Patients' outcome after ICU transfer reflect hospital's post-ICU care status. This study assessed association of after-hour ICU transfer on patient outcome.Single-centre, retrospective analysis of data between March 2016 and April 2017 was performed at a tertiary-care hospital in India. Patient data were collected on all consecutive ICU admissions during study period. Patients were categorized according to ICU transfer time into daytime (08:00-19:59 hours) and after-hour (20:00-07:59 hours). Patients transferred to other ICUs/hospitals, died in ICU, or discharged home from ICU were excluded. Only ?rst ICU admission was considered for outcome analysis. Primary outcome-hospital mortality; secondary outcomes-ICU readmission and hospital length of stay (LOS). All analysis were adjusted for illness severity.vs. after-hour 65.7±15.2 vs. 66.3±16.2 years) was similar (p = 0.7). Mean APACHE IV score was comparable between daytime vs. after-hour transfers . Unadjusted hospital mortality rate of after-hour-transfers was significantly higher compared to daytime-transfers . After adjustment with illness severity, after-hour-transfers were associated with significantly higher hospital mortality compared to daytime-transfers. Median duration of hospital LOS and ICU readmission though higher for after-hour-transfers, was not statistically significant in adjusted analysis .Of 1857 patients admitted during study period,1356 were eligible for study; out of which 53.9% were males and 383(28%) patients transferred during after-hour. Mean age of two groups :115-121.Chatterjee S, Sinha S  Studies show approximately 10.8% ICU patients dying in general wards after being transferred from the ICU4. Safe and efficient transition of patients from ICU to the general ward often requires a proper transfer-out planning from the ICU7. Most deaths after ICU transfer have been attributed to higher disease severity  scores), older age, organ failure and do-not-resuscitate orders4. However, recent studies also demonstrate an association between ICU transfer time to wards and hospital morality rates. After-hours transfer, defined as transfer from ICU at night and out-of-office hours have been reported to be associated with adverse hospital outcomes such as higher hospital mortality8, higher ICU readmission rate10, and prolonged hospital length of stay (LOS)10. The excess mortality associated with after- hours transfer demonstrated in these studies also infer that the observed mortality is possibly due to premature transfer of patients or post-ICU suboptimal ward care in the after- hours10. Premature transfers are much more common at night11 and are generally the reflection of limited ICU bed capacity14, an increased demand for ICU beds or lack of nursing staff15.Intensive care unit (ICU) patients account for about 20 to 50% of in-hospital mortality rates16. Another study also showed night-time transfers to be associated with increased mortality in busy tertiary care hospitals17. Such discrepancies have been reported to be due to variations in night time definition, differences in patient population, study design and diverse local healthcare systems.Despite these results, some studies even failed to establish an association with after-hours transfer and hospital outcome. A Finnish multicenter study conducted in 18 ICUs did not ?nd “out-of-of?ce hour” transfer to be significantly associated with increased mortality after adjusting for illness severity, intensity of care, and presence of advanced directives (Odds ratio (OR) 1.1, 95% confidence Interval (CI) 0.93-1.3)Patients' hospital outcome after ICU transfer depends upon post ICU care in the hospital and is often regarded as a quality indicator of the hospital. Furthermore, to date, there have been no studies from India that have investigated the effect of ICU transfer time on patient outcomes. We hypothesized that outcomes would be adverse for ICU patients transferred during after-hours compared to day-time transferred patients. A retrospective study was thus performed to assess the association of after-hour transfer from ICU to ward on subsequent hospital mortality, hospital LOS and ICU readmission.This retrospective cohort study was conducted in a 23 bedded ICU of a tertiary care hospital in India over a 14 month period between March, 2016 and April, 2017. The study was approved by the Institutional Review Board and informed consent was waived because the study was observational in nature and involves the use of de-identified data from a pre-existing ICU database.The study included all adult patients (=18 years age) consecutively admitted to the ICU with = 24 hours of ICU stay during study period, and discharged alive from ICU to wards. Patients who died in the ICU, transferred to other hospitals or nursing homes, discharged home from ICU or discharged against medical advice were excluded. Patients with missing data were also excluded. Only the first admission was considered for patients with multiple ICU admissions during a single hospitalization.18. Hospital LOS was defined as the total number of days that a patient stayed in hospital, including ICU stay, from the time of admission. ICU support status was determined by whether patients required invasive mechanical ventilation (IMV), non-invasive mechanical ventilation (NIMV), ionotrope/vasopressor support or blood transfusion during their ICU stay.For the purpose of this study, we defined “after-hour” transfer as transfer from ICU occurring between 08:00 pm and 07:59 am, and “daytime” transfer as transfer from ICU between 08:00 am and 07:59 pm. ICU readmission was defined as patients' getting back to ICU from wards within the current hospitalization irrespective of the time between their ICU discharge and readmission to ICU. ICU admission source was categorized into those arriving from the emergency, ward, other hospitals, operation theaters, and high dependency units (HDU). Admission diagnosis was used to classify the body system involved. Presence of any cardiovascular disease, chronic obstructive airway disease, diabetes mellitus, neurological diseases and chronic kidney diseases were the major comorbidities considered in our study. The APACHE IV score was used to determine severity of illness on admission. The APACHE IV determines the severity of illness by including a number of physiological, biochemical and demographic  variables to calculate a numerical score to assess the predicted risk of deathOther variable information collected included patient demographics and ICU discharge status , or discharged against medical advice) and hospital discharge status as discharged alive or dead.In-patient information was extracted from the ICU database. The database regularly updated by two trained data entry operators, contain information on 220 variables of ICU patients. The data entry operators scrutinize in-patient records and investigation files daily to collect information on all relevant variables. Two full-time ICU consultants supervise the collected data daily. Any data discrepancy in the database is cross-checked with patient records for errors during entry. For this study, all patient personal identifiers were removed from data files to maintain patient confidentiality and all patients in the database were provided with a unique ID number. Quality of data was assessed by screening 50 randomly selected records every month. Any difference was resolved by consensus. All data were collected on a pre formed structured Excel data sheet.vs. daytime) was the primary exposure. The primary outcomes of our study were crude and risk-adjusted in-hospital mortality and secondary outcomes were hospital LOS and ICU readmissions. Descriptive data has been expressed as mean (SD), median (interquartile range), or percentages. Student's t test was used to describe normally distributed data while Wilcoxon's rank sum test was used for analyzing nonparametric data. Chi-square test was used to analyze categorical data. Bivariate and multivariable logistic regression models were used to estimate crude and risk adjusted estimates for “after-hours” transfer risk, with adjustment for APACHE IV and other co-variates. Results were reported as odds ratios and 95 % con?dence interval. Two-tailed tests were used with a significance level at a =0.05. All statistical analysis was performed using the PC-SAS program .Time of ICU discharge , or discharged against medical advice (DAMA) (n = 108) and patients who died in the ICU (n = 108), survival till ICU transfer to ward occurred in 77.5% (n = 1439) of admitted patients. Another 83 (4.4%) were excluded due to missing data and the final study population consisted of 1356 patients. Of these, 383 (28.2%) transfers occurred during after-hours, from 08:00 pm to 07:59 am, and 973 (71.8 %) were daytime transfers (from 08:00 am to 07:59 pm) . Sixty-nvs. 65.7 ± 15.2 years, p = 0.7). The sex distribution of patients was also similar in the two transfer periods . Significantly higher number of patients transferred during after-hours were admitted from the HDU  compared to daytime transferred patients. Day- time transferred patients were more commonly admitted from the operating theaters . There was no significant difference in comorbidities between after-hour and daytime transfers . Mean APACHE IV scores and predicted mortality rates were significantly higher for after- hour transfer patients compared to day time transfer patients respectively . After- hour transfer patients were sicker patients and more likely to have received mechanical ventilation and ionotrope support  during their ICU stay. Significantly higher number of patients with diagnosis of sepsis were transferred during after- hours . The characteristics of all patients transferred during daytime and after-hours are described in The mean age of patients transferred during after-hours did not significantly differ from those transferred during daytime . ICU readmissions and the median LOS in hospital also differed significantly among the two transfer groups , presence of comorbidities , higher APACHE IV score at admission , receipt of ICU support  and after-hour transfer  (p=0.04) .On bi-variate analysis, factors that were seen to be associated with increased risk of hospital mortality were higher age  . However(p=0.04) . After-hOf the 383 patients transferred out of the ICU at after-hours, 43 (11.2%) had an adverse outcome - death or ICU readmission. These patients significantly differed from those who were eventually discharged alive in terms of their mean age, APACHE IV scores, comorbidities, ICU support status and predicted mortality rates (PMR). Differences between the after-hour discharged patients with and without adverse outcome are listed in 11 who first demonstrated that patients transferred during after-hours had a significantly higher crude as well as case mix adjusted mortality compared to daytime transfers . They postulated that the increase in mortality among after-hour transfer patients was a reflection of rising demand on ICU beds leading to premature ICU discharges11. The adverse impact of after-hour discharges were further documented by several studies from UK19, USA10, Australia19 and Canada20. After-hour ICU discharge, not considered optimal care or standard practice, is often due to increased pressure on ICU beds to accommodate a new patient, or organizational aspects such as unavailability of a bed in the ward until late hours. Both these factors are likely to have played a role in our study as the average ICU occupancy rates are high causing premature discharges and delays in transfer occur when designated bed in the ward to which the patient is to be transferred is not vacant. Moreover less surveillance, lower nurse-to-patient ratios and decreased staff availability in the wards during after-hours could also attribute to increased mortality for patients transferred from ICU14. Transfers in the middle of the night may cause both physical and psychological trauma to patients11.Our study demonstrated increased mortality (crude and risk- adjusted) associated with after-hour transfer from ICU compared to daytime transferred patients. These findings are in agreement with findings from Goldfrad and Rowan in UK16. The difference could be due to differing after-hour definitions and methods for assessing illness severity. The Finnish study adjusted for illness severity using the SAPS II-scores and defined after-hour as 16:00 hours to 08:00 hours. In contrast, our study used APACHE IV score for assessing illness severity and defined after-hour as 20:00 hours to 08:00 hours. Two other studies also did not find any relation between ICU discharge time and mortality. While the first study10 stated adequate availability of ICU beds in their setting making premature transfers unlikely and also optimum staf?ng round the clock, the latter21 had a different methodological design.Our study findings, however, differ from a Finnish study from 18 universities and central hospital ICUs which failed to demonstrate an association between after-hour transfer and increased mortality22. There was no significant difference in the demographic characteristics between patients transferred during daytime and those transferred during after- hours and they were also similar in terms of baseline comorbidities. However, a higher proportion of patients admitted to ICU after surgery from the operation theaters were transferred to ward during daytime. This likely represents a group of elective admissions who were probably kept for post operative monitoring and their transfer planning was therefore relatively straightforward. As opposed to this, patients transferred during after-hours had higher APACHE IV scores with higher predicted mortality, and they were more likely to have sepsis and organ support requirement in terms of mechanical ventilation and/or vasopressors. This constitutes a sicker population of patients which as shown in earlier studies13, might explain increased risk of mortality associated with transfers during after-hours.The proportion of night time discharges in our study (28.2%) was higher compared to the mean of 15.3% (range:3.6% to 34.7%) in a recently reported meta analysis22 in their meta analysis of fourteen studies which showed night time discharge to significantly impact mortality even after adjustment for disease severity at ICU admission and discharge. Unadjusted analysis in our study also showed a higher ICU readmission rate as well as a longer hospital LOS for patients transferred during after-hours compared to daytime transferred patients. However, both these secondary outcomes did not achieve statistical significance in the adjusted analysis.Crude bi-variate analysis showed association of older age, presence of comorbidities, APACHE IV score and organ support (ICU support) with increased hospital mortality. However, after adjustment for these variables, after-hour transfer remained the single independent predictor of hospital mortality. This has also been convincingly demonstrated by Yang et al.22. Intensivists should thus recognize this high-risk group and exercise caution while transferring such patients from the ICU in after-hours when continuity of care might be compromised. Placing limitations on care and resuscitation measures may also impact outcome of such sicker patients after ICU discharge. Finally in the Indian scenario, financial constraints influencing decisions to transfer patients prematurely from the ICU when a patient would ideally have benefited from 24-48 hours of additional ICU care, is a common phenomenon and can impact patient outcome.Several factors that contribute to a patient's outcome following ICU discharge include comorbidities, age and APACHE IV score not only at time of admission but also at time of transfer, as well as continuing organ support requirement after ICU discharge. The staffing of wards both in terms of manpower and ability to provide continuity of care is of paramount importance. It has been shown that presence of organ dysfunction as well as requirement of higher levels of support following ICU discharge could contribute to higher mortalityOur study has limitations. The study was observational in nature with retrospective analysis thereby limiting us to information that was already collected in the database. Severity of illness at ICU discharge is an important factor influencing post ICU outcome. Our study did not have this data. This was a single-centered study. Our institute also has unique organizational characteristics such as limited ICU and HDU beds, and limited skilled manpower in after-hours in the ward - both medical and nursing especially for high-risk patients. The scenario from our ICU thus, might not be generalizable to other hospitals where rapid response teams, ICU outreach services or medical emergency teams are available who can provide extension of ICU care to ward patients round the clock. Also limitation of medical treatment is a major subgroup of patients which has been analyzed in almost all prior studies; however, we had few such patients and excluded them from our analysis. Finally, in an observational study, finding an association cannot be interpreted as causation. However, this is the first study from India to study association of ICU transfer time and outcome. The findings from this study may help physicians take decisions on after-hour transfer of patients.In conclusion, this study has identified and also supports an association between after-hour transfer and mortality of ICU survivors. Further research will likely identify precise factors, linking mortality associated with ICU transfer time and the organizational processes that could be put in place to reduce mortality rates.


Tuberculous spondylitis required long-term anti-tuberculosis (TB) medication therapy, and the optimal duration of therapy is controversial. There is still no clear way to tell when the anti-TB therapy can safely be discontinued.max) of 1.83 in one patient. However, the other two patients continued further anti-TB medication therapy based on the high SUVmax of 4.14 and 7.02, which were suspected to indicate active residual lesions in the abscess or granulation tissues. Continuous TB was confirmed by the bacterial and histological examinations.Three patients with tuberculous spondylitis were evaluated for therapeutic response using 18F-FDG PET/magnetic resonance imaging (MRI). Clinical and hematological improvements were achieved after about 12 months of anti-TB medication therapy, and we considered whether to discontinue the therapy. There was no relapse during one year of follow-up after discontinuation of 12 months anti-TB medication based on the low maximum standardized uptake value (SUV18F-FDG PET/MRI has metabolic and anatomical advantages for assessing therapeutic response in TB spondylitis, and can be considered as a helpful independent and alternative method for determining the appropriate time to discontinue anti-TB medication. Skeletal tuberculosis (TB) accounts for about 10–20% of extra-pulmonary TB, which comprises about 2% of total TB cases . In most18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) for diagnosis and assessing therapeutic response of tuberculous spondylitis [As of yet, there is no definitive guideline for treatment period and regimen, and also no clear assessing modality for the therapeutic response. Several studies have recently been reported on the role of ndylitis , 6. HoweThe first patient was a 43-year-old woman who had been suffering from back pain for about eight months. Infectious spondylitis on L2–3 with pre- and intra-vertebral abscesses was suspected from the MRI. The blood inflammatory indexes including C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were increased by 1.57 mg/dL and 88 mm/h from the initial 0.7 mg/dL and 30 mm/h, respectively .max, from 9.75 to 1.83) compared with PET/MRI at 4-month anti-TB medication therapy , polymerase chain reaction (PCR), and caseation necrosis were detected and finally confirmed as tuberculous spondylitis. Although there was a medical history of pulmonary TB, the sputum test showed negative result. A 12-month anti-TB medication therapy  was carried out without drug-susceptibility test (DST) under percutaneous biopsy due to favorable progress during the follow-up periods. PET/MRI at 12-month anti-TB medication therapy confirmed the loss of pre- and intra-vertebral abscesses with the decreased maximum standardized uptake value (SUVmax (from 7.88 to 4.14) had decreased on the PET/MRI conducted just before surgery compared with PET/MRI at diagnosis . The territory of the lesion and SUVmax (from 6.67 to 7.02) even though decreased bone marrow edema and epidural abscess compared with PET/MRI at diagnosis . Infectious spondylitis on T8–9 with paravertebral abscesses was confirmed on the MRI, and the result of the percutaneous needle biopsy showed positive AFB, PCR, and caseation necrosis, finally confirmed as tuberculous spondylitis. At the same time, active pulmonary TB was also confirmed and anti-TB medication therapy  started. Afterwards, a fistula was formed along the biopsy tract between deep lesion and skin, which resulted in repeated wound debridement and closure. Discontinuation of anti-TB medication therapy was considered after 12-month, because there were improvements in the pulmonary lesions and overall clinical features with healing of fistula. However, PET/MRI at 12-month anti-TB medication therapy showed sustained abscesses around the paravertebral space with intra-abscess SUVsis Fig. . After aplus  are performed on the samples positive for M. tuberculosis. Phenotypic DST will be determined by the absolute concentration method using Lowenstein-Jensen media as recommended by WHO [Culture-based phenotypic DST and GenoType MTBDRd by WHO  at the sd by WHO .Clinical characteristics and assessment for therapeutic response of the patients are summarized in Table The definitive diagnosis of tuberculous spondylitis is based on the result of cultural and pathological tests conducted in tissues collected from lesions. However, this method is only found to be positive at 50–75%, and it is often necessary to conduct re-examination due to the high risk of false negatives , 9. SputAn MRI is a highly sensitive test, and it can also be used to determine therapeutic response. Recent study has defined a significant regression in the epidural or paraspinal abscess/granulation tissues, marrow reconversion, and fatty reconstitution of the diseased bone as features of radiological healing . Le PageFor this reason, many efforts have been made to apply the 18F-FDG PET to evaluating therapeutic response, and several reports have recently been introduced. Using 18F-FDG PET measures the metabolic activity of the tissues in a non-invasive and semi-quantitative way, providing very accurate localization of the hypermetabolic activity. Active TB lesions are often proliferative lesions composed of epithelioid cells, Langerhans giant cells, and lymphocytes. These cells have high metabolisms of glucose and show a high uptake of FDG , 17. Chamax. The first patient, whose treatment had been completed, showed SUVmax of 1.83, which is a very low as much as physiological FDG uptake in normal structures. In the second and third cases, SUVmax of 4.14 and 7.02, respectively, were found to be the higher uptake of SUVmax continuously within the paravertebral abscesses. These are judged to be a more accurate and consistent indication of the state of the TB lesion than MRI. The lesion presenting higher uptake of FDG can be explained by the overpopulation of the inflammatory cells described above, which are consistently present within the infected structures such as abscesses or vertebrae.From the results of the 18F-FDG PET in our patients, we expected the therapeutic response and completion of anti-TB medication therapy to accord with the SUVThe optimal duration of anti-TB medication therapy is controversial. The Medical Research Council (MRC) advocates short-course chemotherapy (six months) for uncomplicated spinal TB . Howevermax (7.02) was kept very high regardless of the treatment duration, which meant that active TB was sustained and eventually led to abscess discharge through fistula again. However, as with the second patient, it was difficult to determine whether anti-TB medication should be discontinued, considering the healing process of the overall lesions and constantly reduced SUVmax (4.14). Successfully treated pyogenic spondylitis sometimes shows sustained high level of FDG uptake of 18F-FDG PET following weeks of antibiotics treatment, which can be explained by severe tissue damage and its healing process. Unlike pyogenic spondylitis, tuberculous spondylitis takes more time to sterilize than pyogenic spondylitis. The damaged tissues are also expected to be restored over long periods of sterilizing TB, resulting in lower FDG uptake (SUVmax 1.83 of the first patient) at the end of treatment than that of pyogenic spondylitis. Given this, the second patient can be determined to have a continuous TB and require further anti-TB medication therapy.There is a difference in the degree of FDG uptake depending on the presence of TB even after 12 months of anti-TB medication therapy. Especially in the third patient with active TB, the SUVWe think that 18F-FDG PET/MRI can be considered as a helpful independent and alternative method for determining the appropriate time to discontinue anti-TB medication. However, 18F-FDG PET/MRI is still very expensive examination and has low accessibility, which is limited to apply generally in the patients with TB spondylitis. Further studies with more patients are required to demonstrate our results and to overcome the limitations.


P = 0.361). HIV-monoinfected patients had a higher incidence than HIV/HCV-coinfected patients during all follow-up , but PE incidence decreased in HIV-monoinfected patients (P < 0.001) and increased in HIV/HCV-coinfected patients (P < 0.001). Concretely, the rate of PE-related hospitalizations decreased significantly in patients monoinfected with HIV , while patients coinfected with HIV/HCV had a significant increase . The mortality rate of PE-related hospitalizations showed a similar trend as PE incidence. In conclusion, the epidemiological trends of PE in PLWH changed during the cART era, with decreases in incidence and mortality in HIV-monoinfected and increases in both variables in patients coinfected with HIV/HCV.Chronic infections are a major factor in the development of pulmonary embolism (PE). We aimed to evaluate the trends of PE-related hospitalizations and PE-related deaths in people living with HIV (PLWH) during the era of combination antiretroviral therapy (cART) through a retrospective study in Spain. Data were collected from the Minimum Basic Data Set (MBDS) between 1997 and 2013. The study period was fragmented into four calendar periods . The rate of PE-related hospitalizations remained stable in PLWH ( In Spain, the current prevalence of HIV-infected patients with HCV antibodies and active HCV infection is 37.7% and 22.1%, respectively. However, this is significantly lower than the prevalences recorded in 2002 and 20092.Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections overlap in both modes of transmission and affected populations. Around 2.3 million people living with HIV are coinfected with HCV globally, and of these, 1.3 million are injection drug users (IDUs)3. Patients infected with HIV are living long enough to face significant morbidity from chronic illnesses such as cardiovascular disease5. Moreover, chronic hepatitis C has become significant comorbidity in HIV-infected subjects with HCV infection and seems to have a negative impact on the clinical course of HIV-infected patients, since it increases both HIV-associated mortality and overall mortality7.HIV infection is currently a manageable chronic disease in high-income countries since the introduction of combination antiretroviral therapy (cART)8. PE causes significant morbidity and mortality and a substantial economic burden in developed countries10. The risk factors associated with PE seem to be a combination of patient-specific factors  and precipitating factors 11. Chronic infections can act as a trigger factor by inducing immune activation, synthesis of hepatic proteins associated with inflammation, and modification of the fibrinolysis and coagulation pathways11.Pulmonary embolism (PE) is the most clinical severe presentation of thromboembolic disease, and its incidence varies from country to country, with Spain having around 20–35 events per 100,000 person-year in the general population13. Malek et al. found that HIV-infected individuals are more likely to have clinically detected PE compared to non-HIV-infected individuals14. Regarding chronic hepatitis C, in a recent meta-analysis, HCV-infected patients showed a significantly increased risk of venous thromboembolism15, but no significant association was found for PE. Moreover, HIV/HCV-coinfected patients, when compared to HIV- or HCV-monoinfected subjects, are a subgroup that may differ regarding inflammatory profile and risk factor distribution16, which might influence the risk of PE differently.There is little knowledge of PE epidemiology in people living with HIV (PLWH). The incidence of venous thromboembolism in PLWH is higher than in non-HIV patientsWe aimed to evaluate the epidemiological trends of hospitalizations related to PE and PE-related deaths in PLWH during the cART era in Spain.P < 0.001) and chronic pulmonary disease (P < 0.001) than HIV-monoinfected subjects.Overall, 267,507 patients discharged with a PE diagnosis were found from 1997 to 2013 in Spanish hospitals. Among those patients, 1,356 were HIV-infected subjects (899 monoinfected with HIV and 457 coinfected with HIV/HCV)  during the four study periods in HIV-infected patients are displayed in Fig. P = 0.532]. When we stratified the population by HCV status, HIV-monoinfected patients had a higher rate of PE-related hospitalizations than patients coinfected with HIV/HCV throughout the complete follow-up (P < 0.001). However, the incidence of hospitalizations related to PE had a significant decrease in HIV-monoinfected patients (P < 0.001) and a significant increase in patients coinfected with HIV/HCV (P < 0.001). Concretely, the incidence of hospitalizations related to PE decreased significantly in patients monoinfected with HIV , while HIV/HCV-coinfected patients had a significant increase .Overall, the incidence of hospitalizations related to PE did not show a significant variation in all HIV-infected patients from 1997–1999 to 2008–2013 . When we stratified the population by HCV status, HIV-monoinfected patients had a higher rate of mortality in PE-related hospitalizations than patients coinfected with HIV/HCV in the early calendar period (1997–1999) . Next, the mortality of PE-related hospitalizations fell sharply in patients monoinfected with HIV [from 41.9  in 1997–1999 to 17.4  in  in 2004–2007 and 11.5  in 2008–2013]. On the contrary, the mortality rate of PE-related hospitalizations increased in patients coinfected with HIV/HCV . In the calendar period 2008–2013, patients monoinfected with HIV and patients coinfected with HIV/HCV had similar mortality rates (P = 0.225).The mortality rate from PE-related hospitalizations  during the four study periods in HIV-infected patients are displayed on Fig. The CFR rates for PE hospitalizations related to PE are displayed in Supplementary Table In this study, trends in both incidence and mortality of PE-related hospitalizations did not show a significant variation in all PLWH (patients monoinfected with HIV plus patients coinfected with HIV/HCV) during the entire follow-up (1997–2013). However, we found significant differences when PLWH were stratified by HCV status. Thus, both incidence and mortality of PE-related hospitalizations decreased in patients monoinfected with HIV during the follow-up, whereas both rates increased in HIV/HCV-coinfected subjects. However, patients monoinfected with HIV had a higher incidence of PE in the last cART period (2008–2013) than in patients coinfected with HIV/HCV, whereas the mortality from PE-related hospitalizations was similar in both groups. To our knowledge, our study is the first report evaluating epidemiological trends of PE-related hospitalizations in patients monoinfected with HIV stratified by their HCV serostatus.18. Altered parameters related to inflammation  and coagulation  have been found in these patients both without antiretroviral therapy and while on cART20. However, cART may improve the hypercoagulable state, but does not normalize most parameters21. Moreover, HCV coinfection and severity of liver disease are related to an increased prothrombotic state, since elevated levels of inflammation and coagulation have been described in HIV/HCV-coinfected patients24. Although there are fewer data in patients coinfected with HIV/HCV, there also appears to be a reduction in the prothrombotic state after achieving sustained virological response with HCV antiviral therapy26.The prothrombotic state in PLWH seems to be multifactorial8. In a recent article made with data from the Spanish MBDS, Miguel-Dıez et al.8 found that the PE incidence increased from 20.4 to 32.7 hospitalizations per 100,000 person-years in Spain and the mean in-hospital mortality decreased from 12.9% in 2002 to 8.32% in 2011. Another remarkable finding in our study was that the incidence, mortality, and CFR in PLWH (patients monoinfected with HIV plus patients coinfected with HIV/HCV) did not change during the follow-up. However, the incidence of hospitalizations related to PE was higher than in HIV seronegative patients in Spain, whereas CFR values were only slightly higher in HIV-infected patients8.Our study shows that the epidemiological trends of PE in PLWH were different from the data of the general population in Spain27, increasing the percentage of patients with undetectable HIV viral load and higher CD4+ T-cell counts27, and decreasing their risk of cardiovascular events28. Furthermore, the enhancement in preventive interventions to reduce the cardiovascular risk in PLWH on cART has decreased the mortality related to cardiovascular disease in high-income countries3.In our study, HIV-monoinfected patients showed a significant decrease both in incidence and mortality for PE-related hospitalizations. The increasing use of cART may have influenced these findings. The percentage of PLWH on cART increased significantly in Spain during the last decade29. On the other hand, the death could have been an important competing risk for PE in patients coinfected with HIV/HCV during all follow-up, since the mortality trend for HIV-infected subjects declined significantly in Spain, primarily at the expense of patients monoinfected with HIV, while mortality among patients coinfected with HIV/HCV did not decline30. Additionally, the primary mode of HIV acquisition in patients infected with HCV was the injection drug use29, and these subjects had a high risk of death2. In fact, intravenous drug use in HIV-infected patients is a significant factor for right-sided endocarditis and PE31. However, we did not have data on active or recent intravenous drug use to evaluate its influence on PE trends and the real impact of chronic hepatitis C. Also note that more efficacious and safer cART regimens32 and an increasing treatment uptake of anti-HCV therapy2 in patients coinfected with HIV/HCV have been associated with mortality reduction in these patients35.In this study, patients coinfected with HIV/HCV had a reverse temporal trend of both incidence and mortality for PE-related hospitalizations compared to patients monoinfected with HIV. In the calendar period 1997–1999, the values of incidence and mortality of hospitalizations related to PE was far lower in patients coinfected with HIV/HCV than in patients monoinfected with HIV; but both rates increased significantly in patients coinfected with HIV/HCV in the following years. In the last calendar period (2008–2013), the PE incidence related to hospitalizations was lower in patients coinfected with HIV/HCV than in patients monoinfected with HIV, but the mortality of PE-related hospitalizations was similar for both groups. The explanation for these epidemiological trends is not simple, especially if we consider that our data source was the MBDS. On the one hand, over the study period, HCV screening might have been different in patients admitted to hospitals with a PE diagnosis , but HCV screening in PLWH has not changed significantly in Spain over the study period (around 95%)Finally, several aspects must be considered for the correct interpretation of the results.36. However, NCE did not provide data of gender, age or comorbidities and we could not calculate the rates stratified by the main cardiovascular risk factors . Secondly, it was not known how many patients with thrombosis did not need any hospital admission for systemic anticoagulation or how many patients died before hospital admission, since the MBDS only provides information about hospitalized patients. Additionally, the hospitalization may be avoided in many patients with thrombosis due to the development of better drugs for outpatient treatment37. This fact may be more likely to occur for patients monoinfected with HIV than patients coinfected with HIV/HCV because coinfection with HCV leads to more frequent liver disease that requires hospitalization. Thirdly, we did not have access to critical clinical and epidemiological data related to HIV infection and PE management, which could have helped us to interpret our results more thoroughly. Fourthly, the presence of anti-HCV antibodies defined the HCV status because we did not have any data about active HCV infection (HCV-RNA in serum or plasma), which creates an overestimation of the number of HCV-infected patients. Finally, we could not assess the impact of HCV therapy on the PE trends in patients coinfected with HIV/HCV.Firstly, we did not have figures for the global number of PLWH in Spain from 1997 to 2013, since there was no data of national coverage of HIV diagnoses in our country during this period. Instead, we used PLWH estimation data from the National Centre of Epidemiology In conclusion, the epidemiological trends of PE in PLWH changed during the cART era, with decreasing values of both incidence and mortality in patients monoinfected with HIV and increases of both rates in patients coinfected with HIV/HCV. Further studies are needed to investigate the impact of lifestyle, active HCV infection, and HCV clearance following HCV therapy.38: (a) 1997–1999; (b) 2000–2003; (c) 2004–2007; and (d) 2008–2013.We performed a retrospective study of all subjects older than 16 years who were discharged with a PE diagnosis from Spanish hospitals from January 1, 1997, to December 31, 2013. The study period was divided into four calendar periods39. Additionally, 100% of the Spanish population has free medical care provided by the National Health System (MHCSW).Data of patients were collected from the Minimum Basic Data Set (MBDS) of the Ministry of Health, Consumption and Social Welfare (MHCSW). Data were collected in 2016 and analyzed in 2017. The MBDS contains clinical and epidemiological data recorded at the hospital discharge. The MDBS has 92% coverage of all Spanish hospitals [public hospitals (84.14%) and private hospitals (15.86%)]International Classification of Diseases, 9th ed, Clinical Modification (ICD-9-CM). Furthermore, the MBDS provided the date of birth, sex, dates of hospital admission and discharge, and outcome at discharge. The Spanish MHCSW has established standards for record keeping and conducts periodic audits.The MBDS included 14 discharge diagnoses and 20 procedures performed during the hospital stay according to the 40. The MHCSW approved our study and the data were treated with full confidentiality and. The signed patient’s consent was not needed since MBDS is an anonymous dataset and has a mandatory nature. Moreover, the Research Ethics Committee  of the Instituto de Salud Carlos III  approved our study.The MHCSW requested hospitals the health-related personal data, which were added to Spanish MBDS according to Spanish legislationViral infection status was defined by ICD-9-CM codes 41 and the “Asociación Médica VACH de Estudios Multicéntricos (AMVACH)”42.The NCE provided the estimation of the number of PLWH in Spain  and PE mortality  as the ratio between the number of events and the number of persons at risk within each calendar period, according to reference populations (see the previous section). The case fatality rate (CFR) was the ratio between the number of patients with PE-related deaths and the number of patients with a PE-related hospitalization .The chi-squared test and Fisher’s exact test were used to analyze categorical data and proportions, as was required. Continuous variables were studied using the T-Test or Mann-Whitney U test. The Extended Mantel Haenszel Chi-Square was used for evaluating the temporal trends of rates. Multivariate logistic regressions were used to calculate the odds for in-hospital PE-related death adjusted by age, sex, tobacco usage, and Charlson co-morbidity index (CCI).The R statistical package version 3.1.1  was used to perform the statistical analysis. All the statistical tests were considered significant with values of p < 0.05 (two-tailed).Supplementary Information


We used data from 660 people living with HIV in southern India to evaluate thereliability, validity, and factor structure of the Internalized AIDS-Related Stigma Scale.Exploratory factor analysis revealed the presence of 2 factors: a 2-item factor related todisclosure concerns and a 4-item factor related to self-hatred. The self-hatred factordemonstrated acceptable internal consistency (Cronbach α = .80). As evidence of constructvalidity, both factors were correlated with depression symptom severity as measured by thePatient Health Questionnaire-9. Further study is needed to understand the correlates ofthese factors and their impact on the Indian HIV care continuum. HIV-related stigma, the social discrediting or devaluation associated with HIV, remains amajor impediment to prevention and treatment initiatives worldwide and specifically inIndia, which has the world’s third largest HIV epidemic.In this assessment of the factor structure, reliability , andconstruct validity of the 6-item Internalized AIDS-Related Stigma Scale (IARSS) in asample of people living with HIV in southern India, we found evidence for 2 distinctfactors related to disclosure concerns and self-hatred.Although the IARSS may be useful in the Indian context, more study is needed tounderstand the correlates of the disclosure concerns and self-hatred factors and theimpact these factors may have on the Indian HIV care continuum.1 Among people living with HIV (PLHIV), internalized stigma has been associated withworsened outcomes such as poor mental health3 and suboptimal antiretroviral therapy (ART) adherence.4 In India, where ART scale-up continues to be hampered by high levels of HIV-related stigma,5 there is need for a validated internalized stigma scale brief enough to be used incommon clinical and research settings. HIV-related stigma scales validated previously inIndia have focused on stigma in the community6 or targeted multiple dimensions of stigma.7 As such, we used data from southern India to assess the factor structure, reliability, and construct validity of an internalized stigma scale previouslyused in settings such as southern8 and eastern Africa.9HIV-related stigma, the social discrediting or devaluation associated with HIV, remains amajor impediment to prevention and treatment initiatives worldwide. Internalized stigmaoccurs when members of a stigmatized group internalize and accept negative attitudes held bythe majority group, leading to the development of self-defacing beliefs.10 as there are other local organizations in Chennai perceived as specializing in carefor sexual and gender minorities.Located in Chennai, Tamil Nadu state, the Y. R. Gaitonde Centre for AIDS Research andEducation (YRG CARE) is one of the largest private organizations providing HIV care inIndia, having treated more than 20 000 PLHIV since its founding in 1993. Patients from allover India seek care at YRG CARE, although a majority of patients are from Tamil Nadu andAndhra Pradesh states. Historically, most patients at YRG CARE have self-identified as heterosexual,10 we collected data on internalized stigma and depression on a convenience sample ofpatients 18 years of age and older who were presenting for their first clinical visitafter HIV diagnosis between January 2015 and November 2016. Study materials were writtenin English, professionally translated into Tamil or Telugu and back-translated bydifferent professional translators . We scrutinized theback-translations and found no important discrepancies between the original English andback-translated versions. We pilot-tested the questionnaire on 5 Tamil and 5 Teluguspeakers to ensure comprehensibility, face and content validity, and conceptualequivalence between the English and Tamil/Telugu versions. Interviews were conductedface-to-face in the patient’s preferred language by 1 of 2 female HIV counselors.As part of a parent study on prevalence and correlates of psychosocial conditions amongIndian PLHIV,We obtained signed or thumbprint-marked (in cases of illiteracy) informed consentdocuments from all participants. Ethical approval was obtained from the InstitutionalReview Boards of Fenway Health  and YRG CARE .8 which includes items related to concerns about disclosure as well as items relatedto feelings of shame and/or self-hatred. Responses are elicited on a dichotomic scale(agree/disagree) and scores represent the sum of endorsed items. We assessed fordepressive symptoms using the Patient Health Questionnaire-9 (PHQ-9), which has beenpreviously validated in Indian settings and translated into Tamil and Telugu.11 Sociodemographic variables of interest included gender, age, educationalattainment, marital status, employment status, rural/urban residence, language(Tamil/Telugu/other), sexual orientation, alcohol use (“yes” versus “no” or “stopped”),and injection drug use.We focused our analysis on the 6-item Internalized AIDS-Related Stigma Scale (IARSS),8 we sought to assess its dimensionality by performing exploratory factor analysis(EFA) on the IARSS items using principal-factors extraction and orthogonal varimaxrotation, returning all factors with eigenvalues >1.0. We then graphed the eigenvaluesin decreasing order to identify the scree, if any. Next, we examined the loadings of theindividual items on the factor(s), assigning an item to a factor if its factor loading was≥0.40. To assess the internal consistency of any identified factors, we calculatedCronbach α, using 2000 bootstrap replications to compute the standard errors. We examineditem–test correlations and recalculated the Cronbach α after sequentially deletingindividual items. We then conducted the EFA stratified by gender.As the IARSS was developed to measure one dimension of stigma ,3 We fitted linear regression models, adjusted for sociodemographic variables,specifying the factor(s) as the exposure and PHQ-9 score (0-27) as the outcome. Astatistically significant regression coefficient was considered evidence that anassociation existed between the factor(s) and depressive symptoms. In addition, for anyfactors with multiple items, we calculated the Spearman correlation coefficient betweenthe factor(s) and the PHQ-9 score. All analyses were performed using Stata software.We did not have access to a gold standard to assess criterion-related validity. Instead,we used the PHQ-9 score to assess construct validity of the factor(s), as an associationbetween internalized stigma and poor mental health status has been demonstrated inmultiple settings.We collected data on 660 persons, including 388 men, 268 women, and 4 Hijras . Turning next to the second factor, theSpearman correlation coefficient between fears of disclosure and PHQ-9 score was 0.26 (95%CI: 0.23-0.29). In a linear regression model with fears of disclosure as the exposure, weestimated a statistically significant positive association between fears of disclosure andPHQ-9 score .The Spearman correlation coefficient between self-hatred and PHQ-9 score was 0.41 (95% CI:0.37-0.45), indicating a correlation of moderate magnitude. This correlation was consistentwith the findings of a linear regression model fitted to the data. We estimated astatistically significant positive association between self-hatred  and PHQ-9 score  rather than an individual’s level of depression symptoms. In total, our findingssuggest that while the IARSS may be useful, it captures concepts of fears of disclosure andself-hatred that are likely to be distinct phenomena in India. Confirmatory factor analysisto test and confirm this factorial structure would be a worthwhile extension for futurestudy.We found that both the disclosure concerns and self-hatred factors were associated withdepression symptom severity, evidence for the construct validity of these factors. The scaleitems for the 4-item self-hatred factor had a high internal consistency and the magnitude ofthe correlation between the self-hatred factor and PHQ-9 score was similar to the magnitudeof the correlation between IARSS and depression found in the original IARSS validation study.16 and care-seeking,17 the participants in our sample are likely to have had lower levels of internalizedstigma compared to PLHIV who are out of care. Second, this study was conducted at a singlecenter where most patients self-identify as heterosexual; thus, the findings may not begeneralizable to the entire country. However, the type of private, multiservice programexemplified by YRG CARE can be found in many other Indian cities, as well as other countriesin Asia. Future studies should be undertaken at ART centers with greater numbers of sexualand gender minorities, especially given the intersectionality of HIV-related stigma withgender identity and sexual orientation stigmas. Third, we could not establishcriterion-related validity, as we did not have access to a gold standard measure ofinternalized stigma. However, this limitation appears to be inherent to validation studiesof internalized stigma scales. Finally, in the interest of limiting the length of the surveyinstrument, this study focused on internalized stigma and did not address other stigmadimensions. However, there exists a growing consensus that internalized stigma is aparticularly important predictor of poor HIV-related outcomes.4Our study has several limitations. First, our sample was a convenience sample of PLHIVpresenting for HIV care. As stigma has been associated with lower rates of HIV testingWe assessed the factor structure, reliability , and constructvalidity of the 6-item IARSS in a sample of PLHIV in southern India. We found evidence for 2distinct factors related to disclosure concerns and self-hatred. Although the IARSS may beuseful in the Indian context, more study is needed to understand the correlates of thesefactors and the impact these factors may have on the Indian HIV care continuum.Click here for additional data file.Supplemental Material, IARSSIndia-JIAPAC_revised_Supplemental_material for Reliability,Validity, and Factor Structure of the Internalized AIDS-Related Stigma Scale in SouthernIndia by Brian T. Chan, Amrose Pradeep, Ezhilarasi Chandrasekaran, Lakshmi Prasad,Vinothini Murugesan, Nagalingeswaran Kumarasamy, Kenneth H. Mayer, and Alexander C. Tsaiin Journal of the International Association of Providers of AIDS Care (JIAPAC)


Obsessive-compulsive disorder (OCD) is a disabling condition with a wide variety of clinical presentations including contamination fears, fear of harm, and relationship-related obsessions. Cognitive behavioral models of OCD suggest that OC symptoms result from catastrophic misinterpretations of commonly occurring intrusive experiences and associated dysfunctional strategies used to manage them. OCD-related maladaptive beliefs including inflated responsibility, importance and control of thoughts, perfectionism, and intolerance for uncertainty increase the likelihood of such misinterpretations.Considering accumulating evidence suggesting that mobile health  apps based on cognitive-behavioral principles may lead to significant reductions in psychopathological symptoms, we assessed the effectiveness of a novel cognitive training app (GGRO) designed to challenge OCD-related beliefs.A total of 97 students were randomized to groups undertaking immediate-use (iApp) or delayed use (dApp) of GGRO. All participants were requested to complete Web-based assessments, with questionnaires relating to maladaptive beliefs, mood, and OC symptoms at baseline (T1), 15 days from baseline (T2), and 30 days from baseline (T3). Participants in iApp group started using the app at baseline and continued using the app for 15 consecutive days. They were then requested to stop using the app until T3. Participants in the dApp group were requested to wait for 15 days and only then start using the app (crossover) for 15 consecutive days.All participants used the app for a mean of 14.07 (SD 1.41) days with 2.94 levels per day. Consistent with previous findings, app use was associated with medium-large effect size reductions in both iApp (n=51) and dApp (n=46) groups. In the iApp group, all effects remained significant during the 15 days of follow-up. Analyses focusing on the first two assessment occasions revealed significant treatment × repeated measures interactions on maladaptive beliefs, several OC symptom measures, and self-esteem.This study provides further evidence for the efficacy of GGRO as a mobile-delivered training exercise that is useful for reducing OCD-related beliefs and symptoms.ClinicalTrials.gov NCT03571464; https://clinicaltrials.gov/ct2/show/NCT03571464 (Archived by WebCite at http://www.webcitation.org/7675sYPsH) Obsessive-compulsive disorder (OCD) is a disabling disorder that causes impairment in multiple areas of patients’ lives ,2. OCD iCognitive behavioral therapy (CBT) combined with exposure and ritual prevention is the first choice of psychological treatment recognized by the National Institute for Clinical Excellence . CBT modMany individuals, however, have great difficulties in accessing CBT therapy, either because of their high cost, the stigma associated with treatment, or the lack of available trained professionals ,15. InfoInformation and Communication Technologies have been implemented to a significantly smaller extent in the treatment or prevention of OCD symptoms than in that of other mental disorders. Most studies assessed the efficacy of video-conference or telephone therapy used in exposure and response prevention -22. In aRecently, an exploratory study evaluated a brief, game-like training exercise for challenging OCD beliefs delivered via a mobile app platform named “GGRO - GG relationship doubt and obsessions V1.1” . GGRO isThe results of this study, which included 20 participants from a nonclinical population, suggested that training for 3 min a day for a period of 15 days was associated with significant, large effect-size reductions in the levels of OCD-related beliefs measured by the Obsessive Beliefs Questionnaire (OBQ) - Short form . ParticiThe aim of this study was to further evaluate the efficacy of GGRO in reducing OCD-related maladaptive beliefs and OCD symptoms. Specifically, a randomized controlled trial with crossover design was carried out in a nonclinical student population to assess pre-post changes in the levels of OCD-related maladaptive beliefs and OCD symptoms, including relationship OCD (ROCD) symptoms, self-esteem, and depression symptoms following 15 days of GGRO use. Our main hypothesis was that students using GGRO immediately following baseline assessment  would exhibit greater declines in obsessive compulsive–related beliefs than students who did not use GGRO in this phase of the study . Inclusion criteria included native Spanish speaking, experience of at least one stable romantic relationship, and possession of a mobile device capable of installing GGRO (available for download via Google Play or the App Store).Consistent with common practice in OCD-related research, the sample used in the present study comprised nonclinical participants . Like inAll participants volunteered and were included in a draw for a prize of a dinner for two . A total of 98 students attended a recruitment seminar wherein they were explained the general procedure of the research. They were then asked to download that app and complete the pretreatment evaluation  on Qualtrics , which iThe study was a randomized controlled trial with a crossover design . The intRandomization was carried out in a 1:1 ratio and based on a prespecified computer-generated randomization list . Group aGGRO was developed by the author GD, an expert in OCD and related disorders, in collaboration with Gur Ilany, a mobile platform developer. This app consists of training exercises intended to help people increase accessibility to functional self-statements that facilitate adaptive interpretations of thoughts, emotions, and events associated with OCD . Users aUsers progressively completed 45 levels dedicated to OCD-related maladaptive beliefs (3 levels per belief) such as dealing with threat, importance of thoughts, and overcoming perfectionism. In this way, the user is exposed to alternative interpretations of the relevant maladaptive belief in each stage, increasing accessibility to functional self-statements that encourage adaptive interpretations for thoughts, emotions, and events  associated with OCD. For instance, statements challenging perfectionism may include “Mistakes teach me to overcome my fears” and “Imperfect[ion] is human.” Users are also encouraged to adopt approach behavioral strategies (rather than avoidance) including tolerance of negative emotions by responding to statements such as “I can tolerate doubts.”Following the completion of each level, the user receives feedback, depending on the length of time it took them to complete the level (0 to 3 stars). A short memory-evaluation screen  follows this feedback. In this screen, three statements are presented to the user. The user has to recall which of the statements appeared in the level he/she just completed. The correct response results in a “Correct!” message, and an incorrect response is followed by “You’ll get it next time” feedback message. The two types of feedback increase attention to the training and encourage engagement.The user then progresses to the next level. Three levels address a specific maladaptive belief. Before dealing with a new belief, a screen is presented with the rationale for challenging the specific maladaptive belief. For example, before learning to challenge overestimation of threat, users are presented the statement, “The world can be dangerous, but the tendency to look for danger all the time increases fears and anxieties. Let’s learn to reduce this tendency!” Following completion of six levels pertaining to two beliefs , users may see an encouraging statement such as “Excellent! Now you’ve learned how to better deal with your thoughts and to better recognize the way you overestimate threat.” Push notifications remind users to use the app each day. Following the completion of 3 levels on a given day, a screen prompting users to stop using the app for that day appears. Users are also advised to train once a day at a preset time rather than in response to distressing thoughts or events. GGRO requires a mobile device with an operating system iOS 7 or above or android 4.2 or above.not at all) to 4 (extremely), which assess OCD symptoms. The OCI-R possesses good internal consistency for the total score  [The OCI-R ,27 is a samples) . In our disagree very much) to 7 (agree very much). The OBQ-20 has shown satisfactory psychometric properties [The OBQ-20  is the aoperties ,36. The The ROCI - Short version (S) is a shortened version of the ROCI , a 12-itThe PROCSI - 6-item version (Si)  is an abbreviated version of the PROCSI , a 24-itdid not apply to me at all) to 3 (applied to me very much or most of the time). In this study, only the depression scale (7 items) was used. The DASS scales have been shown to have high internal consistency [The short version of the Depression, Anxiety, Stress Scale (DASS) -42 is a not very true for me) to 9 (very true for me). The SISE has been found to have high test-retest reliability, criterion validity coefficients above .80 (median=.93 after correcting for unreliability) with the Rosenberg Self-Esteem Scale, and a similar pattern of construct validity coefficients as the Rosenberg Self-Esteem Scale with 35 different constructs [The Single-Item Self-Esteem Scale (SISE)  is a selnstructs . Using lnstructs  estimatet and χ2 tests were performed to assess differences between groups and in age, relationship duration (in months), sex, socioeconomic level, belief, and symptoms measures . A series of repeated measures analysis of variance with Bonferroni adjustments was performed to evaluate pre-post scores in both study groups. The Effect Size Determination Program [d values.Statistical analyses were performed using Statistical Package for the Social Sciences . In order to avoid overoptimistic estimates of the efficacy of the training , an inte Program  was usedA total of 97 participants met the inclusion criteria and participated in the study. Mean scores for outcome measures and characteristics of the two groups did not differ significantly at baseline .t95= 0.58,  P=.56), gender , relationship duration , or socioeconomic status  compared to participants who did not drop out (At 15 days (T2), 79 of 97 participants (81.4%) completed the study and 62 of 97 (65.1%) completed the 15-day follow-up (T3). Participants who dropped out during the study period did not differ in age , and SISE . These results indicated that students in the iApp group exhibited fewer OCD-related beliefs, fewer partner-focused ROCD symptoms, and higher self-esteem than their waiting list counterparts on the second assessment occasion  revealed significant treatment × repeated measures interactions in OBQ  would be associated with a significant decrease in OCD beliefs and symptom measures. Indeed, within-group differences between T2 and T3 following the crossover indicated significant reductions in the OBQ, PROCSI-Si, ROCI-S, and SISE scores. No differences were found in the DASS scores.Unexpectedly, participants showed a significant decrease in OCD symptoms (OCI-R) between T1 and T2. Nevertheless, additional significant reduction in OCI-R scores was found between T2 and T3 .Mobile apps based on CBT principles have unique advantages including wide reach, continuous availability, appeal to young people, very low cost, and progress monitoring. Accumulating evidence shows that such apps can lead to significant reductions in psychopathological symptom and maladaptive behaviors -49. The Relative to the waitlist control group in our study, individuals using GGRO for 2 weeks showed fewer OCD-related beliefs, fewer ROCD symptoms, and higher self-esteem. Moreover, the change after the training was stably maintained after 15 days (follow-up). Once our waiting list group started using GGRO (after crossover), participants in this group showed a reduction in OCD-related beliefs, OCD, and ROCD symptoms. Interestingly, an exception was partner-focused OC symptoms, which showed further improvements at follow-up, indicating a generalization of results and suggesting that the maladaptive beliefs targeted in GGRO may be particularly relevant to this ROCD presentation. Indeed, GGRO includes levels related to partner-value contingency of self , which Unexpectedly, OCD symptoms declined in both the iApp and dApp groups during the initial 2 weeks. Fluctuations in the intensity of student requirements/evaluations may have coincided with the time period of our study and attenuated participants’ OCD symptoms in the waitlist group. Indeed, most of the student data were collected during the mid-semester, a period when students have fewer exams and other evaluations. Importantly, however, the use of GGRO was associated with a further reduction in OCD symptoms following the crossover, thus supporting the efficacy of GGRO in reducing OCD symptoms.Consistent with a previous study , the levOur findings are consistent with those of previous research showing the efficacy of CBT-based apps in cognitive and behavioral change ,53. AccoThe GGRO app evaluated in this study was designed to challenge maladaptive beliefs associated with OCD. By introducing users to interpretations that are inconsistent with their OCD-related beliefs, adherence to such beliefs was expected to weaken. This, in turn, was expected to reduce catastrophic interpretations of intrusions and decrease OCD symptoms. Indeed, previous findings showed that a change in OCD belief levels among users of GGRO was associated with a reduction in OCD symptoms further from the OCD symptom levels before using GGRO . ConsistAlthough the findings of our study are consistent with the expectations, our study has some important limitations. The sample used in our study comprised mainly female students from the general population. Indeed, the prevalence of OCD has been observed to be equal between men and women, or slightly higher in women . Recent Previous research using similar methodologies showed dropout rates comparable to ours ,56. We aA great majority of mobile apps designed for OCD are oriented toward self-applied therapy and track or guide exposure and response prevention ,58. HoweGGRO was designed as a brief and easy training platform to challenge maladaptive beliefs and associated interpretations of thoughts and events. As such, this platform could complement traditional CBT interventions as an intersession work or relapse-prevention tool; thus, it is an instrument at the service of the therapist, and not a way to replace CBT. Moreover, this cost-effective and accessible mobile platform could be used in populations at risk of OCD and related disorders to reduce levels of maladaptive beliefs. Future studies should assess the usefulness of similar apps for other symptoms such as body image distress and depression. Indeed, reducing the levels of maladaptive beliefs in at-risk populations using cost-effective, accessible mobile platforms such as the one used in this study may increase resilience to a wide variety of psychological disorders. Furthermore, such a platform may be useful for relapse prevention following treatment.


Treatment of head and neck cancers (HNC) often leads to impairment in speech and swallowing functions. This study evaluated swallowing problems and the impact of complications on swallowing-related QOL after free flap surgery for HNC.Swallowing-related QOL was assessed using MDADI and SWAL questionnaires.p = 0.024) and sleep (77.6 (23.0) vs 52.3 (24.3), p = 0.003).Of 45 assessed patients, 25 (45.5%) had at least one postoperative complication. Patients reported less than < 86 points in 8/9 SWAL-QOL domains. The SWAL-QL total score or MDADI composite scores were not related to surgical complications. Those with medical complications had lower scores in SWAL-QOL domains of mental health (82.8 (21.8) vs 65.5 (24.2), In conclusion, swallowing related QOL is significantly impaired after 2 years of the tumor resection and free flap reconstruction for cancer of the head and neck, when using the cut-off value of 86 points in SWAL-QOL assessment tool. Surgical complications did not have an impact on swallowing-related QOL but medical complications were related to impairment in general QOL-related domains. Cancer of the head and neck and its surgical and oncological treatment include high risk of complications and also the reported 5-year mortality is high . MoreoveThe few available studies report the swallowing problems as a part of disease-specific QOL or focus on evaluating the function and physiology of swallowing, but not its impact on QOL , 6. AccoThis study was conducted in Oulu University Hospital and the study protocol was approved by the hospital administration 239/2016) and local ethics committee . The present study is a substudy of our previously published paper examining general QOL in relation with postoperative complications in patients with free flap reconstruction due to cancer of the head and neck  , reported worse scores in a total of 3 of 8 RAND-36 domains [vitality 67.4 15.1) vs 81.9 (12.8), .1 vs 81.The main finding of our study is that swallowing-related QOL is still impaired after 2 year recovery from free flap surgery for the cancer of head and neck; more than 60% of the patients had significantly impaired swallowing-related QOL when using the SWAL-QOL cut-off value 86. Interestingly, we found only minor relation between complications and swallowing-related QOL; the scores for SWAL-QOL domains “sleep” and “mental health” were lower in those with medical complications. These domains are likely to be less swallowing-related instead of general domains. Finally, according to our results, impairment in swallowing-related QOL is not easily detected using RAND-36 tool.There are no previous studies focusing the impact of complications on the swallowing-related QOL. Previous studies are mainly focusing on swallowing function at 6 and 12 months  have useIn our patients, the medical complications had an impact on swallowing-related QOL in SWAL-QOL domains of sleep and mental health. These domains present rather general QOL instead of disease-specific QOL or functional problems in daily life. In addition, nearly, all the patients with medical complications reported SWAL-QOL less than 86. These results are in line with our previous findings concerning general QOL in this patient group and highlight the important role of medical complications on compromising the recovery process .According to our results, recognition of risk population for swallowing problems is demanding. It is previously reported that patients with tongue, soft palate, and laryngeal reconstructions are in risk of impaired swallowing function postoperatively, but we were not able to show any other patient-related risk factors , 5, 20. This study has its limitations. First, we were able to include a limited number of patients and a limited number of different of tumours. Second, the retrieved data concerning operative care, patient demographics, and postoperative complications were retrospective. Third, it would have been interesting if we could have been able to include objective measurement of swallowing function, i.e., naso-fiberoscopy in the present study. Fourth, we were not able to include assessment of nutritional status, such as BMI or albumin levels to the analysis, which could have had been compromised in those with deteriorated swallowing-related QOL. We also did not analyse the impact of other treatment modalities including oncological treatment on swallowing-related QOL.In conclusion, swallowing-related QOL is significantly impaired after 2 years of the tumor resection and free flap reconstruction for cancer of the head and neck when using the cut-off value of 86 points in SWAL-QOL assessment tool. Surgical complications did not lead to impairment of swallowing-related QOL and patients with medical complications reported more often impairment in general QOL-related domains such as sleep and mental health.


To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target.Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score. The BoneXpert-method was used to determine the Bone Age  and bone mineral density (BMD) of the wrist. These scores were evaluated over time and compared between the treatment arms and mean JADAS10-score using linear mixed models corrected for age and symptom duration.p < 0.05 vs arm 1).In 60 patients, 252 radiographs were analysed. Baseline age and symptom duration were different between the arms. No difference in comparison to the healthy reference population was found at baseline for the Poznanski-score , nor for BA (varying from − 0.88 to 0.74). Baseline BMD was statistically significantly lower in arm 3   compared to arm 1  and arm 2 . After treatment to target inactive disease, the Poznanski-scores and the BA remained clinically unchanged, while the BMD in arm 3 improved  either at baseline or at follow-up, irrespective of treatment arm. A lower BMD at baseline in arm 3, initially treated with methotrexate and etanercept, improved significantly after treatment.NL1504 (NTR1574). Registered 01-06-2009.NTR, The online version of this article (10.1186/s12969-019-0362-1) contains supplementary material, which is available to authorized users. Juvenile idiopathic arthritis (JIA) is a potentially chronic disease that comprises 7 categories of childhood arthritis of unknown cause, that persists for more than 6 weeks and starts before the age of 16 –5. PreviWe have recently performed a randomized clinical trial using the treatment-to-target approach in recent-onset JIA patients, comparing 3 strategy-arms with different initial and subsequent treatment steps, aiming at inactive disease, including tapering and stopping DMARD therapy , 11. In The Best-for-Kids-study (NTR 1574), a multicenter randomized single-blinded clinical trial, was designed to investigate the effectiveness of three different treatment-strategies in newly diagnosed patients with the following JIA categories: oligoarticular JIA, rheumatoid factor (RF) negative polyarticular JIA and juvenile psoriatic arthritis. DMARD-naive patients with a disease duration of less than 18 months were randomized to one of the three treatment arms.Patients in arm 1 were treated with initial monotherapy with methotrexate (MTX) or sulfasalazine (SSZ); patients in arm 2 were treated with initial MTX and prednisone bridging and patients in arm 3 were initially treated with etanercept and MTX. Patients were treated to target, aimed at inactive disease, with three-monthly assessments. If predefined targets of suppression of inflammation were not met, treatment was intensified, as can be seen in Fig. The BeSt-for-Kids-study was approved by the Institutional Review Board at Leiden University Medical Center and written informed consent was obtained from all participants before enrollment.All radiographs were anonymized and randomized by an independent computer-technician, and then evaluated using two different scoring methods: the Poznanski-score  and the Next, all radiographs were imported as DICOM-files in the BoneXpert-software for automatic assessment of the BA (using the average Greulich and Pyle bone age ), and BMn = 10 imputed data sets  or BMD . Tables and graphs from this analysis are reported in Additional file To investigate whether mean JADAS10-score over time correlated with any of the radiological outcomes, we have performed separate analyses for the 3 radiological outcome measures. Mean JADAS10-score over time did not influence Poznanski score, [β (95% CI) 0.0010 , Our study is the first to describe longitudinal radiological outcomes of a tightly controlled treat-to-target approach, aimed at inactive disease during 24 months of treatment, in recent onset poly- and oligoarticular JIA patients. Despite a symptom duration of mean (SD) 7.6 (4.9) months and a JADAS-10 of 18.7 (5.6), at baseline, we found no significant differences in Poznanski-score and BA (as measured by the BoneXpert-method) of wrist radiographs compared to healthy children. Only in arm 3 BMD as measured by the BoneXpert-method was significantly lower than the normal reference population. After 24 months of treatment, there was no deterioration in any of the scores and in arm 3 BMD had statistically significantly improved. Mean JADAS10-scores over time were not associated with any of the radiological outcomes in this analysis.Combined with rapid suppression of symptoms of active arthritis, prevention of damage is an important treatment goal in JIA. Damage has been most notably found in patients with longstanding and/or seropositive polyarticular JIA, but may also occur in seronegative polyarticular JIA and oligoarticular JIA –21. As hCompared to older cohorts , 24 or rTo score differences in potentially little damage, we needed a sensitive scoring method. Conventional radiography has proven to be a useful modality to monitor wrist damage of JIA patients , 28–31. The Poznanski-score, which measures relative carpal length on radiographs of the wrist, is able to detect deviating growth in absence of distinct joint space narrowing or erosions . A disadThe BoneXpert method, based on digital X-ray radiogrammetry (DXR), allows to determine the Bone Age and BMD compared to a normal reference population, at lower costs and with lower radiation than manually comparing the hand radiograph with images in the atlas by Greulich and Pyle  and thanIn JIA patients, BMD is often reduced , 43–45. Future studies are needed to delineate the effect of the treatment-to-target concept on improving bone health as reflected by bone maturation and BMD in JIA.n = 60), and we may have lacked power to detect small differences. In previous studies, results were based on clinically inflamed wrists only. Since we have examined also 6 patients with wrist radiographs of unaffected wrists, in this study we may have underestimated damage, although sensitivity analyses excluding patients who never had any clinical wrist arthritis over 24 months showed similar results. It remains to be determined whether joint damage is mainly due to local inflammation or  to systemic inflammatory processes of JIA.Our study has some limitations. Although comparable with other studies , 26, 49 Due to our choice of scoring methods, patients were excluded who had closed growth plates. Also we disregarded results of radiographs made outside the selected time frame. Follow-up time was relatively short compared to previous cohorts. However, often radiographic damage is expected to occur within the first one or two years . FinallyWe conclude that in our cohort of patients with recent-onset JIA who were treated-to-target aiming at inactive disease, wrist-radiographs showed neither damage according to Poznanski at baseline, nor progression after 2 years. Bone age was within normal values at baseline and after follow-up. In arm 3, BMD was lower at baseline but improved significantly towards normalization during treatment. We propose that with earlier start of treatment and treatment to target, the focus of current treatment regimens shifts to damage prevention rather than suppression of damage progression. This will likely also prevent long-term disability. Future JIA-cohorts with more patients and longer follow-up are warranted to confirm these promising results for children with JIA.Additional file 1:Flow chart of patient selection process for the Poznanski-score. (DOCX 23 kb)Additional file 2:Bland-Altman plots with 95% limits of agreement. (DOCX 245 kb)Additional file 3:LMM for Poznanski, BA and BMD adjusted for age and/or symptom duration. (DOCX 14 kb)Additional file 4:n = 6 with never wrist arthritis. B Sensitivity analysis of patients with polyarticular JIA. C LMM for mean JADAS10 score in relation to Poznanski, BA and BMD. (DOCX 804 kb)A Sensitivity analysis of patients with wrist arthritis, without