The Role of Knowledge and Attitudes About Nonsteroidal Anti-inflammatory Drugs in Determining Treatment Use.

OBJECTIVE: The objective of this study was to evaluate how patient knowledge and beliefs regarding nonsteroidal anti-inflammatory drugs (NSAIDs) may influence the use of NSAIDs for osteoarthritis (OA). METHODS: Surveys of 334 adults with knee and/or hip OA were analyzed in this cross-sectional study. Familiarity with and perceptions of benefits/risks of NSAID use were measured to assess associations with the use of prescription and nonprescription oral NSAIDs. Multinomial logistic regression models were adjusted for sociodemographic and clinical variables. RESULTS: In this sample, 35.9% and 35.6% reported use of oral prescription and nonprescription-only NSAIDs, respectively. Hispanic participants, compared with non-Hispanic White participants, had lower perceived benefit (P = 0.005) and risk (P = 0.001) of prescription NSAIDs. The following were associated with prescription NSAID use instead of no NSAID use: having family/friends who used prescription (relative risk ratio [RRR] 3.91; 95% confidence interval [CI] 2.05-7.47) and over-the-counter (OTC) (RRR 3.10; 95% CI 1.65-5.83) NSAIDs for OA, understanding the consequences of using both prescription (RRR 3.50; 95% CI 1.79-6.86) and OTC (RRR 2.80; 95% CI 1.39-5.65) NSAIDs, higher perceived benefit of both prescription (RRR 2.51; 95% CI 1.71-3.66) and OTC (RRR 1.44; 95% CI 1.01-2.06) NSAIDs, and lower perceived risk of both types of NSAIDs (prescription: RRR 0.63 [95% CI 0.46-0.87]; OTC: RRR 0.53 [95% CI 0.37-0.75]). Similar results were found when we assessed the relationship between these variables and OTC NSAID use versus no oral NSAID use. CONCLUSION: Adults with knee and/or hip OA were more likely to use NSAIDs if they were more familiar with, had an increased perceived benefit of, and had a decreased perceived risk of these drugs. Patients' perceptions and beliefs about NSAIDs should be evaluated when considering them for treatment.

A luminescent europium hairpin for DNA photosensing in the visible, based on trimetallic bis-intercalators.

Luminescence monitoring of DNA intercalator complexes is important for assessing their localisation and targeting: We report herein a luminescent hetero-trimetallic complex with europium as a luminescent reporter and two attached platinum acetylide terpyridyl units as the DNA recognition units. The ligand, based on a bisamide derivative of diethylenetriaminepentaacetic acid functionalized with two ethynyl groups, provides a backbone to anchor two platinum terpyridyl units, Pt-tpy, leading to the hairpin-shaped heterometallic complex 1. We also prepared a related mono-nuclear platinum complex 2 to compare its intercalation properties with 1. Linear dichroism, UV-visible and melting experiments show the ability of both complexes to interact with calf thymus DNA, with linear dichroism confirming intercalation and demonstrating the expected greater DNA stiffening by the bis-intercalator 1. Importantly, the tri-metallic complex 1 shows a three-fold enhancement in europium luminescence upon addition of calf thymus DNA; other mono-intercalator lanthanide designs have commonly shown a decrease in emission on binding. The ability of the complex to monitor DNA interactions gives the potential use as a luminescence switch in sensing experiments and highlights the design of heterometallic bis-intercalator complexes as an effective approach for DNA-responsive sensitisation of a lanthanide luminescence signal.

Predicting knee replacement in participants eligible for disease-modifying osteoarthritis drug treatment with structural endpoints.

OBJECTIVE: Evaluate associations between 2-year change in radiographic or quantitative magnetic resonance imaging (qMRI) structural measures, and knee replacement (KR), within a subsequent 7-year follow-up period. METHOD: Participants from the Osteoarthritis Initiative were selected based on potential eligibility criteria for a disease-modifying osteoarthritis (OA) drug trial: Kellgren-Lawrence grade 2 or 3; medial minimum joint space width (mJSW) ≥2.5 mm; knee pain at worst 4-9 in the past 30 days on an 11-point scale, or 0-3 if medication was taken for joint pain; and availability of structural measures over 2 years. Mean 2-year change in structural measures was estimated and compared with two-sample independent t-tests for KR and no KR. Area under the receiver operating characteristic curve (AUC) was estimated using 2-year change in structural measures for prediction of future KR outcomes. RESULTS: Among 627 participants, 107 knees underwent KR during a median follow-up of 6.7 years after the 2-year imaging period. Knees that received KR during follow-up had a greater mean loss of cartilage thickness in the total femorotibial joint and medial femorotibial compartment on qMRI, as well as decline in medial fixed joint space width on radiographs, compared with knees that did not receive KR. These imaging measures had similar, although modest discrimination for future KR (AUC 0.62, 0.60, and 0.61, respectively). CONCLUSIONS: 2-year changes in qMRI femorotibial cartilage thickness and radiographic JSW measures had similar ability to discriminate future KR in participants with knee OA, suggesting that these measures are comparable biomarkers/surrogate endpoints of structural progression.

MRI-based screening for structural definition of eligibility in clinical DMOAD trials: Rapid OsteoArthritis MRI Eligibility Score (ROAMES).

PURPOSE: Our aim was to introduce a simplified MRI instrument, Rapid OsteoArthritis MRI Eligibility Score (ROAMES), for defining structural eligibility of patients for inclusion in disease-modifying osteoarthritis drug trials using a tri-compartmental anatomic approach that enables stratification of knees into different structural phenotypes and includes diagnoses of exclusion. We also aimed to define overlap between phenotypes and determine reliability. METHODS: 50 knees from the Foundation for National Institutes of Health Osteoarthritis Biomarkers study, a nested case-control study within the Osteoarthritis Initiative, were selected within pre-defined definitions of phenotypes as either inflammatory, subchondral bone, meniscus/cartilage, atrophic or hypertrophic. A focused scoring instrument was developed covering cartilage, meniscal damage, inflammation and osteophytes. Diagnoses of exclusion were meniscal root tears, osteonecrosis, subchondral insufficiency fracture, tumors, malignant marrow infiltration and acute traumatic changes. Reliability was determined using weighted kappa statistics. Descriptive statistics were used for determining concordance between the a priori phenotypic definition and ROAMES and overlap between phenotypes. RESULTS: ROAMES identified 43 of 50 (86%) pre-defined phenotypes correctly. Of the 50 participants, 27 (54%) had no additional phenotypes other than the pre-defined phenotype. 18 (36%) had one and 5 (10%) had two additional phenotypes. None had three or four additional phenotypes. All features of ROAMES showed almost perfect agreement. One case with osteonecrosis and one with a tumor were detected. CONCLUSIONS: ROAMES is able to screen and stratify potentially eligible knees into different structural phenotypes and record relevant diagnoses of exclusion. Reliability of the instrument showed almost perfect agreement.

Mitochondrial DNA haplogroups associated with MRI-detected structural damage in early knee osteoarthritis.

OBJECTIVE: Magnetic resonance imaging (MRI)-detected structural features are associated with increased risk of radiographic osteoarthritis (ROA). Specific mitochondrial DNA (mtDNA) haplogroups have been associated with incident ROA. Our objective was to compare the presence of MRI-detected structural features across mtDNA haplogroups among knees that developed incident ROA. DESIGN: Knees from the Osteoarthritis Initiative (OAI) that developed incident ROA during 48 months follow-up were identified from Caucasian participants. mtDNA haplogroups were assigned based on a single base extension assay. MRIs were obtained annually between baseline and 4-year follow-up and scored using the MRI Osteoarthritis Knee Score (MOAKS). The association between mtDNA haplogroups and MRI-detected structural features was estimated using log-binomial regression. Participants who carried haplogroup H served as the reference group. RESULTS: The sample included 255 participants contributing 277 knees that developed ROA. Haplogroups included H (116, 45%), J (17, 7%), T (26, 10%), Uk (61, 24%), and the remaining less common haplogroups ("others") (35, 14%). Knees of participants with haplogroup J had significantly lower risk of medium/large bone marrow lesions (BMLs) in the medial compartment [3.2%, relative risks (RR) = 0.17; 95%CI: 0.05, 0.64; P = 0.009] compared to knees of participants who carried haplogroup H [16.3%], as did knees from participants within the "others" group [2.8%, RR = 0.20; 95%CI: 0.08, 0.55; P = 0.002], over the 4 year follow-up period. CONCLUSIONS: mtDNA haplogroup J was associated with lower risk of BMLs in the medial compartment among knees that developed ROA. Our results offer a potential hypothesis to explain the mechanism underlying the previously reported protective association between haplogroup J and ROA.

Signal intensity alteration within infrapatellar fat pad predicts knee replacement within 5 years: data from the Osteoarthritis Initiative.

OBJECTIVE: To investigate whether infrapatellar fat pad (IPFP) signal intensity (SI) alteration predicts the occurrence of knee replacement (KR) in knee osteoarthritis (OA) patients over 5 years. DESIGN: The subjects were selected from Osteoarthritis Initiative (OAI) study. Case knees (n = 127) were defined as those who received KR during 5 years follow-up visit. They were matched by gender, age and radiographic status with control knees (n = 127). We used T2-weighted MR images to measure IPFP SI alteration using a newly developed algorithm in MATLAB. The measurements were assessed at baseline (BL), T0 (the visit just before KR) and 1 year before T0 (T-1). Conditional logistic regression was used to analyse the associations between IPFP SI alterations and the risk of KR. RESULTS: Participants were mostly female (57%), with an average age of 63.7 years old and a mean body mass index (BMI) of 29.5 kg/m2. In multivariable analysis, the standard deviation (SD) of IPFP SI [sDev (IPFP)] and the ratio of high SI region volume to whole IPFP volume [Percentage (H)] measured at BL were significantly associated with increased risks of KR after adjustment for covariates. IPFP SI alterations measured at T-1 including sDev (IPFP), Percentage (H) and clustering effect of high SI [Clustering factor (H)] were significantly associated with higher risks of KR. All measurements were significantly associated with higher risks of KR at T0. CONCLUSIONS: IPFP SI is associated with the occurrence of KR suggesting it may play a role in end-stage knee OA.

Clinical outcomes following unilateral adrenalectomy in patients with primary aldosteronism.

BACKGROUND: In approximately half of cases of primary aldosteronism (PA), the cause is a surgically-resectable unilateral aldosterone-producing adrenal adenoma. However, long-term data on surgical outcomes are sparse. AIM: We report on clinical outcomes post-adrenalectomy in a cohort of patients with PA who underwent surgery. DESIGN: Retrospective review of patients treated for PA in a single UK tertiary centre. METHODS: Of 120 consecutive patients investigated for PA, 52 (30 male, median age 54, range 30-74) underwent unilateral complete adrenalectomy. Blood pressure, number of antihypertensive medications, and serum potassium were recorded before adrenalectomy, and after a median follow-up period of 50 months (range 7-115). Recumbent renin and aldosterone were measured, in the absence of interfering antihypertensive medication, ≥3months after surgery, to determine if PA had been biochemically cured. RESULTS: Overall, blood pressure improved from a median (range) 160/95 mmHg (120/80-250/150) pre-operatively to 130/80 mmHg (110/70-160/93), P < 0.0001. 24/52 patients (46.2%) had cured hypertension, with a normal blood pressure post-operatively on no medication. 26/52 (50%) had improved hypertension. 2/52 patients (3.8%) showed no improvement in blood pressure post-operatively. Median (range) serum potassium level increased from 3.2 (2.3-4.7) mmol/l pre-operatively to 4.4 mmol/l (3.3-5.3) post-operatively, P < 0.0001). Median (range) number of antihypertensive medications used fell from 3 (0-6) pre- to 1 post-operatively (range 0-4), P < 0.0001. CONCLUSIONS: Unilateral adrenalectomy provides excellent long-term improvements in blood pressure control, polypharmacy and hypokalaemia in patients with lateralizing PA. These data may help inform discussions with patients contemplating surgery.

Heterogenous patterns of recovery of thirst in adult patients with adipsic diabetes insipidus.

BACKGROUND: The natural history of adipsic diabetes insipidus (ADI) is not well described, and reports of recovery of thirst are rare. DESIGN AND METHODS: Case histories presentation. ADI was identified by demonstrating absent thirst and arginine vasopressin (AVP) responses to hypertonic saline infusion. RESULTS: Twelve patients with ADI were identified (craniopharyngioma 5, anterior communicating artery aneurysm (ACOM) repair 4, congenital 1, neurosarcoidosis 1, prolactinoma 1). Three patients died. Six patients had permanent ADI. Three patients had recovery of thirst, with a heterogenous pattern of recovery. In the first case, ADI had developed after clipping of an ACOM aneurysm. Ten years after surgery; he sensed the return of thirst; repeated hypertonic saline infusion showed recovery of thirst and AVP secretion. In the second case, a 41-year-old female with an intrasellar craniopharyngioma developed post-operative ADI with persistent hypernatremia. Two years post-operatively, she complained of thirst, and hypertonic saline infusion showed normalization of thirst but absent AVP responses, confirming recovery of thirst, but with persistent diabetes insipidus (DI). In the third case, a 29-year-old Caucasian had craniotomy and radiotherapy for craniopharyngioma and developed ADI post-operatively. Eight years post-op, she presented with thirst, seizures and pNa of 112 mmol/l. Hypertonic saline infusion showed persistent DI but thirst responses typical of compulsive water drinking; she has had recurrent hyponatraemia since then. CONCLUSIONS: We report that 3/12 patients with ADI recovered thirst after longstanding adipsia with heterogenous pattern of recovery. Both the mortality of 25% and the recovery rate of 25% should be considered when planning long-term surveillance.

Synovitis in knee osteoarthritis: a precursor of disease?

OBJECTIVES: It is unknown whether joint inflammation precedes other articular tissue damage in osteoarthritis. Therefore, this study aims to determine if synovitis precedes the development of radiographic knee osteoarthritis (ROA). METHODS: The participants in this nested case-control study were selected from persons in the Osteoarthritis Initiative with knees that had a Kellgren Lawrence grading (KLG)=0 at baseline (BL). These knees were evaluated annually with radiography and non-contrast-enhanced MRI over 4 years. MRIs were assessed for effusion-synovitis and Hoffa-synovitis. Case knees were defined by ROA (KLG≥2) on the postero-anterior knee radiographs at any assessment after BL. Radiographs were assessed at P0 (time of onset of ROA), 1 year prior to P0 (P-1) and at BL. Controls were participants who did not develop incident ROA (iROA) from BL to 48 months). RESULTS: 133 knees of 120 persons with ROA (83 women) were matched to 133 control knees (83 women). ORs for occurrence of iROA associated with the presence of effusion-synovitis at BL, P-1 and P0 were 1.56 (95% CI 0.86 to 2.81), 3.23 (1.72 to 6.06) and 4.7 (1.10 to 2.95), respectively. The ORs for the occurrence of iROA associated with the presence of Hoffa-synovitis at BL, P-1 and P0 were 1.80 (1.1 to 2.95), 2.47 (1.45 to 4.23) and 2.40 (1.43 to 4.04), respectively. CONCLUSIONS: Effusion-synovitis and Hoffa-synovitis strongly predicted the development of iROA.

Loss of anterior cruciate ligament integrity and the development of radiographic knee osteoarthritis: a sub-study of the osteoarthritis initiative.

INTRODUCTION: The aim of this study was to determine whether loss of ACL integrity in an older cohort precedes the onset of radiographic OA (ROA). METHODS: Participants in this nested case-control study were selected from the Osteoarthritis Initiative (OAI) study who had risk factors for OA development but did not have ROA (Kellgren-Lawrence grading (KLG) of 0 or 1) in both knees at baseline. The MRIs were assessed for the presence of ACL tears. Case knees were defined by the development of ROA on knee radiographs between the 12 and 48 month visits. Their radiographs were assessed at P0 (time of onset of radiographic knee OA), 1 year prior to P0 (P-1) and at baseline. Controls were selected from amongst those who did not develop incident ROA and were matched to cases. RESULTS: 355 persons who developed ROA were matched to 355 controls. No relationship between loss of ACL integrity and incident ROA was found at any assessment time point. Odds ratios (OR) for baseline, 1 year prior to incident ROA (P1) and at point of occurrence of incident ROA (P0) were 2.00 (0.66-6.06), 2.5 (0.76-8.24) and 2.75 (0.85-8.88) respectively. A significant risk of incident ROA was found in participants who had a history of knee injury with an OR of 1.51 (1.05-2.16). CONCLUSION: Loss of ACL integrity does not confer a significantly increased risk of incident ROA in an older adult cohort. In contrast, a history of knee injury was associated with an increased risk of incident ROA.

Brief report: symmetricity of radiographic and MRI-detected structural joint damage in persons with knee pain--the Joints on Glucosamine (JOG) Study.

OBJECTIVE: Most MRI-based osteoarthritis (OA) studies have focused on a single knee per person and thus, data on bilaterality is sparse. Study aim was to describe symmetricity of MRI-detected OA features in a cohort of subjects with knee pain. DESIGN: Participants were 169 subjects with chronic knee pain who had 3 T MRI of both knees using the same protocol as in the Osteoarthritis Initiative. Knees were read for cartilage damage, bone marrow lesions (BMLs), and meniscal damage according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. Chi(2) tests were used to compare the proportion of knees with unilateral tissue pathology to the proportion what would be expected if both knees were independent. We further used percent agreement and linear weighted kappa statistics to describe agreement of cartilage damage and BMLs in the same articular plates. RESULTS: 51.2% of participants were men, mean age was 52.1 (±6.2), mean BMI was 29.0 kg/m(2) (±4.1). All plates showed a significant higher degree of symmetricity for cartilage damage as evidenced by weighted kappas ranging from 0.32 to 0.59. For BMLs the degree of symmetricity was higher for the patella, trochlea, medial tibia, lateral femur, and medial femur; for meniscal damage the degree of unilaterality was lower for all medial meniscal subregions but not all lateral. Kappas ranged between 0.52 and 0.68 for cartilage and 0.30 and 0.55 for BMLs for the four subregions with highest agreement. CONCLUSION: A higher degree of symmetricity of tissue damage than expected by chance was observed in this cohort of subjects with knee pain.

Chronic hypopituitarism is uncommon in survivors of aneurysmal subarachnoid haemorrhage.

OBJECTIVE: The incidence of hypopituitarism after aneurysmal subarachnoid haemorrhage (SAH) is unclear from the conflicting reports in the literature. As routine neuroendocrine screening for hypopituitarism for all patients would be costly and logistically difficult, there is a need for precise data on the frequency of hypopituitarism and on factors which might predict the later development of pituitary dysfunction. We aimed to: (i) Establish the incidence of long-term hypopituitarism in patients with aneurysmal SAH. (ii) Determine whether data from patients' acute admission with SAH could predict the occurrence of long-term hypopituitarism. DESIGN: One hundred patients were studied prospectively from the time of presentation with acute SAH. Plasma cortisol, plasma sodium and a variety of clinical and haemodynamic parameters were sequentially measured for the first 12 days of their acute admission. Forty-one patients then underwent dynamic pituitary testing at median 15 months following SAH (range 7-30 months), with insulin tolerance test (ITT) or, if contraindicated, a glucagon stimulation test (GST) plus short synacthen test (SST). If symptoms of cranial diabetes insipidus (CDI) were present, a water deprivation test was also performed. RESULTS: Forty-one patients attended for follow-up dynamic pituitary testing. Although 14 of 100 had acute glucocorticoid deficiency immediately following SAH, only two of 41 had long-term adrenocorticotrophic hormone (ACTH) deficiency and four of 41 had growth hormone (GH) deficiency. None were hypothyroid or gonadotrophin deficient. None had chronic CDI or hyponatraemia. There was no association between acute glucocorticoid deficiency, acute CDI or acute hyponatraemia and long-term pituitary dysfunction. CONCLUSION: Both anterior and posterior hypopituitarism are very uncommon following SAH and are not predicted by acute clinical, haemodynamic or endocrinological parameters. Routine neuroendocrine screening is not justified in SAH patients.

Susceptibility artifacts detected on 3T MRI of the knee: frequency, change over time and associations with radiographic findings: data from the joints on glucosamine study.

OBJECTIVE: To determine the prevalence of intraarticular susceptibility artifacts and to detect longitudinal changes in the artifacts, on 3T magnetic resonance imaging (MRI) of the knee in a cohort of patients with knee pain, and to assess the association of susceptibility artifacts with radiographic intraarticular calcifications. DESIGN: Three hundred and forty-six knees of 177 subjects aged 35-65 were included. 3T MRI was performed at baseline and at 6 months. Baseline radiographs were assessed for presence/absence of linear/punctate calcifications within the tibiofemoral joint (TFJ) space. Corresponding MRIs were assessed for susceptibility artifacts (i.e., linear/punctate hypointensities) in the TFJ space on coronal dual-echo steady-state (DESS) sequences. Kappa statistics were applied to determine agreement between findings on baseline DESS and radiography. Changes in artifacts over time were recorded. RESULTS: In the medial compartment, 13 (4%) of the knees showed susceptibility artifacts at baseline. Six knees had persistent artifacts and six knees had incident artifacts at follow-up. Agreement between DESS and radiography was κ = 0.18 (-0.15, 0.51) in the medial compartment. Frequency of artifacts in the lateral compartment was low (2%). CONCLUSION: Susceptibility artifacts detected on knee MRI are not frequent, and likely correspond to vacuum phenomena as they commonly change over time and are not associated with intraarticular calcifications. Radiologists should be aware of these artifacts as they can interfere with cartilage segmentation.

Trajectory of cartilage loss within 4 years of knee replacement--a nested case-control study from the osteoarthritis initiative.

OBJECTIVE: Knee replacement (KR) represents a clinically important endpoint of knee osteoarthritis (KOA). Here we examine the 4-year trajectory of femoro-tibial cartilage thickness loss prior to KR vs non-replaced controls. METHODS: A nested case-control study was performed in Osteoarthritis Initiative (OAI) participants: Cases with KR between 12 and 60 month (M) follow-up were each matched with one control (without KR through 60M) by age, sex, and baseline radiographic stage. Femoro-tibial cartilage thickness was measured quantitatively using magnetic resonance imaging (MRI) at the annual visit prior to KR occurrence (T0), and at 1-4 years prior to T0 (T-1 to T-4). Cartilage loss between cases and controls was compared using paired t-tests and conditional logistic regression. RESULTS: One hundred and eighty-nine knees of 164 OAI participants [55% women; age 64 ± 8.7; body mass index (BMI) 29 ± 4.5] had KR and longitudinal cartilage data. Comparison of annualized slopes of change across all time points revealed greater loss in the central medial tibia (primary outcome) in KRs than in controls [94 ± 137 vs 55 ± 104 µm; P = 0.0017 (paired t); odds ratio (OR) 1.36 (95% confidence interval (CI): 1.08-1.70)]. The discrimination was stronger for T-2 → T0 [OR 1.61 (1.33-1.95), n = 127] than for T-1 → T0, and was not statistically significant for intervals prior to T-2 [i.e., T-4 → T-2, OR 0.97 (0.67-1.41), n = 60]. Results were similar for total medial femoro-tibial cartilage loss (secondary outcome), and when adjusting for pain and BMI. CONCLUSIONS: In knees with subsequent replacement, cartilage loss accelerates in the 2 years, and particularly in the year prior to surgery, compared with controls. Whether slowing this cartilage loss can delay KR remains to be determined.

Hyponatremia following mild/moderate subarachnoid hemorrhage is due to SIAD and glucocorticoid deficiency and not cerebral salt wasting.

CONTEXT: Hyponatremia is common after acute subarachnoid hemorrhage (SAH) but the etiology is unclear and there is a paucity of prospective data in the field. The cause of hyponatremia is variously attributed to the syndrome of inappropriate antidiuresis (SIAD), acute glucocorticoid insufficiency, and the cerebral salt wasting syndrome (CSWS). OBJECTIVE: The objective was to prospectively determine the etiology of hyponatremia after SAH using sequential clinical examination and biochemical measurement of plasma cortisol, arginine vasopressin (AVP), and brain natriuretic peptide (BNP). DESIGN: This was a prospective cohort study. SETTING: The setting was the National Neurosurgery Centre in a tertiary referral centre in Dublin, Ireland. PATIENTS: One hundred patients with acute nontraumatic aneurysmal SAH were recruited on presentation. INTERVENTIONS: Clinical examination and basic biochemical evaluation were performed daily. Plasma cortisol at 0900 hours, AVP, and BNP concentrations were measured on days 1, 2, 3, 4, 6, 8, 10, and 12 following SAH. Those with 0900 hours plasma cortisol<300 nmol/L were empirically treated with iv hydrocortisone. MAIN OUTCOME MEASURES: Plasma sodium concentration was recorded daily along with a variety of clinical and biochemical criteria. The cause of hyponatremia was determined clinically. Later measurement of plasma AVP and BNP concentrations enabled a firm biochemical diagnosis of the cause of hyponatremia to be made. RESULTS: Forty-nine of 100 developed hyponatremia<135 mmol/L, including 14/100<130 mmol/L. The cause of hyponatremia, and determined by both clinical examination and biochemical hormone measurement, was SIAD in 36/49 (71.4%), acute glucocorticoid insufficiency in 4/49 (8.2%), incorrect iv fluids in 5/49 (10.2%), and hypovolemia in 5/49 (10.2%). There were no cases of CSWS. CONCLUSIONS: The most common cause of hyponatremia after acute nontraumatic aneurysmal SAH is SIAD. Acute glucocorticoid insufficiency accounts for a small but significant number of cases. We found no cases of CSWS.

Acute glucocorticoid deficiency and diabetes insipidus are common after acute traumatic brain injury and predict mortality.

CONTEXT: Published data demonstrates that hypopituitarism is common after traumatic brain injury (TBI). Hormone deficiencies are transient in many, but the natural history of the acute changes after TBI has not been documented. In addition, it is not clear whether there are any early parameters that accurately predict the development of permanent hypopituitarism. OBJECTIVES: There were 3 main objectives of this study: 1) to describe the natural history of plasma cortisol (PC) changes and sodium balance after TBI; 2) to identify whether acute hypocortisolemia or cranial diabetes insipidus (CDI) predict mortality; and 3) to identify whether the acute pituitary dysfunction predicts the development of chronic anterior hypopituitarism. DESIGN: Each TBI patient underwent sequential measurement of PC, plasma sodium, urine osmolality, and fluid balance after TBI. All other anterior pituitary hormones were measured on day 10 after TBI. The results from 15 surgical comparisons defined a PC less than 300 nmol/L as inappropriately low for an acutely ill patient. CDI was diagnosed according to standard criteria. Surviving TBI patients underwent dynamic anterior pituitary testing at least 6 months after TBI. SETTING: The patients were recruited from the Irish National Neurosurgery Centre. PATIENTS: One hundred sequential TBI patients were recruited. Fifteen patients admitted to Intensive Therapy Unit (ITU) after major surgery were recruited as comparison patients. MAIN OUTCOME MEASURES: PC in TBI patients was compared with that of comparison patients. The mortality rate was compared between TBI patients with and without acute hypocortisolemia. Results of follow-up dynamic pituitary testing were compared between those with and without acute hypocortisolemia. RESULTS: Most of the TBI patients (78%) developed inappropriately low PC after TBI. Low PC and CDI were predictive of mortality. Thirty-nine percent of the patients who had follow-up testing had at least 1 pituitary hormone deficit, all of whom had had previous acute hypocortisolemia or CDI. CONCLUSIONS: Acute hypocortisolemia and CDI are predictive of mortality and long-term pituitary deficits in TBI.

Anterior hypopituitarism is rare and autoimmune disease is common in adults with idiopathic central diabetes insipidus.

OBJECTIVE: Central diabetes insipidus is a rare clinical condition with a heterogenous aetiology. Up to 40% of cases are classified as idiopathic, although many of these are thought to have an autoimmune basis. Published data have suggested that anterior hypopituitarism is common in childhood-onset idiopathic diabetes insipidus. We aimed to assess the incidence of anterior hypopituitarism in a cohort of adult patients with idiopathic diabetes insipidus. DESIGN AND PATIENTS: We performed a retrospective review of the databases of two pituitary investigation units. This identified 39 patients with idiopathic diabetes insipidus. All had undergone magnetic resonance imaging scanning and dynamic pituitary testing (either insulin tolerance testing or GHRH/arginine and short synacthen testing) to assess anterior pituitary function. RESULTS: One patient had partial growth hormone deficiency; no other anterior pituitary hormonal deficits were found. Thirty-three percent had at least one autoimmune disease in addition to central diabetes insipidus. CONCLUSIONS: Our data suggest that anterior hypopituitarism is rare in adult idiopathic diabetes insipidus. Routine screening of these patients for anterior hypopituitarism may not, therefore, be indicated. The significant prevalence of autoimmune disease in this cohort supports the hypothesis that idiopathic diabetes insipidus may have an autoimmune aetiology.

Pituitary dysfunction following traumatic brain injury or subarachnoid haemorrhage - in "Endocrine Management in the Intensive Care Unit".

Traumatic brain injury and subarachnoid haemorrhage are important causes of morbidity and mortality in the developed world. There is a large body of evidence that demonstrates that both conditions may adversely affect pituitary function in both the acute and chronic phases of recovery. Diagnosis of hypopituitarism and accurate treatment of pituitary disorders offers the opportunity to improve mortality and outcome in both traumatic brain injury and subarachnoid haemorrhage. In this article, we will review the history and pathophysiology of pituitary function in the acute phase following traumatic brain injury and subarachnoid haemorrhage, and we will discuss in detail three key aspects of pituitary dysfunction which occur in the early course of TBI; acute cortisol deficiency, diabetes insipidus and SIAD.

Gastric pacing for diabetic gastroparesis--does it work?

The management of diabetic gastroparesis resistant to medical therapy is very difficult Gastric electrical stimulation (GES) is a relatively new therapeutic modality which has shown some promise in international trials. It has seen use in four patients in Ireland. Our aim was to determine if GES improved patients' outcomes in terms of duration and cost of inpatient stay and glycaemic control. We reviewed the patients' case notes and calculated the number of days spent as an inpatient with symptomatic gastroparesis pre and post pacemaker, the total cost of these admissions, and patients' average HbA1c pre and post GES. Mean length of stay in the year pre GES was 81.75 days and 62.25 days in the year post GES (p=0.89). There was also no improvement in glycaemic control following GES. GES has been ineffective in improving length of inpatient stay and glycaemic control in our small patient cohort.