Mahir A Hamad

Emergency colectomy for fulminant Clostridium difficile colitis: Striking the right balance

Abstract The number of reported cases of Clostridium difficile (CD) infections has increased markedly worldwide. CD causes a spectrum of clinical syndromes, ranging from mild diarrhea to a very severe illness in the form of pseudomembranous colitis (PMC), toxic megacolon, leading to colonic perforation, peritonitis, and even death. In todays practice, toxic megacolon is more often caused by pseudomembranous colitis than ulcerative colitis. There is urgent need to establish clear guidelines about how and when to refer patients with fulminant CD colitis to surgeons. Furthermore, there is no strict protocol for the timing of surgical intervention. The aim of this review is to review the available evidence about the criteria for referral to surgeons and timing for surgery. Medline search was carried out for articles published on fulminant CD colitis with emergency colectomy from 1966 to 2010. There were no prospective randomized trails. All retrospective cohort and case control studies were included. We excluded case reports, letters, and studies with less than five patients. Our search showed that patients with confirmed or suspected CD who failed to respond to maximum medical therapy and develop three of the following should be referral for surgical assessment: abdominal pain, abdominal distension, localized tenderness, pyrexia >38°C, and tachycardia >100 beats per minute. In addition to the above, if the patient is above 65 years old and develops four of the following, they should be considered for an emergency colectomy: WBC >16 × 109/l, lactate >2.2 mmol/l, albumin <30 g/l, blood pressure <90 mm Hg, CT/endoscopy evidence of severe colitis in spite of maximum anti-clostridial therapy. Colectomy still carries a high mortality rate; however, timely surgical intervention in fulminant CD colitis (FCDC) prevents many deaths in selected cases. In the absence of published prospective multicenter trial, we suggest that our criteria may enhance early diagnosis and consideration of early referral for surgery. Ultimately, this may reduce the significant morbidity and mortality associated with FCDC.

Statins as potential treatment for cholesterol gallstones: an attempt to understand the underlying mechanism of actions

Introduction: Statin therapy is widely used across the globe for the treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is associated with significant decreases in low-density lipoprotein cholesterol (LDL-C) and plasma cholesterol levels. Cholesterol gallstones are a common problem, resulting in hospital admission and surgery, throughout western healthcare systems. Areas covered: This review describes the mechanisms, and addresses the potential, for statins to be used as a treatment for gallstones. Medline was searched for the risk factors and treatment of cholesterol gallstones. Expert opinion: Obesity, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), insulin resistance and high-fat diets (unsaturated fats) rich in cholesterol are all associated risk factors for cholesterol gallstones. In view of the high prevalence of cholesterol gallstones, there is an urgent need to understand whether pharmacological therapies can be harnessed for the treatment of cholesterol gallstones. Gallstones are shown to be associated with an increased risk, not only of mortality, but also of CVD. Statins, widely used in prevention of CVD and hypercholesteremia, have been shown to dissolve cholesterol gallstones in animal models and human studies, highlighting the potential for a pharmacological therapy for gallstones. More studies are required to understand the role of statins in the treatment of gallstones and for comparison with current treatment strategies.

Treatment of idiopathic pulmonary fibrosis: Is there anything new?

Abstract:  Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic fibrosing interstitial pneumonia of unknown aetiology and is associated with the histological picture of usual interstitial pneumonia. Treatment in most cases is unsatisfactory and the prognosis remains poor. There is insufficient evidence to suggest that any treatment, apart from lung transplantation, improves survival or halts disease progression for IPF patients. Data on treatment response are limited by the paucity of clinical trails, the lack of homogenous clinical features, the small number of patients, and the absence of histological and radiological documentation in many cases. Anti‐inflammatory medications such as corticosteroids, azathioprine and cyclophosphamide remain the commonly used medications. More recently, it has been proposed that IPF is a primary fibrotic disease rather than an inflammatory condition. Antifibrotic agents such as colchicine, pirfenidone and interferon‐gamma (IFN‐γ) have been tried. However, a recent placebo‐controlled trial has failed to demonstrate a significant effect of IFN‐γ on disease progression, lung function or quality of life in IPF patients, though a clinically significant survival benefit of the drug could not be ruled out.

The safety and effectiveness of statins as treatment for HIV-dyslipidemia: the evidence so far and the future challenges

Introduction: Statin therapy is widely used across the globe for the treatment and prevention of cardiovascular disease (CVD). It is well established that statin therapy is associated with significant decrease in low-density lipoprotein cholesterol (LDL-C) and plasma cholesterol levels. HIV-dyslipidemia is a common problem with extensive use of combination antiretroviral therapy (CART), and is associated with an increase in incidence of cardiovascular disease (CVD), resulting in hospital admission and surgery throughout the western healthcare systems. Areas covered: This review describes the effectiveness and safety of statins in the treatment of HIV-dyslipidemia. Medline was searched for different statins as treatment for HIV-dyslipidemia. Expert opinion: Dyslipidemia in patients with HIV is different from the normal population, due to the fact that HIV treatment may not only cause dyslipidemia, but may also interact with lipid lowering medication. Statin-unresponsive HIV-dyslipidemia can be treated with the addition of ezetimibe, fenofibrate, fish oil and niacin. Current guidelines recommend the use of pravastatin and atorvastatin as first-line therapy, whereas European guidelines include rosuvastatin. There is an urgent need to confirm whether the use of statins in HIV-dyslipidemia is associated with an increase in the incidence of diabetes; this is significant because HIV patients are known to be insulin-resistant. HIV is also associated with Non-alcoholic Fatty Liver Disease (NAFLD), a condition known to be associated with insulin resistance. Further clinical trials are urgently needed to assess the impact of statins on CVD in HIV patients, and future challenges for researchers in this area are enormous.

Article conflates academic standards at UMST with student radicalisation

Gardham asserts that because it is easier to get into Sudanese medical schools academic standards are lower (even though they are endorsed by the General Medical Council) and that this draws British candidates who are then at risk of radicalisation.1 Is he suggesting that there is a conspiracy to radicalise through easy to enter medical schools? As a …

Pulmonary embolism: A diagnostic approach

Despite the availability of many diagnostic modalities and the advent of new tests, the diagnosis of pulmonary embolism (PE) remains a challenge. Clinical manifestations can be notoriously deceptive and there is not a single test, that can be relied on solely, to exclude PE. Although it has been regarded as the gold standard test, pulmonary angiography has not been tested against a reference standard and thromboembolic events have been reported after a normal study. Therefore the diagnosis of PE depends on judicious utilization of the available tests in the right clinical setting, as the accuracy of the results of the investigations, depends largely on the pretest clinical probability. Simple investigations such as chest radiograph, electrocardiogram and arterial blood gas, are used to enhance the clinical probabilities, rather than confirming or refuting the diagnosis of PE. On the other hand, Perfusion ventilation (VQ) scan and computerized tomographic pulmonary angiography (CTPA), are the main screening tests used for patients with suspected PE. Recently CTPA has largely replaced VQ scan, in many centres. As both VQ scan and CTPA have their limitations, other diagnostic modalities, such as D-dimer and Compression ultrasound of the legs (CUS), are used as adjunctive diagnostic investigations. High probability and normal VQ scan, especially when combined with the concordant clinical probability, has a high positive and negative predicative value, respectively. On the other hand, CTPA is more sensitive and specific than VQ scan, though it has to be combined with CUS and clinical probability, to reduce the chance of missing PE. Although many diagnostic algorithms have been advocated, the discretion of the clinician and clinical experience, still has a major role to play in the diagnosis of PE. In this article, we try to come with a plausible approach to the diagnosis of PE, based on the current literature.

Ambulatory emergency care – improvement by design

ABSTRACT Ambulatory emergency care (AEC) has been developed by clinicians as a means of providing emergency care without the traditional bed base of a hospital. Given that AEC is provided in a clinic-style setting, it can continue to operate during periods of high bed occupancy, alleviating bed pressures and continuing to provide timely care for selected patients. Although different models of AEC have developed according to local context, there are common principles that apply to AEC services, including early access to senior decision-makers, opening hours matching demand, access to diagnostics, close collaboration with other clinical services, a mixed workforce and patient selection processes. Some of the key AEC developments have been related to technology, including high-sensitivity troponin, low-molecular-weight heparins and computer tomography (CT) pulmonary angiography. Risk stratification tools are useful for assessing the appropriateness of using AEC as a care model for patients.

CHAPTER 38:Function and Effects of Niacin (Niacinamide, Vitamin B3)

Niacin is important in maintaining the pathway of generating energy within the cell and has shown benefits in protecting cells from apoptosis and DNA damage. Niacin also has an important role in the regulation of appetite, sleep and mood. Severe deficiency of niacin is associated with diarrhoea, dermatitis and dementia. Niacin has been widely used in the management of dyslipidaemia, atherosclerosis and coronary heart disease. Niacin is regarded as a wide spectrum lipid-lowering medication because it can decrease low density lipoprotein cholesterol (LDL-c) and triglyceride, and at the same time, increase high density lipoprotein cholesterol (HDL-c). Other unique benefits are that it is the only lipid-lowering medication that can decrease lipoprotein a, associated with an increase in cardiovascular disease (CVD). Niacin also possesses potent antioxidant and anti-inflammatory properties. Furthermore, niacin has shown potential benefit in lowering high plasma phosphate in chronic kidney disease (CKD) and in treating dyslipidaemia associated with CKD. Administration of niacin with statins has proved to be safe and effective in decreasing atherosclerosis, though flushing is a potential limitation of the wide use of niacin. Two important clinical trials will enhance our understanding of niacin and its impact on CVD. AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) is designed to test whether the drug combination of extended-release niacin plus simvastatin or simvastatin and ezetimibe is superior to simvastatin alone, at comparable levels of on-treatment LDL-c, for delaying the time to a first major cardiovascular disease outcome over a four-year median follow-up in patients with atherogenic dyslipidemia. The HPS2-THRIVE trial (Treatment of HDL to Reduce the Incidence of Vascular Events) will look at combining niacin with a new drug (MK-0524A) that minimizes niacins side-effects (chiefly facial flushing) to determine whether this can further drive down the risk of serious heart attacks and strokes among people already taking treatment to lower their bad ‘LDL’ cholesterol levels effectively.

Author's reply: statins and cholesterol gallstones: what we know, thought we knew and hope to gain

We thank the author for his comments [1]. Human studies have shown potential benefit of statins in treating cholesterol gallstones [2,3]. A summary of the mechanisms involved have been reviewed by Ahmed et al. [4]. Research to assess the impact of lipid-lowering medication on cholesterol gallstones is urgently needed due to various reasons, which include the association between cholesterol gallstones and cardiovascular disease [4]. The wide use of statins as treatment for cardiovascular disease may allow easy recruitment to studies looking at the effects of statins on cholesterol gallstones. The adverse effect of statins on insulin sensitivity and how that may modulate the formation of cholesterol gallstones is an exciting area for research [5]. It is well known that obesity and excess lithogenic diet are associated with formation of cholesterol gallstones [6]. Medication that prevents the absorption of intestinal lipid may provide an additional potential benefit in treating cholesterol gallstones. For example, the administration of ezetimibe (acts by decreasing intestinal cholesterol absorption) was associated with significant reduction in gallbladder stones in human and animal studies. Ezetimibe reduces intestinal cholesterol absorption by inhibiting the action of NiemannPick C1-like 1 (NPC1-L1), the main transporter of intestinal cholesterol which is highly expressed in the jejunum [7]. NPC1-L1 is also expressed in human liver. Administration of ezetimibe in a mouse gallstone model decreased serum cholesterol, prevented biliary crystals, normalized gallbladder wall fat and function, reduced intestinal cholesterol absorption by 35% and prevented the appearance of cholesterol crystals and gallstones [5]. Studies are needed to assess the effect of ezetimibe and the combination of statin and ezetimibe on cholesterol gallstones. The list of questions can be extended but at least finding an answer for these and the author’s [1] questions is what we hope to achieve in the near future.

Diagnostic approach to pulmonary embolism and lessons from a busy acute assessment unit in the UK

The diagnosis of pulmonary embolism (PE) can be very elusive and, if missed, may have fatal consequences. Conversely, PE can be over-diagnosed, with the concomitant risks associated with unnecessary anticoagulation. Although there are many tests that used in the diagnosis of PE, no test can exclude this condition with 100% certainty, and PE has been reported even after a negative pulmonary angiography. The diagnosis of PE depends on the interpretation of the available tests in the context of pre-test clinical probabilities. Ventilation/perfusion (V′/Q′) scan and computerised tomographic pulmonary angiography (CTPA) are the main screening tests used for patients with suspected PE. However, both V′/Q′ scan and CTPA have to be supplemented by other diagnostic modalities because of their diagnostic limitations. This article reviews the literature concerning the diagnosis of PE, with particular reference to the approach in our acute assessment unit. We conclude by describing two learning points from real cases presenting with suspected PE, in order to highlight how the diagnosis can be missed or made inaccurately.