Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study

Background

Statins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.

Methods

A case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n?=?325). Patients diagnosed with diabetes mellitus type II (DM II n?=?65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a ‘recent’ statin user or not at the time of diagnosis.

Results

Statin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6–29.0%, p?=?0.601). When comparing groups 20–64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0–26.6%, p?=?0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing ‘former/never’ statin users as reference category with ‘recent’ users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89–2.16).

Conclusions

No significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between ‘recent’ statin use at the time of diagnosis and cancer-specific survival.

     

Alcohol consumption as a risk factor for poor outcome after aneurysmal subarachnoid haemorrhage.

OBJECTIVE--To evaluate the effect of factors existing before aneurysmal subarachnoid haemorrhage on outcome of haemorrhage. DESIGN--Prospective follow up study. SETTING--Helsinki University Hospital. PATIENTS--291 consecutive patients (149 men) aged 15 to 65 years admitted within 96 hours after the bleeding. MAIN OUTCOME MEASURES--Potential risk factors (baseline characteristics, health habits, and clinical variables) for poor outcome after haemorrhage (dependent state in the activities of daily living, or death) were studied using multiple logistic regression. RESULTS--One year after haemorrhage, 179 (62%) patients were independent in the activities of daily living and 28 (10%) dependent; 84 (29%) had died. Risk of poor outcome was predicted, after adjustment for sex and age, by clinical condition at admission according to the Glasgow coma scale (p less than 0.0001); occurrence of rebleeding (relative risk 7.1, 95% confidence interval 2.8 to 18.0, p less than 0.0001) or delayed cerebral ischaemia (10.3, 4.2 to 25.4, p less than 0.0001); surgery on an aneurysm (0.13, 0.05 to 0.35, p less than 0.0001); and heavy consumption of alcohol (4.5, 1.8 to 11.0, p = 0.0014). Heavy drinking remained a significant risk factor after additional adjustment for hypertension, body mass index, and presence of intracerebral haematoma. Heavy drinkers had a more unfavourable outcome after rebleeding and delayed ischaemia than did others with rebleeding or ischaemia. Those who had salicylates in urine on admission had delayed ischaemia with fixed neurological deficits less commonly than others. CONCLUSIONS--Heavy drinking impairs outcome mainly through severe rebleeding and delayed ischaemia and to a lesser extent through a poor initial condition and presence of intracerebral haematoma.     

Ageing as a risk factor for disease

Age is the main risk factor for the prevalent diseases of?developed countries: cancer, cardiovascular disease and?neurodegeneration. The ageing process is deleterious for fitness, but can nonetheless evolve as a consequence of the declining force of natural selection at later ages, attributable to extrinsic hazards to survival: ageing can then occur as a side-effect of accumulation of mutations that lower fitness at later ages, or of natural selection in favour of mutations that increase fitness of the young but?at the cost of a higher subsequent rate of ageing. Once thought of as an inexorable, complex and lineage-specific process of accumulation of damage, ageing has turned out to be influenced by mechanisms that show strong evolutionary conservation. Lowered activity of the nutrient-sensing insulin/insulin-like growth factor/Target of Rapamycin signalling network can extend healthy lifespan in yeast, multicellular invertebrates, mice and, possibly, humans. Mitochondrial activity can also promote?ageing, while genome maintenance and autophagy?can protect against it. We discuss the relationship between evolutionarily conserved mechanisms of ageing and disease, and the associated scientific challenges and opportunities.     

Low consumption of seafood in early pregnancy as a risk factor for preterm delivery: prospective cohort study

Objective To determine the relation between intake of seafood in pregnancy and risk of preterm delivery and low birth weight.DesignProspective cohort study.Setting Aarhus, Denmark.Participants8729 pregnant women.Results The occurrence of preterm delivery differed significantly across four groups of seafood intake, falling progressively from 7.1% in the group never consuming fish to 1.9% in the group consuming fish as a hot meal and an open sandwich with fish at least once a week. Adjusted odds for preterm delivery were increased by a factor of 3.6 (95% confidence interval 1.2 to 11.2) in the zero consumption group compared with the highest consumption group. Analyses based on quantified intakes indicated that the working range of the dose-response relation is mainly from zero intake up to a daily intake of 15 g fish or 0.15 g n-3 fatty acids. Estimates of risk for low birth weight were similar to those for preterm delivery.Conclusions Low consumption of fish was a strong risk factor for preterm delivery and low birth weight. In women with zero or low intake of fish, small amounts of n-3 fatty acids—provided as fish or fish oil—may confer protection against preterm delivery and low birth weight.

What is already known on this topic

Long chain n-3 fatty acids in amounts above 2 g a day may delay spontaneous delivery and prevent recurrence of preterm deliveryLarge studies have not been carried out to determine to what extent low consumption of n-3 fatty acids is a risk factor for preterm deliveryThe dose-response relation has not been described

What this study adds

Low consumption of fish seems to be a strong risk factor for preterm delivery and low birth weight in Danish womenThis relation is strongest below an estimated daily intake of 0.15 g long chain n-3 fatty acids or 15 g fish     

Stochastic models for the spread of HIV in a mobile heterosexual population

An important factor in the dynamic transmission of HIV is the mobility of the population. We formulate various stochastic models for the spread of HIV in a heterosexual mobile population, under the assumptions of constant and varying population sizes. We also derive deterministic and diffusion analogues for these models, using a convenient rescaling technique, and analyze their stability conditions and equilibrium behavior. We illustrate the dynamic behavior of the models and their approximations via a range of numerical experiments.     

Mercury as a risk factor for cardiovascular diseases

Mercury is a heavy metal that exists naturally in the environment. Major sources include the burning of fossil fuels (especially coal) and municipal waste incineration. Mercury can exist in several forms, with the most hazardous being organic methylmercury. In waterways (lakes, rivers, reservoirs, etc.), mercury is converted to methylmercury, which then accumulates in fish, especially in large predatory fish. Fish and fish products are the major--if not the only--source of methylmercury in humans. Mercury has long been recognized as a neurotoxin for humans, but in the last 10 years, its potentially harmful effects on cardiovascular diseases (CVD) have raised a cause for concern, mostly due to the proposed role of mercury in oxidative stress propagation. Some epidemiological studies have indeed found an association between increased levels of mercury in the body and risk of CVD. There are several plausible mechanisms to explain the association; these are discussed in this review. We also review the epidemiological studies that have investigated the association between mercury and CVD.     

Smoking of crack cocaine as a risk factor for HIV infection among people who use injection drugs

Background

Little is known about the possible role that smoking crack cocaine has on the incidence of HIV infection. Given the increasing use of crack cocaine, we sought to examine whether use of this illicit drug has become a risk factor for HIV infection.

Methods

We included data from people participating in the Vancouver Injection Drug Users Study who reported injecting illicit drugs at least once in the month before enrolment, lived in the greater Vancouver area, were HIV-negative at enrolment and completed at least 1 follow-up study visit. To determine whether the risk of HIV seroconversion among daily smokers of crack cocaine changed over time, we used Cox proportional hazards regression and divided the study into 3 periods: May 1, 1996–Nov. 30, 1999 (period 1), Dec. 1, 1999–Nov. 30, 2002 (period 2), and Dec. 1, 2002–Dec. 30, 2005 (period 3).

Results

Overall, 1048 eligible injection drug users were included in our study. Of these, 137 acquired HIV infection during follow-up. The mean proportion of participants who reported daily smoking of crack cocaine increased from 11.6% in period 1 to 39.7% in period 3. After adjusting for potential confounders, we found that the risk of HIV seroconversion among participants who were daily smokers of crack cocaine increased over time (period 1: hazard ratio [HR] 1.03, 95% confidence interval [CI] 0.57–1.85; period 2: HR 1.68, 95% CI 1.01–2.80; and period 3: HR 2.74, 95% CI 1.06–7.11).

Interpretation

Smoking of crack cocaine was found to be an independent risk factor for HIV seroconversion among people who were injection drug users. This finding points to the urgent need for evidence-based public health initiatives targeted at people who smoke crack cocaine.People who inject illegal drugs are known to be at heightened risk of HIV infection and other blood-borne diseases. In 2007, more than 20% of all new cases of HIV infection recorded in Canada were attributed to injection drug use.¹ Behaviours associated with the use of particular injection drugs (e.g., cocaine and heroin) have been identified as key factors driving HIV transmission among drug users in various settings.² However, over the last decade, significant changes in the popularity of specific illegal drugs have been observed.^3,4 In recent years, cities across Canada have experienced an explosive increase in the use of crack cocaine, whereas some drugs, including heroin, appear to be less commonly used.^5–7 The proportion of drug users who smoke crack cocaine and are homeless or have marginal housing has recently been reported to be as high as 86.6% in Vancouver, 66.7% in Edmonton and 62.4% in Toronto.⁸In the United States, a seminal cross-sectional study involving inner-city young adults showed that smoking of crack cocaine was associated with HIV infection.⁹ However, in Canada, despite the documentation of changing patterns of drug use in many communities,⁸ little is known about the impact that increased smoking of crack cocaine has had on the HIV epidemic. This is problematic because public health programs for people who smoke crack cocaine have been highly controversial in Canada.⁶ We conducted a longitudinal study to evaluate whether smoking of crack cocaine has emerged as a risk factor for HIV infection among people who inject drugs.     

Differences in HIV natural history among African and non-African seroconverters in Europe and seroconverters in sub-Saharan Africa

Introduction

It is unknown whether HIV treatment guidelines, based on resource-rich country cohorts, are applicable to African populations.

Methods

We estimated CD4 cell loss in ART-naïve, AIDS-free individuals using mixed models allowing for random intercept and slope, and time from seroconversion to clinical AIDS, death and antiretroviral therapy (ART) initiation by survival methods. Using CASCADE data from 20 European and 3 sub-Saharan African (SSA) cohorts of heterosexually-infected individuals, aged ≥15 years, infected ≥2000, we compared estimates between non-African Europeans, Africans in Europe, and Africans in SSA.

Results

Of 1,959 (913 non-Africans, 302 Europeans - African origin, 744 SSA), two-thirds were female; median age at seroconversion was 31 years. Individuals in SSA progressed faster to clinical AIDS but not to death or non-TB AIDS. They also initiated ART later than Europeans and at lower CD4 cell counts. In adjusted models, Africans (especially from Europe) had lower CD4 counts at seroconversion and slower CD4 decline than non-African Europeans. Median (95% CI) CD4 count at seroconversion for a 15–29 year old woman was 607 (588–627) (non-African European), 469 (442–497) (European - African origin) and 570 (551–589) (SSA) cells/µL with respective CD4 decline during the first 4 years of 259 (228–289), 155 (110–200), and 199 (174–224) cells/µL (p<0.01).

Discussion

Despite differences in CD4 cell count evolution, death and non-TB AIDS rates were similar across study groups. It is therefore prudent to apply current ART guidelines from resource-rich countries to African populations.     

Waterpipe smoking as a public health risk: Potential risk for transmission of MERS-CoV

The Middle East Respiratory Syndrome (MERS-CoV) emerged in the Kingdom of Saudi Arabia in 2012 causing a critical challenge to public health. The epidemiology of MERS-CoV remain enigmatic as human-to-human transmission is not fully understood. One possible scenario that might play a role in the virus transmission is the cultural waterpipe smoking. Cafés providing waterpipe smoking in cities within Saudi Arabia have been moved to areas outside city limits that frequently place them close to camels markets. We report results of a surveillance study wherein waterpipe hoses throughout several regions in Saudi Arabia were tested for the presence of MERS-CoV. A total of 2489 waterpipe samples were collected from cities where MERS-CoV cases were continuously recorded. MERS-CoV RNA wasn’t detected in collected samples. Irrespective of the negative results of our survey, the public health risk of waterpipe smoking should not be underestimated. To avoid a possible transmission within country where MERS-CoV is prevalent, we recommend the replacement of resusable hoses with “one-time-use” hoses in addition to a close inspection of waterpipe components to assure the appropriate cleaning and sanitization.     

Cerumen as a potential risk for transmission of Hepatitis B virus

Hepatitis B virus (HBV) transmission via blood and other body fluids from infected individuals to healthy people has been largely demonstrated. However, in the current literature, there is little information available on the potential role of cerumen in HBV transmission. Cerumen and blood were collected from 70 patients infected with HBV and 70 volunteer healthy people were selected as the control group, and the samples were evaluated by ELISA and Real-time PCR. All the patients proved positive for HBsAg and anti HBc total. Sixty-one of the 70 cerumen samples of cases (82.1%) and 5 (7%) of controls were positive for HBV DNA with ranges from 1.53 × 102 to 2.9 × 108 and 1.3 × 102-2.6 × 105/ml, respectively. In three patients, the level of HBV DNA in cerumen was higher than that in the serums. The patients who were positive for HBeAg showed a higher rate of HBVDNA in the serum and cerumen.The results of this study showed the level of HBV DNA as a probably indicator of high risk transmission factor, which was present in the cerumen of chronic hepatitis B patients in west of Iran.     

Socioeconomic status as a risk factor for HIV infection in women in East, Central and Southern Africa: a systematic review

This is a critical, systematic review of the relationship between socioeconomic status (SES) and HIV infection in women in Southern, Central and Eastern Africa. In light of the interest in micro-credit programmes and other HIV prevention interventions structured to empower women through increasing women's access to funds and education, this review examines the epidemiological and public health literature, which ascertains the association between low SES using different measurements of SES and risk of HIV infection in women. Also, given the focus on structural violence and poverty as factors driving the HIV epidemic at a structural/ecological level, as advocated by Paul Farmer and others, this study examines the extent to which differences in SES between individuals in areas with generalized poverty affect risk for SES. Out of 71 studies retrieved, 36 studies met the inclusion criteria including 30 cross-sectional, one case-control and five prospective cohort or nested case-control studies. Thirty-five studies used at least one measurement of female's SES and fourteen also included a measurement of partner's SES. Studies used variables measuring educational level, household income and occupation or employment status at the individual and neighbourhood level to ascertain SES. Of the 36 studies, fifteen found no association between SES and HIV infection, twelve found an association between high SES and HIV infection, eight found an association between low SES and HIV infection and one was mixed. In interpreting these results, this review examines the role of potential confounders and effect modifiers such as history of STDs, number of partners, living in urban or rural areas and time and location of study in sub-Saharan Africa. It is argued that STDs and number of partners are on the causal pathway under investigation between HIV and SES and should not be adjusted as confounders in any analysis. In conclusion, it is argued that in low-income sub-Saharan Africans countries, where poverty is widespread, increasing access to resources for women may initially increase risk of HIV or have no effect on risk-taking behaviours. In some parts of Southern Africa where per capita income is higher and within-country inequalities in wealth are greater, studies suggest that increasing SES may decrease risk. This review concludes that increased SES may have differential effects on married and unmarried women and further studies should use multiple measures of SES. Lastly, it is suggested that the partner's SES (measured by education or income/employment) may be a stronger predictor of female HIV serostatus than measures of female SES.     

C-reactive protein as a risk factor versus risk marker

PURPOSE OF REVIEW: C-reactive protein (CRP) is consistently associated with cardiovascular disease in prospective and cross-sectional clinical and epidemiological studies. Inflammation is an important mechanism in cardiovascular disease, and the plasma level of CRP is considered to reflect the inflammatory condition of the patient and/or the vessel wall. In addition, there are also a number of indications for a causal role of CRP in cardiovascular disease. RECENT FINDINGS: A number of new publications show potential causal effects of CRP on cardiovascular disease, and evidence from human-CRP transgenic animals also indicates a causal contribution of CRP to cardiovascular disease. On the other hand, a new large prospective study and an updated meta-analysis indicate that the contribution of CRP to cardiovascular disease is less impressive than reported earlier (odds ratio, 1.58; 95% confidence interval, 1.48-1.68). SUMMARY: We review here the most recent evidence on mechanisms by which CRP is involved as a causal factor in the precipitation of cardiovascular disease. Evidence for such a role is accumulating.     

Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes

Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets. Amylin oligomerization was implicated in the apoptosis of the insulin-producing β-cells. Recent studies showed that brain tissue from diabetic patients with cerebrovascular dementia or Alzheimer’s disease contains significant deposits of oligomerized amylin. It has also been reported that the brain amylin deposition reduced exploratory drive, recognition memory and vestibulomotor function in a rat model that overexpresses human amylin in the pancreas. These novel findings are reviewed here and the hypothesis that type II diabetes is linked with cognitive decline by amylin accumulation in the brain is proposed. Deciphering the impact of hyperamylinemia on the brain is critical for both etiology and treatment of dementia.