Diabetes and Covid-19: Clinical implications and novel management strategies.

From the outset of the Covid-19 pandemic, diabetes has been identified as attracting higher rates of severe infection and associated mortality. Our understanding of the mechanisms behind these observations continue to develop but it is clear that the comorbidities associated with diabetes play a key role. Here we provide a brief overview of the clinical implications relevant to Covid-19 infection in diabetes and outline the changes we have instituted to adapt the management of both acute hyperglycaemic emergencies and routine diabetes care during the current pandemic.

Playing Performance After Anterior Cruciate Ligament Reconstruction Among Australian Football League Players From 1999 to 2013.

BACKGROUND: Achieving preinjury levels of athletic performance has been challenging for elite athletes after anterior cruciate ligament (ACL) reconstruction. Although a recent study found that 77% of Australian Football League (AFL) players who underwent ACL reconstruction from 1999 to 2013 returned to play at the highest level, the study did not indicate how consistently or well they were able to play. PURPOSE: To identify the number of AFL players who returned to play consistently over 2 seasons after ACL reconstruction, compare their playing performance in these seasons with preinjury performance, and evaluate factors associated with returning to preinjury levels of performance. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Analysis included 104 AFL players who underwent ACL reconstruction between 1999 and 2013. All had played at least 10 AFL matches in 1 season before ACL injury. Ranking points, as devised by AFL statisticians, were used to measure individual playing performance. RESULTS: Of the 104 players who played at least 10 matches in 1 season before ACL injury, 53 (51%) returned to play at least 10 matches in 2 seasons after surgery. Of these 53 players, 36 (68%) returned to their preinjury levels of performance. The 17 remaining players who did not return to their preinjury performance still performed comparably to the AFL average level after surgery. Players <25 years old (odds ratio = 2.9, P = .01) or <90 kg (odds ratio = 2.7, P = .03) had greater odds of returning to their preinjury levels of performance. CONCLUSION: Returning to play on a consistent basis was a substantial challenge for AFL players after ACL reconstruction. However, among players who did return to play consistently over 2 seasons, their postsurgery average performance was comparable with the AFL average level of performance, and two-thirds returned to their preinjury levels of performance. Younger and lighter players were more likely to return to their preinjury levels of performance, possibly given the nature of AFL club playing list management decisions.

Fifteen-Year Audit of Anterior Cruciate Ligament Reconstructions in the Australian Football League From 1999 to 2013: Return to Play and Subsequent ACL Injury.

BACKGROUND: Anterior cruciate ligament (ACL) injury has been a major cause of missed game time among Australian Football League (AFL) players. Return to play after ACL reconstruction is not always achieved, even among elite athletes. The rate of subsequent ACL injury in the AFL from 1990 to 2000 was high as compared with that of other elite sports. PURPOSE: To determine the rates of return to play and subsequent ACL injury after ACL reconstruction among AFL players from 1999 to 2013 and to explore factors associated with differing rates of return to play and subsequent ACL injury. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 158 AFL players who underwent ACL reconstruction were identified from a prospectively maintained registry of AFL player injuries. Further data were gathered from official playing statistics, surgical records, and structured phone interviews. RESULTS: The rate of return to play after an initial ACL injury was 77% (121 of 158 players). Greater preinjury playing experience and earlier selection in the AFL draft were associated with higher rates of return to play. The rate of subsequent ACL injury to either knee was 30% (48 of 158 players) and was especially high among players aged <21 years (23 of 46 players, 50%). After subsequent ACL injury, 34 of 48 players (71%) returned to play. In primary ACL reconstruction, the use of Ligament Augmentation and Reconstruction System grafts resulted in a faster return to play ( P = .001) but had a higher risk of subsequent revision reconstruction (risk ratio = 2.8, P = .048). Family history of ACL injury was associated with an increased risk of subsequent contralateral ACL injury (risk ratio = 3.8, P = .002). CONCLUSION: Most AFL players who underwent ACL reconstruction returned to play at least 1 AFL match. The high rate of subsequent ACL injury among AFL players demonstrates the highly demanding nature of Australian football, particularly at the elite level. The risk factors for subsequent ACL injury should be considered carefully when treatment and rehabilitation decisions are made for these high-demand athletes.

Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: a systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes.

OBJECTIVES: The primary objective was to calculate the rate of return to sport (RTS) following anterior cruciate ligament (ACL) reconstruction in elite athletes. Secondary objectives were to estimate the time taken to RTS, calculate rates of ACL graft rupture, evaluate postsurgical athletic performance and identify determinants of RTS. DESIGN: Pooled RTS and graft rupture rates were calculated using random effects proportion meta-analysis. Time to RTS, performance data and determinants of RTS were synthesised descriptively. DATA SOURCES: MEDLINE, EMBASE, AMED, CINAHL, AMI, PEDro, SPORTDiscus and The Cochrane Library were searched from inception to 19 January 2016. Hand searching of 10 sports medicine journals and reference checking were also performed. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they reported the ratio of elite athletes who returned to their preinjury level of sport following ACL reconstruction. Twenty-four studies were included. RESULTS: The pooled RTS rate was 83% (95% CI 77% to 88%). The mean time to RTS ranged from 6 to 13 months. The pooled graft rupture rate was 5.2% (95% CI 2.8% to 8.3%). Six out of nine studies that included a noninjured control group found no significant deterioration in athletic performance following ACL reconstruction. Indicators of greater athletic skill or value to the team were associated with RTS. SUMMARY AND CONCLUSIONS: Eighty-three per cent of elite athletes returned to sport following ACL reconstruction, while 5.2% sustained a graft rupture. Most athletes who returned to sport performed comparably with matched, uninjured controls. This information may assist in guiding expectations of athletes and clinicians following ACL reconstruction.

Exogenous T3 toxicosis following consumption of a contaminated weight loss supplement.

A 42-year-old male presented with a one-week history of palpitations and sweating episodes. The only significant history was of longstanding idiopathic dilated cardiomyopathy. Initial ECG demonstrated a sinus tachycardia. Thyroid function testing, undertaken as part of the diagnostic workup, revealed an un-measureable thyroid-stimulating hormone (TSH) and free thyroxine (T4). Upon questioning the patient reported classical thyrotoxic symptoms over the preceding weeks. Given the persistence of symptoms free tri-iodothyronine (T3) was measured and found to be markedly elevated at 48.9 pmol/L (normal range: 3.1-6.8 pmol/L). No goitre or nodular disease was palpable in the neck. Historically there had never been any amiodarone usage. Radionucleotide thyroid uptake imaging (123I) demonstrated significantly reduced tracer uptake in the thyroid. Upon further questioning the patient reported purchasing a weight loss product online from India which supposedly contained sibutramine. He provided one of the tablets and laboratory analysis confirmed the presence of T3 in the tablet. Full symptomatic resolution and normalised thyroid function ensued upon discontinuation of the supplement. LEARNING POINTS: Free tri-iodothyronine (T3) measurement may be useful in the presence of symptoms suggestive of thyrotoxicosis with discordant thyroid function tests.Thyroid uptake scanning can be a useful aid to differentiating exogenous hormone exposure from endogenous hyperthyroidism.Ingestion of thyroid hormone may be inadvertent in cases of exogenous thyrotoxicosis.Medicines and supplements sourced online for weight loss may contain thyroxine (T4) or T3 and should be considered as a cause of unexplained exogenous hyperthyroidism.

Patellofemoral osteoarthritis is prevalent and associated with worse symptoms and function after hamstring tendon autograft ACL reconstruction.

OBJECTIVES: To evaluate the compartmental distribution of knee osteoarthritis (OA) after anterior cruciate ligament reconstruction (ACLR), to determine if patellofemoral or tibiofemoral OA is more strongly associated with knee symptoms and function, and to evaluate the contribution of associated injuries and surgical delay to the development of OA. METHODS: This cross-sectional study recruited 70 participants who underwent hamstring tendon (HT) ACLR 5-10 years previously. Radiographic OA was assessed according to the Osteoarthritis Research Society International (OARSI) criteria. Knee symptoms were assessed with the Knee Injury and Osteoarthritis Outcome Score (KOOS) and Anterior Knee Pain Scale (AKPS), while function was assessed with three lower limb tasks (hop-for-distance, one-leg rise and side-hop). Multivariate and binary logistic regression analyses were performed to assess the relationship between OA and symptomatic/functional outcomes and associated injuries/surgical delay, respectively. RESULTS: Radiographic OA was observed in the patellofemoral (47%) and tibiofemoral joints (31%). Pain, symptoms and quality of life on the KOOS and the AKPS were associated with severity of patellofemoral OA (standardised regression coefficient (ß)=-0.3 to -0.5, p=0.001-0.042), whereas only the KOOS-pain subscale was associated with tibiofemoral OA (ß=-0.3, p=0.037). For each functional task, greater patellofemoral OA severity was associated with worse performance, independent of tibiofemoral OA severity (ß=-0.3 to -0.4, p=0.001-0.026). Medial meniscal and patellofemoral chondral lesions at surgery were associated with tibiofemoral and patellofemoral OA development at follow-up, respectively, while a longer surgery delay was associated with patellofemoral OA. CONCLUSIONS: Patellofemoral OA is common following HT ACLR and is associated with worse knee-related symptoms, including anterior knee pain, and decreased functional performance.

Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double-blind, placebo-controlled study.

OBJECTIVE: Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism. DESIGN: Randomized, double-blind, placebo-controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks. PATIENTS: Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled. MEASUREMENTS: Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment. RESULTS: Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 µm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone-binding globulin (SHBG) or IGF-1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 µmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged. CONCLUSION: There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.

Joint British Diabetes Societies guideline for the management of diabetic ketoacidosis.

The Joint British Diabetes Societies guidelines for the management of diabetic ketoacidosis (these do not cover Hyperosmolar Hyperglycaemic Syndrome) are available in full at: (i) http://www.diabetes.org.uk/About_us/Our_Views/Care_recommendations/The-Management-of-Diabetic-Ketoacidosis-in-Adults; (ii) http://www.diabetes.nhs.uk/publications_and_resources/reports_and_guidance; (iii) http://www.diabetologists-abcd.org.uk/JBDS_DKA_Management.pdf. This article summarizes the main changes from previous guidelines and discusses the rationale for the new recommendations. The key points are: Monitoring of the response to treatment (i) The method of choice for monitoring the response to treatment is bedside measurement of capillary blood ketones using a ketone meter. (ii) If blood ketone measurement is not available, venous pH and bicarbonate should be used in conjunction with bedside blood glucose monitoring to assess treatment response. (iii) Venous blood should be used rather than arterial (unless respiratory problems dictate otherwise) in blood gas analysers. (iv) Intermittent laboratory confirmation of pH, bicarbonate and electrolytes only. Insulin administration (i) Insulin should be infused intravenously at a weight-based fixed rate until the ketosis has resolved. (ii) When the blood glucose falls below 14 mmol/l, 10% glucose should be added to allow the fixed-rate insulin to be continued. (iii) If already taking, long-acting insulin analogues such as insulin glargine (Lantus(®), Sanofi Aventis, Guildford, Surry, UK) or insulin detemir (Levemir(®), Novo Nordisk, Crawley, West Sussex, UK.) should be continued in usual doses. Delivery of care (i) The diabetes specialist team should be involved as soon as possible. (ii) Patients should be nursed in areas where staff are experienced in the management of ketoacidosis.

Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.

CONTEXT: Macroprolactinemia is a common finding in patients with hyperprolactinemia. There are no published long-term follow-up studies. OBJECTIVE: The aim of this study was to describe findings after prolonged follow-up in a previously published cohort of patients with macroprolactinemia. STUDY POPULATION: We studied 51 patients identified as having macroprolactinemia after polyethylene glycol precipitation. DESIGN: Clinical assessment and serum prolactin assay were repeated in 51 patients with macroprolactinemia after a median follow-up of 9.9 yr (range, 9-11 yr). RESULTS: Median age at presentation was 41 yr (range, 18-55 yr). Mean serum prolactin concentration at presentation was 1885 mU/liter, and after follow-up 1370 mU/liter. At follow-up, headache had been experienced in 12 patients (24%) and oligomenorrhea in five (10%). Galactorrhea was present in only two patients (4%). No visual deterioration was noted in 50 patients. One had a transient bitemporal hemianopia. No patients developed an autoimmune condition. Microadenoma had been identified in four patients at presentation with no new pituitary imaging abnormalities identified at follow-up. CONCLUSIONS: During prolonged follow-up, no symptomatic progression was noted in any of our patients. This study suggests that patients with macroprolactinemia and normal concentrations of monomeric prolactin can be reassured, and extended endocrine review of such patients is not required.

Effect of feeding Mucuna pruriens on helminth parasite infestation in lambs.

ETHNOPHARMACOLOGICAL RELEVANCE: Mucuna pruriens is a tropical legume anecdotally reputed to have anthelmintic properties. This study was conducted to examine the validity of such claims. AIM OF THE STUDY: The aim of this study was to determine if ingestion of Mucuna seeds reduces helminth parasite infestation in lambs. MATERIALS AND METHODS: Thirty-six Dorper x Katahdin ram lambs were assigned to three treatments, a cottonseed meal based control diet, a diet in which Mucuna replaced cottonseed meal and the control diet with levamisole (7.5mg/kg body weight) administration. All diets were isonitrogenous and isocaloric. The 12 lambs in each treatment were assigned randomly to 4 pens, each containing 3 lambs. Lambs were trickle infected three times per week by gavage with infectious Haemonchus contortus larvae (2000 larvae/lamb) for 3 weeks. RESULTS: Levamisole treatment decreased fecal egg counts by 87% and abomasal worm counts by 83%. Mucuna intake did not statistically affect fecal egg counts or abomasal worm counts, though numerical (P>0.10) reductions of 7.4% and 18.1%, respectively were evident. Anemia indicators, feed intake, and lamb growth were unaffected by treatment. CONCLUSIONS: Levamisole reduced the Haemonchus parasite burden in lambs significantly but feeding Mucuna reduced the burden by levels unlikely to eliminate the clinical effects of parasitism.

Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.

Cellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPARgamma ligands. We characterized 72 human subjects by relating their clinical phenotypes with functional pathway alterations. We transcriptionally profiled 364 biopsies harvested before and after hyperinsulinemic-euglycemic clamp studies, at baseline and after 3-month TZD treatment. We have identified molecular and functional characteristics of insulin resistant subjects and distinctions between TZD treatment responder and nonresponder subjects. Insulin resistant subjects exhibited alterations in skeletal muscle (e.g., glycolytic flux and intramuscular adipocytes) and adipose tissue (e.g., mitochondrial metabolism and inflammation) that improved relative to TZD-induced insulin sensitization. Pre-TZD treatment expression of MLXIP in muscle and HLA-DRB1 in adipose tissue from insulin resistant subjects was linearly predictive of post-TZD insulin sensitization. We have uniquely characterized coordinated cellular and tissue functional pathways that are characteristic of insulin resistance, TZD-induced insulin sensitization, and potential TZD responsiveness.

The effect of manipulation of basal pulsatile insulin on insulin action in Type 2 diabetes.

AIM: Disordered insulin pulsatility is associated with insulin resistant states including Type 2 diabetes. However, whether abnormal basal insulin pulses play a role in the pathogenesis of insulin resistance or are simply an associated feature remains undetermined. We investigated this relationship further by studying the effect of overnight (10 h) pulsatile insulin infusion on subsequent insulin sensitivity. METHODS: We studied 17 Type 2 diabetic patients who underwent one of two protocols. In protocol A (10 patients) on two separate nights we infused insulin 0.1 mU/kg/min either in a constant infusion or in pulses every 13 min. Octreotide (0.43 microg/kg/h) was given to suppress endogenous insulin secretion and physiological replacement of glucagon (30 ng/kg/h) administered. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp (2 mU/kg/min) next morning. In protocol B (seven patients), we employed the same experimental procedure but used a basal insulin infusion rate of 0.09 mU/kg/min in 7-min or 13-min pulses. RESULTS: Appropriate pulse patterns were confirmed in each protocol. In protocol A, after overnight infusions, glucose infusion rates required to maintain euglycaemia at steady state hyperinsulinaemia were similar (33.9 +/- 5.2 vs. 31.2 +/- 4.1 micromol/kg/min; P = NS). In protocol B, after overnight infusions the glucose infusion rates required during hyperinsulinaemia were significantly lower during 7-min pulses (39.9 +/- 5.7 vs. 44.7 +/- 5.6 micromol/kg/min; P < 0.05). CONCLUSION: There was no demonstrable priming effect derived from overnight pulsatile insulin compared with constant insulin infusion on subsequent insulin sensitivity in Type 2 diabetic subjects. The failure of 7-min pulses to exhibit an advantageous effect over 13-min pulses raises questions about the natural frequency of basal insulin pulses and their biological effect.

Comparison of the priming effects of pulsatile and continuous insulin delivery on insulin action in man.

Insulin is normally secreted in man in regular pulses every 5 to 15 minutes. Disordered pulsation has been demonstrated in several insulin-resistant states and it is unclear whether this represents a primary beta-cell defect contributing to impairment of peripheral insulin action or rather is a consequence of insulin resistance. Basal or near basal insulin administration by pulsatile infusion augments hypoglycemic effect and improves insulin-mediated glucose uptake compared with insulin by continuous infusion. To date no study has examined whether normal basal insulin pulsatility is required to preserve subsequent insulin sensitivity during hyperinsulinemia. We studied the effect of overnight pulsatile versus continuous basal insulin on a subsequent hyperinsulinemic euglycemic clamp. Nineteen normal volunteers (male:female ratio, 17:2; mean age +/- SEM, 26.1 +/- 2.3 years) were studied on 2 occasions each. Endogenous insulin secretion was inhibited by octreotide (0.43 microg kg(-1). h(-1)) and replaced overnight at 5.4 mU kg(-1). h(-1) either by continuous infusion or in 2-minute pulses every 13 minutes (n = 10) or every 7 minutes (n = 9). Glucagon was replaced at physiological concentration by continuous infusion (30 ng. kg(-1). h(-1)). Venous plasma glucose overnight was not significantly different between the pulsatile and continuous protocols. After discontinuing the overnight insulin infusion, insulin action was assessed during a hyperinsulinemic euglycemic clamp (1 mU kg(-1). h(-1)). Glucose infusion rates at steady-state during the hyperinsulinemic clamp were similar between continuous and both frequencies of pulsatile infusion (continuous 44.6 +/- 4.3 micromol. kg(-1). min(-1) v 13-minute pulsatile 41.7 +/- 5.9 micromol. kg(-1). min(-1), P =.27; continuous 34.6 +/- 2.5 micromol. kg(-1) min(-1) v 7-minute pulsatile 41.4 +/- 3.2 micromol. kg(-1). min(-1), P =.08). We conclude that overnight pulsatile compared with continuous insulin administration has no different effect on subsequent peripheral insulin-mediated glucose uptake. A priming effect cannot therefore explain the previously demonstrated association between endogenous insulin pulse frequency and peripheral insulin action.

Laboratory and clinical experience in 55 patients with macroprolactinemia identified by a simple polyethylene glycol precipitation method.

PRL exists in different forms in human serum. The predominant form is little PRL (molecular mass 23 kDa) with smaller amounts of big PRL (molecular mass 50--60 kDa) and at times big big or macroprolactin (molecular mass 150--170 kDa). The frequency and clinical consequences of macroprolactinemia have not been clearly established, mainly because of difficulty in identifying these patients biochemically. This previously required the use of gel filtration chromatography, which could not be used routinely. Recently, a screening test using polyethylene glycol (PEG) has been used to identify macroprolactin in serum. Consequently, this study was designed to examine the use of PEG precipitation in the identification of patients with a predominance of macroprolactin and to establish the clinical characteristics of such a cohort. Over 12 months, 18,258 requests for serum PRL were received and of these 1225 patients had a serum PRL more than 700 mU/L. A total of 322 of these patients (26%) had a percentage recovery after PEG precipitation of less than 40%, thus indicating the presence of a predominance of macroprolactin. Fifty-five of these patients were referred for detailed clinical assessment. Symptoms typical of hyperprolactinemia were not common in this cohort. None had sustained amenorrhea and eight have had oligomenorrhea at age less than 40 yr. One had galactorrhea. All had pituitary imaging, and four had a microadenoma with none having a macroadenoma. PEG precipitation allows easy identification of macroprolactin in routine clinical practice. As the clinical consequences of this entity at this stage seem relatively benign, referral and intensive investigation of these patients may not be necessary. However, follow-up of a large cohort is required to ensure that the long-term outlook is likewise benign. This would have important implications for both patients and healthcare systems.

Seasonal prevalence of third-stage larvae of Dirofilaria immitis in mosquitoes from Florida and Louisiana.

Heads of 109,597 mosquitoes collected during 1996 and 1997 from Gainesville, Florida (1996, n = 39,131; 1997, = 34,209), Bartow, Florida (1996, n = 12,000; 1997, n = 12,000), and Baton Rouge, Louisiana (1996, n = 12,257) were tested by a polymerase chain reaction and Southern hybridization-based test for the presence of third-stage larvae of the canine heartworm Dirofilaria immitis. Mosquito heads were pooled (1-200 heads) by month, locality, and species for testing. The test used was species specific for D. immitis and was capable of detecting DNA from a single larva in a pool of 200 mosquito heads. Specificity for the third larval stage was achieved by probing only mosquito heads. One or more D. immitis-infected mosquito heads were detected in each month of the year from Barrow in both 1996 and 1997. No infected mosquito heads were detected from Gainesville or Baton Rouge in December, January, February, or March. These results are in general agreement with previous sentinel dog and model prediction studies that showed heartworm transmission in the warm temperate Gulf coast region of the United States to be seasonal rather than continuous as previously believed.

Comparison of heartworm antigen test kit performance in dogs having low heartworm burdens.

Sensitivity and specificity of four in-clinic heartworm antigen test kits, AbboScreen (Abbott Laboratories), Snap PF (IDEXX Laboratories), Solo Step (HESKA Corporation), Witness (Synbiotics Corporation) and two heartworm antigen microwell plate assays, DiroCHEK (Synbiotics) and PetChek PF (IDEXX) were compared in a blinded study using serum or plasma drawn from 237 random source dogs, including 140 with necropsy-confirmed, low worm burden infections (minimum 1 worm, maximum 10, mean 2.3, median 3) and 97 confirmed heartworm-free at necropsy. In general, microwell format tests were more sensitive than membrane format tests and tests using ELISA technology were more sensitive than tests using lateral flow immunochromatographic technology. Percent sensitivity and specificity, respectively, were PetChek PF 76 and 97, DiroCHEK 71 and 94, SNAP PF 67 and 98, Solo Step 60 and 98, and AbboScreen 52 and 96. The Witness test protocol was changed by the manufacturer midway through the study, and the newer version of this test kit arrived containing a package insert alerting the user to a change in procedure, which purportedly resulted in improved sensitivity. PetChek was significantly more sensitive than all other tests except DiroCHEK and the new version of Witness. DiroCHEK was significantly more sensitive than all tests except PetCheck, SNAP and the new version of Witness. Snap was more sensitive than AbboScreen and the old version of Witness. Differences in specificity were not significant (P>0.05).

Relationship between microfilaria count and sensitivity of the direct smear for diagnosis of canine dirofilariosis.

Direct blood smear examination (using 0.05 ml of whole blood) detected 168 (80.9%) of 204 microfilaremic canine blood samples as determined by the modified Knott test for microfilariae (mff) of Dirofilaria immitis (using 1 ml of whole blood). Direct smear examination detected all of 134 microfilaremias greater than 50 mff ml(-1), but only 31 of 70 (44.3%) microfilaremias having less than 50 mff ml(-1). In a separate retrospective query of a database of 963 dogs with necropsy-confirmed heartworm infections, 834 (86.6%) were positive by the DiroCHEK heartworm antigen test, and 504 (52.3%) were microfilaremic by the modified Knott test. Only 2 (0.4%) of the microfilaremic dogs were DiroCHEK negative and another 18 (3.6%) were very weak positives. Although these microfilaremic dogs were not tested by direct smear, only one of the two DiroCHEK-negative and six of 18 weakly DiroCHEK-positive dogs had microfilaremias so low that a direct smear may have given a false negative result. Significant adverse reactions to either diethylcarbamazine or the macrolide endectocides have not been reported for microfilaremias less than 500 mff ml(-1), thus substitution of the direct smear for a concentration test for mff, such as the modified Knott test or membrane filtration, does not appear to increase the risk of an unexpected adverse reaction to heartworm prophylactic drugs. Such a substitution results in only a very slight decrease (on the order of 0.1%) in the overall sensitivity of heartworm screening, provided a test for mff is run concurrently with an antigen test. If a test for mff is the only screening test used, then substitution of a direct smear for a concentration test may decrease the sensitivity of heartworm screening by nearly 20%, depending on the prevalence of low level microfilaremias in the population of dogs tested.

The insulin hypoglycaemia and overnight metyrapone tests in the assessment of the hypothalamic-pituitary-adrenal axis following pituitary surgery.

OBJECTIVE: To compare the insulin hypoglycaemia test with the short overnight metyrapone test in the assessment of the hypothalamic-pituitary-adrenal (HPA) axis posthypophysectomy. DESIGN: Prospective comparative study of the insulin hypoglycaemia test and the overnight metyrapone test in 32 patients 4-6 weeks after pituitary surgery. SUBJECTS: Thirty-two patients with known pituitary disease. None with present or previous Cushing's syndrome. OUTCOME MEASUREMENTS: Maximum serum cortisol achieved during insulin induced hypoglycaemia compared with 0900 hours serum 11-deoxycortisol level following a weight related oral dose of metyrapone at 0000 h. RESULTS: One of the 32 patients required further surgery and was studied twice after each operation. Thirty-three results are therefore compared. Twenty-six of these had a normal cortisol response of 550 nmol/l or above leading to the cessation of replacement hydrocortisone. Six of these 26 patients however, failed the metyrapone test (11-deoxycortisol level less than 200 nmol/l). After 3-40 months (median 20 months) of follow-up off steroid therapy, no patient to date has displayed any clinical evidence of steroid deficiency. Of the seven patients who failed the insulin hypoglycaemia test, six also failed the metyrapone test. CONCLUSIONS: The overnight metyrapone test identified more patients with possible ACTH deficiency than the insulin hypoglycaemia test. Further follow-up of these patients is required before a final judgement can be made as to whether more subtle but clinically relevant ACTH deficiency can be detected by the metyrapone test. Our clinical follow-up to date would not support this.