ABSTRACT
Although most medical treatments are designed for the average patient with a one-size-fits-all-approach, they may not benefit all. Better understanding of the function of genes, proteins, and metabolite, and of personal and environmental factors has led to a call for personalized medicine. Personalized reproductive medicine is still in its infancy, without clear guidance on treatment aspects that could be personalized and on trial design to evaluate personalized treatment effect and benefit-harm balance. While the rationale for a personalized approach often relies on retrospective analyses of large observational studies or real-world data, solid evidence of superiority of a personalized approach will come from randomized trials comparing outcomes and safety between a personalized and one-size-fits-all strategy. A more efficient, targeted randomized trial design may recruit only patients or couples for which the personalized approach would differ from the previous, standard approach. Multiple monocenter studies using the same study protocol (allowing future meta-analysis) might reduce the major center effect associated with multicenter studies. In certain cases, single-arm observational studies can generate the necessary evidence for a personalized approach. This review describes each of the main segments of patient care in assisted reproductive technologies treatment, addressing which aspects could be personalized, emphasizing current evidence and relevant study design.
Subject(s)
Evidence-Based Practice/methods , Ovulation Induction/methods , Precision Medicine/methods , Reproductive Techniques, Assisted , Evidence-Based Practice/standards , Female , Humans , Ovulation Induction/standards , Precision Medicine/standards , Research DesignABSTRACT
UNLABELLED: This is an integrated analysis of data from patients with cystic fibrosis (CF) aged 6-21 years who were treated with up to seven cycles of tobramycin powder for inhalation (TIP(TM) ) over a period of at least 1 year. Safety and key efficacy endpoints were analyzed. RESULTS: The improvement in lung function and decrease in sputum P. aeruginosa (Pa) density from baseline were sustained over the 1-year treatment period. The number of adverse events (AEs) was low and did not increase with additional cycles of TIP treatment. Some increase in tobramycin minimum inhibitory concentration (MIC) was observed, but there was no significant increase in emergence of resistant strains based on the parenteral breakpoint for tobramycin. CONCLUSION: Efficacy of TIP was maintained for up to seven cycles. Long-term treatment with TIP was generally safe and well tolerated with no increase in AEs.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Cystic Fibrosis/complications , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Sputum/drug effects , Tobramycin/therapeutic use , Administration, Inhalation , Adolescent , Child , Cystic Fibrosis/microbiology , Cystic Fibrosis/physiopathology , Double-Blind Method , Female , Humans , Male , Microbial Sensitivity Tests , Powders , Pseudomonas Infections/etiology , Sputum/microbiology , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: To investigate the association of whole-blood fatty acids and reported intakes of fats with risk of prostate cancer (PCa). DESIGN: Case-control study of 209 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 226 cancer-free men attending the same urology clinics. Whole-blood fatty acid composition (mol%) was measured by gas chromatography and diet assessed by food frequency questionnaire. RESULTS: High whole-blood oleic acid composition (tertile 3 vs. tertile 1: OR, 0.37; CI, 0.14-0.0.98) and moderate palmitic acid proportions (tertile 2: OR, 0.29; CI, 0.12-0.70) (tertile 3: OR, 0.53; CI, 0.19-1.54) were inversely related to risk of PCa, whereas men with high linolenic acid proportions were at increased likelihood of PCa (tertile 3 vs. tertile 1: OR, 2.06; 1.29-3.27). Blood myristic, stearic and palmitoleic acids were not associated with PCa. Higher intakes of dietary MUFA were inversely related to prostate cancer (tertile 3 vs. tertile 1: OR, 0.39; CI 0.16-0.92). The principal source of dietary MUFA was avocado intake. Dietary intakes of other fats were not associated with PCa. CONCLUSIONS: Whole-blood and dietary MUFA reduced the risk of prostate cancer. The association may be related to avocado intakes. High blood linolenic acid was directly related to prostate cancer. These associations warrant further investigation.
Subject(s)
Dietary Fats, Unsaturated/administration & dosage , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids/blood , Oleic Acid/blood , Prostatic Neoplasms/blood , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/blood , Case-Control Studies , Feeding Behavior , Humans , Jamaica , Male , Middle Aged , Persea , Risk Factors , alpha-Linolenic Acid/bloodABSTRACT
We investigated the associations between body size and risk of prostate cancer in a hospital-based case-control study in Jamaica. Height, weight, waist, and hip circumference were measured at enrollment, and data collected on medical and lifestyle factors for newly diagnosed cases (n = 243) and controls (n = 275). Compared with men in the normal range of waist-hip ratio (WHR), men with WHR > or =0.95 were at greater risk of total prostate cancer (OR,1.72; CI, 1.01-3.00) and high-grade cancer (OR, 2.02; CI, 1.03-3.96). With additional control for BMI, the association with WHR remained significant for total prostate cancer (OR, 1.90; CI, 1.01-3.53) and high-grade disease (OR, 2.94; CI, 1.34-6.38). There was no association between waist circumference and cancer without control for BMI but after controlling for BMI, waist circumference >90 cm (OR, 2.45; CI, 1.01-5.94) and >102 cm (OR, 5.57; CI, 1.43-18.63) showed a dose-response relationship with high-grade disease. Height and BMI were not associated with risk of prostate cancer. Abdominal obesity may be associated with risk of high-grade prostate cancer. Risk may be greater in those with higher abdominal obesity relative to overall size. The results further highlight the importance of investigating relationships by characteristics of the tumor.
Subject(s)
Body Size/physiology , Abdomen/pathology , Body Composition , Body Weight , Case-Control Studies , Humans , Jamaica , Life Style , Male , Obesity, Abdominal , Prostatic Neoplasms/pathology , Risk Factors , Waist Circumference , Waist-Hip RatioABSTRACT
PURPOSE: Jamaica has the highest incidence of prostate cancer in the world. Dietary fat is associated with prostate cancer. The Omega6 polyunsaturated fatty acids have been shown to stimulate prostate carcinogenesis and the Jamaican diet is rich in linoleic acid. We hypothesized positive correlations between Omega6 polyunsaturated fatty acid, prostate specific antigen and prostate biopsy pathology. MATERIALS AND METHODS: A total of 148 men were enrolled in Kingston, Jamaica. Serum prostate specific antigen and erythrocyte membrane polyunsaturated fatty acids were analyzed. Men with prostate specific antigen 2.6 ng/ml or greater underwent biopsy. Histopathological and statistical analyses were performed on available data. RESULTS: Of the 54 men who underwent biopsy 24 had prostate cancer, 17 had a Gleason score of 7 or greater and 11 had a tumor volume of 50% or greater. There were significant positive correlations between linoleic acid and Gleason score (p = 0.009), and the linoleic acid-to-docosahexaenoic acid (Omega3) ratio and tumor volume (p = 0.03). There was a significant negative correlation between the arachidonic acid (Omega6)-to-docosapentanoic acid (Omega3) ratio and Gleason score (p = 0.04). Statistical correlations between prostate specific antigen and polyunsaturated fatty acids were inconsistent. CONCLUSIONS: The positive correlations between linoleic acid and Gleason score, and the linoleic acid-to-docosahexaenoic acid ratio and tumor volume support studies showing that Omega6 polyunsaturated fatty acids stimulate and Omega3 polyunsaturated fatty acids inhibit prostate cancer growth. The negative correlation between the arachidonic acid-to-docosapentanoic acid ratio and Gleason score supports studies that demonstrate increased metabolism of arachidonic acid in prostate cancer to form carcinogenic metabolites, namely prostaglandin E2. Our findings support the association between dietary fatty acids and prostate cancer, and they warrant further dietary and tissue studies in high risk populations.
Subject(s)
Fatty Acids, Omega-3/blood , Fatty Acids, Omega-6/blood , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Aged , Biopsy , Dietary Fats , Fatty Acids , Humans , Jamaica , MaleABSTRACT
The incidence of prostate cancer varies according to countries and races. Among Asian men the incidence is low, but it is especially high among African Americans. A recent epidemiology study has revealed a very high level in the Jamaican male, exceeding that in American blacks. In this study 146 Jamaican men who underwent TRUS guided prostate biopsies from January 1996 to December 1997 in a private urology practice were reviewed. All were referred by their family physician, so they were screened before being seen by a urologist. Their ages ranged from 45 to 93 years (mean 67 years). 86 biopsies (60 percent) were positive for prostate cancer. In men with prostate specific antigen levels greater than 10ng/ml, the rate was 70 percent. The high percentage of positive biopsies may be due to the fact that this was a select group. The high referral rate suggests that Jamaican men and/or their family physicians have a high suspicion of prostate cancer.(AU)
Subject(s)
Adult , Middle Aged , Aged , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnosis , /genetics , Case-Control Studies , Jamaica , United StatesABSTRACT
PURPOSE: Before this study, the highest reported incidence of prostate cancer in the world was thought to be among United States black men. The age adjusted rates in 1992 for United States black and white men were 249 and 182/100,000 respectively. The epidemiology of prostate cancer in Jamaica, a country of 2.5 million people of primarily African descent, was studied and compared with that of white and black Americans. MATERIALS AND METHODS: The study included 1,121 cases of prostate cancer diagnosed from 1989 to 1994. Sources of information included the Jamaican Cancer Registry, government pathology laboratory, hospital and clinic records, and physician office records. Incidence rates were computed using data from the 1991 Jamaican census. Age adjustments were made using the 1970 United States standard population. RESULTS: The average age adjusted incidence of prostate cancer in Kingston, Jamaica was 304/100,000 men. Median patient age at diagnosis was 72 years. More than 80 percent of the cases were pathologically confirmed. Of the patients 30 percent presented with acute urinary retention, 16 percent presented with bone metastases, 15 percent had gross hematuria at the time of diagnosis and an abnormal rectal examination suspicious for cancer was noted in 42 percent. Prostate specific antigen was measured in only 7 percent of cases in 1989 but in 48 percent of cases by 1994. CONCLUSIONS: These data demonstrate that Jamaican men in Kingston have a high incidence of prostate cancer, much higher than even black Americans during a similar period. Furthermore, the cancers are more significant clinically with greater morbidity in Jamaica than in the United States(AU)
Subject(s)
Adult , Aged , Humans , Male , Middle Aged , Prostatic Neoplasms/epidemiology , Prostatic Neoplasms/blood , Prostate-Specific Antigen/blood , United States/epidemiology , Jamaica/epidemiology , Aged, 80 and over , IncidenceABSTRACT
The Mathieu technique and MAGPI repair have traditionally been the standard choices for distal hypospadias repair. Plate urethroplasty has recently been suggested as an alternative. Over a 2 year period, of 31 patients who presented with distal hypospadias 19 had the Mathieu repair and 12 had plate urethroplasty (Snodgrass repair). The results in the latter group were superior.(AU)
Subject(s)
Humans , Male , Hypospadias/surgeryABSTRACT
With over 100 gunshot injuries seen at the University Hospital of the West Indies and the Kingston Public Hospital annually and with lower GU injuries occurring in approximately eight per cent of cases, it is not surprising that unusual trauma pathology will occur in this region. Described are four cases seen over a six-month period where the courses of the bullets almost defy an anatomical explanation. In two, the entry site was in the buttock with entry into the bladder through the posterior wall without causing bowel injury. In another, the entry wound was also lodge in the lumen of the bulbous urethra. In the other case, the skin entry wound was in the lower anterior abdominal wall with exit through the posterior inferior wall of the urinary bladder just above the mid trigone, again somehow avoiding bowel to finally lodge in the buttock. It is impossible to explain any of the above pathology if it is assumed that the bullets travelled on a straight course. Seemingly, their trajectories were altered, allowing the path of least resistance to be taken, thereby pushing structures with mobile walls out of their way. It is theoretically possible that the high pressure area that precedes a high velocity bullet pushes mobile structures out of harm's way (AU)
Subject(s)
Humans , Wounds, Gunshot , Urinary Bladder/injuries , Abdominal InjuriesABSTRACT
All cases of ectopia vesica treated at the Bustamante Children's Hospital from 1977 to 1984 were reviewed, to assess the effectiveness of treatment. During this period, eight cases were seen, one was lost to follow-up. Seven cases are therefore reported. There were no other associated congenital abnormalities. Three patients were not seen until after they were five months of age which is surprising because of the severity of this condition. Our policy has been to attempt staged reconstruction of the lower genito-urinary tract and to attain a funcitonally closed bladder. Cystectomy and urinary diversion (uretero-sigmoidostomy) were reserved for cases of failed bladder closure or an unacceptable level of incontinence. All patients had multiple surgical procedures. Three have undergone cystectomy and uretero-sigmoidostomy. Three have satisfactory bladder closure and are partially continent. One presently has a bladder neck fistula and is totally incontinent (AU)