Position Paper: SGIM Sex- and Gender-Based Women's Health Core Competencies.

Women's health care has evolved significantly since it was first acknowledged as an integral part of internal medicine training more than two decades ago. To update and clarify core competencies in sex- and gender-based women's health for general internists, the Society of General Internal Medicine (SGIM) Women and Medicine Commission prepared the following Position Paper, approved by the SGIM council in 2023. Competencies were developed using several sources, including the 2021 Accreditation Council for Graduate Medical Education Program Requirements for Internal Medicine and the 2023 American Board of Internal Medicine Certification Examination Blueprint. These competencies are relevant to the care of patients who identify as women, as well as gender-diverse individuals to whom these principles apply. They align with pivotal advances in women's health and acknowledge the changing context of patients' lives, reaffirming the role of general internal medicine physicians in providing comprehensive care to women.

Development and Pilot Testing of a Patient-Centered Web-Based Reproductive Decision Support Tool for Primary Care.

BACKGROUND: Patient-centered counseling to help women achieve their reproductive goals is an essential yet often absent component of primary care. OBJECTIVE: We developed and piloted MyPath, a novel web-based decision support tool integrating reproductive goals assessment, information about optimizing health before pregnancy, and contraceptive decision support, for use prior to primary care visits in the Veterans Administration (VA). DESIGN: We created MyPath using best practices for decision tool development, including a conceptual framework informed by theory and user-centered design with input from patients, providers, and scientific experts. We conducted a non-randomized pilot in two VA Women's Health primary care clinics. A control group (n = 28) was recruited prior to and intervention group (n = 30) recruited after introduction of MyPath into clinics. PARTICIPANTS: Women Veterans ages 18-44 with an upcoming visit scheduled with one of eight providers. INTERVENTIONS: After recruitment of controls, providers and staff received a brief introduction to MyPath. Patients scheduled to see providers in the intervention phase used MyPath on an iPad in the waiting room prior to their visit. MAIN MEASURES: Acceptability, feasibility, discussions about pregnancy and/or contraceptive needs, and contraceptive decision quality by a survey of participants and providers. KEY RESULTS: Nearly all participants who used MyPath reported they learned new information (97%) and would recommend it to other Veterans (93%). No providers reported that MyPath significantly increased workload. A greater proportion of intervention participants reported having discussions about reproductive needs in their visit compared to controls (93% vs 68%; p = 0.02). Intervention participants also experienced greater increases in pre-/post-visit knowledge and communication self-efficacy and a trend towards greater reduction in contraceptive decision conflict compared to controls. CONCLUSIONS: MyPath was highly acceptable to women, increased the proportion of primary care visits addressing reproductive needs, and improved decision quality without increasing providers' perceived workload. A larger randomized evaluation of effectiveness is warranted.

IgG4-specific responses in patients with Staphylococcus aureus bone infections are not predictive of postoperative complications.

The most prevalent pathogen in bone infections is Staphylococcus aureus; its incidence and severity are partially determined by host factors. Prior studies showed that anti-glucosaminidase (Gmd) antibodies are protective in animals, and 93.3 % of patients with culture-confirmed S. aureus osteomyelitis do not have anti-Gmd levels > 10 ng/mL in serum. Infection in patients with high anti-Gmd remains unexplained. Are anti-Gmd antibodies in osteomyelitis patients of the non-opsonising, non-complement-fixing IgG4 isotype? The relative amounts of IgG4 and total IgG against Gmd and 7 other S. aureus antigens: iron-surface determinants (Isd) IsdA, IsdB, and IsdH, amidase (Amd), α-haemolysin (Hla), chemotaxis inhibitory protein from S. aureus (CHIPS), and staphylococcal-complement inhibitor (SCIN) were determined in sera from healthy controls (Ctrl, n = 92), osteomyelitis patients whose surgical treatment resulted in infection control (IC, n = 95) or an adverse outcome (AD, n = 40), and post-mortem (PM, n = 7) blood samples from S. aureus septic-death patients. Anti-Gmd IgG4 levels were generally lower in infected patients compared to controls; however, levels among the infected were higher in AD than IC patients. Anti-IsdA, IsdB and IsdH IgG4 levels were increased in infected patients versus controls, and Jonckheere-Terpstra tests of levels revealed an increasing order of infection (Ctrl < IC < AD < PM) for anti-Isd IgG4 antibodies and a decreasing order of infection (Ctrl > IC > AD > PM) for anti-autolysin (Atl) IgG4 antibodies. Collectively, this does not support an immunosuppressive role of IgG4 in S. aureus osteomyelitis but is consistent with a paradigm of high anti-Isd and low anti-Atl responses in these patients.

Bone infection: a clinical priority for clinicians, scientists and educators.

Bone infection has received increasing attention in recent years as one of the main outstanding clinical problems in orthopaedic-trauma surgery that has not been successfully addressed. In fact, infection may develop across a spectrum of patient types regardless of the level of perioperative management, including antibiotic prophylaxis. Some of the main unknown factors that may be involved, and the main targets for future intervention, include more accurate and less invasive diagnostic options, more thorough and accurate debridement protocols, and more potent and targeted antimicrobials. The underlying biology dominates the clinical management of bone infections, with features such as biofilm formation, osteolysis and vascularisation being particularly influential. Based on the persistence of this problem, an improved understanding of the basic biology is deemed necessary to enable innovation in the field. Furthermore, from the clinical side, better evidence, documentation and outreach will be required to translate these innovations to the patient. This review presents the findings and progress of the AO Trauma Clinical Priority Program on the topic of bone infection.

Effectiveness and cost effectiveness of a stress management training for leaders of small and medium sized enterprises - study protocol for a randomized controlled-trial.

BACKGROUND: Leaders in small and medium-sized enterprises (SMEs) are exposed to increased stress as a result of a range of challenges. Moreover, they rarely have the opportunity to participate in stress management trainings. Therefore, KMU-GO (ger: Kleine und mittlere Unternehmen - Gesundheitsoffensive; en: small and medium-sized enterprises - health campaign) aims at conducting and evaluating such a stress management training. The focus of evaluation does not only lie on the effects on leaders participating but also on their employees. METHODS: The study is planned as a 2 × 3 mixed design with two groups (intervention and waiting control group) as a between factor and point in time (at baseline, 6 and 12 months later) as a within factor. We aim at collecting data from N = 200 leaders. Based on the results of a preceding assessment, an already successfully implemented stress management training was adapted to SME needs and now serves as the framework of this intervention. The stress management training comprises one and a half days and is followed by two booster sessions (each 180 min) about 3 and 6 months after the training. The main focus of this intervention lies on specifying leaders stress reactivity while at the same time investigating its effects on employees' mental health. Further dependent variables are leaders´ depression and anxiety scores, effort-reward imbalance, sick days and psychophysiological measures of heart rate variability, hair cortisol, and salivary alpha-amylase. Cost-effectiveness analyses will be conducted from a societal and employers' point of view. DISCUSSION: Stress management is a highly relevant issue for leaders in SMEs. By providing an adequate occupational stress management training, we expect to improve leaders´ and also employees` mental health, thereby preventing economic losses for SMEs and the national economy. However, collecting data from employees about the success of a stress management training of their leader is a highly sensitive topic. It requires a carefully planned proceeding ensuring for example a high degree of transparency, anonymity, and providing team incentives. TRIAL REGISTRATION: The KMU-GO trial is registered at the German Clinical Trial Register (DRKS): DRKS00023457 (05.11.2020).

Deriving a dose and regimen for anti-glucosaminidase antibody passive-immunisation for patients with Staphylococcus aureus osteomyelitis.

Staphylococcus aureus (S. aureus) osteomyelitis remains a major clinical problem. Anti-glucosaminidase (Gmd) antibodies (1C11) are efficacious in prophylactic and therapeutic murine models. Feasibility, safety and pharmacokinetics of 1C11 passive immunisation in sheep and endogenous anti-Gmd levels were quantified in osteomyelitis patients. 3 sheep received a 500 mg intravenous (i.v.) bolus of 1C11 and its levels in sera were determined by enzyme-linked immunosorbent assay (ELISA) over 52 d. A humanised anti-Gmd monoclonal antibody, made by grafting the antigen-binding fragment (Fab) portion of 1C11 onto the fragment crystallisable region (Fc) of human IgG1, was used to make a standard curve of mean fluorescent intensity versus concentration of anti-Gmd. Anti-Gmd serum levels were determined in 297 patients with culture-confirmed S. aureus osteomyelitis and 40 healthy controls. No complications or adverse events were associated with the sheep 1C11 i.v. infusion and the estimated circulating half-life of 1C11 was 23.7 d. Endogenous anti-Gmd antibody levels in sera of osteomyelitis patients ranged from < 1 ng/mL to 300 µg/mL, with a mean concentration of 21.7 µg/mL. The estimated circulating half-life of endogenous anti-Gmd antibodies in sera of 12 patients with cured osteomyelitis was 120.4 d. A clinically relevant administration of anti-Gmd (500 mg i.v. = 7 mg/kg/70 kg human) was safe in sheep. This dose was 8 times more than the endogenous anti-Gmd levels observed in osteomyelitis patients and was predicted to have a half-life of > 3 weeks. Anti-Gmd passive immunisation has potential to prevent and treat S. aureus osteomyelitis. Further clinical development is warranted.

A murine femoral ostectomy model with hardware exchange to assess antibiotic-impregnated spacers for implant-associated osteomyelitis.

Implant-associated osteomyelitis is a chronic infection that complicates orthopaedic surgeries. Once infected, 50 % of patients suffer treatment failure, resulting in high healthcare costs. While various small animal models have been developed to investigate the efficacy of prophylactic and therapeutic treatments, the minute scale of murine-model bone and hardware has been prohibitive for evaluating interventions with a complete implant exchange in the setting of an infected critical defect. To address this, the aim of the present study was to develop a murine femur model in which an initial mid-diaphyseal infection was established by surgical implantation of a titanium screw contaminated with bioluminescent Staphylococcus aureus (Xen36). 7 d after the infection was established, an ostectomy was performed to remove the middle segment (3 mm flanking the infected screw hole) and a bone-cement spacer, with or without impregnated gentamicin, was secured with a plate and screws to fix the septic segmental defect. Longitudinal bioluminescent imaging revealed a significant decrease in Xen36 growth following one-stage revision, with the antibiotic-impregnated spacer treated systemically with vancomycin (p < 0.05). This result was corroborated by a significant decrease in colony forming units (CFU) recovered from spacer, bone, soft tissue and hardware 12 d post-operative (p < 0.05). However, ~ 105 CFU/g Xen36 still persisted within the bone despite a clinical therapeutic regimen. Therefore, the model enables the investigation of new therapeutic strategies to improve upon the current standard of care in a mouse model of implant-associated osteomyelitis that employs reconstruction of a critical defect.

Cerebellar volume and cerebellocerebral structural covariance in schizophrenia: a multisite mega-analysis of 983 patients and 1349 healthy controls.

Although cerebellar involvement across a wide range of cognitive and neuropsychiatric phenotypes is increasingly being recognized, previous large-scale studies in schizophrenia (SZ) have primarily focused on supratentorial structures. Hence, the across-sample reproducibility, regional distribution, associations with cerebrocortical morphology and effect sizes of cerebellar relative to cerebral morphological differences in SZ are unknown. We addressed these questions in 983 patients with SZ spectrum disorders and 1349 healthy controls (HCs) from 14 international samples, using state-of-the-art image analysis pipelines optimized for both the cerebellum and the cerebrum. Results showed that total cerebellar grey matter volume was robustly reduced in SZ relative to HCs (Cohens's d=-0.35), with the strongest effects in cerebellar regions showing functional connectivity with frontoparietal cortices (d=-0.40). Effect sizes for cerebellar volumes were similar to the most consistently reported cerebral structural changes in SZ (e.g., hippocampus volume and frontotemporal cortical thickness), and were highly consistent across samples. Within groups, we further observed positive correlations between cerebellar volume and cerebral cortical thickness in frontotemporal regions (i.e., overlapping with areas that also showed reductions in SZ). This cerebellocerebral structural covariance was strongest in SZ, suggesting common underlying disease processes jointly affecting the cerebellum and the cerebrum. Finally, cerebellar volume reduction in SZ was highly consistent across the included age span (16-66 years) and present already in the youngest patients, a finding that is more consistent with neurodevelopmental than neurodegenerative etiology. Taken together, these novel findings establish the cerebellum as a key node in the distributed brain networks underlying SZ.

[Pulmonary hypertension in connective tissue disease]. / Pulmonale Hypertonie bei Kollagenosen.

Pulmonary arterial hypertension (PAH) is a major complication of systemic sclerosis (SSc) and screening is recommended for a timely initiation of disease-targeted drug therapy to modify disease progression. Patients with SSc-PAH have a better prognosis when detected and treated early. The PAH can occur in all disease stages and subsets of SSc. Regular screening tests, which are indicative for PAH, e.g. echocardiography, diffusion capacity, brain natriuretic protein (BNP) and a 6-min walking test, are recommended to enhance the suspicion, since clinical symptoms are unspecific and occur late in the course of PAH. In patients with suspected PAH, the diagnosis should be confirmed by right heart catheterization. A multidisciplinary approach in expert centres including rheumatologists and respiratory physicians and cardiologists specialized in pulmonary hypertension is mandatory for management of patients with SSc at risk for or with manifest pulmonary arterial hypertension.

[The Aut-idem Rule and the Importance of Patient-Individual Selection of Inhalers for the Therapy of Airway Diseases in Practices of Pneumologists and General Practitioners - Assessment and Implementation by Pneumologists and General Practitioners]. / Aut-idem-Regelung und Inhalatorauswahl bei inhalativer Therapie in pneumologischen und hausärztlichen Praxen unter Alltagsbedingungen ­ Einschätzung und Umsetzung durch Pneumologen und Hausärzte.

Drug therapy of obstructive airway diseases mainly relies on inhaled medication. The success of this therapy depends primarily on the selection of the appropriate inhaler considering patient's choice and the correct application. The aut-idem-rule, an active exclusion of the optional substitution by the pharmacist, allows prescribing physicians to ensure the delivery of a particular inhaler, which was selected for that patient, who was trained to use specifically that inhaler. This survey shows that pneumologists and, to a greater extent general practitioners, do not consistently make use of this option, although they unanimously agree on the importance of targeted inhaler selection. As a result, patients may receive different inhalers in the pharmacy, where the inhaler is chosen under consideration of market-driven aspects such as rebate contracts or stock. This causes that patients get confused by the exchange of their inhaler. Thus the exchange of the inhaler by the pharmacist leads to uncertainty and application problems in patients. Hence, the success of the comparatively complex inhaled therapy is endangered. This could be prevented, if prescribing physicians were informed and supported consistently regarding the use of aut-idem exclusion to ensure an optimal therapy for each individual patient.

Unintended Pregnancy and Contraceptive Use Among Women Veterans: The ECUUN Study.

BACKGROUND: Little is known about contraceptive care for the growing population of women veterans who receive care in the Veterans Administration (VA) healthcare system. OBJECTIVE: To determine rates of contraceptive use, unmet need for prescription contraception, and unintended pregnancy among reproductive-aged women veterans. DESIGN AND PARTICIPANTS: We conducted a cross-sectional, telephone-based survey with a national sample of 2302 women veterans aged 18-44 years who had received primary care in the VA within the prior 12 months. MAIN MEASURES: Descriptive statistics were used to estimate rates of contraceptive use and unintended pregnancy in the total sample. We also estimated the unmet need for prescription contraception in the subset of women at risk for unintended pregnancy. For comparison, we calculated age-adjusted US population estimates using data from the 2011-2013 National Survey of Family Growth (NSFG). KEY RESULTS: Overall, 62% of women veterans reported current use of contraception, compared to 68% of women in the age-adjusted US population. Among the subset of women at risk for unintended pregnancy, 27% of women veterans were not using prescription contraception, compared to 30% in the US population. Among women veterans, the annual unintended pregnancy rate was 26 per 1000 women; 37% of pregnancies were unintended. In the age-adjusted US population, the annual rate of unintended pregnancy was 34 per 1000 women; 35% of pregnancies were unintended. CONCLUSIONS: While rates of contraceptive use, unmet contraceptive need, and unintended pregnancy among women veterans served by the VA are similar to those in the US population, these rates are suboptimal in both populations, with over a quarter of women who are at risk for unintended pregnancy not using prescription contraception, and unintended pregnancies accounting for over a third of all pregnancies. Efforts to improve contraceptive service delivery and to reduce unintended pregnancy are needed for both veteran and civilian populations.

A large animal model for a failed two-stage revision of intramedullary nail-related infection by methicillin-resistant Staphylococcus aureus.

The treatment of chronic orthopaedic device-associated infection (ODRI) often requires multiple surgeries and prolonged antibiotic therapy. Despite this extensive treatment protocol, the procedure is associated with significant failure rates. Currently, no large animal model is available that recapitulates a failed revision. Therefore, our aim was to establish a large animal model for failed treatment of an ODRI in order to serve as a testbed for future interventional strategies. Adult Swiss Alpine sheep received an intramedullary nail in the tibia and a localised inoculum of either a methicillin-sensitive or methicillin-resistant Staphylococcus aureus (MSSA, MRSA respectively). After 8 weeks, when chronic infection had been established, the animals underwent a staged revision with debridement and temporary placement of an antibiotic-loaded cement spacer. Antibiotics were delivered systemically in a standard or pathogen-adapted manner. Debridement and implant exchange alone failed to treat the MSSA infection. Neither local therapy alone nor systemic therapy alone were effective in resolving infection with MSSA, but a combination of local and systemic therapy was effective against it. MRSA infection was not resolved by the combination of local and systemic antibiotics (standard or pathogen-adapted). A model for failed revision of MRSA infection is described despite the use of local and systemic antibiotics. Novel interventions may be assessed using this model, including antibiotic and non-antibiotic interventions.

Unprotected intercourse in the 2 weeks prior to requesting emergency intrauterine contraception.

BACKGROUND: Previous emergency contraception studies have excluded women who report >1 episode of unprotected or underprotected intercourse. Thus, clinical recommendations are based on exposure to a single episode of underprotected intercourse. OBJECTIVE: We sought to assess the prevalence and timing of underprotected intercourse episodes among women requesting emergency contraception and to examine the probability of pregnancy following an emergency contraception regimen including placement of either a copper intrauterine device or a levonorgestrel intrauterine device with simultaneous administration of an oral levonorgestrel pill in women reporting multiple underprotected intercourse episodes, including episodes beyond the Food and Drug Administration-approved emergency contraception time frame (6-14 days). STUDY DESIGN: Women seeking emergency contraception who had a negative pregnancy test and desired either a copper intrauterine device or levonorgestrel emergency contraception regimen enrolled in this prospective observational study. At enrollment, participants reported the number and timing of underprotected intercourse episodes in the previous 14 days. Two weeks later, participants reported the results of a self-administered home pregnancy test. RESULTS: Of the 176 women who presented for emergency contraception and received a same-day intrauterine device, 43% (n = 76) reported multiple underprotected intercourse episodes in the 14 days prior to presenting for emergency contraception. Women with multiple underprotected intercourse episodes reported a median of 3 events (range 2-20). Two-week pregnancy data were available for 172 (98%) participants. Only 1 participant had a positive pregnancy test. Pregnancy occurred in 0 of 97 (0%; 95% confidence interval, 0-3.7%) women with a single underprotected intercourse episode and 1 of 75 (1.3%; 95% confidence interval, 0-7.2%) women reporting multiple underprotected intercourse episodes; this includes 1 of 40 (2.5%; 95% confidence interval, 0-13.2%) women reporting underprotected intercourse 6-14 days prior to intrauterine device insertion. CONCLUSION: Women seeking emergency contraception from clinics commonly reported multiple recent underprotected intercourse episodes, including episodes occurring beyond the Food and Drug Administration-approved emergency contraception time frame. However, the probability of pregnancy was low following same-day intrauterine device placement.

Differential melatonin alterations in cerebrospinal fluid and serum of patients with major depressive disorder and bipolar disorder.

BACKGROUND: Melatonin, which plays an important role for regulation of circadian rhythms and the sleep/wake cycle has been linked to the pathophysiology of major depressive and bipolar disorder. Here we investigated melatonin levels in cerebrospinal fluid (CSF) and serum of depression and bipolar patients to elucidate potential differences and commonalities in melatonin alterations across the two disorders. METHODS: Using enzyme-linked immunosorbent assays, CSF and serum melatonin levels were measured in 108 subjects (27 healthy volunteers, 44 depressed and 37 bipolar patients). Covariate adjusted multiple regression analysis was used to investigate group differences in melatonin levels. RESULTS: In CSF, melatonin levels were significantly decreased in bipolar (P<0.001), but not major depressive disorder. In serum, we observed a significant melatonin decrease in major depressive (P=0.003), but not bipolar disorder. No associations were found between serum and CSF melatonin levels or between melatonin and measures of symptom severity or sleep disruptions in either condition. CONCLUSION: This study suggests the presence of differential, body fluid specific alterations of melatonin levels in bipolar and major depressive disorder. Further, longitudinal studies are required to explore the disease phase dependency of melatonin alterations and to mechanistically explore the causes and consequences of site-specific alterations.

3D printed bioceramics for dual antibiotic delivery to treat implant-associated bone infection.

Surgical implant-associated bone infections (osteomyelitis) have severe clinical and socioeconomic consequences. Treatment of chronic bone infections often involves antibiotics given systemically and locally to the affected site in poly (methyl methacrylate) (PMMA) bone cement. Given the high antibiotic concentrations required to affect bacteria in biofilm, local delivery is important to achieve high doses at the infection site. PMMA is not suitable to locally-deliver some biofilm-specific antibiotics, including rifampin, due to interference with PMMA polymerisation. To examine the efficacy of localised, combinational antibiotic delivery compared to PMMA standards, we fabricated rifampin- and vancomycin-laden calcium phosphate scaffolds (CPS) by three-dimensional (3D) printing to treat an implant-associated Staphylococcus aureus bone infection in a murine model. All vancomycin- and rifampin-laden CPS treatments significantly reduced the bacterial burden compared with vancomycin-laden PMMA. The bones were bacteria culture negative in 50 % of the mice that received sustained release vancomycin- and rifampin-laden CPS. In contrast, 100 % of the bones treated with vancomycin monotherapy using PMMA or CPS were culture positive. Yet, the monotherapy CPS significantly reduced the bacterial metabolic load following revision compared to PMMA. Biofilm persisted on the fixation hardware, but the infection-induced bone destruction was significantly reduced by local rifampin delivery. These data demonstrate that, despite the challenging implant-retaining infection model, co-delivery of rifampin and vancomycin from 3D printed CPS, which is not possible with PMMA, significantly improved the outcomes of implant-associated osteomyelitis. However, biofilm persistence on the fixation hardware reaffirms the importance of implant exchange or other biofilm eradication strategies to complement local antibiotics.

A systematic review of animal models for Staphylococcus aureus osteomyelitis.

Staphylococcus aureus (S. aureus) osteomyelitis is a significant complication for orthopaedic patients undergoing surgery, particularly with fracture fixation and arthroplasty. Given the difficulty in studying S. aureus infections in human subjects, animal models serve an integral role in exploring the pathogenesis of osteomyelitis, and aid in determining the efficacy of prophylactic and therapeutic treatments. Animal models should mimic the clinical scenarios seen in patients as closely as possible to permit the experimental results to be translated to the corresponding clinical care. To help understand existing animal models of S. aureus, we conducted a systematic search of PubMed and Ovid MEDLINE to identify in vivo animal experiments that have investigated the management of S. aureus osteomyelitis in the context of fractures and metallic implants. In this review, experimental studies are categorised by animal species and are further classified by the setting of the infection. Study methods are summarised and the relevant advantages and disadvantages of each species and model are discussed. While no ideal animal model exists, the understanding of a model's strengths and limitations should assist clinicians and researchers to appropriately select an animal model to translate the conclusions to the clinical setting.

Identification of a biological signature for schizophrenia in serum.

Biomarkers are now used in many areas of medicine but are still lacking for psychiatric conditions such as schizophrenia (SCZ). We have used a multiplex molecular profiling approach to measure serum concentrations of 181 proteins and small molecules in 250 first and recent onset SCZ, 35 major depressive disorder (MDD), 32 euthymic bipolar disorder (BPD), 45 Asperger syndrome and 280 control subjects. Preliminary analysis resulted in identification of a signature comprised of 34 analytes in a cohort of closely matched SCZ (n=71) and control (n=59) subjects. Partial least squares discriminant analysis using this signature gave a separation of 60-75% of SCZ subjects from controls across five independent cohorts. The same analysis also gave a separation of ~50% of MDD patients and 10-20% of BPD and Asperger syndrome subjects from controls. These results demonstrate for the first time that a biological signature for SCZ can be identified in blood serum. This study lays the groundwork for development of a diagnostic test that can be used as an aid for distinguishing SCZ subjects from healthy controls and from those affected by related psychiatric illnesses with overlapping symptoms.

[Biomarker research in neuropsychiatry: challenges and potential]. / Biomarkerforschung in der Neuropsychiatrie: Herausforderung und Potenzial.

The introduction of blood-based biomarkers for psychiatric disorders faces numerous challenges. The goal of research efforts is the improvement of the current more or less subjective diagnosis, treatment and patient management. So far attempts to introduce molecular analyses have faced considerable resistance. There is an urgent need for a paradigm shift so that peripheral markers may also deliver insights into pathological states of the brain. Health regulators have called for a reform of research and development approaches, with the goal to enhance the safety and efficiency of future antipsychotic drugs using biomarker-based methods. Here we discuss the potential of the biomarker sector in this context, as exemplified by the recent introduction of Veripsych™, the first blood test aiding the diagnosis of schizophrenia.

Effect of 5 weeks of oral acetazolamide on patients with pulmonary vascular disease: A randomized, double-blind, cross-over trial.

BACKGROUND: The carbonic anhydrase inhibitor acetazolamide stimulates ventilation through metabolic acidosis mediated by renal bicarbonate excretion. In animal models, acetazolamide attenuates acute hypoxia-induced pulmonary hypertension (PH), but its efficacy in treating patients with PH due to pulmonary vascular disease (PVD) is unknown. METHODS: 28 PVD patients (15 pulmonary arterial hypertension, 13 distal chronic thromboembolic PH), 13 women, mean±SD age 61.6±15.0 years stable on PVD medications, were randomised in a double-blind crossover protocol to 5 weeks acetazolamide (250mg b.i.d) or placebo separated by a ≥2 week washout period. Primary endpoint was the change in 6-minute walk distance (6MWD) at 5 weeks. Additional endpoints included safety, tolerability, WHO functional class, quality of life, arterial blood gases, and hemodynamics (by echocardiography). RESULTS: Acetazolamide had no effect on 6MWD compared to placebo (treatment effect: mean change [95%CI] -18 [-40 to 4]m, p=0.102) but increased arterial blood oxygenation through hyperventilation induced by metabolic acidosis. Other measures including pulmonary hemodynamics were unchanged. No severe adverse effects occurred, side effects that occurred significantly more frequently with acetazolamide vs. placebo were change in taste (22/0%), paraesthesia (37/4%) and mild dyspnea (26/4%). CONCLUSIONS: In patients with PVD, acetazolamide did not change 6MWD compared to placebo despite improved blood oxygenation. Some patients reported a tolerable increase in dyspnoea during acetazolamide treatment, related to hyperventilation, induced by the mild drug-induced metabolic acidosis. Our findings do not support the use of acetazolamide to improve exercise in patients with PVD at this dosing. GOV IDENTIFIER: NCT02755298.