Clinical approach to renal tubular acidosis in adult patients.

Int J Clin Pract. 2011 Mar;65(3):350-60

Authors: Reddy P

Renal tubular acidosis (RTA) is a group of disorders observed in patients with normal anion gap metabolic acidosis. There are three major forms of RTA: A proximal (type II) RTA and two types of distal RTAs (type I and type IV). Proximal (type II) RTA originates from the inability to reabsorb bicarbonate normally in the proximal tubule. Type I RTA is associated with inability to excrete the daily acid load and may present with hyperkalaemia or hypokalaemia. The most prominent abnormality in type IV RTA is hyperkalaemia caused by hypoaldosteronism. This article extensively reviews the mechanism of hydrogen ion generation from metabolism of normal diet and various forms of RTA leading to disruptions of normal acid-base handling by the kidneys.

PMID: 21314872 [PubMed - in process]

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Nonagenarian surgical admissions for the acute abdomen: who benefits?

Int J Clin Pract. 2010 Oct;64(11):1570-1572

Authors: Toumi Z, Kesterton A, Bhowmick A, Beveridge AJ, Scott NA

Introduction:  Patients 90 years and older form an increasing proportion of the general population. Outcomes of their acute surgical admissions are not well documented. Methods and materials:  Surgical management of 49 consecutive nonagenarian admissions (median age: 92 years) with an acute abdomen was compared with the management and outcome of 50 younger patients (median age: 53.5) admitted with a suspected acute abdomen over the same period. Results:  Nonagenarian group consisted of mainly women (71% vs. 50%; p = 0.003). The use of laboratory investigations and imaging was similar for the patients aged over 90 and the younger patients, although proportionately fewer nonagenarians were investigated by abdominal CT scan (8% vs. 24%). Of the 49 nonagenarian patients admitted, only 4% (n = 2) were operated on. In contrast, 38% (n = 19) of patients aged 50-59 (p = 0.0001) underwent a surgical intervention. A much greater proportion of nonagenarians died in hospital than patients in the 50-59 comparator group (16% nonagenarians vs. 4% comparator patients; p = 0.04). The very large majority of survivors in both age groups were discharged back to their preadmission domicile [39 (95%) nonagenarians vs. 46 (96%) comparator 50-59 year group]. Conclusions:  In this study, when compared with younger patients, very few nonagenarian patients (2%) with a suspected acute abdomen benefited from surgical admission. Instead, the large majority of nonagenarians either died or were discharged back to their home address without surgery.

PMID: 20846205 [PubMed - as supplied by publisher]

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Adherance to protocol during the acute management of diabetic ketoacidosis: would specialist involvement lead to better outcomes?

Int J Clin Pract. 2010 Oct;64(11):1580-1582

Authors: Devalia B

Background:  Diabetic ketoacidosis (DKA) is a hyperglycaemic emergency associated with major morbidity and mortality. It has been shown that treating patients admitted with DKA using an integrated care pathway, or protocol, reduces time taken to initiate management thus optimising care. Early input from diabetes specialist services should also be sought. A new protocol for managing DKA was introduced in Sherwood Forest Trust in July 2008. Aims:  To assess whether the trust DKA protocol is being followed at Kingsmill and Newark District General Hospitals during acute management (first 4 h) of patients. Methods:  Retrospective case note review of all adult patients coded as DKA from July 2008 to February 2009. Results:  Seventy-eight percent of patients were correctly diagnosed according to protocol. Hundred percent of patients had IV access and correct blood tests within 1 h of admission. Eighty percent were given appropriate fluid resuscitation within the first hour. Seventy-two percent had correct insulin prescribed and 73% were on the correct sliding scale. Seventy-eight to ninety percent of patients had correct initial investigations ordered. However only 46% of patients requiring High Dependency Unit care were referred appropriately. Between hours 2 and 4 only 38% had repeat electrolytes checked and only 35-60% of patients had the correct fluid prescribed. Conclusions:  The findings indicated that there was awareness of the new DKA protocol. It was referred to and placed in clinical notes but not always followed. Management of patients with DKA within the first hour was compliant. However, subsequent fluid management and electrolyte monitoring was poor. It was found that using a protocol does help to standardise initial management of patients but further education is needed and referral criteria need clarifying. Access to 24-hour specialist services may also help to optimise management.

PMID: 20846206 [PubMed - as supplied by publisher]

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Statin use and the prevention of venous thromboembolism: a meta-analysis.

Int J Clin Pract. 2010 Sep;64(10):1375-83

Authors: Agarwal V, Phung OJ, Tongbram V, Bhardwaj A, Coleman CI

Aims: Statins are thought to have antithrombotic properties and may attenuate patients’ odds of developing venous thromboembolism (VTE), but clinical studies have yielded variable estimates of this effect. The aim was to conduct a meta-analysis to evaluate the effect of statin use on development of VTE. Methods: Randomised controlled trials (RCTs) and observational studies evaluating the effects of statins on the incidence of VTE were selected from MEDLINE (1996 to August 2009), Cochrane CENTRAL (second quarter, 2009), Cochrane Database of Systematic Reviews (second quarter, 2009) and a manual review of references. While no further restrictions were placed on RCTs, observational studies were only included if they reported adjusted effect sizes using appropriate methods. Development of deep vein thrombosis (DVT), pulmonary embolism (PE) and any VTE from RCTs and observational studies were pooled using traditional meta analytic techniques with a random-effects model. Results: Ten studies were identified and eligible for meta-analysis. Upon meta-analysis, statin use was associated with a statistically significant reduction in the odds of developing VTE (AOR 0.68, 95% CI 0.54-0.86), DVT (AOR 0.59, 95% CI 0.43-0.82) and PE (AOR 0.70, 95% CI 0.53-0.94). Discussion: Statin use is associated with significantly reduced odds of developing VTE, DVT or PE by 32%, 41% and 30% respectively. Our meta-analysis included one RCT, JUPITER, which alone provided statistically significant reduction in the odds of developing VTE and DVT (43% and 55% respectively), and a nonsignificant reduction on PE. Conclusion: Currently available evidence suggests that statins can reduce patients’ odds of developing VTE.

PMID: 20716146 [PubMed - in process]

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Lack of effect of statins on maintenance of normal sinus rhythm following electrical cardioversion of persistent atrial fibrillation.

Int J Clin Pract. 2010 Jul;64(8):1116-20

Authors: Bhardwaj A, Sood NA, Kluger J, Coleman CI

Summary Randomised controlled trials evaluating the effect of statin use on maintenance of normal sinus rhythm (NSR) after electrical cardioversion (ECV) of persistent atrial fibrillation (AF) have demonstrated conflicting results. However, many of these trials were of relatively small size and thus underpowered to adequately evaluate this end-point. The aim of this study was to conduct a meta analysis evaluating the effect of statin use on maintenance of NSR after ECV of persistent AF. Randomised controlled trials evaluating the use of statins to maintain NSR after ECV of AF were identified through a systematic search including Medline (1950 through December 2009), the Cochrane CENTRAL Register (4th quarter, 2009) and a manual review of references without any language restrictions. Pooled estimates of effect are reported as relative risks (RRs) with accompanying 95% confidence intervals (CIs) using a random-effects model. Four trials (n = 424; range: 48-212) were identified and subject to meta analysis. Evaluated statins included atorvastatin 10 and 80 mg and pravastatin 40 mg/day. Over a mean of 2.1 months (range: 1-3 months) statins did not increase the likelihood of maintaining NSR following ECV (RR, 1.12; 95%CI, 0.85-1.46) compared with control. Current evidence does not suggest that statins are associated with an increased probability of maintaining NSR following ECV of persistent AF.

PMID: 20642710 [PubMed - in process]

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How should we treat a patient with early Parkinson’s disease?

Int J Clin Pract. 2010 Aug;64(9):1210-9

Authors: Tsouli S, Konitsiotis S

Parkinson’s disease (PD) is characterised by the progressive degeneration of dopaminergic nigro-striatal neurons and severe striatal dopaminergic deficiency, leading to bradykinesia. Levodopa was the first drug used for PD treatment and is still considered the most useful weapon for the control of PD symptoms. However, levodopa treatment induces motor complications, which is considered as a major problem as the disease progresses. Dopamine agonists, catechol-O-methyltransferase inhibitors and monoamine oxidase B inhibitors are some more recently developed drug categories which are expected to have a more favourable effect on motor complications. The choice of the best initial treatment in PD remains a controversial matter. Early therapeutic decisions in PD should balance the need for efficient short-term symptom control against long-term complication profile. The individualisation of the treatment seems to be the key for the best approach of early PD patients.

PMID: 20653797 [PubMed - in process]

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Evaluation of NT-proBNP to predict outcomes in advanced heart failure.

Int J Clin Pract. 2010 Jun;64(7):892-9

Authors: Macgowan GA, Neely D, Peaston R, Wrightson N, Parry G

Aims: To determine which factors predict outcomes in a group of patients with advanced heart failure, and in particular if NT-proBNP provides additional clinical and prognostic information to other haemodynamic and biochemical data. Methods and Results: Ninety-one patients were studied who were being evaluated for heart transplantation, with 166 assessments. The patients had advanced heart failure as determined by median cardiac index of 2.0 l/min/m(2), left ventricular end-diastolic diameter of 7.0 mm and levels of NT-proBNP of 2473 pg/ml. Median follow-up time was 359 days. Clinicians were blinded to NT-proBNP levels. NT-proBNP significantly correlated with cardiac index (R = -0.44, p < 0.001), right atrial pressure (R = 0.40, p < 0.001), pulmonary arterial wedge pressure (R = 0.38, p < 0.001) and albumin (R = -0.52, p < 0.001), and total bilirubin with right atrial pressure (R = 0.59, p < 0.001). Cardiac index was the most important independent predictor of outcome (p = 0.0001), although bilirubin (p = 0.001) and NT-proBNP (p < 0.05) were also significant. In patients with a 50% increase in NT-proBNP, 64% had adverse outcomes, whereas those in whom levels were stable, 22% had adverse outcomes (p < 0.05). Conclusion: Cardiac index is the primary independent predictor of outcome in advanced heart failure when haemodynamic deterioration is evident. In situations where invasive haemodynamics are not available, total bilirubin (reflecting hepatic congestion) and NT-proBNP (related to haemodynamics) also provide important prognostic information.

PMID: 20584222 [PubMed - in process]

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Rhythm control agents and adverse events in patients with atrial fibrillation.

Int J Clin Pract. 2010 May 12;

Authors: Taylor CJ, Hodgkinson J, Hobbs FD

Summary Background: Atrial fibrillation (AF) is the commonest rhythm disorder and has major impact on patients. Controversy remains about the best treatment strategy between rate and rhythm control (in addition to adequate thromboprophylaxis). Rhythm control agents are associated with clinically important adverse events. Aim: The aim of this study was to assess the risk of adverse events in patients with AF receiving rhythm control agents. Design of study: This is a retrospective case control note review and outcome linkage analysis. Setting: Setting of this study included patients with a diagnosis of AF receiving amiodarone, flecainide or sotalol in practices registered with the General Practice Research Database (GPRD) in the UK. Method: This is a retrospective case control note review and outcome linkage analysis on the GPRD routine clinical dataset to evaluate the adverse events and predictors of treatment discontinuation in patients using licenced rhythm modifying medication. Results: Adverse events are more common in patients currently or previously taking amiodarone, flecainide or sotalol than age- and gender-matched controls. All three antiarrhythmics were associated with increased all-cause mortality. Congestive heart failure was more common in all amiodarone and sotalol users as well as past users of flecainide. Thyroid disease was more common in patients treated with amiodarone and sotalol but only amiodarone had an increased risk of pulmonary toxicity. The number of patients with liver failure was too small in all cases for statistical analysis. Conclusion: The rhythm control agents amiodarone, flecainide and sotalol have significant adverse effects which can lead to discontinuation of their use. This should be considered when deciding the most appropriate treatment option for patients with AF.

PMID: 20487051 [PubMed - as supplied by publisher]

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Diagnostic issues in the clinical management of pericarditis.

Int J Clin Pract. 2010 May 10;

Authors: Imazio M, Spodick DH, Brucato A, Trinchero R, Markel G, Adler Y

Summary Aims: To review the current major diagnostic issues on the diagnosis of acute and recurrent pericarditis. Methods: To review the current available evidence, we performed a through search of several evidence-based sources of information, including Cochrane Database of Systematic Reviews, Clinical Evidence, Evidence-based guidelines from National Guidelines Clearinghouse and a comprehensive Medline search with the MeSH terms 'pericarditis', 'etiology' and 'diagnosis'. Results: The diagnosis of pericarditis is based on clinical criteria including symptoms, presence of specific physical findings (rubs), electrocardiographical changes and pericardial effusion. Although the aetiology may be varied, most cases are idiopathic or viral, even after an extensive diagnostic evaluation. In such cases, the course is often benign following anti-inflammatory treatment, and management would be not affected by a more precise diagnostic evaluation. A triage of pericarditis can be safely performed on the basis of the clinical and echocardiographical presentation. Specific diagnostic tests are not warranted if no specific aetiologies are suspected on the basis of the epidemiological background, history and presentation. High-risk features associated with specific aetiologies or complications include: fever > 38 degrees C, subacute onset, large pericardial effusion, cardiac tamponade, lack of response to aspirin or a NSAID. Conclusions: A targeted diagnostic evaluation is warranted in acute and recurrent pericarditis, with a specific aetiological search to rule out tuberculous, purulent or neoplastic pericarditis, as well as pericarditis related to a systemic disease, in selected patients according to the epidemiological background, presentation and clinical suspicion.

PMID: 20487049 [PubMed - as supplied by publisher]

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Fluoroquinolones in the management of community-acquired pneumonia.

Int J Clin Pract. 2010 Feb;64(3):378-88

Authors: Albertson TE, Dean NC, El Solh AA, Gotfried MH, Kaplan C, Niederman MS

AIMS: Review of the current guidelines for the use of respiratory fluoroquinolones in the management of community-acquired pneumonia (CAP). METHODS: Data were collected from recent clinical trials on fluoroquinolone therapy in patients with CAP and from updated recommendations of antimicrobial therapy in managing CAP, with a focus on current North American guidelines. RESULTS: Randomised clinical trials of respiratory fluoroquinolones (moxifloxacin, levofloxacin and gemifloxacin) in the treatment of CAP were identified and analysed. The bacteriology of CAP, and susceptibility rates, resistance rates and pharmacokinetic and pharmacodynamic properties of fluoroquinolones against causative pathogens in CAP, and adverse event profiles of these agents were described. Respiratory fluoroquinolones have broad-spectrum antibacterial activities against common causative pathogens in CAP and provide an important treatment option as monotherapy for outpatients with comorbidities and inpatients who are not admitted to the intensive care unit (ICU), including those with risk factors of drug-resistant Streptococcus pneumoniae. For treatment of ICU patients with severe CAP, it is recommended that fluoroquinolones be used in combination with a beta-lactam. Recent studies also demonstrated a more rapid resolution of clinical symptoms with the use of highly potent respiratory fluoroquinolones. DISCUSSION: Appropriate use of fluoroquinolone agents may shorten the duration of antimicrobial therapy and the length of hospital stay and contribute to the decreased development of resistance in patients with CAP. Adverse event profiles of these agents should be considered to facilitate the selection of an appropriate fluoroquinolone for appropriate CAP patients. CONCLUSION: The fluoroquinolone class, specifically those with adequate activity against respiratory pathogens, represents an important and convenient treatment option for patients with CAP.

PMID: 20456176 [PubMed - in process]

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Low-grade fever: how to distinguish organic from non-organic forms.

Int J Clin Pract. 2010 Feb;64(3):316-21

Authors: Affronti M, Mansueto P, Soresi M, Abbene AM, Affronti A, Valenti M, Giannitrapani L, Montalto G

BACKGROUND AND AIM: Low-grade fever (LGF) is defined as a body temperature between 37.5 and 38.3 degrees C, which is below the classical value reported for fever of unknown origin (FUO). We attempted to characterise its epidemiology, aetiology and clinical aspects to improve the methodological approach to diagnosis. DESIGN AND METHODS: We reviewed and evaluated a survey of patients with LGF, followed as outpatients of our Department, a tertiary referral centre from 1997 to 2008. The same classifications were applied for classical FUO, and in the patients diagnosed with LGF, we also investigated for habitual hyperthermia (HH). RESULTS: Seventy-three patients were selected and divided into two groups: group A included 32 patients classified with organic fever and group B included 41 patients with HH. Aetiology of organic LGF was: infectious disease 59%; neoplasm 3.1%; inflammatory non-infectious disease 6.2%; miscellaneous 18.7%; undiagnosed 12.5%. Mean age was significantly higher in the organic fever than in the HH group (p < 0.02). Splenomegaly and loss of weight were significantly associated with organic fever (p < 0.05), while dizziness and general malaise were associated with HH. Lack of any pathological signs at physical examination was significantly more frequent in HH (p < 0.0001). Among the biochemical tests, white blood cells and C-reactive protein were more frequently above normal limits in group A than in group B (p < 0.05). CONCLUSIONS: In our experience, LGF requires the same methodological diagnostic approach as FUO, because there is no relationship between body temperature values and the severity of the underlying diseases, and the aetiological spectrum is also the same.

PMID: 20456171 [PubMed - in process]

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Sitagliptin: review of preclinical and clinical data regarding incidence of pancreatitis.

Int J Clin Pract. 2010 Apr 14;

Authors: Engel SS, Williams-Herman DE, Golm GT, Clay RJ, Machotka SV, Kaufman KD, Goldstein BJ

Summary Recent case reports of acute pancreatitis in patients with type 2 diabetes (T2DM) treated with incretin-based therapies have triggered interest regarding the possibility of a mechanism-based association between pancreatitis and glucagon-like peptide-1 mimetics or dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review was to describe the controlled preclinical and clinical trial data regarding the incidence of pancreatitis with sitagliptin, the first DPP-4 inhibitor approved for use in patients with T2DM. Tissue samples from multiple animal species treated with sitagliptin for up to 2 years at plasma exposures substantially in excess of human exposure were evaluated to determine whether any potential gross or histomorphological changes suggestive of pancreatitis occurred. Sections were prepared by routine methods, stained with haematoxylin and eosin and examined microscopically. A pooled analysis of 19 controlled clinical trials, comprising 10,246 patients with T2DM treated for up to 2 years, was performed using patient-level data from each study for the evaluation of clinical and laboratory adverse events. Adverse events were encoded using the Medical Dictionary for Regulatory Activities (MedDRA) version 12.0 system. Incidences of adverse events were adjusted for patient exposure. Tissue samples from preclinical studies in multiple animal species did not reveal any evidence of treatment-related pancreatitis. The pooled analysis of controlled clinical trials revealed similar incidence rates of pancreatitis in patients treated with sitagliptin compared with those not treated with sitagliptin (0.08 events per 100 patient-years vs. 0.10 events per 100 patient-years, respectively). Preclinical and clinical trial data with sitagliptin to date do not indicate an increased risk of pancreatitis in patients with T2DM treated with sitagliptin.

PMID: 20412332 [PubMed - as supplied by publisher]

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The Glasgow Blatchford scoring system enables accurate risk stratification of patients with upper gastrointestinal haemorrhage.

Int J Clin Pract. 2010 Mar 10;

Authors: Srirajaskanthan R, Conn R, Bulwer C, Irving P

Summary Background: Upper gastrointestinal (UGI) haemorrhage is a frequent cause of hospital admission. Scoring systems have been devised to identify those at risk of adverse outcomes. We evaluated the Glasgow Blatchford score's (GBS) ability to identify the need for clinical and endoscopic intervention in patients with UGI haemorrhage. Methods: A retrospective observational study was performed in all patients who attended the A&E department with UGI haemorrhage during a 12-month period. Patients were separated into low and high risk categories. High risk encompassed patients who required blood transfusions, operative or endoscopic interventions, management on high dependency or intensive care units, and those who re-bled, represented with further bleeding, or who died. Results: A total of 174 patients were seen with UGI bleeding. Eight of them self-discharged and were excluded. Of the remaining 166, 94 had a 'low risk' bleed, and 72 'high risk'. The GBS was significantly higher in the high risk (median = 10) than in the low risk group (median 1, p < 0.001). To assess the validity of the GBS at separating low and high risk groups, receiver-operator characteristic (ROC) curves were plotted. The GBS had an area under ROC curve of 0.96 (95% CI 0.95-1.00). When a cut-off value of >/= 3 was used, sensitivity and specificity of GBS for identifying high risk bleeds was 100% and 68%. Thus at a cut-off value of </= 2 the GBS is useful for distinguishing those patients with a low risk UGI bleed. Conclusions: The GBS accurately identifies low risk patients who could be managed safely as outpatients.

PMID: 20337750 [PubMed - as supplied by publisher]

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Intensification with prandial insulin.

Int J Clin Pract. 2009 Oct;63(s164Insulin Intensification Summit):11-14

Authors: Pfützner A, Forst T

Aims: Many patients with type 2 diabetes will ultimately need insulin therapy to maintain their target for glycaemic control. This review considers how best to achieve the target for glycaemic control in primary care. Methods: Literature review and workshop discussions among participants at the Insulin Intensification Summit. Results: Treatment aimed at reducing postprandial glucose is more effective in improving glycaemic control near target levels. Adding prandial doses of a short-acting insulin is superior to switching to a twice-daily premixed insulin. Short-acting analogue insulins offer advantages over animal insulins for intensification of basal insulin therapy, which can be achieved either by sequentially adding prandial doses or immediate introduction of three-times daily prandial dose. Each approach has benefits depending on the health care system and can be supported in primary care by a simple algorithm. Conclusion: Intensification of basal insulin therapy is most effectively achieved by adding a prandial short-acting insulin analogue, using a simple clinical algorithm. The regimen should be selected according to local needs.

PMID: 19930415 [PubMed - as supplied by publisher]

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Underutilisation of cardiovascular medications among at-risk individuals.

Int J Clin Pract. 2009 Nov 11;

Authors: Lewis SJ, Robinson JG, Fox KM, Grandy S,

Summary Aims: Guidelines recommend antihypertensive, lipid-lowering and/or antiplatelet therapy for prevention of cardiovascular disease (CVD). This study examined the utilisation of cardiovascular therapies among individuals at CVD risk to assess adherence to guidelines. Methods: Respondents to the SHIELD study were classified based on National Cholesterol Education Program Adult Treatment Panel III risk categories. High coronary heart disease (CHD) risk (n = 7510) was defined as self-reported diagnosis of heart disease/heart attack, narrow or blocked arteries, stroke or diabetes; moderate risk (n = 4823) included respondents with >/= 2 risk factors (i.e., men > 45 years, women > 55 years, hypertension, low high-density lipoprotein cholesterol, smoking and family history of CHD); and low risk (n = 5307) was 0-1 risk factor. Respondents reporting a myocardial infarction, stroke or revascularisation at baseline (prior CVD event) (n = 3777), those reporting a new CVD event during 2 years of follow up (n = 953), and those with type 2 diabetes mellitus (n = 3937) were evaluated. The proportion of respondents reporting treatment with lipid-lowering, antiplatelet or antihypertensive agents was calculated. Results: Utilisation of lipid-lowering therapy was low (</= 25%) in each group. Prescription antithrombotic therapy was minimal among respondents with prior CVD events, but 47% received antihypertensive medication. No use before or after a new CVD event was reported by 36% of respondents for lipid-lowering, 32% for antithrombotic and > 50% for antihypertensive medications. Conclusions: More than 50% of at-risk respondents and > 33% of respondents with new CVD events were not taking CVD therapy as recommended by guidelines.

PMID: 19909379 [PubMed - as supplied by publisher]

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