Disruption of rat forebrain development by glucocorticoids: critical perinatal periods for effects on neural cell acquisition and on cell signaling cascades mediating noradrenergic and cholinergic neurotransmitter/neurotrophic responses.

Glucocorticoids are the consensus treatment for the prevention of respiratory distress in preterm infants, but there is evidence for increased incidence of neurodevelopmental disorders as a result of their administration. We administered dexamethasone (Dex) to developing rats at doses below or within the range of those used clinically, evaluating the effects on forebrain development with exposure in three different stages: gestational days 17-19, postnatal days 1-3, or postnatal days 7-9. At 24 h after the last dose, we evaluated biomarkers of neural cell acquisition and growth, synaptic development, neurotransmitter receptor expression, and synaptic signaling mediated by adenylyl cyclase (AC). Dex impaired the acquisition of neural cells, with a peak effect when given in the immediate postnatal period. In association with this defect, Dex also elicited biphasic effects on cholinergic presynaptic development, promoting synaptic maturation at a dose (0.05 mg/kg) well below those used therapeutically, whereas the effect was diminished or lost when doses were increased to 0.2 or 0.8 mg/kg. Dex given postnatally also disrupted the expression of adrenergic receptors known to participate in neurotrophic modeling of the developing brain and evoked massive induction of AC activity. As a consequence, disparate receptor inputs all produced cyclic AMP overproduction, a likely contributor to disrupted patterns of cell replication, differentiation, and apoptosis. Superimposed on the heterologous AC induction, Dex impaired specific receptor-mediated cholinergic and adrenergic signals. These results indicate that, during a critical developmental period, Dex administration leads to widespread interference with forebrain development, likely contributing to eventual, adverse neurobehavioral outcomes.     

Whole-abdomen, single-dose consolidation radiotherapy in patients with pathologically confirmed complete remission of advanced ovarian epithelial carcinoma: a long-term survival analysis

The value of consolidation therapy in advanced epithelial ovarian carcinoma patients is controversial. The aim of the present study was to assess the long-term survival of patients with a pathologically confirmed complete remission who had consolidation by single-dose, whole-abdominopelvic radiotherapy. Of 96 histologically confirmed stage II-IV epithelial ovarian carcinoma patients who underwent cytoreductive surgery followed by high-dose, platin-based chemotherapy, 57 were in complete clinical remission at the end of therapy and 50 underwent a second-look laparotomy. The study group comprises 32 consecutive patients who had no pathological evidence of disease and who received 800 cGy single-dose, whole-abdominal radiotherapy by an 8 MEV linear accelerator in a single fraction. The absolute 5-year survival and the actuarial 10-year survival were 78.7 and 63.3%, respectively. The survival was significantly better in patients who had < or =2 cm residual disease at the completion of the original operation. No severe postradiation complications were encountered. Mild complications were seen in three (9.4%) patients. Our data indicate a favorable long-term survival of patients with a negative second-look laparotomy who had consolidation with single-dose, whole-abdominal radiotherapy. These results seem to suggest that a collaborative, prospective, randomized multiarm study is indicated to solve the controversial issue of consolidation therapy.     

Assessment of functioning in Dutch primary care: Development study of a consultation tool for patients with chronic conditions and multimorbidity

BackgroundIn primary care, a shift from a disease‐oriented approach for patients with multimorbidity towards a more person‐centred approach is needed.AimTo transform a self‐report questionnaire for patients with chronic conditions in primary care, the Primary Care Functioning Scale (PCFS), into an understandable, visually attractive and feasible consultation tool for patients and health care providers. The consultation tool consists of a web‐based version of the PCFS, which is filled in by the patient and is processed to a feedback report that summarizes and visualizes the main findings. The feedback report can be discussed with the patient to facilitate a more person‐centred conversation for patients with chronic conditions and multimorbidity in general practice.Design and SettingIn this qualitative study, we developed the consultation tool by using design thinking in a participatory developmental process.MethodsIn the first phase, we constructed five different feedback report templates to summarize and display the results of a completed PCFS questionnaire in a series of two expert meetings with patients and general practitioners (GPs). In the second phase, we performed an exploratory qualitative interview study involving dyads of patients with chronic conditions and their practice nurses. In an iterative process, we explored their experiences with the consultation tool.ResultsPatients, as well as GPs, preferred a clear manner of presenting the results of the questionnaire in a feedback report. In 18 interviews with patients and practice nurses during three different interview rounds, we adjusted the feedback report and consultation tool based on the input from patients and practice nurses. After the final interview round, patients and practice nurses consented that the consultation tool was useful for having a more in‐depth consultation about functioning and patients'' preferences when integrated into the regularly scheduled consultations.ConclusionWe were able to develop an understandable and feasible consultation tool that is applicable in already existing chronic disease management programmes in general practice in the Netherlands.Patient or Public ContributionTo increase the understandability and feasibility of the consultation tool, we collaborated with end‐users and actively involved patients, GPs and practice nurses in a participatory development process.     

Circadian rhythm and diurnal excursion of plasma cortisol in diabetic pregnant women

The effect of type I and II diabetes in pregnancy on the circadian rhythm and diurnal excursion of plasma cortisol was studied in the second and third trimesters and post partum. Cosignor analysis demonstrated persistence during gestation of the significant circadian rhythm of the nonpregnant state. As previously reported in control pregnancies, plasma cortisol levels (24-hour mean, nadir, peak, and nadir-peak excursion) increased during gestation while the relative excursion of cortisol (expressed as the percent deviation from the 24-hour mean) was blunted. No significant difference was found between diabetic groups or when diabetic groups were compared with control subjects. Nocturnal hypoglycemia was common among diabetic women during pregnancy and post partum. Although these episodes were usually asymptomatic, the mean concomitant cortisol levels were increased over the corresponding cortisol levels of nonhypoglycemic diabetic and control subjects. We conclude that differences between control and type I and II diabetic subjects in carbohydrate tolerance or glycemic excursion are not explained by differences in cortisol levels or rhythm. The pregnancy-associated blunting of the excursion of cortisol is consistent with an autonomous source of adrenocorticotropin. Asymptomatic nocturnal hypoglycemia is common in insulin-requiring diabetic women and is associated with increased cortisol secretion.     

Pseudophakic retinal detachments in the presence of various IOL types

A series of 600 pseudophakic retinal detachments in 578 patients undergoing surgical repair between 1974 and 1984 was reviewed. Patients with previous retinal surgery of less than six months follow-up were excluded. The series included 395 iris-fixated (IF) lenses, 130 anterior chamber (AC) lenses, and 75 posterior chamber (PC) lenses. The overall success rate for retinal detachment was 88% but was significantly better in the PC lens group and significantly worse in the AC lens group. Forty-one percent of all cases achieved 20/40 visual acuity or better, although the AC lens group did worse (28%), while the PC lens group did significantly better (48%). Risk factors that were predictive of failure also were identified. Many of these factors occurred more frequently in the AC lens group and probably are related to the overall worse outcome in eyes with AC lens implants. The implications of these results for retinal and cataract surgeons are discussed.     

The past,present, and future of sleep measurement in mild cognitive impairment and early dementia—towards a core outcome set: a scoping review

Study ObjectivesSleep abnormalities emerge early in dementia and may accelerate cognitive decline. Their accurate characterization may facilitate earlier clinical identification of dementia and allow for assessment of sleep intervention efficacy. This scoping review determines how sleep is currently measured and reported in Mild Cognitive Impairment (MCI) and early dementia, as a basis for future core outcome alignment.MethodsThis review follows the PRISMA Guidelines for Scoping Reviews. CINAHL, Embase, Medline, Psychinfo, and British Nursing Index databases were searched from inception—March 12, 2021. Included studies had participants diagnosed with MCI and early dementia and reported on sleep as a key objective/ outcome measure.ResultsNineteen thousand five hundred and ninety-six titles were returned following duplicate removal with 188 studies [N] included in final analysis. Sleep data was reported on 17 139 unique, diagnostically diverse participants (n). “Unspecified MCI” was the most common diagnosis amongst patients with MCI (n = 5003, 60.6%). Despite technological advances, sleep was measured most commonly by validated questionnaires (n = 12 586, N = 131). Fewer participants underwent polysomnography (PSG) (n = 3492, N = 88) and actigraphy (n = 3359, N = 38) with little adoption of non-PSG electroencephalograms (EEG) (n = 74, N = 3). Sleep outcome parameters were reported heterogeneously. 62/165 (37.6%) were described only once in the literature (33/60 (60%) in interventional studies). There was underrepresentation of circadian (n = 725, N = 25) and micro-architectural (n = 360, N = 12) sleep parameters.ConclusionsAlongside under-researched areas, there is a need for more detailed diagnostic characterization. Due to outcome heterogeneity, we advocate for international consensus on core sleep outcome parameters to support causal inference and comparison of therapeutic sleep interventions.     

Diagnosis and Management of Dural Sinus Thrombosis following Resection of Cerebellopontine Angle Tumors

Objective Lateral sinus thrombosis is a potentially devastating but seldom studied complication of cerebellopontine angle (CPA) tumor surgery. Systemic anticoagulation in the early postoperative period has often been avoided due to the potential risks of intracranial hemorrhage. Design Retrospective review. Setting Tertiary referral center. Main Outcome Measures The goal of this study was to identify the frequency, treatment, and outcomes in patients who develop postoperative venous sinus thrombosis following CPA tumor surgery and receive early systemic anticoagulation. Results Of 43 patients with CPA tumors, we report five patients (11.6%) with transverse and/or sigmoid sinus thrombosis following resection of the tumor, four of which were detected on routine early postoperative noncontrast computed tomography (CT) scan. The thrombosis was confirmed in all cases with CT venography or magnetic resonance venography. Affected patients had significantly larger tumors than controls and tended to undergo longer operations. These patients were treated with immediate anticoagulation (intravenous heparin, followed by Coumadin for 6 months) without complication. Conclusion Venous sinus thrombosis is an underrecognized complication of CPA surgery, but it can be diagnosed in the early postoperative period by noncontrast CT imaging. Early postoperative initiation of systemic anticoagulation appears safe and effective to prevent the progression of thrombosis and its consequences.