurrence is one of the major problems in liver hydatidosis surgery and has been reported around 10% in the literature . Common The operative time was longer in Group 1, and the difference reached a statistically significant level . We think that the operative time may be affected from heterogeneity of surgical team and would be decreased with the increased experience.Main limitations of this study were retrospective design, relatively small number of the cases, relatively short follow-up time, and unfeasible design to evaluate the learning curve of laparoscopy due to the several surgeons took participate in these operations.Laparoscopy is a safe and feasible approach for the surgical treatment of liver hydatidosis. Recurrence may be prevented by selection of appropriate cases in which exposure of cysts does not pose an intraoperative difficulty.


ADHD diagnosis at T1 was strongly associated with development of psychotic symptoms at T2  and psychotic disorder . Our findings that inattention symptoms and the diagnosis of ADHD are associated with subsequent psychotic outcomes in 22q11.2DS have important clinical implications. Future studies examining the effects of stimulant and other ADHD treatments on individuals with 22q11.2DS are warranted.Individuals with 22q11.2 Deletion Syndrome (22q11.2DS) are at substantially heightened risk for psychosis. Thus, prevention and early intervention strategies that target the antecedents of psychosis in this high-risk group are a clinical priority. Attention Deficit Hyperactivity Disorder (ADHD) is one the most prevalent psychiatric disorders in children with 22q11.2DS, particularly the inattentive subtype. The aim of this study was to test the hypothesis that ADHD inattention symptoms predict later psychotic symptoms and/or psychotic disorder in those with 22q11.2DS. 250 children and adolescents with 22q11.2DS without psychotic symptoms at baseline took part in a longitudinal study. Assessments were performed using well-validated structured diagnostic instruments at two time points  and T2 ). Inattention symptoms at T1 were associated with development of psychotic symptoms at T2 (OR:1.2,  Approximately 1 in 4000 individuals are affected by 22q11.2DS, rendering this the most common chromosomal microdeletion syndrome . While tNumerous studies of individuals with 22q11.2DS have observed a range of psychiatric and cognitive problems in childhood and adolescence; that is, prior to the typical age of onset for psychosis. These include anxiety disorders, Autism Spectrum Disorder (ASD) and intellectual disability . Attenti22.1n = 73) were excluded from the main analyses but included in sensitivity analyses .The International 22q11.2 Deletion Syndrome Brain Behavior Consortium (IBBC) was established in 2013 with the aim of harmonizing existing well-characterized cohorts of participants with 22q11.2DS with both phenotypic and genotypic data available . For theThe study was approved by the appropriate local ethics committees and institutional review boards. Each participant and his or her caregiver, when appropriate, provided informed written consent/assent to participate prior to recruitment.2.2Assessments were conducted using well-validated structured diagnostic instruments . ADHD sy2.3Standardized IQ scores were available across the sites using age-appropriate Wechsler scales and were examined as confounders. Taking into account that intellectual disability is frequently present in 22q11.2DS, some sites assessed the presence/absence of ADHD symptoms taking into account whether the individual with 22q11.2DS had intellectual disability. To account for this, we included ‘site assessment differences’ as a covariate variable. We also included age at baseline and sex as covariates.2.4Logistic regressions were conducted to examine whether T1 inattention symptoms and ADHD diagnosis (independent variables) predicted T2 outcome (dependent variable) status . We repeated the analyses by also including age, sex, IQ and the variable ‘site assessment differences’ (see confounders above) as covariates. We also examined whether longitudinal change in inattention symptoms and ADHD diagnosis were associated with psychotic symptoms and/or any psychotic disorder at T2. Change in inattention symptoms in relation to psychotic symptoms and psychotic disorder was examined using principal components analysis (PCA) following previously reported methods . The PCA33.1The sample started with a total of 323 individuals  aged 11.8 years at the first assessment (SD = 3.3) and 15.1 years (SD = 4.0) at the second assessment. Excluding 73 participants who reported psychotic symptoms at T1, our final sample included 250 individuals  with complete data on psychotic symptoms and ADHD diagnosis and 188 individuals  with complete data on psychotic symptoms and inattention symptoms . The mea3.2p = 0.01 and OR = 4.5, p < 0.001 respectively) (p = 0.15). ADHD diagnosis at T1 was associated with psychotic disorder at T2   . There w = 0.02) .Table 3Ap = 0.27) or with psychotic disorder at T2  (Table S2). There was weak evidence for associations between total ADHD symptoms (i.e. hyperactive-impulsiveness and inattention symptom scores combined) and development of T2 psychotic symptoms  but no evidence for associations with psychotic disorder at T2  (Table S2).Sensitivity analyses revealed no association between T1 hyperactive-impulsiveness symptoms at T1 and psychotic symptoms at T2 . We found significant age and IQ differences, with the group reporting psychotic symptoms at T1 being older than the group without psychotic symptoms at T1 and of lower mean IQ score. There were no significant mean differences in terms of inattention symptoms and ADHD diagnosis.Table S4 shows the summary statistics for change in inattention symptom levels and ADHD diagnosis over time in relation to psychotic symptoms at T2. There was no evidence that change over time in inattention symptom levels or ADHD diagnosis was associated with psychotic symptoms or psychotic disorder at T2 . Results4In the largest longitudinal study examining the presence of ADHD symptoms and diagnosis in individuals with 22q11.2DS to date, we observed that inattention symptom levels and ADHD diagnosis predicted the development of psychotic symptoms and were weakly associated with psychotic disorder. Moreover, we found that the presence of inattention symptoms at any time point rather than the change in inattention symptom levels over time was associated with psychotic symptoms. The evidence was weaker for the outcome of psychotic disorder, but this is likely due to low power, since in this young sample (mean age 14.3 years) only 6% were diagnosed with psychotic disorder.These longitudinal findings are in accordance with our previous study that found cross-sectional associations between inattention symptoms and psychotic symptoms in individuals with 22q11.2DS . PreviouThere are a number of potential explanations for our findings. One is that the 22q11.2 deletion increases risk for inattention symptoms and ADHD, which in turn increase risk for psychotic outcomes . AnotherOn the other hand, we did not observe cross-sectional associations between inattention symptoms/ADHD diagnosis and psychotic symptoms at T1. ADHD diagnosis was equally comorbid in those with and without psychotic symptoms and the mean levels of inattention symptoms were similar between the two groups. A previous study that examined the dimensional structure of a wide spectrum of psychopathology in 22q11.2DS has found evidence of a general psychopathology factor in addition to more specific factors  . TherefoWe did not observe association between hyperactive-impulsive symptoms and psychotic outcomes, which accords with cross-sectional studies of 22q11.2DS  and popu4.1Our study is the first to show that inattention symptom levels and ADHD diagnosis in those with 22q11.2DS are associated with later emerging psychotic outcomes. If inattention and ADHD are risk factors for future psychosis, then effective treatment is a priority for reducing the risk of psychosis in this high-risk group. However, if ADHD is a prodromal feature of psychosis in this group, then taking into account that stimulant medication is often prescribed for ADHD, future studies are needed to examine potential effects of such treatment in individuals with 22q11.2DS. A randomized controlled trial in thirty-four children with 22q11.2DS and ADHD indicated that methylphenidate can be safe and effective after a 6-month treatment and led to a 40% reduction of ADHD symptoms as reported by parents . InteresAlthough the link between ADHD and psychosis is not adequately studied , our fin4.2Although this study benefitted from recruitment of a number of sites of the 22q11.2 IBBC, resulting in a relatively large sample, the study may have been underpowered for some analyses . Moreover, the mean age at follow up was 14.3 years and therefore the individuals with 22q11.2DS had not yet passed the peak age of onset for schizophrenia. Therefore, the associations that we report are likely to represent an underestimate. Another limitation is that we could not consider the impact of medication, since at the time of this analysis medication information was not consistently reported from all sites. However, failing to adjust for medication is more likely to have attenuated the magnitude of association between ADHD symptoms and psychotic outcomes. Although the assessments were conducted by experienced clinicians and psychologists, we cannot exclude the possibility of diverse diagnostic practices across sites that might have influenced our findings. However, we attempted to account for differences between centres in our analyses and did not find that site assessment differences explained our findings. Ascertainment bias is also likely, considering that genetic testing was conducted on the basis of a phenotype that was sufficient to warrant genetic testing . Finally, taking into account that comorbidity is common in 22q11.2DS, it could be that other disorders , in addition to ADHD, might be longitudinally associated with psychotic outcomes in 22q11.2DS. However, this question was outside the remits of this study. Also, it could be argued that ADHD is more easily amenable to symptom reduction by treatment than other potential clinical risk factors for psychosis in 22q11.2DS . Interestingly, a recent study on 89 children with 22q11.2DS did not find longitudinal associations between autism spectrum disorders and psychosis .4.3Our study is the first to examine the longitudinal associations between ADHD symptoms and psychotic outcomes in 22q11.2DS. Our findings that inattention symptoms and ADHD diagnosis were associated with subsequent psychotic symptoms and psychotic disorder in 22q11.2DS have important clinical implications. Future studies examining the effects of ADHD medication in individuals with 22q11.2DS are warranted.Study concept and design: Maria Niarchou, Anita Thapar.Acquisition of data: Maria Niarchou, Marianne B.M. van den Bree, Samuel J.R.A. Chawner, Ania M. Fiksinski, Jacob A.S. Vorstman, Maude Schneider, Stephan Eliez, Marco Armando, Maria Pontillo, Donna M. McDonald-Mcginn, Beverly S. Emanuel, Elaine H. Zackai, Carrie Bearden, Vandana Shashi, Stephen Hooper, Michael J. Owen, Raquel E. Gur.Analysis of data: Maria Niarchou, Naomi Wray, Marianne B.M. van den Bree, Anita Thapar.Interpretation of data: Maria Niarchou, Naomi Wray, Marianne B.M. van den Bree, Anita Thapar, Michael J. Owen, Raquel E. Gur.Critical revision of the manuscript for important intellectual content: All authors.National Institute of Mental Health grants USA U01MH101719, U01MH0101720, Wellcome Trust Fellowship (M.N. 110222/Z/15/Z), R01 MH085953 (CEB), U54 EB020403 (CEB), Swiss National Science Foundation (324730_144260) to SE, National Center of Competence in Research (NCCR) “Synapsy-The Synaptic Bases of Mental Diseases” (51NF40-158776) to S.E.This study was funded by the The funding sources had no participation in any of the aspects of this study .None reported.