A Nationwide Enumeration of the Surgical Workforce, its Production and Disparities in Operative Productivity in Liberia.

BACKGROUND: Any health care system that strives to deliver good health and well-being to its population relies on a trained workforce. The aim of this study was to enumerate surgical provider density, describe operative productivity and assess the association between key surgical system characteristics and surgical provider productivity in Liberia. METHODS: A nationwide survey of operation theatre logbooks, available human resources and facility infrastructure was conducted in 2018. Surgical providers were counted, and their productivity was calculated based on operative numbers and full-time equivalent positions. RESULTS: A total of 286 surgical providers were counted, of whom 67 were accredited specialists. This translated into a national density of 1.6 specialist providers per 100,000 population. Non-specialist physicians performed 58.3 percent (3607 of 6188) of all operations. Overall, surgical providers performed a median of 1.0 (IQR 0.5-2.7) operation per week, and there were large disparities in operative productivity within the workforce. Most operations (5483 of 6188) were categorized as essential, and each surgical provider performed a median of 2.0 (IQR 1.0-5.0) different types of essential procedures. Surgical providers who performed 7-14 different types of essential procedures were more than eight times as productive as providers who performed 0-1 essential procedure (operative productivity ratio = 8.66, 95% CI 6.27-11.97, P < 0.001). CONCLUSION: The Liberian health care system struggles with an alarming combination of few surgical providers and low provider productivity. Disaggregated data can provide a high-resolution picture of local challenges that can lead to local solutions.

Tumour texture features from preoperative CT predict high-risk disease in endometrial cancer.

BACKGROUND: To enable more individualised treatment of endometrial cancer, improved methods for preoperative tumour characterization are warranted. Texture analysis is a method for quantification of heterogeneity in images, increasingly reported as a promising diagnostic tool in oncological imaging, but largely unexplored in endometrial cancer AIM: To explore whether tumour texture features from preoperative computed tomography (CT) are related to known prognostic histopathological features and to outcome in endometrial cancer patients. MATERIALS AND METHODS: Preoperative pelvic contrast-enhanced CT was performed in 155 patients with histologically confirmed endometrial cancer. Tumour ROIs were manually drawn on the section displaying the largest cross-sectional tumour area, using dedicated texture analysis software. Using the filtration-histogram technique, the following texture features were calculated: mean, standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis. These imaging markers were evaluated as predictors of histopathological high-risk features and recurrence- and progression-free survival using multivariable logistic regression and Cox regression analysis, including models adjusting for high-risk status based on preoperative biopsy, magnetic resonance imaging (MRI) findings, and age. RESULTS: High tumour entropy independently predicted deep myometrial invasion (odds ratio [OR] 3.7, p=0.008) and cervical stroma invasion (OR 3.9, p=0.02). High value of MPP (MPP5 >24.2) independently predicted high-risk histological subtype (OR 3.7, p=0.01). Furthermore, high tumour kurtosis tended to independently predict reduced recurrence- and progression-free survival (HR 1.1, p=0.06). CONCLUSION: CT texture analysis yields promising imaging markers in endometrial cancer and may supplement other imaging techniques in providing a more refined preoperative risk assessment that may ultimately enable better tailored treatment strategies.

Impact of surgical infrastructure and personnel on volume and availability of essential surgical procedures in Liberia.

BACKGROUND: Essential surgical procedures rank among the most cost-effective of all healthcare interventions. The aim of this study was to enumerate surgical volumes in Liberia, quantify surgical infrastructure, personnel and availability of essential surgical procedures, describe surgical facilities, and assess the influence of human resources and infrastructure on surgical volumes. METHODS: An observational countrywide survey was done in Liberia between 20 September and 8 November 2018. All healthcare facilities performing surgical procedures requiring general, regional or local anaesthesia in an operating theatre between September 2017 and August 2018 were eligible for inclusion. Information on facility infrastructure and human resources was collected by interviewing key personnel. Data on surgical volumes were extracted from operating theatre log books. RESULTS: Of 70 healthcare facilities initially identified as possible surgical facilities, 52 confirmed operative capacity and were eligible for inclusion; all but one shared surgical data. A national surgical volume of 462 operations per 100 000 population was estimated. The median hospital offered nine of 26 essential surgical procedures. Unequal distributions of surgical infrastructure, personnel, and essential surgical procedures were identified between facilities. In multivariable regression analysis, surgical human resources (ß = 0·60, 95 per cent c.i. 0·34 to 0·87; P < 0·001) and infrastructure (ß = 0·03, 0·02 to 0·04; P < 0·001) were found to be strongly associated with operative volumes. CONCLUSION: The availability of essential surgical procedures in Liberia is extremely low. Descriptive tools can quantify inequalities, guide resource allocation, and highlight rational investment areas.

ANTECEDENTES: Los procedimientos quirúrgicos esenciales se encuentran entre los más coste-efectivos de todas las intervenciones de salud. El objetivo de este estudio fue enumerar los volúmenes quirúrgicos en Liberia, cuantificar la infraestructura quirúrgica, personal y disponibilidad de procedimientos quirúrgicos esenciales, describir las instalaciones quirúrgicas y evaluar la influencia de los recursos humanos e infraestructura en los volúmenes quirúrgicos. MÉTODOS: Se realizó una encuesta observacional a nivel nacional en Liberia entre el 20 de septiembre y 8 de noviembre de 2028. Todos los centros médicos que realizaban procedimientos quirúrgicos que precisasen anestesia general, regional o local en un quirófano entre septiembre 2017 y agosto 2018 fueron elegibles para su inclusión. La información sobre la infraestructura de las instalaciones y los recursos humanos fue recogida entrevistando a personal clave. Los datos sobre los volúmenes quirúrgicos se extrajeron de los libros de registro de quirófano. RESULTADOS: De 70 centros médicos inicialmente identificados como posibles instalaciones quirúrgicas, 52 confirmaron disponer de capacidad quirúrgica y fueron elegibles para la inclusión; todos menos uno, compartieron los datos quirúrgicos. Se estimó un volumen quirúrgico nacional de 462 operaciones por 100.000 habitantes. El hospital promedio ofrecía nueve de 26 procedimientos quirúrgicos esenciales. Se identificaron distribuciones desiguales de infraestructura quirúrgica, personal y procedimientos quirúrgicos esenciales entre los centros. Se encontró que los recursos humanos quirúrgicos (ß = 0,60, P < 0,001, i.c. del 95% 0,34-0,87) y la infraestructura (ß = 0,029, P < 0,001, i.c. del 95% 0,019-0,039) estaban fuertemente asociadas con los volúmenes quirúrgicos. CONCLUSIÓN: La disponibilidad de procedimientos quirúrgicos esenciales en Liberia es extremadamente bajo. Instrumentos descriptivos pueden cuantificar desigualdades, orientar las decisiones de asignación de recursos y destacar las áreas para una inversión racional.

Effect of preoperative pelvic floor muscle training on pelvic floor muscle contraction and symptomatic and anatomical pelvic organ prolapse after surgery: randomized controlled trial.

OBJECTIVES: To evaluate the effect of preoperative pelvic floor muscle training (PFMT) on pelvic floor muscle (PFM) contraction, symptoms of pelvic organ prolapse (POP) and anatomical POP, 6 months after prolapse surgery, and to assess the overall changes in PFM contraction, POP symptoms and pelvic organ descent after surgery. METHODS: This was a randomized controlled trial of 159 women with symptomatic POP, Stage 2 or higher, scheduled for surgery. Participants were randomized to intervention including daily PFMT from inclusion to surgery (n = 81) or no intervention (controls; n = 78). Participants were examined at inclusion, on the day of surgery and 6 months after surgery. PFM contraction was assessed by: vaginal palpation using the Modified Oxford scale (MOS; 0-5); transperineal ultrasound, measuring the percentage change in levator hiatal anteroposterior diameter (APD) from rest to maximum PFM contraction; vaginal manometry; and surface electromyography (EMG). POP distance from the hymen in the compartment with the most dominant prolapse and organ descent in the anterior, central and posterior compartments were measured on maximum Valsalva maneuver. POP symptoms were assessed based on the sensation of vaginal bulge, which was graded using a visual analog scale (VAS; 0-100 mm). Linear mixed models were used to assess the effect of PFMT on outcome variables. RESULTS: Of the 159 women randomized, 151 completed the study, comprising 75 in the intervention and 76 in the control group. Mean waiting time for surgery was 22 ± 9.7 weeks and follow-up was performed on average 28 ± 7.8 weeks after surgery. Postoperatively, no difference was found between the intervention and control groups with respect to PFM contraction assessed by vaginal palpation (MOS, 2.4 vs 2.2; P = 0.101), manometry (19.4 vs 19.7 cmH2 O; P = 0.793), surface EMG (33.5 vs 33.1 mV; P = 0.815) and ultrasound (change in hiatal APD, 20.9% vs 19.3%; P = 0.211). Furthermore, no difference between groups was found for sensation of vaginal bulge (VAS, 7.4 vs 6.0 mm; P = 0.598), POP distance from the hymen in the dominant prolapse compartment (-1.8 vs -2.0 cm; P = 0.556) and sonographic descent of the bladder (0.5 vs 0.8 cm; P = 0.058), cervix (-1.3 vs -1.1 cm; P = 0.569) and rectal ampulla (0.3 vs 0.4 cm; P = 0.434). In all patients, compared with findings at initial examination, muscle contraction improved after surgery, as assessed by palpation (MOS, 2.1 vs 2.3; P = 0.007) and ultrasound (change in hiatal APD, 17.5% vs 20.1%; P = 0.001), and sensation of vaginal bulge was reduced (VAS, 57.6 vs 6.7 mm; P < 0.001). In addition, compared with the baseline examination, POP distance from the hymen in the dominant prolapse compartment (1.9 vs -1.9 cm; P < 0.001) and sonographic descent of the bladder (1.3 vs 0.6 cm; P < 0.001), cervix (0.0 vs -1.2 cm; P < 0.001) and rectal ampulla (0.9 vs 0.4 cm; P = 0.001) were reduced. CONCLUSIONS: We found no effect of preoperative PFMT on PFM contraction, POP symptoms or anatomical prolapse after surgery. In all patients, PFM contraction and POP symptoms were improved at the 6-month follow-up, most likely due to the anatomical correction of POP. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Efecto de los ejercicios preoperatorios de los músculos del suelo pélvico en la contracción de los músculos del suelo pélvico y en el prolapso sintomático y anatómico de los órganos pélvicos después de la cirugía: ensayo controlado aleatorizado OBJETIVOS: Evaluar el efecto de los ejercicios preoperatorios para los músculos del suelo pélvico (EMSP) en la contracción de los músculos del suelo pélvico (MSP), los síntomas del prolapso de órganos pélvicos (POP) y el POP anatómico, seis meses después de la cirugía de prolapso, y evaluar los cambios generales en la contracción de los MSP, los síntomas del POP y el descenso de los órganos pélvicos después de la cirugía. MÉTODOS: Este fue un ensayo controlado aleatorizado de 159 mujeres con POP sintomático, en Etapa 2 o superior, y en lista de espera para cirugía. Las participantes se asignaron al azar a una intervención que incluía EMSP diarios desde el ingreso hasta la cirugía (n=81) o ninguna intervención (controles; n=78). Las participantes fueron examinadas en el momento de su ingreso, el día de la cirugía y 6 meses después de la cirugía. La contracción de los MSP se evaluó mediante: palpación vaginal mediante la escala Oxford modificada (EOM; 0-5); ecografía transperineal, medición del porcentaje de cambio en el diámetro anteroposterior (DAP) del levador hiatal desde el reposo hasta la máxima contracción de los MSP; manometría vaginal; y electromiografía (EMG) de superficie. Se midió la distancia del POP desde el himen en el compartimento con el prolapso más dominante y el descenso de los órganos en los compartimentos anterior, central y posterior en la maniobra de Valsalva máxima. Los síntomas del POP fueron evaluados en base a la sensación de abultamiento vaginal, la cual fue calificada usando una escala análoga visual (EAV; 0-100 mm). Se utilizaron modelos mixtos lineales para evaluar el efecto de los EMSP en las variables de resultado. RESULTADOS: De las 159 mujeres asignadas al azar, 151 completaron el estudio, de las cuales 75 eran el grupo bajo intervención y 76 el grupo de control. El tiempo medio de espera para la cirugía fue de 22±9,7 semanas y el seguimiento se realizó en promedio a las 28±7,8 semanas después de la cirugía. En el postoperatorio, no se encontraron diferencias entre los grupos de intervención y de control con respecto a la contracción de los MSP evaluada mediante palpación vaginal (EOM, 2,4 vs 2,2; P=0,101), manometría (19,4 vs 19,7cm H2O; P=0,793), EMG de superficie (33,5 vs 33,1 mV; P=0,815) y ecografía (cambio en DAP del hiato, 20,9% vs 19,3%; P=0,211). Además, no se encontró ninguna diferencia entre los grupos en cuanto a la sensación de abultamiento vaginal (EAV, 7,4 vs 6,0 mm; P=0,598), la distancia del POP desde el himen en el compartimento dominante del prolapso (-1.8 vs -2,0 cm; P=0,556) y el descenso de la vejiga medido en ecografía (0,5 vs 0,8 cm; P=0,058), del cuello uterino (-1,3 vs -1,1 cm; P=0,569) y de la ampolla rectal (0,3 vs 0,4 cm; P=0,434). En todas las pacientes, en comparación con los hallazgos del examen inicial, la contracción muscular mejoró después de la cirugía, según se evaluó mediante la palpación (EOM, 2,1 vs 2,3; P=0,007) y la ecografía (cambio en la DPA del hiato, 17,5% vs 20,1%; P=0,001), y se redujo la sensación de abultamiento vaginal (EAV, 57.6 vs 6.7 mm; P<0.001). Además, en comparación con el examen de referencia, se redujeron la distancia del POP del himen en el compartimento dominante del prolapso (1,9 vs -1,9 cm; P<0.001) y el descenso de la vejiga medido en ecografía (1,3 vs 0,6 cm; P<0.001), del cuello uterino (0,0 vs −1,2 cm; P<0.001) y de la ampolla rectal (0,9 vs 0,4 cm; P=0.001). CONCLUSIONES: No se encontró ningún efecto de los EMSP preoperatorios en la contracción de los MSP, los síntomas del POP o el prolapso anatómico después de la cirugía. En todas las pacientes, la contracción de los MSP y los síntomas del POP mejoraron en el seguimiento a los 6 meses, debido muy probablemente a la corrección anatómica del POP. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound assessment of pelvic floor muscle contraction: reliability and development of an ultrasound-based contraction scale.

OBJECTIVES: To determine intra- and interrater reliability and agreement for ultrasound measurements of pelvic floor muscle contraction and to assess the correlation between ultrasound and vaginal palpation. We also aimed to develop an ultrasound scale for assessment of pelvic floor muscle contraction. METHODS: This was a cross-sectional study of 195 women scheduled for stress urinary incontinence (n = 65) or prolapse (n = 65) surgery or who were primigravid (n = 65). Pelvic floor muscle contraction was assessed by vaginal palpation using the Modified Oxford Scale (MOS) and by two- and three-dimensional (2D/3D) transperineal ultrasound. Proportional change in 2D and 3D levator hiatal anteroposterior (AP) diameter and 3D levator hiatal area between rest and contraction were used as measures of pelvic floor muscle contraction. One rater repeated all ultrasound measurements on stored volumes, which were used for intrarater reliability and agreement analysis, and three independent raters analyzed 60 ultrasound volumes for interrater reliability and agreement analysis. Reliability was assessed using the intraclass correlation coefficient (ICC) and agreement using Bland-Altman analysis. Tomographic ultrasound was used to identify women with major levator injury. Spearman's rank correlation coefficient (rS ) was used to assess the correlation between ultrasound measurements of pelvic floor muscle contraction and MOS score. The proportion of women allocated to each category of muscle contraction (absent, weak, moderate or strong) by palpation was used to determine the cut-offs for the ultrasound scale. RESULTS: Intrarater ICC was 0.81 (95% CI, 0.74-0.85) for proportional change in 2D levator hiatal AP diameter. Interrater ICC was 0.82 (95% CI, 0.72-0.89) for proportional change in 2D AP diameter, 0.80 (95% CI, 0.69-0.88) for proportional change in 3D AP diameter and 0.72 (95% CI, 0.56-0.83) for proportional change in hiatal area. The prevalence of major levator injury was 22.6%. The strength of correlation (rS ) between ultrasound measurements and MOS score was 0.52 for 2D AP diameter, 0.62 for 3D AP diameter and 0.47 for hiatal area (P < 0.001 for all). On the ultrasound contraction scale, proportional change in 2D levator hiatal AP diameter of < 1% corresponds to absent, 2-14% to weak, 15-29% to normal and > 30% to strong contraction. CONCLUSIONS: Ultrasound seems to be an objective and reliable method for evaluation of pelvic floor muscle contraction. Proportional change in 2D levator hiatal AP diameter had the highest ICC and moderate correlation with MOS score assessed by vaginal palpation, and we constructed an ultrasound scale for assessment of pelvic floor muscle contraction based on this measure. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Evaluation of a surgical task sharing training programme's logbook system in Sierra Leone.

BACKGROUND: Personal logbooks are universally applied for monitoring and evaluation of surgical trainees; however, the quality and accuracy of such logbooks in low income countries (LICs) are poorly examined. Logbooks are kept by the individual trainee and detail every surgical procedure they perform and their role during the procedure. The aim of this study was to evaluate the quality of such a logbook system in Sierra Leone and to identify areas of improvement. METHODS: The last 100 logbook entries for students and graduates participating in a surgical task sharing training programme were compared with hospital records (HRs). The logbook entries were categorized as matching, close matching or over-reported. Moreover, HRs were checked for under-reported procedures. Semi-structured interviews were conducted with the study participants on logbook recording routines. The results were analysed using mixed effects logistic regression models. RESULTS: Three thousand one hundred sixty-nine database entries from 35 participants were analysed. Of that amount, 62.2% of the entries matched the HRs, 10.4% were close matches and 26.9% were over-reported. 20.7% of the investigated HRs were under-reported. CONCLUSIONS: Information gathered from surgical logbook systems must be applied with care, and great efforts must be made to ensure that the logbook systems used provide reliable data. Based on analysis of the logbook data and interviews, focus areas are suggested to ensure reliable logbook data in LICs. Clear instructions and proper training should be provided when introducing the logbook system to the users. The importance of logging all procedures, including minor ones, should be emphasized. The logbook system should be user friendly and only as extensive as necessary. Lastly, keeping the logbooks exclusively digital is recommended, combined with sufficient IT equipment and training.

Caesarean section performed by medical doctors and associate clinicians in Sierra Leone.

BACKGROUND: Many countries lack sufficient medical doctors to provide safe and affordable surgical and emergency obstetric care. Task-sharing with associate clinicians (ACs) has been suggested to fill this gap. The aim of this study was to assess maternal and neonatal outcomes of caesarean sections performed by ACs and doctors. METHODS: All nine hospitals in Sierra Leone where both ACs and doctors performed caesarean sections were included in this prospective observational multicentre non-inferiority study. Patients undergoing caesarean section were followed for 30 days. The primary outcome was maternal mortality, and secondary outcomes were perinatal events and maternal morbidity. RESULTS: Between October 2016 and May 2017, 1282 patients were enrolled in the study. In total, 1161 patients (90·6 per cent) were followed up with a home visit at 30 days. Data for 1274 caesarean sections were analysed, 443 performed by ACs and 831 by doctors. Twin pregnancies were more frequently treated by ACs, whereas doctors performed a higher proportion of operations outside office hours. There was one maternal death in the AC group and 15 in the doctor group (crude odds ratio (OR) 0·12, 90 per cent confidence interval 0·01 to 0·67). There were fewer stillbirths in the AC group (OR 0·74, 0·56 to 0·98), but patients were readmitted twice as often (OR 2·17, 1·08 to 4·42). CONCLUSION: Caesarean sections performed by ACs are not inferior to those undertaken by doctors. Task-sharing can be a safe strategy to improve access to emergency surgical care in areas where there is a shortage of doctors.

Breastfeeding and long-term maternal metabolic health in the HUNT Study: a longitudinal population-based cohort study.

OBJECTIVE: Breastfeeding (BF) has been reported to improve long-term maternal metabolic health in observational studies, but not in the randomised controlled PROBIT study. Research also suggests that maternal pre-pregnant metabolic health may affect BF. We aimed to disentangle effects of BF on long-term maternal metabolic health from effects of pre-pregnant metabolic health on BF duration and long-term metabolic health. DESIGN: Longitudinal population-based cohort study. SETTING: Nord-Trøndelag county, Norway. POPULATION: Women with a first live-born baby (1987-2008) participating in the Nord-Trøndelag Health Study (HUNT). METHODS: Odds ratios (ORs) for short BF duration (<3 months) by pre-pregnant body mass index (BMI), waist circumference (WCF), blood pressures (BPs), and heart rate (HR) were adjusted for age and smoking using logistic regression. Mixed linear models were used to estimate effects of BF duration (<3, 3-6, >6 months) on mean values of metabolic health parameters from baseline to follow-up. MAIN OUTCOME MEASURES: Mean change in BMI, WCF, BPs, HR, serum-glucose, and serum-lipids from baseline to follow-up by BF duration categories. RESULTS: We analysed 1403 women with a median follow-up of 12 years (interquartile range 11-22). Pre-pregnant WCF and HR correlated inversely with BF duration. Pre-pregnant BMI had a u-shaped correlation-pattern with BF duration. We observed similar between-group differences in metabolic health parameters at baseline and at follow-up, which implies that mean change in metabolic health parameters was similar across BF groups. Those women who started out with the best health had the longest BF duration and ended up with the best health, and those women who started out with the poorest health had shortest BF duration and ended up with the poorest health. CONCLUSIONS: Our results do not support a causal relationship between long BF duration and improved metabolic health. It is more likely that pre-pregnant metabolic health affects both BF duration and long-term metabolic health. Reverse causality can explain previously observed improved long-term metabolic health after BF. TWEETABLE ABSTRACT: Breastfeeding seems not to affect long-term maternal metabolic health, but good pre-pregnant metabolic health does.

Resistance band training or general exercise in multidisciplinary rehabilitation of low back pain? A randomized trial.

Multidisciplinary biopsychosocial rehabilitation has been recommended for chronic low back pain (LBP), including physical exercise. However, which exercise modality that is most advantageous in multidisciplinary biopsychosocial rehabilitation is unclear. In this study, we investigated whether multidisciplinary biopsychosocial rehabilitation could be more effective in reducing pain-related disability when general physical exercise was replaced by strength training in the form of progressive resistance training using elastic resistance bands. In this single-blinded (researchers), randomized controlled trial, 99 consenting adults with moderate-to-severe non-specific LBP were randomized to three weeks of multidisciplinary biopsychosocial rehabilitation with either general physical exercise or progressive resistance band training and were then instructed to continue with their respective home-based programs for nine additional weeks, in which three booster sessions were offered. The primary outcome was between-group difference in change on the Oswestry Disability Index (ODI) at 12 weeks. Due to early dropouts, data from 74 participants (mean age: 45 years, 57% women, mean ODI: 30.4) were obtained at baseline, 61 participants were followed-up at 3 weeks, and 46 at 12 weeks. There was no difference in the change in ODI score between groups at 12 weeks (mean difference 1.9, 95% CI: -3.6, 7.4, P = .49). Likewise, the change in secondary outcomes did not differ between groups, except for the patient-specific functional scale (0-10), which favored general physical exercise (mean difference 1.4, 95% CI: 0.1, 2.7, P = .033). In conclusion, this study does not support that progressive resistance band training compared to general physical exercise improve outcomes in multidisciplinary biopsychosocial rehabilitation for patients with non-specific LBP.

LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface.

BACKGROUND: The cellular prion protein (PrPC) is an evolutionary conserved protein abundantly expressed not only in the central nervous system but also peripherally including the immune system. A line of Norwegian dairy goats naturally devoid of PrPC (PRNP Ter/Ter) provides a novel model for studying PrPC physiology. METHODS: In order to explore putative roles for PrPC in acute inflammatory responses, we performed a lipopolysaccharide (LPS, Escherichia coli O26:B6) challenge of 16 goats (8 PRNP +/+ and 8 PRNP Ter/Ter) and included 10 saline-treated controls (5 of each PRNP genotype). Clinical examinations were performed continuously, and blood samples were collected throughout the trial. Genome-wide transcription profiles of the choroid plexus, which is at the blood-brain interface, and the hippocampus were analyzed by RNA sequencing, and the same tissues were histologically evaluated. RESULTS: All LPS-treated goats displayed clinical signs of sickness behavior, which were of significantly (p < 0.01) longer duration in animals without PrPC. In the choroid plexus, a substantial alteration of the transcriptome and activation of Iba1-positive cells were observed. This response included genotype-dependent differential expression of several genes associated with the immune response, such as ISG15, CXCL12, CXCL14, and acute phase proteins, among others. Activation of cytokine-responsive genes was skewed towards a more profound type I interferon response, and a less obvious type II response, in PrPC-deficient goats. The magnitude of gene expression in response to LPS was smaller in the hippocampus than in the choroid plexus. Resting state expression profiles revealed a few differences between the PRNP genotypes. CONCLUSIONS: Our data suggest that PrPC acts as a modulator of certain pathways of innate immunity signaling, particularly downstream of interferons, and probably contributes to protection of vulnerable tissues against inflammatory damage.

Twelve months effect of self-referral to inpatient treatment on patient activation, recovery, symptoms and functioning: A randomized controlled study.

OBJECTIVE: To investigate the effect of having a contract for self-referral to inpatient treatment (SRIT) in patients with severe mental disorders. METHODS: A randomized controlled trial with 53 adult patients; 26 participants received a SRIT contract, which they could use to refer themselves into a Community Mental Health Centre up to five days for each referral without contacting a doctor in advance. Outcomes were assessed after 12 months with the self-report questionnaires Patient Activation Measure (PAM-13), Recovery Assessment Scale (RAS), and the Behavior and Symptom Identification Scale (BASIS-32) and analyzed using linear mixed and regression models. RESULTS: There was no significant effect on PAM-13 (estimated mean difference (emd) -0.41, 95% CI (CI):-7.49-6.67), nor on the RAS (emd 0.02, CI:-0.27-0.31) or BASIS-32 (0.09, CI:-0.28-0.45). An exploratory post hoc analysis showed effect of SRIT in those with low PAM below ≤47 (p=0.049). CONCLUSION: There were no group differences after 12 months, but both groups maintained their baseline levels. PRACTICE IMPLICATIONS: SRIT contracts can be recommended as it supports the rights to self-determination, promote user participation in decision-making in own treatment without any indication of adverse effects.

Cardiac function associated with previous, current and repeated depression and anxiety symptoms in a healthy population: the HUNT study.

OBJECTIVE: Symptoms of anxiety and depression often co-exist with cardiovascular disease (CVD), yet little is known about the association with left ventricular (LV) subclinical dysfunction. We aimed to study the cross-sectional associations of previous, current and repeated depression or anxiety symptoms, with sensitive indices of LV systolic and diastolic function, based on tissue Doppler (TD) and speckle tracking (ST) imaging methods. METHODS: A random selection of 1296 individuals free from known CVD, hypertension and diabetes were examined with echocardiography at baseline of the third Nord-Trøndelag Health Study, (HUNT3, 2006-2008). The primary outcomes were LV diastolic function (e') and LV systolic function (longitudinal global strain). The primary exposures were self-report on the Hospital Anxiety and Depression Scale (HADS). Associations between outcomes and baseline exposures were available for 1034 (80%), and with previous and repeated exposures for 700 participants who also participated in HUNT2 (1995-1997). RESULTS: Previous and repeated depression symptoms, but not current depression, were linearly associated with a reduction in e'. The average sum of two repeated HADS-D scores 10 years apart had the strongest effect on e' (-8.3%; 95% CI -13.9% to -2.7%) per 5 units. We observed a sex difference between depression symptoms and longitudinal global strain (p for interaction 0.019), where women had a marginal negative effect. Anxiety symptoms, neither previous, current nor repeated were associated with subclinical LV dysfunction. CONCLUSIONS: In a healthy sample, confirmed free of CVD, past and repeated depression symptoms were associated with subclinical LV dysfunction. Thus, depression symptoms might represent a modifiable risk factor for future CVD.

Assessment of pelvic floor muscle contraction with palpation, perineometry and transperineal ultrasound: a cross-sectional study.

OBJECTIVE: To study the correlation between palpation, perineometry and transperineal ultrasound for assessment of pelvic floor muscle contraction and to define a contraction scale for ultrasound measurements. METHODS: This was a cross-sectional study of 608 women examined with palpation of pelvic floor muscle contraction, using the Modified Oxford Scale, and measurement of the vaginal squeeze pressure with a vaginal balloon connected to a fiber-optic microtip transducer (perineometry). Transperineal ultrasound was used for measurements of levator hiatal area and anteroposterior (AP) diameter in the plane of minimal hiatal dimensions, at rest and on contraction. The pelvic floor muscle contraction was expressed as the percentage difference between values at rest and on contraction. Spearman's rank was used to test for correlation between the different methods of assessment. RESULTS: Significant correlations were found between all assessment methods (P < 0.001). Palpation correlated with perineometry (rs = 0.74) and with proportional change in hiatal area (rs = 0.67) and AP diameter (rs = 0.69) on ultrasound. Perineometry correlated with proportional change in hiatal area (rs = 0.60) and AP diameter (rs = 0.66) on ultrasound. We defined a contraction scale based on the proportional change in AP diameter. In this population, a change in AP diameter of < 7% corresponded to absence of contractions, 7-18% corresponded to weak contractions, 18-35% corresponded to normal contractions and > 35% corresponded to strong contractions. CONCLUSIONS: We found moderate to strong correlation between ultrasound measurements, palpation and perineometry for assessing pelvic floor muscle contraction. The proportional change in levator hiatal AP diameter was the ultrasound measurement with strongest correlation to palpation and perineometry and formed the basis for the contraction scale for ultrasound measurements. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Mitosin and pHH3 predict poorer survival in astrocytomas WHO grades II and III.

AIMS: The limitations of the current WHO classification of astrocytomas call for a sustained effort to improve diagnostic and prognostic accuracy. The relationship between tumour growth and clinical outcome suggests that proliferative activity should be examined. The objective of this study was to evaluate the diagnostic and prognostic value of the proliferation markers mitosin and phosphohistone H3 (pHH3) in infiltrative astrocytomas WHO grades II and III and compare the findings with mitotic count and Ki-67/MiB-1 immunostaining. METHODS: Fifty-nine and thirty-three infiltrative astrocytomas WHO grades II and III, respectively, were immunostained with the proliferation markers mitosin and pHH3 using standard immunohistochemical procedures. The expression was quantified as a proliferative index (PI) and statistically evaluated with Spearman's rank correlation test, Wilcoxon-Mann-Whitney U test, and univariable and multivariable COX regression survival analyses. RESULTS: Significant positive correlations were found between these proliferation markers. The number of mitoses, pHH3 mitotic figures (MFs), the Ki-67/MiB-1 PI and the mitosin PI were greater in WHOgrade III anaplastic astrocytomas compared to WHO grade II diffuse astrocytomas, while pHH3 PI only showed a trend. All proliferation markers were associated with poorer prognosis, but mitotic count was not. Ki-67/MiB-1, mitosin and pHH3 MF achieved statistical significance in the univariable analyses of both time to relapse (TTR) and overall survival (OS). Only mitosin remained significant in both multivariable analyses. pHH3 was significant in the multivariable analysis of OS but not of TTR. Clinical factors including age, extent of surgical resection and WHO performance status were also significantly correlated with survival. CONCLUSIONS: In conclusion, mitosin and pHH3 immunostaining have prognostic and diagnostic value in the clinical assessment of patients with infiltrative astrocytomas. The inclusion of proliferation markers in a layered diagnosis should be considered in the upcoming revision of the WHO classification system.

Forceps delivery is associated with increased risk of pelvic organ prolapse and muscle trauma: a cross-sectional study 16-24 years after first delivery.

OBJECTIVES: To study possible associations between mode of delivery and pelvic organ prolapse (POP) and pelvic floor muscle trauma 16-24 years after first delivery and, in particular, to identify differences between forceps and vacuum delivery. METHODS: This was a cross-sectional study including 608 women who delivered their first child in 1990-1997 and were examined with POP quantification (POP-Q) and pelvic floor ultrasound in 2013-2014. Outcome measures were POP ≥ Stage 2 or previous prolapse surgery, levator avulsion and levator hiatal area on Valsalva. Univariable and multivariable logistic regression analyses and ANCOVA were applied to identify outcome variables associated with mode of delivery. RESULTS: Comparing forceps to vacuum delivery, the adjusted odds ratios (aOR) were 1.72 (95% CI, 1.06-2.79; P = 0.03) for POP ≥ Stage 2 or previous prolapse surgery and 4.16 (95% CI, 2.28-7.59; P < 0.01) for levator avulsion. Hiatal area on Valsalva was larger, with adjusted mean difference (aMD) of 4.75 cm(2) (95% CI, 2.46-7.03; P < 0.01). Comparing forceps with normal vaginal delivery, the adjusted odds ratio (aOR) was 1.74 (95% CI, 1.12-2.68; P = 0.01) for POP ≥ Stage 2 or surgery and 4.35 (95% CI, 2.56-7.40; P < 0.01) for levator avulsion; hiatal area on Valsalva was larger, with an aMD of 3.84 cm(2) (95% CI, 1.78-5.90; P < 0.01). Comparing Cesarean delivery with normal vaginal delivery, aOR was 0.06 (95% CI, 0.02-0.14; P < 0.01) for POP ≥ Stage 2 or surgery and crude OR was 0.00 (95% CI, 0.00-0.30; P < 0.01) for levator avulsion; hiatal area on Valsalva was smaller, with an aMD of -8.35 cm(2) (95% CI, -10.87 to -5.84; P < 0.01). No differences were found between vacuum and normal vaginal delivery. CONCLUSIONS: We found that mode of delivery was associated with POP and pelvic floor muscle trauma in women from a general population, 16-24 years after their first delivery. Forceps was associated with significantly more POP, levator avulsion and larger hiatal areas than were vacuum and normal vaginal deliveries. There were no statistically significant differences between vacuum and normal vaginal deliveries. Cesarean delivery was associated with significantly less POP and pelvic floor muscle trauma than were normal or operative vaginal delivery.

Tumour apparent diffusion coefficient is associated with depth of myometrial invasion and is negatively correlated to tumour volume in endometrial carcinomas.

AIM: To explore possible correlations between tumour apparent diffusion coefficient (ADC), morphological tumour volume, and clinical and histological characteristics in endometrial carcinomas and to evaluate interobserver agreement for preoperative staging by MRI and for ADC measurements. MATERIALS AND METHODS: Preoperative conventional MRI including diffusion-weighted imaging (DWI) was performed in 105 endometrial carcinoma patients. Three radiologists independently reviewed the images for the presence of deep myometrial invasion, cervical stromal invasion, and lymph node metastases, and measured tumour ADC in regions of interest (ROIs). ADC values were analysed in relation to histomorphological characteristics and tumour volume. Kappa coefficients (κ) and intraclass correlation coefficients (ICC) for interobserver agreement for MRI staging results and ADC measurements, respectively, were calculated, and receiver operating characteristic (ROC) curves for identification of deep of myometrial invasion were generated. RESULTS: Mean tumour ADC was significantly lower in tumours with deep myometrial invasion (ADC = 0.75 × 10(-3) mm(2)/s) compared to tumours with superficial or no myometrial invasion (ADC = 0.85 × 10(-3) mm(2)/s; p < 0.001). ADC was negatively correlated to tumour size (p = 0.007). The interobserver agreement was fair (κ = 0.32) for depth of myometrial invasion, good for cervical stromal invasion (κ = 0.66), and moderate for lymph node metastases (κ = 0.54), and the interobserver variability for ADC value measurements was low (ICC = 0.60). CONCLUSION: Tumour ADC measurements may in the future provide an adjunct tool, aiding in the preoperative identification of high-risk patients with deep myometrial infiltration.

Pelvic organ prolapse and incontinence 15-23 years after first delivery: a cross-sectional study.

OBJECTIVE: To study the association between pelvic floor dysfunction (PFD) and mode of delivery and to calculate the risks of PFD comparing caesarean delivery and operative vaginal delivery to normal vaginal delivery 15-23 years after childbirth. A subgroup analysis comparing forceps and vacuum delivery was planned. DESIGN: Cross-sectional study. SETTING: Postal questionnaire. POPULATION: 1641 (53%) of 3115 women who delivered their first child in Trondheim, Norway, between January 1990 and December 1997. METHODS: A questionnaire including questions on symptomatic pelvic organ prolapse, urinary and fecal incontinence and surgery for these conditions. MAIN OUTCOME MEASURES: Prevalence of PFD measured by symptomatic pelvic organ prolapse or surgery (sPOP), urinary incontinence or surgery (UI) and fecal incontinence or surgery (FI). RESULTS: When caesarean delivery was compared to normal vaginal delivery the adjusted odds ratio (aOR) for sPOP was 0.42 (95% confidence interval, CI, 0.21-0.86) and the aOR for UI was 0.65 (95% CI 0.46-0.92). Operative vaginal delivery was associated with increased risk of sPOP (aOR 1.73, 95% CI 1.21-2.48) and FI (aOR 1.96, 95% CI 1.26-3.06) when compared with normal vaginal delivery. There were no differences in sPOP, UI or FI in a subgroup analysis comparing forceps and vacuum delivery. CONCLUSIONS: Caesarean delivery was associated with decreased risk and operative vaginal delivery with increased risk of pelvic floor dysfunction 15-23 years after first delivery, but there were no differences between forceps and vacuum delivery.

Concentrations of remifentanil, propofol, fentanyl, and midazolam during rewarming from therapeutic hypothermia.

BACKGROUND: The clearance of sedatives and analgesics may be reduced by therapeutic hypothermia. However, little is known about the concentrations of such drugs during rewarming. The aim of this study was to describe the serum concentrations of sedatives and analgesics during rewarming from therapeutic hypothermia. METHODS: Blood samples were collected for quantification of drug concentrations in 22 patients given analgesia/sedation with either remifentanil/propofol or fentanyl/midazolam during rewarming from therapeutic hypothermia (33-34°C) after cardiac arrest. Samples for were drawn before (-2 h) and during rewarming (0-8 h). Linear mixed effects models were used to describe serum concentrations and adjust for rates of infusion during rewarming from therapeutic hypothermia. RESULTS: Subjects with samples analyzed were remifentanil (n = 8), propofol (n = 14), fentanyl (n = 8), and midazolam (n = 8). Age, body mass index, and simplified acute physiology score II [mean (standard deviation)] were 64 (14.2) years, 27.3 (3.7) kg/m(2), and 69 (13.2), respectively. While the concentration of fentanyl was not significantly affected by temperature, concentrations of remifentanil, propofol, and midazolam decreased with core temperature by 16%, 12%, and 11% (mean values) from 33°C to 37°C after adjusting for rates of infusion, respectively. CONCLUSION: Concentrations of remifentanil, propofol, and midazolam decreased during rewarming from therapeutic hypothermia when adjusting for rates of infusion. No changes were demonstrated for fentanyl.

Levosimendan improves contractility in vivo and in vitro in a rodent model of post-myocardial infarction heart failure.

AIM: As few studies have presented a thorough analysis of the effect of levosimendan (LEV) on contractility, our purpose was to investigate in vivo cardiac function as well as in vitro cardiomyocyte function and calcium (Ca(2+) ) handling following LEV treatment. METHODS: Rats with post-myocardial infarction heart failure (HF) induced by ligation of the left anterior descending coronary artery and sham-operated animals were randomized to the infusion of LEV (2.4 µg kg(-1) min(-1) ) or vehicle for 40 min. Echocardiographic examination was coupled to pressure-volume sampling in the left ventricle before (B) and after (40 min) infusion. Isolated left ventricular cardiomyocytes were studied in an epifluorescence microscope. RESULTS: HF LEV (n = 6), HF vehicle (n = 7), sham LEV (n = 5) and sham vehicle (n = 6) animals were included. LEV infusion compared to vehicle in HF animals reduced left ventricular end-diastolic pressure and mean arterial pressure (both P < 0.001) and improved the slope of the preload-recruitable stroke work (P < 0.05). Administrating LEV to HF cardiomyocytes in vitro improved fractional shortening and Ca(2+) sensitivity index ratio, and increased the diastolic Ca(2+) (all P < 0.01). CONCLUSION: In HF animals, LEV improved the contractility by increasing the Ca(2+) sensitivity. Furthermore loading conditions were changed, and LEV could consequently change organ perfusion. An observed increase in diastolic Ca(2+) following LEV treatment and clinical implications of this should be further addressed.