Dyslipidaemia and the military patient.

Dyslipidaemias refer to abnormal levels of circulating lipids and high cholesterol and is related to cardiovascular death. This paper examines the types and prevalence of dyslipidaemia with specific reference to a military population and describes who to target in screening strategies used to detect people with abnormal lipid profiles. The diagnostic limits for a diagnosis of dyslipidaemia are explored. Finally, medical management of hyperlipidaemia is discussed and how this may affect military medical grading.

Novel substituted pyrimidines as HCV replication (replicase) inhibitors.

Compound 1 was identified as a HCV replication inhibitor from screening/early SAR triage. Potency improvement was achieved via modulation of substituent on the 5-azo linkage. Due to potential toxicological concern, the 5-azo linkage was replaced with 5-alkenyl or 5-alkynyl moiety. Analogs containing the 5-alkynyl linkage were found to be potent inhibitors of HCV replication. Further evaluation identified compounds 53 and 63 with good overall profile, in terms of replicon potency, selectivity and in vivo characteristics. Initial target engagement studies suggest that these novel carbanucleoside-like derivatives may inhibit the HCV replication complex (replicase).

Pyridofuran substituted pyrimidine derivatives as HCV replication (replicase) inhibitors.

Introduction of nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzofuran inhibitor 2, resulted in the discovery of the more potent pyridofuran analogue 5. Subsequent introduction of small alkyl and alkoxy ligands into the pyridine ring resulted in further improvements in replicon potency. Replacement of the 4-chloro moiety on the pyrimidine core with a methyl group, and concomitant monoalkylation of the C-2 amino moiety resulted in the identification of several inhibitors with desirable characteristics. Inhibitor 41, from the monosubstituted pyridofuran and inhibitor 50 from the disubstituted series displayed excellent potency, selectivity (GAPDH/MTS CC(50)) and PK parameters in all species studied, while the selectivity in the thymidine incorporation assay (DNA·CC(50)) was low.

Synthesis and SAR of geminal substitutions at the C5' carbosugar position of pyrimidine-derived HCV inhibitors.

The installation of geminal substitution at the C5' position of the carbosugar in our pyrimidine-derived hepatitis C inhibitor series is reported. SAR studies around the C5' position led to the installation of the dimethyl group as the optimal functionality. An improved route was subsequently designed to access these substitutions. Expanded SAR at the C2 amino position led to the utilization of C2 ethers. These compounds exhibited good potency, high selectivity, and excellent plasma exposure and bioavailability in rodent as well as in higher species.

Synthesis and SAR of pyridothiazole substituted pyrimidine derived HCV replication inhibitors.

Introduction of a nitrogen atom into the benzene ring of a previously identified HCV replication (replicase) benzothiazole inhibitor 1, resulted in the discovery of the more potent pyridothiazole analogues 3. The potency and PK properties of the compounds were attenuated by the introductions of various functionalities at the R(1), R(2) or R(3) positions of the molecule (compound 3). Inhibitors 38 and 44 displayed excellent potency, selectivity (GAPDH/MTS CC(50)), PK parameters in all species studied, and cross genotype activity.

5-Benzothiazole substituted pyrimidine derivatives as HCV replication (replicase) inhibitors.

Based on a previously identified HCV replication (replicase) inhibitor 1, SAR efforts were conducted around the pyrimidine core to improve the potency and pharmacokinetic profile of the inhibitors. A benzothiazole moiety was found to be the optimal substituent at the pyrimidine 5-position. Due to potential reactivity concern, the 4-chloro residue was replaced by a methyl group with some loss in potency and enhanced rat in vivo profile. Extensive investigations at the C-2 position resulted in identification of compound 16 that demonstrated very good replicon potency, selectivity and rodent plasma/target organ concentration. Inhibitor 16 also demonstrated good plasma levels and oral bioavailability in dogs, while monkey exposure was rather low. Chemistry optimization towards a practical route to install the benzothiazole moiety resulted in an efficient direct C-H arylation protocol.

Case series of non-freezing cold injury: the modern clinical syndrome.

BACKGROUND: Non-freezing cold injury (NFCI) occurs when peripheral tissue is damaged by cold exposure but not to the extent of freezing. Historically, the phenotype of NFCIs sustained was severe, whereas today the spectrum of injury represented in the UK military predominantly comprises subtler injuries. The diagnostic challenge of recognising these injuries, both in the acute and chronic settings, can lead to mismanagement and subsequent morbidity. METHODS: We characterised a recent case series of 100 UK Service Personnel referred with suspected NFCI to a Military UK NFCI clinic. We characterised the acute and chronic phenotype of those diagnosed with NFCI (n=76) and made comparison to those who received alternate diagnoses (n=24), to find discriminatory symptoms and signs. RESULTS: The most common acute symptoms of NFCI were the extremities becoming cold to the point of loss of feeling for more than 30 min (sensitivity 96%, specificity 90%, p<0.001), followed by a period of painful rewarming (sensitivity 81%, specificity 67%, p<0.001). In-field foot/hand inspections took place in half of the NFCI cases. Importantly, remaining in the field and undergoing multiple cycles of cooling and rewarming after an initial NFCI was associated with having double the risk of the NFCI persisting for more than a week. The most common and discriminant chronic symptoms and signs of NFCI were having extremities that behave differently during cold exposures (sensitivity 81%, specificity 75%, p<0.001) and having abnormal pinprick sensation in the affected extremity (sensitivity 88%, specificity 88%, p<0.001). CONCLUSIONS: A small collection of symptoms and signs characterise acute and chronic NFCIs and distinguish this vasoneuropathy from NFCI mimics.

Case series of non-freezing cold injury: epidemiology and risk factors.

BACKGROUND: Non-freezing cold injury (NFCI) occurs when the peripheral tissue is cooled sufficiently that damage occurs, but not to the point of tissue freezing. Historically, the phenotype of the injuries studied was often severe, and it is unclear whether knowledge gained from these cases is entirely relevant to the frequently subtle injuries seen today. METHODS: We therefore sought to characterise a recent case series of 100 patients referred with suspected NFCI to a military UK NFCI clinic. Their demographics, medical history and situational risk factors leading to their injuries were analysed, and comparison was made between those subsequently diagnosed with NFCI (n=76) and those receiving alternate diagnoses (n=24). RESULTS: Statistically significant predisposing factors for NFCI in the UK service personnel (SP) were being of African-Caribbean ethnicity and having a short duration of service in the Armed Forces. Past or current smoking was not identified as a risk factor. Injuries were almost always suffered on training exercises (most commonly in the UK); being generally cold and being on static duties were statistically significant situational risk factors. Non-significant trends of risk were also found for having wet clothing, wet boots and immersion. Self-reported dehydration was not found to be a risk factor for NFCI. CONCLUSIONS: Our demographic findings are in general agreement with those of previous studies. Our situational risk factor findings, however, highlight a pattern of NFCI risk factors to the modern UK SP: winter training exercises, when troops are generally cold and extremities often wet, with static duties frequently implicated in the disease mechanism.

Young Children's Structure Production: A Revision of the Index of Productive Syntax.

Purpose: The Index of Productive Syntax (IPSyn; Scarborough, 1990) is widely used to measure syntax production in young children. The goal of this article is to promote greater clarity and consistency in machine and hand scoring by presenting a revised version of the IPSyn (IPSyn-R) and comparing it with the original IPSyn (IPSyn-O). Method: Longitudinal syntax production in 10 30- and 42-month-old typically developing children drawn from the Child Language Data Exchange System (MacWhinney, 2000) Weismer corpus was examined, using both the IPSyn-O and the IPSyn-R. Results: The IPSyn-R provided nearly identical scores to the IPSyn-O with the exception of scores affected primarily by 1 modified noun phrase structure. Structures ranked as more advanced were produced less frequently. The results also reveal which of the IPSyn-R's 59 structures were most and least likely to be produced by this sample at these ages. Conclusions: The qualitative and quantitative differences between the IPSyn-O and the IPSyn-R are relatively minor. The IPSyn-R can make it easier to score the IPSyn, both by clinicians and researchers, and facilitate the IPSyn's move to machine scoring of language samples.

Topical treatments for fungal infections of the skin and nails of the foot.

BACKGROUND: Fungal infections of the feet normally occur in the outermost layer of the skin (epidermis). The skin between the toes is a frequent site of infection which can cause pain and itchiness. Fungal infections of the nail (onychomycosis) can affect the entire nail plate. OBJECTIVES: To assess the effects of topical treatments in successfully treating (rate of treatment failure) fungal infections of the skin of the feet and toenails and in preventing recurrence. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE and EMBASE (from inception to January 2005). We screened the Science Citation Index, BIOSIS, CAB - Health and Healthstar, CINAHL DARE, NHS Economic Evaluation Database and EconLit (March 2005). Bibliographies were searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) using participants who had mycologically diagnosed fungal infections of the skin and nails of the foot. DATA COLLECTION AND ANALYSIS: Two authors independently summarised the included trials and appraised their quality of reporting using a structured data extraction tool. MAIN RESULTS: Of the 144 identified papers, 67 trials met the inclusion criteria. Placebo-controlled trials yielded the following pooled risk ratios (RR) of treatment failure for skin infections: allylamines RR 0.33 (95% CI 0.24 to 0.44); azoles RR 0.30 (95% CI 0.20 to 0.45); ciclopiroxolamine RR 0.27 (95% CI 0.11 to 0.66); tolnaftate RR 0.19 (95% CI 0.08 to 0.44); butenafine RR 0.33 (95% CI 0.24 to 0.45); undecanoates RR 0.29 (95% CI 0.12 - 0.70). Meta-analysis of 11 trials comparing allylamines and azoles showed a risk ratio of treatment failure RR 0.63 (95% CI 0.42 to 0.94) in favour of allylamines. Evidence for the management of topical treatments for infections of the toenails is sparser. There is some evidence that ciclopiroxolamine and butenafine are both effective but they both need to be applied daily for prolonged periods (at least 1 year). The 6 trials of nail infections provided evidence that topical ciclopiroxolamine has poor cure rates and that amorolfine might be substantially more effective but more research is required. AUTHORS' CONCLUSIONS: Placebo-controlled trials of allylamines and azoles for athlete's foot consistently produce much higher percentages of cure than placebo. Allylamines cure slightly more infections than azoles and are now available OTC. Further research into the effectiveness of antifungal agents for nail infections is required.

Identification, preparation, and characterization of several polymorphs and solvates of terazosin hydrochloride.

The phenomenon of polymorphism is prevalent in pharmaceuticals, yet it is unusual to identify more than three or four forms for any particular drug. Terazosin hydrochloride has been found to exist at room temperature in four solvent-free forms that can be isolated directly, one solvent-free form that can be prepared by desolvation of a methanolate, a methanol solvate, and a dihydrate. This study presents characterization and methods for preparation of each of these forms. Data are also presented demonstrating the relative stability of these forms.

Interventions for chronic palmoplantar pustulosis.

BACKGROUND: Chronic palmoplantar pustulosis (PPP) is a chronic inflammatory skin condition characterised by crops of sterile pustules (yellow pus spots) on the palms and soles which erupt repeatedly over months or years. The affected areas tend to become red and scaly; cracks may form and these are often painful. Many different treatments have been used for palmoplantar pustulosis but none is generally accepted as being reliably effective. OBJECTIVES: To assess the effects of treatments for palmoplantar pustulosis, both in reducing disease severity and in maintaining remission once achieved. SEARCH STRATEGY: We searched the Cochrane Skin Group Specialised Register (January 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2003), MEDLINE (1966 to February 2003), EMBASE (1988 to February 2003). We also cross-checked with the Salford Database of Psoriasis Trials and reference lists of articles. We also contacted authors included trials, members of the Cochrane Skin Group and dermatologists interested in psoriasis. SELECTION CRITERIA: Any randomised controlled trial in which patients with chronic palmoplantar pustulosis were randomised to receive one or more interventions. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed trial eligibility and quality. Study authors were contacted for additional information. Adverse effects information was collected from the trials. MAIN RESULTS: Twenty-three trials involving 724 people were included. There is evidence supporting the use of systemic retinoids (improvement rate difference 44%, 95 CI 28 to 59%), oral PUVA (improvement rate difference 44%, 95 CI 26 to 62%). However, a combination of PUVA and retinoids is better than the individual treatments. The use of topical steroid under hydrocolloid occlusion is beneficial. It would also appear that low dose ciclosporin, tetracycline antibiotics and Grenz Ray Therapy may be useful in treating PPP. Colchicine has a lot of side effects and it is unclear if it is effective and neither was topical PUVA (rate difference of 0.00, 95% CI -0.04 to +0.04). There is no evidence to suggest that short-term treatment with hydroxycarbamide (hydroxyurea) is effective. AUTHORS' CONCLUSIONS: Many different interventions were reported to produce "improvement" in PPP. There is, however, no standardised method for assessing response to treatment, and reductions in pustule counts or other empirical semi-quantitative scoring systems may be of little relevance to the patient. This review has shown that the ideal treatment for PPP remains elusive and that the standards of study design and reporting need to be improved to inform patients and those treating them of the relative merits of the many treatments available to them.

Interventions for photodamaged skin.

BACKGROUND: Photodamage describes skin changes such as fine and coarse wrinkles, roughness, freckles and pigmentation changes that occur as a result of prolonged exposure to the sun. Many treatments are available to reverse the damage, but it is unclear which work and at what cost in terms of unwanted side effects. OBJECTIVES: To assess the effects of topically applied treatments, tablet treatments, laser and surgical procedures for photodamaged skin. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, Issue 1 2002, MEDLINE (1966-June 2002), EMBASE (1974-June 2002), Health Periodicals (1976-June 2002). We checked references of articles and communicated with authors and the pharmaceutical industry. SELECTION CRITERIA: Randomised controlled trials which compared drug or surgical interventions with no treatment, placebo or another drug, in adults with mild, moderate or severe photodamage of the face or forearms. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. MAIN RESULTS: Thirty studies of variable quality were included. Eight trials showed that topical tretinoin cream, in concentrations of 0.02% or higher, was superior to placebo for participants with mild to severe photodamage on the face and forearms (although losses to follow-up were relatively high in most studies). For example, the relative risk of improvement for 0.05% tretinoin cream, compared to placebo (three studies), at 24 weeks, was 1.73 (95% confidence interval 1.39 to 2.14). This effect was not seen for 0.001% topical tretinoin (one study) or 0.01% (three studies). A dose-response relationship was evident for both effectiveness and skin irritation. One small within-patient study showed benefit from topical ascorbic acid compared with placebo. Tazarotene (0.01% to 0.1%) and isotretinoin (0.1%) both showed significant improvement over placebo for moderate photodamage (one study each). There is limited evidence (one trial), to show that the effectiveness of 0.05% tretinoin, is equivalent to the effects of 0.05% and 0.1% tazarotene. One small study showed greater improvement in upper lip wrinkles with CO2 laser technique compared to Baker's phenol chemical peel, at 6 months. Three small RCTs comparing CO2 laser with dermabrasion found no difference in wrinkle score at 4 to 6 months, suggesting that both methods are equally efficacious, but more erythema was reported with the laser. The effectiveness of other interventions such as hydroxy acids and natural polysaccharides was not clear. AUTHORS' CONCLUSIONS: There is conclusive evidence that topical tretinoin improves the appearance of mild to moderate photodamage on the face and forearms, in the short term. However erythema, scaling/dryness, burning/stinging and irritation may be experienced initially. There is limited evidence that tazarotene and isotretinoin benefit patients with moderate photodamage on the face: both are associated with skin irritation and erythema. The effectiveness of other interventions remains uncertain.

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune bullous disease in the West. Oral steroids are considered the standard treatment. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH STRATEGY: We searched the Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE to March 2003 and bibliographies from identified studies. SELECTION CRITERIA: Randomised controlled trials of treatments for patients with immunofluorescence confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the studies in terms of the inclusion criteria, five extracted data independently; disagreements were resolved by discussion. Statistical pooling of the data was inappropriate because of heterogeneity of treatments. MAIN RESULTS: We found seven randomised controlled trials with a total of 634 patients. All studies involved different comparisons, none included a placebo group. Different doses, different formulations of corticosteroids and the addition of azathioprine failed to show significant differences in measures of disease control. However, patients who took azathioprine were able to almost halve the amount of prednisone required for disease control. Plasma exchange plus prednisone achieved significantly better disease control than prednisone alone; this favourable effect was not apparent in another study. The latter study also compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality, although total adverse events at six months almost reached statistical significance in favour of plasma exchange plus prednisone. Comparing tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was shown. A very potent topical corticosteroid was compared to oral prednisone in patients with moderate and extensive disease. In patients with extensive disease, the topical steroid group showed significantly better survival and disease control, and less severe complications, while no significant differences for these outcomes were seen in patients with moderate disease. Most of the reported deaths were in patients taking high doses of oral corticosteroids. AUTHORS' CONCLUSIONS: Very potent topical steroids are effective and safe treatments for bullous pemphigoid; their use in extensive disease may be limited by side effects and practical factors. Starting doses of prednisolone greater than 0.75 mg/kg/day do not seem to give additional benefit, lower doses may be adequate for disease control; this could reduce the incidence and severity of adverse reactions. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide may be useful; this needs further validation.

Interventions for rosacea.

BACKGROUND: Rosacea is a common chronic skin condition affecting the face, characterised by flushing, redness, pimples, pustules, and dilated blood vessels. The eyes are often involved. Frequently it can be controlled, but it is not clear which treatments are most effective. OBJECTIVES: To assess the evidence for the efficacy and safety of treatments for rosacea. SEARCH STRATEGY: We searched the Skin Group Specialised Register (February 2005), Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), EMBASE (1980 to February 2005), BIOSIS (1970 to March 2002) and the Science Citation Index (1988 to February 2005). Reference lists of trials and key review articles were searched. Relevant manufacturers and experts were contacted. SELECTION CRITERIA: Randomised controlled trials in people with moderate to severe rosacea were included. Studies judged by the authors to have seriously flawed methodology were excluded. DATA COLLECTION AND ANALYSIS: Study selection, assessment of methodological quality, data extraction and analysis were carried out by two independent authors. Disagreements were resolved by discussion and consensus. MAIN RESULTS: The evidence provided by twenty-nine included studies was generally weak because of poor methodology and reporting. One of our primary outcome measures, 'quality of life', was not assessed in any of the studies. Only two studies of ocular rosacea were included. Pooled data from two trials involving 174 participants indicated that according to the participants, topical metronidazole is more effective than placebo (odds ratio (OR) 5.96, 95% confidence interval (CI) 2.95 to 12.06). Data pooled from three between-patient trials showed a clear improvement in the azelaic acid group; the rates of treatment success were approximately 70 to 80% versus 50% to 55% (OR 2.45, 95% CI 1.82 to 3.28). A within-patient trial of azelaic cream versus placebo could not be pooled with the other three studies, but also showed good evidence of efficacy. Data pooled from three studies of oral tetracycline versus placebo involving 152 participants showed that, according to physicians, tetracycline was effective (OR 6.06, 95% CI 2.96 to 12.42). Some evidence of efficacy of oral metronidazole was provided by one small study. AUTHORS' CONCLUSIONS: The quality of studies evaluating rosacea treatments was generally poor. There is evidence that topical metronidazole and azelaic acid are effective. There is some evidence that oral metronidazole and tetracycline are effective. There is insufficient evidence concerning the effectiveness of other treatments. Good RCTs looking at these treatments are urgently needed.

Synthesis and pharmacokinetic and pharmacodynamic evaluation of the forodesine HCl analog BCX-3040.

Forodesine HCl is a potent inhibitor of the enzyme purine nucleoside phosphorylase (PNP) and is currently in clinical trials for the treatment of leukemia and lymphoma. Animal models indicated that forodesine HCl would have low oral bioavailability in humans and it was initially developed as an intravenous formulation. We were interested in identifying analogs of forodesine HCl with improved oral bioavailability. The 2'-deoxy analog (BCX-3040) was synthesized and its pharmacokinetic and pharmacodynamic properties compared with forodesine HCl.

The tactile circumferential discriminator. A new, simple screening device to identify diabetic patients at risk of foot ulceration.

OBJECTIVE: To evaluate the tactile circumferential discriminator (TCD) (Tacticon Medical Enterprises, West Chester, PA), a new, simple, handheld quantitative sensory testing device, in the identification of patients at potential risk of neuropathic ulceration. RESEARCH DESIGN AND METHODS: Patients with diabetes (n = 133) attending the Manchester Diabetes Centre or diabetic foot clinic seen within a 5-week period were assessed using the TCD, monofilaments, and vibration perception threshold (VPT) measured over the hallux. The sensitivity and specificity of each method in the identification of "high-risk" patients were compared. RESULTS: The TCD was easy to use, and there was a highly significant correlation between the results obtained compared with both filaments and VPT (P < 0.0001). Similarly, in the identification of patients at risk of ulceration, the TCD agreed with VPT in 75.2% of cases and with the monofilaments in 78.9%. In the identification of the 37 foot ulcer patients, TCD was highly sensitive (100%) but less specific (58.3%) than VPT (86.5%; 79.2%) and the monofilaments (91.9%; 76.0%). CONCLUSIONS: These data suggest that the TCD is a simple and reliable new technique for population screening for neuropathy and foot ulcer risk.

Efficacy of injected liquid silicone in the diabetic foot to reduce risk factors for ulceration: a randomized double-blind placebo-controlled trial.

OBJECTIVE: To investigate the effectiveness of injecting liquid silicone in the diabetic foot to reduce risk factors for ulceration in a randomized double-blind placebo-controlled trial. RESEARCH DESIGN AND METHODS: A total of 28 diabetic neuropathic patients without peripheral vascular disease were randomized to active treatment with 6 injections of 0.2 ml liquid silicone in the plantar surface of the foot or to treatment with an equal volume of saline (placebo). No significant differences were evident regarding age or neuropathy status between the 2 groups. All injections were under the metatarsal heads at sites of calluses or high pressures. Barefoot plantar pressures (pedobarography) and plantar tissue thickness under the metatarsal heads (Planscan ultrasound device) were measured at baseline and at 3, 6, and 12 months after the first injection. Injection sites were photographed at all stages, and callus formation was scored as a change from baseline. Throughout the study, patients were treated by the same podiatrist for all podiatry treatment. RESULTS: Patients who received silicone treatment had significantly increased plantar tissue thickness at injection sites compared with the placebo group (1.8 vs. 0.1 mm) (P < 0.0001) and correspondingly significantly decreased plantar pressures (-232 vs. -25 kPa) (P < 0.05) at 3 months, with similar results at 6 and 12 months. A trend was noted toward a reduction of callus formation in the silicone-treated group compared with no change in the placebo group. CONCLUSIONS: The results confirm the efficacy of plantar silicone injections in reducing recognized risk factors associated with diabetic foot ulceration.

Evaluation of an electrochemical sensor for measuring blood ketones.

OBJECTIVE: To evaluate the performance of a hand-held ketone sensor that is able to measure blood beta-hydroxybutyrate (beta-HBA) concentrations within 30 s in patients with diabetic ketoacidosis (DKA) and patients who attend a weight management clinic. RESEARCH DESIGN AND METHODS: Two groups of patients were studied: 19 patients admitted with DKA and 156 patients attending a weight management clinic. Paired capillary and venous whole blood samples were measured using the ketone sensor and also using an enzymatic laboratory reference method. RESULTS: The ketone sensor accurately measured beta-HBA concentrations in patients with DKA (limits of agreement -0.9 to + 1.0 mmol/l) or starvation-induced ketonemia (limits of agreement -0.5 to +0.5 mmol/l). CONCLUSIONS: This ketone sensor accurately measures whole blood beta-HBA concentrations within 30 s.