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Abstract Background The prevalence of malnutrition in cancer patients ranges from 30 to 60%. While it is known that malnutrition is prevalent among cancer patients, the relationship between undernutrition and quality of life among breast cancer patients has not been adequately explored. Therefore, the present study was aimed at assessing the association between undernutrition and quality of life among Breast Cancer patients under treatment in Addis Ababa, Ethiopia. Methods A cross-sectional study on breast cancer patients under treatment at the outpatient and in-patient departments of oncology centers of two tertiary hospitals in Addis Ababa – Tikur Anbessa Specialized Hospital (TASH) and St. Paul Millennium Medical College (SPHMMC) oncology was conducted from May 12 to August 26,2020. Nutritional status was assessed using Subjective Global Assessment (SGA) screening tool. Quality of life was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Cancer 30 (EORTC QLQ C30) a standard quality of life measurement scale for cancer patients. To determine the relationship between quality of life scores and nutritional status multivariable linear regression was fitted. Results A total of 411 breast cancer patients with mean age of 44.4 (± 11.47) years. And 393 (95.6%) of them female were included in the study. A high prevalence of moderate 127 (30.9%) and severe 106 (25.8%) malnutrition was observed. Moderate (β = −9.21 CI (− 14.59, − 4.67)) and severe (β = −17.81 CI (− 16.6, 2 − 2.91)) malnutrition were negatively associated with the overall quality of life. Malnutrition also showed negative associations with all domains of functional status (P

“Non-tuberculous mycobacteria” (NTM) is a general term for pathogenic mycobacteria other than Mycobacterium tuberculosis and Mycobacterium leprae. Non-tuberculous mycobacteria are widely present in the natural environment, including soil and water, with over 150 reported species. Mycobacterium abscessus is rare among Non-tuberculous mycobacteria, and there are few reports of extrapulmonary lesions due to Mycobacterium abscessus. We describe a case of osteomyelitis in an adult woman's left first toe caused by Mycobacterium abscessus. The osteomyelitis developed due to an injury in a public bathing facility. A combination of surgical debridement and multidrug therapy was effective. When antimicrobial agents are ineffective in trauma linked to water or soil, mycobacterial infections, including Non-tuberculous mycobacteria, should be considered as differential diagnoses, and laboratory culture targeted to mycobacteria would be recommended.

Abstract Background Interstitial lung abnormalities (ILAs) are subtle or mild parenchymal abnormalities observed in more than 5% of the lungs on computed tomography (CT) scans in patients in whom interstitial lung disease was not previously clinically suspected and is considered. ILA is considered to be partly undeveloped stages of idiopathic pulmonary fibrosis (IPF) or progressive pulmonary fibrosis (PPF). This study aims to clarify the frequency of subsequent IPF or PPF diagnosis, the natural course from the preclinical status of the diseases, and the course after commencing treatment. Methods This is an ongoing, prospective, multicentre observational cohort study of patients with ILA referred from general health screening facilities with more than 70,000 annual attendances. Up to 500 participants will be enrolled annually over 3 years, with 5-year assessments every six months. Treatment intervention including anti-fibrotic agents will be introduced in disease progression cases. The primary outcome is the frequency of subsequent IPF or PPF diagnoses. Additionally, secondary and further endpoints are associated with the efficacy of early therapeutic interventions in cases involving disease progression, including quantitative assessment by artificial intelligence. Discussion This is the first prospective, multicentre, observational study to clarify (i) the aetiological data of patients with ILA from the largest general health check-up population, (ii) the natural course of IPF or PPF from the asymptomatic stage, and (iii) the effects and outcomes of early therapeutic intervention including anti-fibrotic agents for progressive cases of ILA. The results of this study could significantly impact the clinical practice and treatment strategy for progressive fibrosing interstitial lung diseases. Trial registration number UMIN000045149.

Composite resin is versatile material for performing several dental procedures in dentistry, and its use has already been consolidated in this field. The clinical success of adhesive restorations is directly related to the knowledge of restorative material properties and light-curing unit factors, among others. The aim of the study was to assess the knowledge about the technical characteristics of light-curing devices and the forms of use and maintenance employed by undergraduate dental students. A total of 230 students answered a questionnaire containing six questions on technical data, use, and maintenance of light-curing units. Of the total number of participants, the majority were students from private educational institutions attending the last two years. With 59.1% of them unaware of the ideal irradiance of a light-curing unit, 73.0% were careful to position the light-curing unit as close as possible to the restoration, and 42.6% followed the light-curing time recommended by textbooks and theoretical texts. As for use and maintenance, 50.4% used the protector attached to the light-curing unit, 57.4% used safety barriers, and 63.0% sanitized the light tip after use. The evaluation suggests that student’s knowledge of “light-curing resin materials” is incomplete. Therefore, it can be inferred that the students have a good understanding of biosafety precautions when using light-curing units, but more knowledge is needed about the technical and clinical aspects of the devices.

Summary: Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine, to reduce reactogenicity, and an updated receptor-binding domain derived from the Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N = 96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with reduced adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.

IntroductionThis present study aimed to compare ultrasonographic measures of femoral articular cartilage during two-year seasons between collegiate rugby players who have attended supervised rehabilitation following intracapsular knee joint injury and those without a history of knee injury.MethodsUsing a prospective observational study design, 12 male collegiate rugby players with a previous history of intracapsular knee joint injury who have received and completed supervised rehabilitation following their injury and 44 players without knee joint injury participated in this study. Ultrasonographic images were used to verify changes in femoral articular cartilage thickness and cross-sectional area (CSA) with or without a previous history of knee joint injury over two consecutive rugby seasons.ResultsSignificant time main effects were observed for the lateral condylar thickness (p

Abstract Objective: This study aimed to objectively evaluate the diet consumed in a workplace cafeteria to group Japanese workers according to vegetables and salt intake and estimate the association of these groups with changes in cardiometabolic measurements. Design: This longitudinal observational study estimated the food and nutrient intake of Japanese workers from data recorded in the cafeteria system of their workplace. The primary outcomes included cardiometabolic measures obtained via regular health check-ups conducted at the workplace. The participants were divided into four groups according to high or low vegetables and salt intake based on their respective medians, and the association of each group with cardiometabolic measurement changes was estimated using robust regression with MM-estimation. Setting: A Japanese automobile manufacturing factory. Subjects: The study included 1140 men and women workers with available cafeteria and health check-up data. Results: An inverse marginal association was observed between changes in TAG levels (mmol/L) and high vegetables and low salt intake (β: –0·11, 95 % CI: –0·23, 0·01, P: 0·065) with reference to low vegetables and high salt intake. This association was stronger in participants who used the cafeteria more frequently (>=71 d; β: –0·15, 95 % CI: –0·29, –0·02, P: 0·027). Conclusions: The participants in the higher vegetables and lower salt intake group were more likely to exhibit decreased TAG levels. These findings encourage using workplace cafeteria meals to promote the health of workers.

Purpose: Achromatopsia (ACHM) is an early-onset cone dysfunction caused by 5 genes with cone-specific functions (CNGA3, CNGB3, GNAT2, PDE6C, and PDE6H) and by ATF6, a transcription factor with ubiquitous expression. To improve the relatively low variant detection ratio in these genes in a cohort of exome-sequenced Japanese patients with inherited retinal diseases (IRD), we performed genome sequencing to detect structural variants and intronic variants in patients with ACHM. Methods: Genome sequencing of 10 ACHM pedigrees was performed after exome sequencing. Structural, non-coding, and coding variants were filtered based on segregation between the affected and unaffected in each pedigree. Variant frequency and predicted damage scores were considered in identifying pathogenic variants. Results: A homozygous deletion involving exon 18 of RPGRIP1 was detected in 5 of 10 ACHM probands, and variant inheritance from each parent was confirmed. This deletion was relatively frequent (minor allele frequency = 0.0023) in the Japanese population but was only homozygous in patients with ACHM among the 199 Japanese IRD probands analyzed by the same genome sequencing pipeline. Conclusion: The deletion involving exon 18 of RPGRIP1 is a prevalent cause of ACHM in Japanese patients and contributes to the wide spectrum of RPGRIP1-associated IRD phenotypes, from Leber congenital amaurosis to ACHM.

BackgroundIn recent years, technologies promoting the digitization of self-monitoring of blood glucose (SMBG) records including app-cloud cooperation systems have emerged. Studies combining these technological interventions with support from remote health care professionals have reported improvements in glycemic control. ObjectiveTo assess the use of an app-cloud cooperation system linked with SMBG devices in clinical settings, we evaluated its effects on outpatient management of diabetes without remote health care professional support. MethodsIn this multicenter, open-label, and single-armed prospective study, 48 patients with diabetes (including type 1 and type 2) at 3 hospitals in Japan treated with insulin or glucagon-like peptide 1 receptor agonists and performing SMBG used the app-cloud cooperation system for 24 weeks. The SMBG data were automatically uploaded to the cloud via the app. The patients could check their data, and their attending physicians reviewed the data through the cloud prior to the patients’ regular visits. The primary outcome was changes in glycated hemoglobin (HbA1c) levels. ResultsAlthough HbA1c levels did not significantly change in all patients, the frequency of daily SMBG following applying the system was significantly increased before induction at 12 (0.60 per day, 95% CI 0.19-1.00; P=.002) and 24 weeks (0.43 per day, 95% CI 0.02-0.84; P=.04). In the subset of 21 patients whose antidiabetic medication had not been adjusted during the intervention period, a decrease in HbA1c level was observed at 12 weeks (P=.02); however, this significant change disappeared at 24 weeks (P=.49). The Diabetes Treatment Satisfaction Questionnaire total score and “Q4: convenience” and “Q5: flexibility” scores significantly improved after using the system (all P

Abstract Alkynylation of aldehydes initiated by cathodic reduction was performed. The cathodic alkynylation required only a semi‐catalytic amount of electricity to consume the starting material completely. Cyclic voltammetry and some control experiments suggest that the electron‐generated base derived from the cathodic reduction of benzaldehyde promotes alkynylation.

AbstractFunctionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)4-lipid imparts nonspecific cellular association to polyethylene glycol (PEG)-modified (PEGylated) liposomes, such as cell-penetrating peptides (CPPs). We investigated whether KK-(EK)4-lipid, which has a near-neutral charge, is a novel CPP-modified lipid that enhances the intracellular translocation of nanoparticles. However, the cellular association mechanism of KK-(EK)4-lipid is unknown. Therefore, we synthesized (EK)n-lipid derivatives based on the sequence of KK-(EK)4-lipid and determined the sequence sites involved in cellular association. In addition, KK-(EK)4-lipid was applied to extracellular vesicles (EVs) and mRNA encapsulated lipid nanoparticles (mRNA-LNPs). KK-(EK)4-lipid-modified EVs and mRNA-LNPs showed higher cellular association and in vitro protein expression, respectively, compared to unmodified ones. We elucidated KK-(EK)4-lipid to have potential for applicability in the intracellular delivery of liposomes, EVs, and mRNA-LNPs.

BackgroundPoly(adenosine diphosphate-ribose) polymerase inhibitors target cancers with defects in homologous recombination repair by synthetic lethality. New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer.MethodsWe conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo. The primary end point was invasive disease-free survival.ResultsA total of 1836 patients underwent randomization. At a prespecified event-driven interim analysis with a median follow-up of 2.5 years, the 3-year invasive disease-free survival was 85.9% in the olaparib group and 77.1% in the placebo group (difference, 8.8 percentage points; 95% confidence interval [CI], 4.5 to 13.0; hazard ratio for invasive disease or death, 0.58; 99.5% CI, 0.41 to 0.82; P

This study demonstrates the potential of friction stir spot welding (FSSW) for producing highly aligned graphene configurations in copper-aluminum joints, resulting in improved mechanical and electrical properties. Pure copper and AA6061 sheet were welded with 0.5% graphene nanoparticles dispersed in ethanol drop cast at the interface. Under optimized experimental conditions, adding a graphene interlayer results in a 15.6% increase in maximum shear strength, a 46% increase in hardness value, and a 23% reduction in joint electrical resistance. Transmission electron microscopy confirmed that the laminar flow behavior of the material aligns the graphene nanoparticles parallel to the tool surface direction. The mechanical improvements are attributed to the reduction of grain size and the plastic incompatibilities that arise at the metal-graphene interface. The highly aligned graphene configuration provides more conductive paths and acts as a bridge between grains to reduce grain boundary resistance, reducing electrical resistance. These findings pave the way for exploring the possibilities of utilizing the anisotropic properties of graphene in material joining applications.

Abstract Background Chromosome 5p partial monosomy (5p-syndrome) and chromosome 6p partial trisomy are chromosomal abnormalities that result in a variety of symptoms, but liver dysfunction is not normally one of them. Alagille syndrome (OMIM #118450) is a multisystem disorder that is defined clinically by hepatic bile duct paucity and cholestasis, in association with cardiac, skeletal, and ophthalmologic manifestations, and characteristic facial features. Alagille syndrome is caused by mutations in JAG1 on chromosome 20 or NOTCH2 on chromosome 1. Here, we report a preterm infant with karyotype 46,XX,der(5)t(5,6)(p15.2;p22.3) and hepatic dysfunction, who was diagnosed as having incomplete Alagille syndrome. Case presentation The Japanese infant was diagnosed based on the cardiac abnormalities, ocular abnormalities, characteristic facial features, and liver pathological findings. Analysis of the JAG1 and NOTCH sequences failed to detect any mutations in these genes. Conclusions These results suggest that, besides the genes that are known to be responsible for Alagille syndrome, other genetic mutations also may cause Alagille syndrome.

The Earth climate system is out of energy balance, and heat has accumulated continuously over the past decades, warming the ocean, the land, the cryosphere, and the atmosphere. According to the Sixth Assessment Report by Working Group I of the Intergovernmental Panel on Climate Change, this planetary warming over multiple decades is human-driven and results in unprecedented and committed changes to the Earth system, with adverse impacts for ecosystems and human systems. The Earth heat inventory provides a measure of the Earth energy imbalance (EEI) and allows for quantifying how much heat has accumulated in the Earth system, as well as where the heat is stored. Here we show that the Earth system has continued to accumulate heat, with 381±61 ZJ accumulated from 1971 to 2020. This is equivalent to a heating rate (i.e., the EEI) of 0.48±0.1 W m−2. The majority, about 89 %, of this heat is stored in the ocean, followed by about 6 % on land, 1 % in the atmosphere, and about 4 % available for melting the cryosphere. Over the most recent period (2006–2020), the EEI amounts to 0.76±0.2 W m−2. The Earth energy imbalance is the most fundamental global climate indicator that the scientific community and the public can use as the measure of how well the world is doing in the task of bringing anthropogenic climate change under control. Moreover, this indicator is highly complementary to other established ones like global mean surface temperature as it represents a robust measure of the rate of climate change and its future commitment. We call for an implementation of the Earth energy imbalance into the Paris Agreement's Global Stocktake based on best available science. The Earth heat inventory in this study, updated from von Schuckmann et al. (2020), is underpinned by worldwide multidisciplinary collaboration and demonstrates the critical importance of concerted international efforts for climate change monitoring and community-based recommendations and we also call for urgently needed actions for enabling continuity, archiving, rescuing, and calibrating efforts to assure improved and long-term monitoring capacity of the global climate observing system. The data for the Earth heat inventory are publicly available, and more details are provided in Table 4.

Abstract Hyperglycemia impairs immune response; however, it remains unknown whether the anti-tumor effects of anti-programmed cell death-1 antibody (PD-1-Ab) treatment are changed in hyperglycemic conditions. We analyzed the effect of PD-1-Ab on tumor growth in streptozotocin-induced diabetic mice (STZ-mice) subcutaneously inoculated with MC38 (a colon carcinoma cell line). Furthermore, we assessed the expression of chemokines by polymerase chain reaction (PCR) array in tumor-draining lymph nodes (dLNs) of these mice and MC38 cells cultured in different glucose concentrations. The suppressive effect of PD-1-Ab on tumor growth was attenuated. This was accompanied by fewer tumor-infiltrating CD8+ T cells, and STZ-mice had fewer tumor-infiltrating CD11c+ dendritic cells (DCs) than normoglycemic mice. mRNA expression levels of CXCL9, a chemokine recruiting CD8+ T cells, were lower in dLNs of STZ-mice than in normoglycemic mice after PD-1-Ab treatment, and its protein was expressed in DCs. In MC38 cells cultured with 25 mM glucose, mRNA expression of CCL7, a chemokine recruiting DCs, was decreased compared to cells cultured with 5 mM glucose. These results suggest that the STZ-induced hyperglycemia impairs the effect of PD-1-Ab treatment on MC38 tumor growth, and is accompanied by reduced infiltration of DCs and CD8+ T cells and decreased expression of CCL7 and CXCL9.

Yisihak Suga,1 Thorsten Kuehn,2 Gessesse W/Ammanuel,1 Goytom Knfe,1 Berhanetsehay Teklewold1 1Department of Surgery, St. Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia; 2Department of Gynecological Oncology and Gynecologic Surgery, Klinikum Esslingen, Esslingen, GermanyCorrespondence: Yisihak Suga, Tel +251913470780, Email yisihaksuga12@gmail.com; yisihak.suga@sphmmc.edu.etBackground: Breast abscess is a prevalent cause of morbidity in women occurring in 0.4% to 11% of patients after mastitis. The majority are benign, but worrisome etiologies such as inflammatory cancer and concomitant immune-compromising diseases should be addressed when a non-lactating patient presents with a breast abscess. The problem is high among women in developing countries (1). The purpose of this study is to assess the magnitude, clinical presentation, and treatment of breast abscess patients at a tertiary hospital.Methodology: A descriptive cross-sectional study was conducted on all patients treated for breast abscesses from September 2015 to August 2020. A retrospective review of the clinical records was performed to collect data on sociodemographic, clinical, and management data using a data extraction form. The collected data were then cleaned and entered into SPSS for analysis.Results: Two hundred and nine patients were included in this study over 5 years and lactational breast abscess (LBA) is more prevalent,182 (87.1%) than non-lactational breast abscess (NLBA), 27 (12.9%). Bilateral breast abscesses occurred in 16 (7.7%) patients. Patients presented at a median duration of 11 days and had been breastfeeding for 2 or more months. A spontaneously ruptured abscess was detected in, 30 (14.4%) of the patients. Comorbidities identified include diabetes mellitus (DM) in, 24 (11.5%), Hypertension in, 7 (3.3%), HIV in, 5 (2.4%) of patients. All women were treated with Incision and Drainage and had a median volume of 60 mL of pus drained. Following surgery, all patients were given ceftriaxone in the immediate post-operative days and either cloxacillin,167 (80.3%), or Augmentin,41 (19.7%) antibiotics p on discharge. Follow-up data were available for 201 (96.1%) patients and the recurrence rate was 5.8%.Conclusions and Recommendations: Lactational breast abscesses are more common than non-lactational breast abscesses, particularly in primiparas. DM is the most common comorbidity in non-lactational breast abscesses and health-seeking behavior should be improved given the delayed presentation.Keywords: breast abscess, lactational, non-lactational, magnitude, clinical presentation

Abstract Background Texture features reflecting tumour heterogeneity enable us to investigate prognostic factors. The R package ComBat can harmonize the quantitative texture features among several positron emission tomography (PET) scanners. We aimed to identify prognostic factors among harmonized PET radiomic features and clinical information from pancreatic cancer patients who underwent curative surgery. Methods Fifty-eight patients underwent preoperative enhanced dynamic computed tomography (CT) scanning and fluorodeoxyglucose PET/CT using four PET scanners. Using LIFEx software, we measured PET radiomic parameters including texture features with higher order and harmonized these PET parameters. For progression-free survival (PFS) and overall survival (OS), we evaluated clinical information, including age, TNM stage, and neural invasion, and the harmonized PET radiomic features based on univariate Cox proportional hazard regression. Next, we analysed the prognostic indices by multivariate Cox proportional hazard regression (1) by using either significant (p

Abstract Tools that can be used to estimate antibody waning following COVID-19 vaccinations can facilitate an understanding of the current immune status of the population. In this study, a two-compartment-based mathematical model is formulated to describe the dynamics of the anti-SARS-CoV-2 antibody in healthy adults using serially measured waning antibody concentration data obtained in a prospective cohort study of 673 healthcare providers vaccinated with two doses of BNT162b2 vaccine. The datasets of 165 healthcare providers and 292 elderly patients with or without hemodialysis were used for external validation. Internal validation of the model demonstrated 97.0% accuracy, and external validation of the datasets of healthcare workers, hemodialysis patients, and nondialysis patients demonstrated 98.2%, 83.3%, and 83.8% accuracy, respectively. The internal and external validations demonstrated that this model also fits the data of various populations with or without underlying illnesses. Furthermore, using this model, we developed a smart device application that can rapidly calculate the timing of negative seroconversion.

Abstract Aim Studies showed that cognitive function affects occupational function in patients with schizophrenia. This study aimed to determine the effects of cognitive function on occupational function in Japanese patients with schizophrenia using the Brief Assessment of Cognition in Schizophrenia (BACS). Methods Participants were 198 outpatients with schizophrenia or schizoaffective disorder (66 females; mean age 34.5 ± 6.8 years). Occupational function was assessed using the work subscale of the Life Assessment Scale for Mental Ill (LASMI‐w). Multiple regression analysis was performed using the BACS as the independent variable and LASMI‐w as the dependent variable. Furthermore, we divided the LASMI‐w score into three groups, 21, and performed a multinomial logistic regression analysis. Results Multiple regression analysis revealed that LASMI‐w score was negatively associated with BACS composite score (β = −0.20, p

Objective Evaluate the association between cancer incidence and immunosuppressive treatment in patients with ocular inflammatory disease (OID).Methods and analysis We performed a retrospective cohort study of patients from 10 US OID subspecialty practices. Patients with non-infectious OID were included; HIV-infected patients were excluded. Time-dependent exposure to drug classes (ie, antimetabolites, calcineurin inhibitors, alkylating agents, tumour necrosis factor (TNF) inhibitors) and drugs were evaluated. Cancer incidence was ascertained by linkage to 12 state cancer registries from 1996 to 2015. Cancer incidence was analysed using Cox regression survival analysis, using 0-year, 3-year and 5-year lags after immunosuppression began.Results The cancer incidence cohort comprised 10 872 individuals at risk of incident cancer and residing in one of the 12 states covered; 812 primary cancers were identified through cancer incidence tracing with median follow-up time of 10 years. Neither TNF inhibitor, antimetabolite, calcineurin inhibitor nor alkylating agent classes were associated with statistically significant increases in cancer incidence adjusting for covariates. We found statistically significant reduced hazards in the systemic inflammatory disease (SID)-including cohort for adalimumab and chlorambucil, increased hazards for tacrolimus and etanercept in the non-SID cohort and reduced hazards for methotrexate in both. Other immunosuppressive drugs were not associated with overall cancer incidence.Conclusions We found no increased risk of overall or site-specific cancer incidence associated with short-term (non-transplant) therapy with most commonly used immunosuppressive drug classes and many specific drugs. Further research may clarify potentially protective or harmful effects of specific agents that were not consistently associated with reduced or increased cancer incidence.Trial registration number NCT00116090.