Gallstones and Clonorchis sinensis infection: A hospital-based case–control study in Korea

Background and Aim:  A high prevalence of intrahepatic stones in some areas of East Asia has been believed to be related with Clonorchis sinensis infection. The authors conducted a hospital-based case–control study to evaluate the role of Clonorchis sinensis infection as a risk factor for the development of gallstones in Korea.
Methods:  The cases of 138 patients with gallstones (intrahepatic 44, gallbladder 67, and extrahepatic 27) and matched controls underwent microscopy for C. sinensis , serological tests for C. sinensis using enzyme-linked immunosorbent assay, radiological examinations, and interviews concerning the history of eating raw freshwater fish. We assessed a relationship of three types of gallstones and variables regarding C. sinensis by using univariate and multivariate statistical analyses.
Results:  Univariate statistical analyses showed that radiological evidence of C. sinensis and recent history of eating raw freshwater fish were related to an increased risk of intrahepatic stones ( P  = 0.0002 and 0.0039, respectively). According to multivariate statistical analyses, radiological evidence of C. sinensis was the only risk factor for intrahepatic stones (odds ratio = 7.835; 95% confidence interval = 1.671–36.724). Any evidence regarding C. sinensis was not related to an increased risk of either gallbladder or extrahepatic stones.
Conclusion:  Radiological evidence of C. sinensis was significantly associated with intrahepatic stones.     

Lifestyle risk factors for intrahepatic stone: Findings from a case–control study in an endemic area, Taiwan

Background and Aim:  To examine associations between lifestyle risk factors and intrahepatic stone (IHS), we conducted a case–control study in Taiwan, which has the highest incidence of IHS in the world.
Methods:  Study subjects were 151 patients newly diagnosed with IHS at Chang Gung Memorial Hospital between January 1999 and December 2001. Two control subjects per case were selected randomly from patients who underwent minor surgery at the same hospital and from family members or neighbors of the hospital staff. Controls were matched to each case by age and gender. Information on lifestyle factors was collected using a self-administered questionnaire. Strength of associations was assessed using odds ratios derived from conditional logistic models.
Results:  Female patients were significantly shorter than female controls. Compared to subjects with two or fewer children, odds ratios for those with six or more children were 20.4 in men (95% confidence interval, 1.89–221) and 2.82 (0.97–8.22) in women. Increasing level of education lowered the risk of intrahepatic stone (trend P  = 0.004 for men and < 0.0001 for women). Women who had consumed ground-surface water for a long period had a somewhat increased risk (trend P  = 0.05).
Conclusion:  Lower socioeconomic status and poor hygiene may be involved in the development of intrahepatic stones.     

Environmental, socio-demographic and behavioural determinants of malaria risk in the western Kenyan highlands: a case–control study

Objective  To identify risk factors for uncomplicated malaria in highland areas of East Africa at higher risk of malaria epidemics, in order to design appropriate interventions.
Methods  Prospective, population-based, case–control study in the Nandi Hills, a highland area of western Kenya, to identify environmental, sociodemographic and behavioural factors associated with clinical malaria. Data were collected using field observation, a structured questionnaire, and a global positioning system device.
Results  We interviewed 488 cases of slide-confirmed malaria and 980 age-matched controls. Multivariate analyses associated higher malaria risk with living <250 m of a forest [OR = 3.3 (95% CI 1.5, 7.1)], <250 m of a swamp [2.8 (1.3, 5.9)], <200 m of maize fields [2.0 (1.2, 3.4)], in the absence of trees <200 m [1.6 (1.2, 2.2)], on flat land [1.6 (1.2, 2.2)], in houses without ceilings [1.5 (1.1, 2.2)], in houses with a separate kitchen building [1.8 (1.4, 2.3)] and in households where the female household head had no education [1.9 (1.1, 3.1)]. Travelling out of the study site [2.2 (1.2, 4.1)] was also associated with increased risk.
Conclusions  In this East African highland area, risk of developing uncomplicated malaria was multifactorial with a risk factor profile similar to that in endemic regions. Households within close proximity to forest and swamp borders are at higher risk of malaria and should be included in indoor residual spraying campaigns.     

Vaccination of patients with haematological malignancies with one or two doses of influenza vaccine: a randomised study

An open, randomised study was performed to determine whether two doses of influenza vaccine were more effective than one to elicit an immune response in 70 patients with haematological malignancies. The responses were not improved by two doses compared with one (influenza A virus serotypes H1/N1 18% vs. 22% and H3/N2 26% vs. 14%; influenza B 25% vs. 22%). The results were similar in patients with ongoing and discontinued therapy. Patients treated with monoclonal antibodies for lymphoma had very poor responses. We conclude that two doses of influenza vaccine do not improve the antibody response in patients with haematological malignancies.     

Differences in incidence and trends of haematological malignancies in Japan and the United States

The incidence of a malignant disease reflects the genetic and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trends of a disease in different populations may provide insights into its aetiology and pathogenesis. To evaluate the incidence of haematological malignancies according to specific subtypes, we used population‐based registry data in Japan (N = 125 148) and the United States (US; N = 172 925) from 1993 to 2008. The age‐adjusted incidence of haematological malignancies in Japan was approximately one‐half that in the US but has been increasing significantly, whereas no significant change was seen in the US [annual percent change (95% C confidence interval): Japan, +2·4% (1·7, 3·1); US, +0·1% (?0·1, 0·2)]. Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) showed the largest differences in incidence, with the most remarkable differences observed for chronic lymphocytic leukaemia, HL‐nodular sclerosis, mycosis fungoides and cutaneous T‐cell lymphoma. HL and NHL are increasing substantially in Japan but not in the US, suggesting that environmental exposures, such as Westernization of the life style may be causing this increase. Differences in the incidence and trends for specific subtypes also showed a marked contrast across subtypes, which, in turn, may provide significant new insights into disease aetiology in the future.     

Exposure to myelotoxic agents and myelodysplasia: case–control study and correlation with clinicobiological findings

To better define the role of exposure to myelotoxic agents in the genesis of myelodysplastic syndrome (MDS), we carried out (a) a case–control study for the determination of the relative risk (RR) of developing MDS, including 178 consecutive patients and 178 sex- and age-matched controls; (b) a study of clinicobiological features in MDS arising after occupational exposure to myelotoxic agents and in MDS in ‘non-exposed’ patients. The definition of the ‘exposure’ status was based on a predetermined questionnaire, with calculation of an ‘exposure’ index (hours/day × days/year × years). Cumulative exposure to pesticides or to organic solvents, for >2400 h, was recorded in 48 and 25 MDS patients, respectively, compared to 27 and four controls (P < 0.00001; RR 3.74; 95% confidence interval 2.02–5.37). Older age and an excess of refractory anaemia with ringed sideroblasts and refractory anaemia with excess of blasts was noted among ‘exposed’ MDS-patients (group 1), compared to non-exposed MDS-patients (group 2). 68.3% patients in group 1 had clonal chromosome changes, compared with 43.2% patients in group 2. Complex karyotypes, ?7/7q?, ?5/5q?, +8, 7p and 17p aberrations were seen more frequently in group 1, whereas a normal karyotype, isolated 5q? or 20q? occurred more frequently in group 2. The association of exposure to myelotoxic agents with older age at presentation and with unfavourable chromosome changes accounted for the shorter survival observed in ‘exposed’ patients. These data show that occupational exposure to pesticides and organic solvents in our region resulted in an increased RR of developing MDS and that a distinct cytogenetic profile was associated with MDS in ‘exposed’ patients. These findings provide strong indirect evidence that these agents may play a role in the pathogenesis of MDS, preferentially targeting some of the chromosome regions which are frequently involved in therapy-related myeloid neoplasias.     

Invasive aspergillosis in haematological malignancies: clinical findings and management for intensive chemotherapy completion.

Sixty-one cases of Aspergillus infection (35 acute myeloid leukemia, 15 acute lymphoid leukemia, one myelodysplastic syndrome, two aplastic anemia, eight non-Hodgkin's lymphoma) seen in our department between January 1989 and July 1999 were studied retrospectively to evaluate the clinical characteristics, to ascertain the factors that influenced the outcome from mycotic infections, and whether early diagnosis and prolonged therapy permitted completion of scheduled intensive chemotherapy and bone marrow transplantation (BMT) without fungal recurrence. The patients were divided into three diagnostic categories: proven aspergillosis (autoptic or histologic diagnosis) n = 39, probable aspergillosis (radiological diagnosis with positive microbiology) n = 9, and possible aspergillosis (radiological diagnosis alone) n = 13. In the same period among 675 acute leukemia patients the incidence of proven or probable aspergillosis was 7.1%. At onset of infection 92% of patients were neutropenic (< 0.5 x 10(9)/L). The most frequent site of infection was the lung (90%); disseminated disease was present in 20 patients. Among 44 assessable patients, 12 (27%) failed to respond to early antifungal therapy and died. Thirty-two patients were cured with antifungal treatment, three of five nonneutropenic with only itraconazole, the others with amphotericin B 1 mg/Kg/day with or without itraconazole subsequently or with liposomal amphotericin, Ambisome, if renal toxicity occurred. Twenty-four of 29 neutropenic responders, all affected by acute leukemia, continued scheduled intensive chemotherapies. Pulmonary lobectomy was successfully combined with medical treatment in two cases before scheduled BMT. After infection nine patients were submitted to BMT (six allo, one marrow unrelated donor (MUD), two auto) with Ambisome or itraconazole as secondary prophylaxis without fungal relapse (follow-up: 25-99 months). The median time from fungal infection to transplant was five months, range 3-10. Thirteen of 29 surviving patients had leukemia relapse, but only three (23%) of these showed also fungal infection recurrence. In conclusion, a high index of suspicion and careful clinical and radiological examinations are the key to identifying infected patients early and to programming the following therapeutic steps. Above all in leukemia patients, prompt and aggressive administration of antifungal agents seems to improve the outcome of invasive fungal disease and to permit intensive chemotherapy completion and transplant.     

Hepatitis B and C virus infection and risk of haematological malignancies

Hepatitis B virus (HBV) and hepatitis C virus (HCV) are classified as oncogenic human viruses. Chronic HBV and HCV infections are associated with higher risk of haematological malignancy development. Direct and indirect oncogenic mechanisms have been demonstrated for both HBV and HCV in several studies. HCV and overt/occult HBV infections in patients with oncohaematological disease constitute an impediment and a threat during immunosuppressive chemotherapy treatment. We review the HBV and HCV oncogenic mechanisms and the impact and the safety of antiviral treatment in patients with haematological malignancies.     

Clinical and laboratory factors associated with platelet transfusion refractoriness: a case–control study

In recent years clinical factors have largely surpassed alloimmunization as the predominant cause of platelet refractoriness. This makes it necessary to properly identify and weigh the non-immune factors that have a major impact on refractoriness. A case–control study is suitable for such an analysis, and to our knowledge has not previously been performed to assess this issue.
Fifty-two refractory patients were compared with 52 control patients who were transfused at the same time. Only one transfusion event was analysed per patient. Clinical and laboratory data were recorded at the time of selected transfusion, and their association with refractoriness was investigated by the contingency table method and the Cox stepwise logistic regression.
There were 16 (31%) patients with HLA antibodies in the index group and only one in the control group. The corrected count increment in the group of patients refractory due to HLA antibodies was significantly lower than that in non-alloimmunized refractory patients [median (range): 48.5 (−3560, 4614) and 4058 (−4417, 6886), respectively; U = 493, P  < 0.0001]. In the multivariate analysis, factors associated with refractoriness were the presence of HLA antibodies (odds ratio (OR) 50.7; 95% CI 5.5–463); fever (odds ratio 7.2; 95% CI 2.5–21) and BMT because of chronic myeloid leukaemia (odds ratio 7.3; 95% CI 1.8–30). The latter two were the only factors that remained independently associated with refractoriness after excluding alloimmunized patients and their controls.
We conclude that HLA antibodies are strongly associated with platelet transfusion refractoriness, but account for less than a third of these patients. Fever and BMT because of chronic myeloid leukaemia were the only non-immune factors independently associated with refractoriness.     

Risk factors for incident diabetes mellitus among HIV-infected patients receiving combination antiretroviral therapy in Taiwan: a case–control study

Objectives

Recent studies suggest that patients with HIV infection are at increased risk for incident diabetes mellitus (DM). We investigated the incidence and risk factors of DM among HIV‐infected patients receiving combination antiretroviral therapy (CART) in Taiwan.

Methods

Incident cases of DM were identified among HIV‐infected patients at the National Taiwan University Hospital between 1993 and 2006. A retrospective case–control study was conducted after matching cases with controls for sex, age at HIV diagnosis, year of HIV diagnosis, mode of HIV transmission and baseline CD4 lymphocyte count. A multivariate analysis was performed to identify risk factors for incident DM among HIV‐infected patients.

Results

In 824 HIV‐infected patients eligible for analysis, 50 cases of incident DM were diagnosed, resulting in an incidence of 13.1 cases per 1000 person‐years of follow‐up. In total, 100 matched controls were identified. Risk factors for incident DM were a family history of DM [odds ratio (OR) 2.656; 95% confidence interval (CI) 1.209–5.834], exposure to zidovudine (OR 3.168; 95% CI 1.159–8.661) and current use of protease inhibitors (OR 2.528; 95% CI 1.186–5.389).

Conclusions

Incident DM was associated with a family history of DM, exposure to zidovudine and current use of protease inhibitors in HIV‐infected patients receiving CART in Taiwan.     

Management of intracranial fungal infections in patients with haematological malignancies

The incidence of, and mortality associated with, invasive fungal infections remains far higher than hoped. As a consequence of the overall increase in the incidence of such infections over time, the incidence of central nervous system (CNS) fungal infections is also increasing and, despite improvements in diagnostic techniques and the introduction of novel antifungal agents, therapy for CNS infections is still associated with discouragingly poor results. In patients with haematological malignancies, opportunistic infections with Candida or Aspergillus remain the most common infections affecting the CNS; however, opportunistic infections with less well-known fungi are becoming more common and must be considered in the differential diagnosis. New techniques for the early diagnosis of invasive fungal infections are emerging. Pharmacologic options for treating invasive fungal infections have also improved during the past few years, with new drugs becoming available that have broader antifungal spectra and better safety profiles. Other novel treatment approaches, such as combination therapy, are also being explored. Early investigations have produced encouraging results; however, large, prospective studies involving many patients are necessary to validate the widespread use of these approaches. This review analyses the existing guidelines for treatment of CNS fungal infections and the literature available on the use of new drugs to generate sets of recommendations for treatment of these life-threatening infections in patients with haematological malignancies.     

Clinical significance of Aspergillus fungaemia in patients with haematological malignancies and invasive aspergillosis

The clinical significance of Aspergillus fungaemia in the setting of a deep-seated aspergillosis has not been clearly established. Among 107 microbiologically documented Aspergillus infections in patients with haematological diseases observed over a 17-year period, blood cultures grew Aspergillus species from 10 cases. Aspergillus fungaemia was documented in 9 out of 89 (10.1%) patients with pulmonary aspergillosis at a median of 5 d from the onset of clinical signs of infection, and in one patient with central venous catheter focal infection. Five (50%) patients died as a result of fungal infection a median of 12 d (range 4--48) from the documentation of Aspergillus fungaemia. A comparison between cases of invasive aspergillosis with or without fungaemia showed that fungaemic patients were similar to those without positive blood cultures regarding clinical presentation, risk factors, clinical course and outcome. The diagnostic role of Aspergillus fungaemia in the setting of a deep-seated infection is limited because blood cultures become positive when a microbiological or clinical diagnosis of aspergillosis has already been performed. Aspergillus fungaemia does not necessarily seem to be correlated with a disseminated infection or a poorer prognosis.     

Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study

This prospective, observational and multicentre study assessed the incidence of, and risk factors for, symptomatic venous thrombotic complications after central venous catheter (CVC) positioning in patients with haematological malignancies. A total of 458 consecutive CVC insertions were registered in 416 patients (81.2% of whom had severe thrombocytopenia). Over the observation period (3 months or up to catheter removal), the incidence of events was: CVC-related deep vein thrombosis (DVT), 1.5%; lower limb DVT, 0.4%; pulmonary embolism (PE), 1.3%; fatal PE, 0.6%; CVC-related superficial thrombophlebitis, 3.9%; CVC-occlusion/malfunction of thrombotic origin, 6.1%; major arterial events, 1.1%. Severe bleeding and CVC-related infections were observed in 3.5% and 4.6% of cases respectively. A composite end point (any venous thromboembolism or superficial thrombophlebitis or CVC occlusion/malfunction) was defined in order to consider venous thrombotic events with a significant impact on clinical practice. With this criterion, the overall incidence was 12.0% (2.54 cases/1000 catheter days). No factor helped to predict venous thrombotic complications: only thrombocytopenia was associated with a weak trend for a reduced risk (odds ratio 0.52; 95% confidence interval 0.26-1.07). No severe bleeding was observed in those patients who received antithrombotic prophylaxis. This study shows that the impact on clinical practice of symptomatic CVC-related thrombotic complications is not negligible in patients with haematological malignancies.