Thyroidectomy for Euthyroid Patients with Hashimoto Disease and Persistent Symptoms: An Observational, Postrandomization Study.

Background: Despite adequate hormone substitution in Hashimoto disease, some patients may have persistent symptoms with a possible autoimmune pathophysiology. A recent randomized trial (RCT) using patient-reported outcome measures as the primary endpoint showed benefit in total thyroidectomy, but at a cost of high complication rates. Objective: To verify results from the RCT in an observational study including a wider range of patients and explore means of predicting who may benefit from such surgery. Design: A total of 154 patients with Hashimoto disease, euthyroid with or without thyroid hormone substitution, and persistent Hashimoto-related symptoms were subjected to total thyroidectomy and followed for 18 months after surgery. The primary outcome was the General Health (GH) dimensional score in the Short Form-36 Health Survey (SF-36). Results: Eighteen months after surgery, a clinically significant improvement in GH was seen, similar to the findings in the previous RCT. Anti-TPO antibody titers were markedly reduced after surgery, but preoperative titers or other preoperative parameters could not predict the outcome of surgery. Three (1.9%) of 154 patients experienced permanent unilateral recurrent nerve palsy and six (3.9%) experienced hypoparathyroidism after surgery. Conclusions: Thyroidectomy had a beneficial symptom-reducing effect in euthyroid patients with Hashimoto disease and persistent symptoms. The pathophysiology of residual symptoms remains unclear, and surgical complication rates are high. If thyroidectomy is considered as a treatment option, it should be performed in dedicated centers with experienced endocrine surgeons and as part of further studies on persistent symptoms. This trial is registered with NCT-02319538.

Extracting physiologic and clinical data from defibrillators for research purposes to improve treatment for patients in cardiac arrest.

Background: A defibrillator should be connected to all patients receiving cardiopulmonary resuscitation (CPR) to allow early defibrillation. The defibrillator will collect signal data such as the electrocardiogram (ECG), thoracic impedance and end-tidal CO2, which allows for research on how patients demonstrate different responses to CPR. The aim of this review is to give an overview of methodological challenges and opportunities in using defibrillator data for research. Methods: The successful collection of defibrillator files has several challenges. There is no scientific standard on how to store such data, which have resulted in several proprietary industrial solutions. The data needs to be exported to a software environment where signal filtering and classifications of ECG rhythms can be performed. This may be automated using different algorithms and artificial intelligence (AI). The patient can be classified being in ventricular fibrillation or -tachycardia, asystole, pulseless electrical activity or having obtained return of spontaneous circulation. How this dynamic response is time-dependent and related to covariates can be handled in several ways. These include Aalen's linear model, Weibull regression and joint models. Conclusions: The vast amount of signal data from defibrillator represents promising opportunities for the use of AI and statistical analysis to assess patient response to CPR. This may provide an epidemiologic basis to improve resuscitation guidelines and give more individualized care. We suggest that an international working party is initiated to facilitate a discussion on how open formats for defibrillator data can be accomplished, that obligates industrial partners to further develop their current technological solutions.

Improvements in Obstetric and Newborn Health Information Documentation following the Implementation of the Safer Births Bundle of Care at 30 Facilities in Tanzania.

This paper examines changes in the completeness of documentation in clinical practice before and during the implementation of the Safer Births Bundle of Care (SBBC) project. This observational study enrolled parturient women with a gestation age of at least 28 weeks at the onset of labour. Data collectors extracted information from facility registers and then a central data manager summarised and reported weekly statistics. Variables of clinical significance for CQI were selected, and the proportion of non-documentation was analysed over time. A Pearson chi-square test was used to test for significant differences in non-documentation between the periods. Between 1 March 2021 and 31 July 2022, a total of 138,442 deliveries were recorded. Overall, 75% of all patient cases had at least one missing variable among the selected variables across both periods. A lack of variable documentation occurred more frequently at the district hospital level (81% of patient cases) and health centres (74%) than at regional referral hospitals (56%) (p < 0.001). Non-documentation decreased significantly from 79% to 70% after the introduction of the SBBC (p < 0.001). A tendency towards negative correlations was noted for most variables. We noted an increased attention to data quality and use which may have a positive impact on the completeness of documentation. However, halfway through the project's implementation, the completeness of documentation was still low. Our findings support the recommendation to establish short-spaced feedback loops of locally collected data using one data platform.

Prevalence of bradycardia in 4876 newborns in the first minute after birth and association with positive pressure ventilation: a population-based cross-sectional study.

OBJECTIVE: To determine the prevalence of bradycardia in the first minute after birth and association with positive pressure ventilation (PPV). METHOD: A population-based cross-sectional study was conducted from June 2019 to December 2021 at Stavanger University Hospital, Norway. Parents consented to participation during pregnancy, and newborns ≥28 weeks' gestation were included at birth. Heart rate (HR) was captured immediately after birth and continuously for the first minute(s). Time of birth was registered on a tablet. Provision of PPV was captured using video. RESULTS: Of 4876 included newborns, 164 (3.4%) did not breathe (two-thirds) or breathed ineffectively (one-third) and received PPV at birth. HR in the first minute had a wide distribution. The prevalence of first measured HR <100 and <60 beats/minute at median 16 s was 16.3% and 0.6%, respectively. HR increased in most cases. At 60 s, 3.7% had HR <100 beats/minute, of which 82% did not require PPV. In total, 25% of newborns had some registered HR <100 beats/minute during the first minute, of which 95% did not require PPV. Among newborns who received PPV, 76% and 62% had HR ≥100 beats/minute at 60 s and at start PPV, respectively. CONCLUSION: Bradycardia with HR <100 bpm in the first minute of life was frequent, but mostly self-resolved. Among the 4% of newborns that remained bradycardic at 60 s, only 20% received PPV. Two-thirds of resuscitated newborns had HR ≥100 beats/minute at start PPV. None of the ventilated newborns were breathing adequately at start PPV. TRIAL REGISTRATION NUMBER: NCT03849781.

Laparoscopic rectal cancer resection yields comparable clinical and oncological results with shorter hospital stay compared to open access: a 5-year national cohort.

PURPOSE: Although widely applied, the results following laparoscopic rectal resection (LRR) compared to open rectal resection (ORR) are still debated. The aim of this study was to assess clinical short- and long-term results as well as oncological resection quality following LRR or ORR for cancer in a 5-year national cohort. METHODS: Data from the Norwegian Registry for Gastrointestinal Surgery and the Norwegian Colorectal Cancer Registry were retrieved from January 2014 to December 2018 for patients who underwent elective resection for rectal cancer. Primary end point was 5-year overall survival. Secondary end points were local recurrence rates within 5 years, oncological resection quality, and short-term outcome measures. RESULTS: A total of 1796 patients were included, of whom 1284 had undergone LRR and 512 ORR. There was no difference in 5-year survival rates between the groups after adjusting for relevant covariates with Cox regression analyses. Crude 5-year survival was 77.1% following LRR compared to 74.8% following ORR (p = 0.015). The 5-year local recurrence rates were 3.1% following LRR and 4.1% following ORR (p = 0.249). Length of hospital stay was median 8.0 days (quartiles 7.0-13.0) after ORR compared to 6.0 (quartiles 4.0-8.0) days after LRR. After adjusting for relevant covariates, estimated additional length of stay after ORR was 3.1 days (p < 0.001, 95% CI 2.3-3.9). Rates of positive resection margins and number of harvested lymph nodes were similar. There were no other significant differences in short-term outcomes between the groups. CONCLUSION: LRR was performed with clinical and oncological outcomes similar to ORR, but with shorter hospital stay.

Less, but not gone-gluten-free diet effects on fatigue in celiac disease: a prospective controlled study.

Introduction: Fatigue is a frequent complaint in patients with celiac disease. A gluten-free diet is the only established treatment for celiac disease, but how this diet influences fatigue is uncertain. We aimed to investigate fatigue prevalence, severity, and associated factors in patients with celiac disease, at diagnosis and at 1 year after commencing a gluten-free diet. Methods: 78 patients with serologically and histologically verified celiac disease, 78 age- and sex-matched healthy subjects. Primary endpoints were Fatigue Visual Analog Scale (fVAS), Fatigue Severity Scale (FSS), and inverted Vitality subscale of the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36vs). Clinically relevant fatigue was defined as: FSS score ≥ 4, fVAS score ≥ 50 mm, or inverted SF-36vs score ≥ 65. Higher scores represented more fatigue. Results: Fatigue was reduced after a 12-month gluten-free diet. Median scores changed from 3.8 (interquartile range [IQR]: 2.2 to 4.8) to 1.9 (IQR: 1.4 to 3.5) for FSS, from 44.5 (IQR: 18.8 to 66.0) to 15.5 (IQR: 7.8 to 43.3) for fVAS, and from 65 (IQR: 40 to 75) to 35 (IQR: 25 to 55) for inverted SF-36vs (p < 0.001 for all). Fatigue prevalence also declined after treatment. However, scores were significantly higher in patients compared to control subjects. Higher fatigue scores were associated with depression and pain, but not with signs of disease activity or nutritional deficiency. Conclusion: At diagnosis, patients with celiac disease frequently had severe fatigue. Fatigue declined after a gluten-free diet, but it remained higher than that observed in healthy subjects. Clinical trial registration: ClinicalTrials.gov, Identifier NCT01551563.

Importance of endocrine treatment adherence and persistence in breast cancer survivorship: a systematic review.

PURPOSE: Adjuvant endocrine treatment is essential for treating luminal subtypes of breast cancer, which constitute 75% of all breast malignancies. However, the detrimental side effects of treatment make it difficult for many patients to complete the guideline-required treatment. Such non-adherence may jeopardize the lifesaving ability of anti-estrogen therapy. In this systematic review, we aimed to assess the consequences of non-adherence and non-persistence from available studies meeting strict statistical and clinical criteria. METHODS: A systematic literature search was performed using several databases, yielding identification of 2,026 studies. After strict selection, 14 studies were eligible for systematic review. The review included studies that examined endocrine treatment non-adherence (patients not taking treatment as prescribed) or non-persistence (patients stopping treatment prematurely), in terms of the effects on event-free survival or overall survival among women with non-metastatic breast cancer. RESULTS: We identified 10 studies measuring the effects of endocrine treatment non-adherence and non-persistence on event-free survival. Of these studies, seven showed significantly poorer survival for the non-adherent or non-persistent patient groups, with hazard ratios (HRs) ranging from 1.39 (95% CI, 1.07 to 1.53) to 2.44 (95% CI, 1.89 to 3.14). We identified nine studies measuring the effects of endocrine treatment non-adherence and non-persistence on overall survival. Of these studies, seven demonstrated significantly reduced overall survival in the groups with non-adherence and non-persistence, with HRs ranging from 1.26 (95% CI, 1.11 to 1.43) to 2.18 (95% CI, 1.99 to 2.39). CONCLUSION: The present systematic review demonstrates that non-adherence and non-persistence to endocrine treatment negatively affect event-free and overall survival. Improved follow-up, with focus on adherence and persistence, is vital for improving health outcomes among patients with non-metastatic breast cancer.

Increase in Newborns Ventilated Within the First Minute of Life and Reduced Mortality After Clinical Data-Guided Simulation Training.

INTRODUCTION: Birth asphyxia-related deaths is a major global concern. Rapid initiation of ventilation within the "Golden Minute" is important for intact survival but reported to be challenging, especially in low-/middle-income countries. Helping Babies Breathe (HBB) is a simulation-based training program for newborn resuscitation. The aim of this HBB quality improvement (QI) intervention was to decrease time from birth to ventilation and document potential changes in perinatal outcomes. METHOD: Prospective observational QI study in a rural Tanzanian hospital, October 1, 2017, to August 31, 2021, first-year baseline, second-year QI/simulation intervention, and 2-year postintervention. Trained research assistants observed wide-ranging information from all births (N = 12,938). The intervention included monthly targeted HBB simulation training addressing documented gaps in clinical care, clinical debriefings, and feedback meetings. RESULTS: During the QI/simulation intervention, 68.5% nonbreathing newborns were ventilated within 60 seconds after birth compared with 15.8% during baseline and 42.2% and 28.9% during the 2 postintervention years (P < 0.001). Time to first ventilation decreased from median 101 (quartiles 72-150) to 55 (45-67) seconds (P < 0.001), before increasing to 67 (49-97) and 85 (57-133) seconds after intervention. More nonbreathing newborns were ventilated in the intervention period (12.9%) compared with baseline (8.5%) and the postintervention years (10.6% and 9.4%) (P < 0.001). Assumed fresh stillborns decreased significantly from baseline to intervention (3.2%-0.7%) (P = 0.013). CONCLUSIONS: This QI study demonstrates an increase in nonbreathing newborns being ventilated within the Golden Minute and a significant reduction in fresh stillborns after introduction of an HBB QI/simulation intervention. Improvements are partially reversed after intervention, highlighting the need for continuous simulation-based training and research into QI efforts essential for sustainable changes.

High mobility group box 1 and a network of other biomolecules influence fatigue in patients with Crohn's disease.

BACKGROUND: Fatigue is common in patients with chronic inflammatory and autoimmune diseases, often with a severe impact on the patient's daily life. From a biological point of view, fatigue can be regarded as an element of the sickness behavior response, a coordinated set of responses induced by pathogens to enhance survival during an infection and immunological danger. The mechanisms are not fully understood but involve activation of the innate immune system, with pro-inflammatory cytokines, in particular interleukin (IL)-1ß, acting on cerebral neurons. These mechanisms are also active during chronic inflammatory conditions. High mobility group box 1 (HMGB1) protein has interleukin-1 like properties and is a strong inducer of innate immune responses. Its role in generation of fatigue is not clarified. Emerging evidence indicates that also other biomolecules may influence sickness behavior. We aimed to elucidate how HMGB1 influences fatigue in patients with Crohn's disease, and how the protein interacts with other candidate biomarkers of fatigue. METHODS: In 56 patients with newly diagnosed Crohn's disease, fatigue was evaluated using three different fatigue instruments: the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and the vitality subscale of Medical Outcomes Study Short-Form Health Survey (SF-36vs). The biochemical markers IL-1 receptor antagonist (RA), soluble IL-1 receptor type 2 (sIL-RII), heat shock protein 90 alpha (HSP90α), HMGB1, anti-fully reduced (fr)HMGB1 antibodies (abs), hemopexin (HPX), and pigment epithelium-derived factor (PEDF) were measured in plasma. Multivariable regression and principal component analyses (PCA) were applied. RESULTS: Multivariable regression analyses revealed significant contributions to fatigue severity for HMGB1 in the FSS model, HSP90α in the fVAS model and IL-1RA in the SF-36vs model. Depression and pain scores contributed to all three models. In PCA, two components described 53.3% of the variation. The "inflammation and cellular stress dimension" was dominated by IL-1RA, sIL-1RII, HSP90α, HPX, and PEDF scores, where the "HMGB1 dimension" was dominated by HMGB1, anti-frHMGB1 abs, and fVAS scores. CONCLUSION: This study supports the hypothesis that HMGB1 and a network of other biomolecules influence fatigue severity in chronic inflammatory conditions. The well-known association with depression and pain is also acknowledged.

"Safer Births Bundle of Care" Implementation and Perinatal Impact at 30 Hospitals in Tanzania-Halfway Evaluation.

Safer Births Bundle of Care (SBBC) consists of innovative clinical and training tools for improved labour care and newborn resuscitation, integrated with new strategies for continuous quality improvement. After implementation, we hypothesised a reduction in 24-h newborn deaths, fresh stillbirths, and maternal deaths by 50%, 20%, and 10%, respectively. This is a 3-year stepped-wedged cluster randomised implementation study, including 30 facilities within five regions in Tanzania. Data collectors at each facility enter labour and newborn care indicators, patient characteristics and outcomes. This halfway evaluation reports data from March 2021 through July 2022. In total, 138,357 deliveries were recorded; 67,690 pre- and 70,667 post-implementations of SBBC. There were steady trends of increased 24-h newborn and maternal survival in four regions after SBBC initiation. In the first region, with 13 months of implementation (n = 15,658 deliveries), an estimated additional 100 newborns and 20 women were saved. Reported fresh stillbirths seemed to fluctuate across time, and increased in three regions after the start of SBBC. Uptake of the bundle varied between regions. This SBBC halfway evaluation indicates steady reductions in 24-h newborn and maternal mortality, in line with our hypotheses, in four of five regions. Enhanced focus on uptake of the bundle and the quality improvement component is necessary to fully reach the SBBC impact potential as we move forward.

Reduction in omission events after implementing a Rapid Response System: a mortality review in a department of gastrointestinal surgery.

BACKGROUND: Hospitals worldwide have implemented Rapid Response Systems (RRS) to facilitate early recognition and prompt response by trained personnel to deteriorating patients. A key concept of this system is that it should prevent 'events of omission', including failure to monitor patients' vital signs, delayed detection, and treatment of deterioration and delayed transfer to an intensive care unit. Time matters when a patient deteriorates, and several in-hospital challenges may prevent the RRS from functioning adequately. Therefore, we must understand and address barriers for timely and adequate responses in cases of patient deterioration. Thus, this study aimed to investigate whether implementing (2012) and developing (2016) an RRS was associated with an overall temporal improvement and to identify needs for further improvement by studying; patient monitoring, omission event occurrences, documentation of limitation of medical treatment, unexpected death, and in-hospital- and 30-day mortality rates. METHODS: We performed an interprofessional mortality review to study the trajectory of the last hospital stay of patients dying in the study wards in three time periods (P1, P2, P3) from 2010 to 2019. We used non-parametric tests to test for differences between the periods. We also studied overall temporal trends in in-hospital- and 30-day mortality rates. RESULTS: Fewer patients experienced omission events (P1: 40%, P2: 20%, P3: 11%, P = 0.01). The number of documented complete vital sign sets, median (Q1,Q3) P1: 0 (0,0), P2: 2 (1,2), P3: 4 (3,5), P = 0.01) and intensive care consultations in the wards ( P1: 12%, P2: 30%, P3: 33%, P = 0.007) increased. Limitations of medical treatment were documented earlier (median days from admission were P1: 8, P2: 8, P3: 3, P = 0.01). In-hospital and 30-day mortality rates decreased during this decade (rate ratios 0.95 (95% CI: 0.92-0.98) and 0.97 (95% CI: 0.95-0.99)). CONCLUSION: The RRS implementation and development during the last decade was associated with reduced omission events, earlier documentation of limitation of medical treatments, and a temporal reduction in the in-hospital- and 30-day mortality rates in the study wards. The mortality review is a suitable method to evaluate an RRS and provide a foundation for further improvement. TRIAL REGISTRATION: Retrospectively registered.

Newborns requiring resuscitation: Two thirds have heart rate ≥100 beats/minute in the first minute after birth.

AIM: The aim was to study the prevalence of bradycardia at birth in newborns requiring positive pressure ventilation (PPV), distribution of first measured heart rate (HR), changes in HR before start of PPV and HR response to PPV. METHODS: A population-based study including newborns ≥30 weeks' gestation receiving PPV at birth. HR was captured immediately after birth and continuously throughout resuscitation using the dry-electrode ECG device NeoBeat. Time of birth was registered in the Liveborn app. Provision of PPV was captured by video. RESULTS: We included 98 newborns receiving PPV at birth. Among newborns with HR measured within 60 s after birth, median (quartiles) first HR was 112 (84, 149) bpm recorded 19 (14, 37) s after birth, of which 33% had first HR <100 and 10% had first HR <60 bpm respectively. First HR was widely distributed. Median HR at start PPV 69 s after birth was 129 bpm. In newborns with an initial low HR, HR typically remained low for 20 s of PPV before increasing rapidly over the next 20-30 s. CONCLUSIONS: First measured HR was ≥100 bpm in two thirds of newborns receiving PPV. In bradycardic infants, HR did not increase until after 20 s of PPV.

Newborn resuscitation simulation training and changes in clinical performance and perinatal outcomes: a clinical observational study of 10,481 births.

BACKGROUND: Annually, 1.5 million intrapartum-related deaths occur; fresh stillbirths and early newborn deaths. Most of these deaths are preventable with skilled ventilation starting within the first minute of life. Helping Babies Breathe is an educational program shown to improve simulated skills in newborn resuscitation. However, translation into clinical practice remains a challenge. The aim was to describe changes in clinical resuscitation and perinatal outcomes (i.e., fresh stillbirths and 24-h newborn deaths) after introducing a novel simulator (phase 1) and then local champions (phase 2) to facilitate ongoing Helping Babies Breathe skill and scenario simulation training. METHODS: This is a 3-year prospective before/after (2 phases) clinical observational study in Tanzania. Research assistants observed all deliveries from September 2015 through August 2018 and recorded labor/newborn information and perinatal outcomes. A novel simulator with automatic feedback to stimulate self-guided skill training was introduced in September 2016. Local champions were introduced in October 2017 to motivate midwives for weekly training, also team simulations. RESULTS: The study included 10,481 births. Midwives had practiced self-guided skill training during the last week prior to a real newborn resuscitation in 34% of cases during baseline, 30% in phase 1, and 71% in phase 2. Most real resuscitations were provided by midwives, increasing from 66% in the baseline, to 77% in phase 1, and further to 83% in phase 2. The median time from birth to first ventilation decreased between baseline and phase 2 from 118 (85-165) to 101 (72-150) s, and time pauses during ventilation decreased from 28 to 16%. Ventilations initiated within the first minute did not change significantly (13-16%). The proportion of high-risk deliveries increased during the study period, while perinatal mortality remained unchanged. CONCLUSIONS: This study reports a gradual improvement in real newborn resuscitation skills after introducing a novel simulator and then local champions. The frequency of trainings increased first after the introduction of motivating champions. Time from birth to first ventilation decreased; still, merely 16% of newborns received ventilation within the first minute as recommended. This is a remaining challenge that may require more targeted team-scenario training and quality improvement efforts to improve.

Epidemiology of abdominal trauma: An age- and sex-adjusted incidence analysis with mortality patterns.

PURPOSE: Abdominal injuries may occur in up to one-third of all patients who suffer severe trauma, but little is known about epidemiological trends and characteristics in a Northern European setting. This study investigated injury demographics, and epidemiological trends in trauma patients admitted with abdominal injuries. METHODS: This was an observational cohort study of all consecutive patients admitted to Stavanger University Hospital (SUH) with a documented abdominal injury between January 2004 and December 2018. Injury demographics, age- and sex-adjusted incidence, and mortality patterns are analyzed across three time periods. RESULTS: Among 7202 admitted trauma patients, 449 (6.2%) suffered abdominal injuries. The median age was 31 years, and the age increased significantly over time (from a median of 25 years to a median of 38.5 years; p = 0.020). Patients with ASA 2 and 3 increased significantly over time. Men accounted for 70% (316/449). The injury mechanism was blunt in 91% (409/449). Transport-related accidents were the most frequent cause of injury in 57% (257/449). The median Injury Severity Score (ISS) was 21, and the median New Injury Severity Score (NISS) was 25. The annual adjusted incidence of all abdominal injuries was 7.2 per 100,000. Solid-organ injuries showed an annual adjusted incidence of 5.7 per 100,000. The most frequent organ injury was liver injury, found in 38% (169/449). Multiple abdominal injuries were recorded in 44% (197/449) and polytrauma in 51% (231/449) of the patients. Overall 30-day mortality was 12.5% (56/449) and 90-day mortality 13.6% (61/449). CONCLUSION: The overall adjusted incidence rate of abdominal injuries remained stable. Age at presentation increased by over a decade, more often presenting with pre-existing comorbidities (ASA 2 and 3). The proportion of polytrauma patients was significantly reduced over time. Mortality rates were declining, although not statistically significant.

Fatigue: a frequent and biologically based phenomenon in newly diagnosed celiac disease.

Fatigue is increasingly recognized as a major complaint in patients with chronic inflammatory and autoimmune diseases. Although fatigue is assumed to represent a significant problem in celiac disease, existing knowledge is scarce, and opinions are conflicting. This study aimed to investigate the prevalence and severity of fatigue in patients with newly diagnosed celiac disease and compare it with healthy control subjects. Ninety patients with newly diagnosed celiac disease were compared with 90 age- and sex-matched healthy subjects. The primary endpoints were fatigue severity as measured by: the fatigue Visual Analog Scale (fVAS), the Fatigue Severity Scale (FSS), and the inverted Vitality subscale of the MOS36 (SF-36vs). Higher scores indicate more severe fatigue. Clinically relevant fatigue was determined using predefined cut-off values. Secondary endpoints were the associations between fatigue, and sex, age, depression, pain, and selected biochemical variables. The median (IQR) fVAS-scores were 43.0 (18.0-64.5) in patients, and 9.0 (2.0-16.0) in the control group (p < 0.001); and the FSS scores 3.8 (2.0-4.8) in patients, and 1.4 (1.0-1.9) in control subjects (p < 0.001). Inverted SF-36vs scores had a mean (SD) value of 58.8 (23.6) in patients, and 29.7 (14.3) in healthy subjects (p < 0.001). The presence of clinically relevant fatigue ranged from 41 to 50% in patients. Increased fatigue severity was associated with female sex, younger age, and elevated pain and depression scores, but not with levels of selected biochemical variables, including hemoglobin. Fatigue is a severe and frequent phenomenon in patients with untreated celiac disease.

Air versus Sulfur Hexafluoride Gas Tamponade for Small and Medium-Sized Macular Holes: A Randomized Noninferiority Trial.

PURPOSE: To investigate whether air tamponade is noninferior to sulfur hexafluoride (SF6) gas tamponade for small (≤ 250 µm) and medium-sized (> 250 µm and ≤ 400 µm) macular holes (MHs). DESIGN: Multicenter, randomized controlled, noninferiority trial. PARTICIPANTS: Patients aged ≥ 18 years undergoing surgery for primary MHs of ≤ 400 µm in diameter. METHODS: The patients in both groups underwent conventional pars plana vitrectomy with peeling of the internal limiting membrane. At the end of the surgery, the patients were randomized to receive either air or SF6 gas tamponades, stratified by MH size. Postoperatively, the patients followed a nonsupine positioning regimen for 3 days. MAIN OUTCOME MEASURES: The primary end point was the MH closure rate after a single surgery, confirmed by OCT after 2 to 8 weeks. The noninferiority margin was set at a 10-percentage-point difference in the closure rate. RESULTS: In total, 150 patients were included (75 in each group). In the intention-to-treat (ITT) analysis, 65 of 75 patients in the air group achieved primary closure. All 75 MHs in the SF6 group closed after a single surgery. Six patients were excluded from the per-protocol (PP) analysis. In the PP analysis, 63 of 70 patients in the air group and all 74 patients in the SF6 group achieved MH closure after a single surgery, resulting in closure rates of 90% (95% confidence interval [CI], 79.9%-95.5%) and 100% (95% CI, 93.9%-100%), respectively. For the difference in closure rates, the lower bound of a 2-sided 95% CI exceeded the noninferiority margin of 10% in both ITT and PP analyses. In the subgroups of small MHs, all 20 patients in the air group and all 28 patients in the SF6 group achieved primary closure. CONCLUSIONS: This prospective randomized controlled trial proved that air tamponade is inferior to SF6 tamponade for MHs of ≤ 400 µm in diameter.

Liquid biopsies and patient-reported outcome measures for integrative monitoring of patients with early-stage breast cancer: a study protocol for the longitudinal observational Prospective Breast Cancer Biobanking (PBCB) study.

INTRODUCTION: Breast cancer is still the most common malignancy among women worldwide. The Prospective Breast Cancer Biobank (PBCB) collects blood and urine from patients with breast cancer every 6 or 12 months for 11 years from 2011 to 2030 at two university hospitals in Western Norway. The project aims to identify new biomarkers that enable detection of systemic recurrences at the molecular level. As blood represents the biological interface between the primary tumour, the microenvironment and distant metastases, liquid biopsies represent the ideal medium to monitor the patient's cancer biology for identification of patients at high risk of relapse and for early detection systemic relapse.Including patient-reported outcome measures (PROMs) allows for a vast number of possibilities to compare PROM data with biological information, enabling the study of fatigue and Quality of Life in patients with breast cancer. METHODS AND ANALYSIS: A total of 1455 patients with early-stage breast cancer are enrolled in the PBCB study, which has a one-armed prospective observational design. Participants consent to contribute liquid biopsies (i.e., peripheral blood and urine samples) every 6 or 12 months for 11 years. The liquid biopsies are the basis for detection of circulating tumour cells, circulating tumour DNA (ctDNA), exosomal micro-RNA (miRNA), miRNA in Tumour Educated Platelet and metabolomic profiles. In addition, participants respond to 10 PROM questionnaires collected annually. Moreover, a control group comprising 200 women without cancer aged 25-70 years will provide the same data. ETHICS AND DISSEMINATION: The general research biobank PBCB was approved by the Ministry of Health and Care Services in 2007, by the Regional Ethics Committee (REK) in 2010 (#2010/1957). The PROM (#2011/2161) and the biomarker study PerMoBreCan (#2015/2010) were approved by REK in 2011 and 2015 respectively. Results will be published in international peer reviewed journals. Deidentified data will be accessible on request. TRIAL REGISTRATION NUMBER: NCT04488614.