Failures in diagnostic processes lead to avoidable patient contacts, diagnostic delays, and inefficient use of healthcare resources. Such failures in both diagnostic and treatment pathways represent a significant source of systemic inefficiency and preventable harm. This study aimed to identify health conditions in which diagnostic-related failure demand is particularly prominent and to explore how it manifests. This systematic review following PRISMA guidelines was registered in PROSPERO (CRD420251035554). Literature searches were performed in Ovid MEDLINE and Scopus in April 2025. Studies were included if they examined diagnostic-related failure demand associated with specific health conditions focusing on missed, delayed, or incorrect diagnoses. Studies from diverse countries and healthcare systems were included, and no geographic restrictions were applied. Studies lacking disease specificity or addressing only patient- or system-level factors were excluded. Key variables included the number of prior healthcare contacts, average diagnostic delay (in years), frequency and nature of misdiagnoses, treatment availability and cost-effectiveness, and symptom patterns. A total of 38 studies covering 33 health conditions were included, encompassing both common and rare diseases. Ten conditions were reported as more prevalent in women and three as more common in men. Patients had multiple healthcare contacts prior to diagnosis, with delays ranging from < 1 year to > 30 years. Diagnostic-related failure demand was observed across diverse conditions and associated with reasoning biases, limited clinical awareness, and structural barriers within healthcare systems. An improved symptom recognition, a strengthened clinician education, and digital tools such as artificial intelligence may support earlier diagnosis and more efficient care pathways.
Persistent physical symptoms (PPS) can significantly impair work ability and daily functioning, exacerbated by comorbid illness worry (IW). This randomized controlled trial (RCT) examined the effectiveness of guided internet-based treatment on work ability and daily functioning of working-aged individuals with PPS associated with indoor environment (IE) and/or chronic fatigue (CF) with disability. The intervention was based on acceptance and commitment therapy (ACT) combined with individual case formulation, compared to treatment as usual (TAU). IW’s role in moderating effects was explored. In this RCT (Clinicaltrials.gov NCT04532827), 103 individuals with PPS linked to IE, CF or both were assigned to a video-based case conceptualization and 10-week internet-based ACT with TAU (iACT + TAU; n = 50) or TAU alone (n = 53). Self-reported work ability and daily functioning were assessed from pre-intervention to 9-month follow-up, examining the potential moderating effect of baseline IW. Analyses used linear mixed models and Type III ANOVA. Of the 103 participants, 62
Antipsychotics (APs) are not officially approved for the treatment of depressive, anxiety, obsessive-compulsive, emotional dysregulation, or sleep disorders among children and adolescents. Despite this, the treatment of these common and comorbid disorders is likely to partially explain the increased AP use. We assessed all studies reporting changes in symptoms or functioning during antipsychotic treatment for these diagnoses among patients < 18 years old. We systematically searched MEDLINE, EBM reviews and PsycINFO databases for all studies published by October 30, 2025, reporting on the effectiveness of APs for obsessive-compulsive, mood dysregulation, depression, anxiety, and sleep-related disorders among patients < 18 years. We evaluated evidence using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). Of the 2237 identified studies, 119 were eligible for full-text review, and 13 were included in the final review. One study compared two antipsychotics, while the rest were uncontrolled open-label studies, case series, or case reports. No randomized controlled trials nor studies on sleep or anxiety disorders were identified. While there were reported changes in standardized mean scores between baseline and endpoint, the level of evidence in obsessive-compulsive, mood dysregulation, and depression related disorders was very low. The identified very low level of evidence stands in stark contrast to clinical practice, where APs are increasingly prescribed. Future methodologically robust studies are needed to demonstrate efficacy. Given the side effects of APs, physicians should carefully consider the benefits and harms when prescribing them for off-label indications.
Swedish family and cancer data constitute the largest source on familial cancer in the world. We analyze here familial risks in prostate cancer (PC) with focus on multiple affected brothers and comparation of full-brothers to maternal and paternal half-brothers. Age-specific incidence and standardized incidence ratios (SIRs) were calculated for PC in brothers. Curves for relative risk (RR) by diagnostic age were plotted for risk distributions. A total of 115,066 PCs were diagnosed in 1.2 million men. Familial SIR for full brothers was 2.23, for maternal half-brothers it was 1.92 and paternal half-brothers was 1.34. Considering SIRs with least possible detection bias (7+ years after first brother's diagnosis) the above SIRs were 2.06, 1.66 and 1.41. SIRs in full brothers increased stepwise by the number of affected brothers reaching 21.33 when 6 brothers were affected. Age-RR curves for two affected brothers declined evenly from RR 2.8 at age 45 to below 2.0 at age 80. When four or more brothers were affected, a discrete high-risk peak (RR 4-7) was detected between ages 60 and 69. Data on full-brothers and half-brothers indicate that familial risk in PC is largely genetic which is also supported by discrete RR peaks in high-risk families at ages matching preferential penetrance age for known predisposition genes of PC. Familial risk increased already when two brothers were affected calling for clinical vigilance concerning family history. Family history should deserve a place as an inclusion criterium in schemes for PC screening.
Immune privilege of the eye is considered to contribute significantly to the excellent survival of transplants in the anterior and posterior segment of the eye. While Sir Peter Medawar proved the existence of this phenomenon scientifically, a prior study by Dr. J.C. van Dooremaal already suggested the existence of ocular immune privilege and was published in this journal in 1873. The original 1873 German paper by J.C. van Dooremaal in Albrecht von Graefe’s Archiv für Ophthalmologie was translated into English and commented on by immunologist Dr. J. Wayne Streilein and other eye specialists. Family of Dr. van Dooremaal supplied information about the author himself. Dr. van Dooremaal was a military doctor when he was confronted with a severe epidemic of trachoma while serving at the Government Institution of Benevolence in the Netherlands (now a UNESCO heritage site). While finding a solution to fight the epidemic, he became familiar with the eye clinic of professor F.C. Donders in Utrecht. He subsequently trained as an ophthalmologist, and worked on a thesis on implantation of foreign tissues in the anterior chamber of different animals. He observed that a piece of skin of a white mouse placed in the eye of a dog survived amazingly long and was integrated into the tissues of the anterior chamber instead of rejected. According to Dr. J. Wayne Streilein, this was the first experimental demonstration of ocular immune privilege. The 1873 paper by Dr. J.C. van Dooremaal can be regarded as the first description of ocular immune privilege, and as Dr. J. Wayne Streilein wrote in 2001: Dr. van Dooremaal is the FATHER of immune privilege – although he could not call it that since immunology had not yet been discovered.
