Diagnostic accuracy of leptospirosis whole-cell lateral flow assays: a systematic review and meta-analysis.

BACKGROUND: Leptospirosis is under-diagnosed by clinicians in many high-incidence countries, because reference diagnostic tests are largely unavailable. Lateral flow assays (LFA) that use antigen derived from heat-treated whole cell Leptospira biflexa serovar Patoc have the potential to improve leptospirosis diagnosis in resource-limited settings. OBJECTIVES: We sought to summarize estimates of sensitivity and specificity of LFA by conducting a systematic review and meta-analysis of evaluations of the accuracy of LFA to diagnose human leptospirosis. DATA SOURCES: On 4 July 2017 we searched three medical databases. Study eligibility criteriaArticles were included if they were a study of LFA sensitivity and specificity. PARTICIPANTS: Patients with suspected leptospirosis. INTERVENTIONS: Nil. METHODS: For included articles, we assessed study quality, characteristics of participants and diagnostic testing methods. We estimated sensitivity and specificity for each study against the study-defined case definition as the reference standard, and performed a meta-analysis using a random-effects bivariate model. RESULTS: Our search identified 225 unique reports, of which we included nine (4%) published reports containing 11 studies. We classified one (9%) study as high quality. Nine (82%) studies used reference tests with considerable risk of misclassification. Our pooled estimates of sensitivity and specificity were 79% (95% CI 70%-86%) and 92% (95% CI 85%-96%), respectively. CONCLUSIONS: As the evidence base for determining the accuracy of LFA is small and at risk of bias, pooled estimates of sensitivity and specificity should be interpreted with caution. Further studies should use either reference tests with high sensitivity and specificity or statistical techniques that account for an imperfect reference standard.

A randomised phase IIb trial to assess the efficacy of ReCharge ice cream in preventing chemotherapy-induced diarrhoea.

PURPOSE: Chemotherapy-induced diarrhoea (CID) has a significant impact. A medicinal food product (ReCharge) containing iron-saturated lactoferrin and anhydrous milk fat reduces the detrimental effects of chemotherapy on the gut in animals. We report results of a randomised blinded placebo-controlled phase IIb trial investigating the efficacy and safety of ReCharge in preventing CID. METHODS: Eligible patients were adults due to start the first cycle of a 2- or 3-week-cycle chemotherapy regimen, had an Eastern Cooperative Oncology Group (ECOG) status of 3 or less, had adequate haematological, liver and renal function and provided written informed consent. Patients (197) were randomised to ReCharge or placebo. They consumed 100-g study product for 2 weeks before and 6 weeks after starting chemotherapy, completed daily diaries for 8 weeks and attended clinic visits until 12 weeks (2-week cycles) or 14 weeks (3-week cycles). The primary outcome was days with CID. RESULTS: The mean number of days with diary-recorded CID was marginally but not statistically significantly lower on ReCharge than placebo (-2.0, 95 % CI (-4.7 to 0.7), p = 0.2). The proportion reporting diarrhoea in the previous cycle at the clinic visit was 30 % lower (p = 0.012) on ReCharge. Missing diary data may have contributed to the discrepancy. No significant differences were found in quality of life or other adverse events. CONCLUSIONS: We found no clear evidence that ReCharge reduced CID as measured by patient self-report diary. The converse finding of benefit as recorded at clinic visits and incomplete adherence to diary completion indicates that further research is required into methods for measuring CID.

A randomized phase II study comparing capecitabine alone with capecitabine and oral cyclophosphamide in patients with advanced breast cancer-cyclox II.

BACKGROUND: Capecitabine and cyclophosphamide are active in patients with advanced breast cancer, have non-overlapping toxic effects and synergy pre-clinically. We explored the efficacy and toxic effect of an all-oral combination of capecitabine with cyclophosphamide versus capecitabine alone in a multicentre, randomized, phase II study. PATIENTS AND METHODS: Patients with locally advanced or metastatic breast cancer were randomized to treatment with capecitabine given continuously (666 mg/m(2) b.i.d. days 1-28) alone (C) or with oral cyclophosphamide (100 mg/m(2) days 1-14 of a 28-day cycle) (CCy) for up to six cycles. RESULTS: Eighty-two patients were randomized. There was no complete response. The proportions with partial response were 36% on C and 44% on CCy, a difference of 7.9% [95% confidence interval (CI) -13.4 to 29.1]. Significant toxic effect was uncommon: grade ≥3 diarrhoea in 4 (10%) versus 1 (3%) patients; grade ≥3 fatigue in 2 (5%) versus 5 patients (13%) and grade ≥2 hand-foot syndrome in 7 (17%) versus 11 (28%) patients receiving C versus CCy, respectively. Median progression-free survival was 3.1 months on C and 6.9 months on CCy, not significantly different statistically. There was no difference in overall survival. CONCLUSION: The difference in tumour response suggests a reasonable chance that CCy is superior to C alone.

Cell cycle times of short-term cultures of brain cancers as predictors of survival.

Tumour cytokinetics estimated in vivo as potential doubling times (T(pot) values) have been found to range in a variety of human cancers from 2 days to several weeks and are often related to clinical outcome. We have previously developed a method to estimate culture cycle times of short-term cultures of surgical material for several tumour types and found, surprisingly, that their range was similar to that reported for T(pot) values. As T(pot) is recognised as important prognostic variable in cancer, we wished to determine whether culture cycle times had clinical significance. Brain tumour material obtained at surgery from 70 patients with glioblastoma, medulloblastoma, astrocytoma, oligodendroglioma and metastatic melanoma was cultured for 7 days on 96-well plates, coated with agarose to prevent proliferation of fibroblasts. Culture cycle times were estimated from relative (3)H-thymidine incorporation in the presence and absence of cell division. Patients were divided into two groups on the basis of culture cycle times of < or =10 days and >10 days and patient survival was compared. For patients with brain cancers of all types, median survival for the < or =10-day and >10-day groups were 5.1 and 12.5 months, respectively (P=0.0009). For 42 patients with glioblastoma, the corresponding values were 6.5 and 9.0 months, respectively (P=0.03). Lower grade gliomas had longer median culture cycle times (16 days) than those of medulloblastomas (9.9 days), glioblastomas (9.8 days) or melanomas (6.7 days). We conclude that culture cycle times determined using short-term cultures of surgical material from brain tumours correlate with patient survival. Tumour cells thus appear to preserve important cytokinetic characteristics when transferred to culture.

Temporal patterns of injury during a rugby season.

The aim of this study was to describe temporal patterns in the frequency, nature and circumstances of injuries occurring among a cohort of 356 rugby players during a club rugby season in New Zealand. It was found that the rate of injury in games decreased significantly over time in both males and females. The reduction in injury rate over the season was more pronounced in some grades, but no differences were found when examined by gender. playing position, age, ethnicity or by health and fitness types. Trends in injury rate were consistent over the rugby season and did not appear to be the result of a bias involving under-reporting of end-of-season injuries. The types and severity of injury remained relatively constant, but the proportion of injuries occurring in back play fell significantly over the season and injuries were more likely to occur in the trunk body region as the season progressed. This study supported the hypothesis that higher rates of injury occur at the start of the rugby season and decrease over the course of the season. This reduction is consistent over time and across player types, and is not attributable either to decreasing injury severity or to increasing player fitness.

Long-term assessment of psychological well-being in a randomized placebo-controlled trial of cholesterol reduction with pravastatin. The LIPID Study Investigators.

BACKGROUND: There is controversial evidence that a low serum cholesterol level is associated with an increased risk of depression, suicide, and violence. The aim of this study was to identify or exclude any small or infrequent adverse effect of long-term reduction of serum cholesterol with pravastatin sodium on psychological well-being. METHODS: The study population consisted of 1130 respondents from a representative sample of 1222 patients with stable coronary artery disease participating in the Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Subjects were randomized in a double-blind manner to treatment with pravastatin sodium, 40 mg/d (n = 559), or placebo (n = 571) for at least 4 years. Psychological well-being was assessed with a standard self-administered questionnaire at baseline and after 6 months, 1 year, 2 years, and 4 years. The questionnaire assessed anxiety and depression, anger, impulsiveness, alcohol consumption, and adverse life events. RESULTS: Serum cholesterol levels decreased by an average of 1.3 mmol/L (50 mg/dL) with pravastatin therapy and did not change with placebo. During follow-up there was no significant difference by treatment group in measures of anxiety and depression, anger expression, or impulsiveness (95% confidence interval excluded differences of >0.2 SD) and no difference in the proportion of subjects with excessive alcohol consumption or adverse life events (odds ratio, 1.0; 95% confidence interval, 0.8-1.2). There was no evidence of a treatment effect for persons whose baseline serum cholesterol level was in the lowest 10% (<4.6 mmol/L [178 mg/dL]) or whose scores for anxiety and depression, anger, or impulsiveness were in the highest 10% at baseline. There was no association between change in the serum cholesterol level and measures of anxiety and depression, anger, or impulsiveness during follow-up. CONCLUSION: Long-term reduction of serum cholesterol with pravastatin has no adverse effect on psychological well-being.

Effect of premanipulative tests on vertebral artery and internal carotid artery blood flow: a pilot study.

BACKGROUND: Neck manipulation occasionally causes stroke after trauma to the vertebral or internal carotid artery. Premanipulativ e tests involving cervical spine rotation or extension have been recommended to detect patients at risk of neurovascular ischemia. However, the effect of these procedures on extracranial blood flow is not well established, and their validity is thus controversial. OBJECTIVE: To determine the effect of premanipulative tests involving cervical spine rotation or extension on vertebral artery and internal carotid artery blood flow parameters. DESIGN: Two-group experimental study. SUBJECTS: Twenty subjects consisting of 16 patients treated with physiotherapy and four volunteers. METHODS: Subjects were tested with a recommended premanipulative protocol by both an independent physiotherapist and an investigator. One group consisted of 10 subjects with signs or symptoms indicative of neurovascular ischemia on premanipulative testing, with 10 subjects with no signs or symptoms indicative of neurovascular ischemia on premanipulative testing comprising the second group. Hemodynamic measurements for both vertebral and both internal carotid arteries were taken by use of duplex Doppler ultrasonography with color-flow imaging with the subjects in the following positions: neutral, end-range extension, 45 degrees contralateral rotation, end-range contralateral rotation, and combined end-range contralateral rotation/extension. RESULTS: The reliability of premanipulative testing was supported. Significant changes in flow velocity of the vertebral artery (and to a lesser extent of the internal carotid artery) were shown in end-range positions involving rotation and extension. No meaningful significant differences were found between the two groups. CONCLUSIONS: Screening procedures that use rotation and extension may be useful tests of the adequacy of collateral circulation. A larger study is needed to determine whether subjects testing positive significantly differ from those testing negative.

An assessment of spatial clustering of leukaemias and lymphomas among young people in New Zealand.

STUDY OBJECTIVE: To assess spatial clustering of childhood leukaemias and lymphomas in New Zealand, using a national dataset from a country with no nuclear installations. DESIGN: New Zealand Map Grid coordinates, derived from the birth addresses of cases and controls were used in clustering analyses that applied Cuzick and Edwards' method. SETTING: The whole of New Zealand. PARTICIPANTS: The cases were ascertained from the New Zealand Cancer Registry. They were diagnosed with leukaemia or lymphoma at ages 0-14 years during the period 1976 to 1987. For Hodgkin's disease, the age range was extended to include those aged from 0-24 years. The cancer registrations were linked with national birth records, to obtain the birth addresses of the cases. The controls were selected at random from birth records, with matching to cases (1:1) on age and sex. The analyses included 600 cases and 600 controls. MAIN RESULTS: There was no statistically significant spatial clustering for any tumour group overall, including acute lymphoblastic leukaemia, acute nonlymphoblastic leukaemia, other leukaemias, non-Hodgkin's lymphomas, Hodgkin's disease, and all these combined. Significant clustering was found in a sub-analysis for one of three age specific subgroups of acute lymphoblastic leukaemia (ages 10-14 years, p = 0.003). CONCLUSION: The subgroup finding may have been real or a chance association, as several comparisons were made. This study found little evidence for spatial clustering of leukaemias or lymphomas in a population with no nuclear installations.

HIV/AIDS in New Zealand: an epidemic in decline?

OBJECTIVE: To describe the AIDS epidemic in New Zealand, and to discuss the reasons for an apparent decline in incidence. METHODS: The AIDS Epidemiology Group collects information on persons diagnosed with AIDS through a compulsory notification system. Data were presented on people diagnosed to the end of 1994, and reported by the end of September 1995. RESULTS: The cumulative incidence of AIDS in New Zealand was similar to that in some other Western countries, such as the United Kingdom, Germany and Sweden, before 1989, but has been declining since 1989. The epidemic is concentrated among men who have sex with men (89%). The median survival after diagnosis with AIDS is 13 months. CONCLUSIONS: The observed decline is not likely to be due to reporting delays or changes in reporting or diagnostic practices. The major factor was probably a rapid decline in HIV incidence among homosexual men a decade ago, and the effective prevention of epidemics in other subgroups. The epidemic in New Zealand started later than in other countries, enabling an earlier response, and there is evidence of behaviour change in high risk groups. Preventive efforts and monitoring must be maintained in order to ensure there is no reversal of this decline.

HIV surveillance by testing saliva from injecting drug users: a national study in New Zealand.

OBJECTIVE: To determine whether the prevalence of HIV infection among injecting drug users in New Zealand has remained low since the introduction of a needle and syringe exchange scheme in May 1988. DESIGN: Anonymous survey of intravenous drug users attending outlets of the exchange scheme, based on questionnaires and saliva testing. SETTING: Twelve pharmacies and community outreach organisation in six cities. SUBJECTS: Altogether 620 people provided saliva specimens and completed questionnaires. These represented 73% of those who visited exchange scheme outlets during a three month period in 1992. MAIN OUTCOME MEASURE: Saliva was tested for antibodies to HIV-1 and HIV-2 using an IgG-capture enzyme linked immunosorbent assay (GACELISA). RESULTS: Of 591 specimens eligible for inclusion, only three (0.5%) were repeatedly reactive in the GACELISA test, while two of these were also positive in a Western blot test. CONCLUSIONS: Although surveys show that sharing of needles and syringes was common in New Zealand until recently, the prevalence of HIV infection in intravenous drug users has remained low. This can probably be attributed to the success of educational campaigns and legislative action to allow a needle and syringe exchange scheme to be set up.

Unlinked anonymous monitoring of HIV prevalence at sexually transmitted disease clinics.

AIM: To determine the prevalence of HIV infection among patients attending the four sexually transmitted disease (STD) clinics in two metropolitan areas of New Zealand. METHODS: The population studied comprised everyone who attended between August 1991 and August 1992 because of concern about a possible new episode of an STD and who had a blood specimen taken for hepatitis B (or syphilis) serology. The study involved unlinked anonymous testing of left-over blood specimens, following ethical guidelines that have been proposed internationally. RESULTS: Among 8478 specimens tested, 23 (2.7 per 1000) were found to be HIV positive. The seroprevalence rates per 1000 among women, heterosexual men, and homosexual or bisexual men were 1.1, 1.3, and 44, respectively. All but five of the infected people were either known to be HIV positive or had an identifiable test during their clinic attendance. CONCLUSIONS: The seroprevalence rates are similar to those reported from STD clinics in England, and suggest that heterosexual transmission of HIV infection has not yet been extensive in New Zealand.

Variation and covariates of the number of benign nevi in adolescents.

Melanocytic nevi of diameter greater than or equal to 2 mm were counted on most of the skin surface of 349 adolescents aged 14-15 years of European race or ethnicity in Dunedin, New Zealand. Total counts are described by means of a form of Poisson-error log-linear modeling suitable for data showing unexplained variation (NE Breslow, Appl Statist 1984;33:38-44). There were marked interpersonal variation in the number of nevi; only some was attributable to observed factors. The mean and median counts were 23.8 and 18 nevi, respectively. The estimated ratio of the number of nevi for females compared with males was 0.7 (95% confidence interval (CI) 0.6-0.8). Greater amounts of sunbathing were associated with greater numbers of nevi. Hair and eye color, socioeconomic status, and sunburn history did not show statistically significant effects. Time since menarche and shaving status also showed no effects. Lack of suntan was associated with lower counts. Freckling was positively correlated with higher counts; the severe freckling group had an estimated ratio of 1.9 (95% CI 1.3-2.8) compared with those with no or very few freckles. The results are consistent with the hypothesis that ultraviolet radiation exposure from recreational sun exposure positively influences the total burden of nevi in normal subjects. Comparison with other epidemiologic studies suggests that the typical ultraviolet radiation dose-nevus yield curve might be steeper in males than females. Unexplained variation of nevus count may reflect heterogeneity of constitutional factors not yet measured in epidemiologic studies.

Cognitive and motor dysfunction in Parkinson's disease. Clinical, performance, and computed tomographic correlations.

The neuropathologic and pathophysiological relationship of specific to more generalized cognitive dysfunction in Parkinson's disease (PD) remains incompletely understood. This issue was examined in a study of 39 patients with PD, utilizing standardized clinical measures, computerized neuropsychological tests, and quantitative computed tomography. Disorders of visuospatial discrimination and perceptual-motor function closely paralleled motor scores, suggesting a common neuropathologic basis. Caudate nuclear and mesocortical dopamine depletion play a role in this context. More generalized cognitive dysfunction occurred in older patients with a somewhat longer disease duration, more advanced parkinsonism, and computed tomographic evidence of subcortical and frontal cortical atrophy but without significant cerebral atrophy when compared with age-matched controls. Further prospective clinicopathologic studies will be required to clarify the relative contribution of the primary dopaminergic dysfunction, age-related changes, Alzheimer-type pathologic condition, and other coexisting neurotransmitter deficits to the dementia seen in PD.