Micafungin was shown to be as efficacious as caspofungin in treating patients with candidaemia and invasive candidiasis (IC). However, it remains unknown if micafungin or caspofungin is a cost-effective definitive therapy for candidaemia and IC in Turkey. The present study aimed to determine the economic impact of using micafungin versus caspofungin for treatment of candidaemia and IC in the Turkish setting. A decision analytic model was constructed and was populated with data (i.e. transition probabilities, duration of initial antifungal treatment, reasons for treatment failure, percentage of patients who stepped down to oral fluconazole, and duration on oral fluconazole) obtained from a published randomised clinical trial. Cost inputs were derived from the latest Turkish resources while data that were not readily available in the literature were estimated by expert panels. One-way sensitivity analyses, threshold analyses, scenario analyses and probabilistic sensitivity analyses were conducted. Caspofungin (€2693) incurred a lower total cost than micafungin (€4422), with a net cost saving of €1729 per treated patient. Drug acquisition cost was the main cost driver for both study arms. The model outcome was robust over wide variations (of ±100.0% from the base case value) for all input parameters except for micafungin drug cost and the duration of initial treatment with micafungin. Caspofungin appears to be a cost-saving option in treating candidaemia and IC from the Turkish hospital perspective.
Immunosuppressive agents are used for the treatment of immune-mediated myocarditis; however, the need to develop a more effective therapeutic approach remains. Nano-sized liposomes may accumulate in and selectively deliver drugs to an inflammatory lesion with enhanced vascular permeability. The aims of this study were to investigate the distribution of liposomal FK506, an immunosuppressive drug encapsulated within liposomes, and the drug's effects on cardiac function in a rat experimental autoimmune myocarditis (EAM) model. We prepared polyethylene glycol-modified liposomal FK506 (mean diameter: 109.5 ± 4.4 nm). We induced EAM by immunization with porcine myosin and assessed the tissue distribution of the nano-sized beads and liposomal FK506 in this model. After liposomal or free FK506 was administered on days 14 and 17 after immunization, the cytokine expression in the rat hearts along with the histological findings and hemodynamic parameters were determined on day 21. Ex vivo fluorescent imaging revealed that intravenously administered fluorescent-labeled nano-sized beads had accumulated in myocarditic but not normal hearts on day 14 after immunization and thereafter. Compared to the administration of free FK506, FK506 levels were increased in both the plasma and hearts of EAM rats when liposomal FK506 was administered. The administration of liposomal FK506 markedly suppressed the expression of cytokines, such as interferon-γ and tumor necrosis factor-α, and reduced inflammation and fibrosis in the myocardium on day 21 compared to free FK506. The administration of liposomal FK506 also markedly ameliorated cardiac dysfunction on day 21 compared to free FK506. Nano-sized liposomes may be a promising drug delivery system for targeting myocarditic hearts with cardioprotective agents.
A young male presented with many years of delusions and hallucinations, with concurrent heroin use and subsequent amphetamine uses. There were no depressive or manic symptoms and psychotic symptoms prior to the amphetamine use. After the trials of two atypical antipsychotics and later clozapine due to treatment resistance, adherence and functionality were poor and there was still persistent drug use. As a result, a long acting injectable adjunct was commenced, but only minimal effects were observed. However after initiation of directly observed treatment of clozapine with methadone, there has been functional and clinical response and drug use has ceased.
Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.
Cancer is one of the most common causes of death in the developed world, with one-third of people diagnosed with cancer during their lifetime. Oral cancer commonly occurs involving the buccal mucosa (cheeks), tongue, floor of the mouth and lip. It is one of the most devastating and disfiguring of malignancies. Morinda citrifolia L., commonly known as ‘noni’, belongs to the Rubiaceae family. It is native to the Pacific islands, Hawaii, Caribbean, Asia and Australia. The plant displays broad curative effects in pharmacological studies. Damnacanthal (DAM) and Nordamnacanthal (NDAM), anthraquinone compounds isolated from the roots of Morinda citrifolia L., has been used for the treatment of several chronic diseases including cancer. The objectives of this study were to evaluate cytotoxicity, morphological changes, cell death mode (apoptosis/necrosis), and cell migration induced by DAM and NDAM on the most common type of oral cancer, oral squamous cell carcinoma (OSCC)cells. Anti-proliferative effects of these compounds against OSCC cell lines were determined by MTT assay. The mode of cell death was analysed by phase contrast and fluorescent microscopy as well as flow cytometry. In addition, cell migration was assessed. The results showed that DAM and NDAM exerted cytotoxicity against OSCC cells with IC50 values of 1.9 to >30 μg/ml after 72 h treatment. Maximum growth inhibition among the tested cell lines for both compounds was observed in H400 cells, and thus it was selected for further study. The study demonstrated inhibition of H400 OSCC cell proliferation, marked apoptotic morphological changes, induction of early apoptosis, and inhibition of cell migration by DAM and NDAM. Therefore, this information suggests that these compounds from noni have potential for used as anti tumor agents for oral cancer therapy.
Gefitinib inhibits the epidermal growth factor receptor tyrosine kinase and improves survival in patients with non-small-cell lung cancer. We report 2 patients with extensive lytic bony metastasis in the spine and pelvis secondary to advanced pulmonary adenocarcinoma who were treated with gefitinib and had remarkable bone formation in the lytic bone lesions in the spine and pelvis. Surgery for stabilisation was avoided.
INTRODUCTION: The introduction of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) has led to the reduction of mortality and the improvement of the quality of life of people living with HIV/AIDS (PLWHA). The present study was conducted to determine the pattern of adherence to HAART among PLWHA, and to assess the factor(s) affecting nonadherence, if any.
METHODS: This study was a hospital-based analytical, cross-sectional epidemiological study conducted between July and October 2011. A total of 370 adult HIV-positive patients registered in the Antiretroviral Therapy Centre of Burdwan Medical College and Hospital, West Bengal, India, were included. Nonadherence was defined as missing at least a single dose of medicine within the last four days. Data was analysed using the Statistical Package for the Social Sciences version 19.0 (IBM Corp, Armonk, NY, USA).
RESULTS: A total of 87.6% of patients were found to be adherent to HAART. Principal causes of nonadherence were forgetting to take medicine (70.2%), being away from home (65.2%), and busyness with other things (64.7%). Multivariate logistic regression analysis revealed that nonadherence was significantly associated with a positive family history of HIV/AIDS (odds ratio [OR] 16; 95% confidence interval [CI] 2.2-114.3; p = 0.01), occurrence of side effects with HAART (OR 9.81; 95% CI 1.9-51.7; p = 0.01) and employment (OR 5.93; 95% CI 1.5-23.2; p = 0.01).
CONCLUSION: Although overall adherence was high, the factors that affect nonadherence can be addressed with proper counselling and motivation of patients and their family members. Adherence to HAART could delay the progression of this lethal disease and minimise the risk of developing drug resistance.
Matched MeSH terms: Acquired Immunodeficiency Syndrome/drug therapy; HIV Infections/drug therapy
We report a case of systemic diffuse large B-cell lymphoma presenting with extensive infiltration of the skin. A 56-year-old woman presented with a two-month history of pruritic erythematous plaques and nodules over the neck, trunk and upper limbs. She also had night sweats, weight loss, lethargy and reduced effort tolerance. Systemic examination revealed a pale, ill appearance with hepatosplenomegaly and lymphadenopathy. Blood investigations showed pancytopenia (haemoglobin 6.3 g/dL, total white cell count 3.0 × 10(9)/L, platelet count 138 × 10(9)/L) with a few suspicious mononuclear cells and a mildly elevated lactate dehydrogenase level (478 U/L). Skin biopsy demonstrated diffuse sheets and nodular infiltrates of CD20 and CD79a positive neoplastic cells in the dermis and subcutis. Computed tomography revealed multiple cervical, axillary, mediastinal, para-aortic and mesenteric lymph nodes. Bone marrow aspiration and trephine biopsy confirmed marrow involvement by non-Hodgkin's lymphoma. The patient was treated with chemotherapy, which resulted in resolution of the skin lesions.
Malignant Otitis Externa (MOE) can cause considerable morbidity and mortality in affected individuals. The outlook is now much improved with the use of ciprofloxacin, but it is important to ascertain that the infection has been completely eradicated before stopping treatment, as undertreatment may lead to a recurrence which is usually more resistant than the initial infection. Gallium-67 Single Photon Emmision Computerised Tomography (SPECT) is a sensitive and cost effective tool in monitoring the disease activity of MOE, and should be used in the assessment of the response to antibiotic therapy.
Candida species is now being increasingly recognised as an important cause of endocarditis especially in immunocompromised patients. A case of Candida albicans endocarditis in a child with acute lymphoblastic leukemia (ALL) is reported. The child did not have a central venous catheter at any time. Treatment consisted of intravenous amphotericin B and fluconazole for 3 weeks followed by oral fluconazole for 2 weeks. No surgical resection was necessary. We highlight here the importance of echocardiography in the management of prolonged febrile neutropenia and discuss the dilemma of continuing chemotherapy in such patients.
Omeprazole has been shown to have a suppressive effect on Helicobacter pylori. The aim of this study was to determine if prolonged treatment with omeprazole would result in a higher eradication rate than short course treatment. Twenty patients with endoscopy proven duodenal ulcers and unequivocal evidence of Helicobacter pylori (HP) infection based on culture, histology, urease test and Gram's stain of a fresh tissue smear were treated with omeprazole 40 mg om for 2-4 weeks. Following ulcer healing, patients received either maintenance omeprazole 20 mg om or placebo for up to one year. All 20 patients had healed ulcers following a 2-4 week course of omeprazole 40 mg om.. All were negative for HP at the end of treatment. Thirteen patients received short course therapy with omeprazole only, followed by placebo. On follow-up endoscopy at 3 months, only one of 13 (7.7%) had eradicated the bacteria. Seven patients received maintenance treatment with omeprazole 20mg om for one year. Following completion of treatment, patients were followed up at 1, 3 and 6 months. Only one of 7 (14.3%) patients had eradicated the infection on long term follow-up. The eradication rates of HP with both short and long course omeprazole monotherapy were low.
INTRODUCTION: The primary purpose of this study was to evaluate the utilisation pattern and seizure outcome of newer and older antiepileptic drugs in paediatric clinical practice in a Malaysian hospital setting.
METHODS: Over a two-month period, all paediatric epilepsy patients from Penang General Hospital, Malaysia who were diagnosed according to the classification of the International League Against Epilepsy were followed up prospectively, and the patients' information was gathered with the help of a validated data collection form. This included demographic characteristics, monotherapy and polytherapy of antiepileptic drugs, as well as the number of seizures experienced.
RESULTS: Partial seizures, including complex and simple partial seizures (47.2 percent), followed by generalised seizures (40 percent), were the most common seizure types found in this study. An average of 1.51 antiepileptic drugs per patient was prescribed, with 54.3 percent of the patients on monotherapy and 45.7 percent on polytherapy. Overall, sodium valproate was the most frequently prescribed antiepileptic drug (36.8 percent), followed by carbamazepine (30.2 percent) and lamotrigine (10.4 percent). Carbamazepine was the most frequently prescribed monotherapy (28.6 percent), followed by sodium valproate (17.1 percent). The newer antiepileptic drugs were also found to be used as monotherapy in 7.2 percent of the cases. Moreover, a significant difference was observed between the older and newer antiepileptic drugs in terms of the number of seizures experienced (p=0.027). Most (75 percent) of the seizure-free patients were on carbamazepine monotherapy.
CONCLUSION: Monotherapy was the most frequently used remedy in all forms of epilepsy. Overall, sodium valproate was the most commonly used drug, while carbamazepine was found to be more frequently used as monotherapy. There was a significant difference found between the older and newer antiepileptic drugs, with 87.5 percent of seizure-free patients on older antiepileptic drugs.
Study site: all paediatric epilepsy patients from Penang General Hospital
Matched MeSH terms: Drug Therapy, Combination; Seizures/drug therapy*
INTRODUCTION: This retrospective review evaluates the prognostic indicators in the management of sudden sensorineural hearing loss (SSNHL) in otorhinolaryngology patients admitted to Brunei RIPAS Hospital.
METHODS: The review covered data collected from 1996 to 1998, and included patients who were treated with naftidrofuryl and dexamethasone. Their hearing improvement (more than 20 dB) in relation to pure tone audiogram patterns, hearing loss severity, vertigo, age of the patients and duration from symptom onset to time of treatment, were evaluated.
RESULTS: After exclusion of three patients with known causes of hearing loss, 50 patients with idiopathic SSNHL were reviewed. Six audiogram patterns were observed with good prognostic indicators in patterns 1 and 4, where respectively, 95 percent and 100 percent of the patients improved. The hearing improvement was noted in the majority of the patients with mild or moderate degree of hearing loss, especially noticeable in audiogram patterns 1 and 4. Initial vertigo gave poor prognosis in hearing (more than 33 percent patients with vertigo improved versus 88 percent patients without vertigo improved). Patients aged between 21 and 60 years appear to have better prognosis of hearing improvement compared to those who are outside of this age range. 92 percent patients whose treatment started within the first week of onset of hearing loss experienced hearing improvement compared to 84 percent patients whose treatment started in the second week after onset.
CONCLUSION: Fairly consistent with the previously-reported prognostic indicators are hearing loss severity, vertigo, age and duration of onset to treatment, though there was reasonably good prognosis when the patients were treated in the second week from hearing loss onset. Further findings of note were the six audiogram patterns and the good prognostic indicators in patterns 1 and 4.
Matched MeSH terms: Drug Therapy, Combination; Hearing Loss, Sensorineural/drug therapy
Non-tuberculous mycobacterial infection (NMI) occurs in elderly women with no pre-existing lung disease, and this has been termed the Lady Windermere syndrome. NMIs are increasing in prevalence and an increasing number of pulmonary mycobacterial infections is due to non-tuberculous mycobacteria. The diagnosis is often difficult because the organism is not readily isolated or cultured, and the condition may not be considered by the radiologist. We report NMI in a 64-year-old woman, based on clinical and radiological findings. Although termed the Lady Windermere syndrome, the name does not correspond to the character in Oscar Wilde's play; hence the eponym is not widely used.
The surgical treatment of Stage III or aggressive giant cell tumour of the bone, whether to perform intralesional or en-bloc resection, remains controversial. The aim of this study is to identify the effectiveness of en-bloc resection for local control and final oncological outcome of the disease.
Melioidosis is caused by an infection by Burkholderia pseudomallei. Osteomyelitis is a recognised manifestation of melioidosis but Burkholderia pseudomallei is a relatively rare aetiological agent in musculoskeletal infections. We report a 32-year-old diabetic man with septicaemia due to melioidotic infection of the spleen, liver and distal femur. The osteomyelitis relapsed despite being treated with the standard radical debridement and insertion of gentamycinimpregnated polymethylmetacrylate (PMMA) beads, followed by an optimal antibiotic therapy. The PMMA-gentamycin beads were then removed. The bone defect was debrided and packed with calcium hydroxyapatite blocks filled with ceftazidime powder. The osteomyelitis was successfully treated and the patient remained free of infection four years postoperatively. Computed tomography demonstrated successful incorporation of the calcium hydroxyapatite into host bone.
A set of twins born to a 24-year-old primigravida had evidence of sepsis 24 to 60 hours after birth and were treated empirically with penicillin and gentamicin. A non-encapsulated H. influenzae biotype IV strain was isolated from the blood cultures of both and from the CSF of twin II. The isolates were beta-lactamase positive and hence showed resistance to ampicillin and therapy was changed to chloramphenicol only. Twin II recovered but Twin I developed a brain abscess in the left occipital region which resolved with extended antibiotic treatment. Although ampicillin-resistant H. influenzae have been reported in Malaysia, invasive disease by such strains are rare.
One hundred and thirty-seven children with Campylobacter diarrhoea were reviewed. The predominant species was C. jejuni. Ninety-five percent of the children were below 5 years of age with 61% of these being 2-12 months old. A slight male preponderance was noted. About half the cases presented with fever and bloody diarrhoea; vomiting was seen in 28% and abdominal colic in only 8%. Moderate to severe diarrhoea was present in 48% of the children. Thirty-seven percent had a history of recent or concurrent illness. Other bacterial enteropathogens together with Campylobacter were isolated in 15% of the children. Erythromycin, the most useful drug, when indicated for Campylobacter infections, had an MIC90 of 2 mg/l with 96.2% of the strains being sensitive.
A study was undertaken to determine the extent of morbidity associated with asthma and to audit the management of asthma in two out-patient clinics of two district hospitals. Patients were recruited for the study during a 3-month period from December 1990 to February 1991. Seventy asthmatic patients were studied. Eighty-six percent of the patients had their sleep disturbed by asthma, 77% took daily medication regularly, 63% felt that their activities were restricted by asthma, 60% had at least one acute exacerbation in the preceding six months. Of those who had their peak expiratory flow rate (PEFR) measured, 40% had a PEFR below 50% predicted, and only 11% had normal PEFR (greater than 80% predicted). The morbidity of asthma was thus considerable. On the other hand, the drug treatment of these asthmatics was grossly inadequate. They were prescribed on average 2.1 item of drugs, which for most patients comprised an oral beta agonist and a theophylline. Only 43% of the patients received inhaler therapy, but no patients were given steroids, inhaled or oral. The drug treatment was unrelated to the severity of patients' asthma. Further, objective measurement of severity was under-used in the assessment of asthma, only 8.5% of patients ever had their PEFR recorded. This study has found that asthma is poorly managed in out-patient clinics. We need to improve the training of doctors in the optimal management of asthma.
Study site: General outpatient clinics, district hospitals, Pahang, Malaysia
Matched MeSH terms: Asthma/drug therapy; Drug Therapy, Combination