An experimental aerosol air-agar interface mouse lymphoma assay methodology.

This work investigates a completely novel and experimental concept of exposing L5178Y cells at the air-agar-interface to mainstream cigarette smoke aerosol (Kentucky reference 3R4F). This study highlights the associated challenges of combining a suspension cell line alongside an in vitro aerosol exposure system. To achieve a monolayer, cells were 'seeded' in a concentrated cell super-mix suspension onto an RPMI/agar-matrix -base. The resulting cell suspension media was adsorbed into the agar base leaving the L5178Y cells lightly suspended on the agar surface, approximating a monolayer. Cells were deemed supportable on the agar-matrix, viable and recoverable. Using Vitrocell VC 10 exposure system and the Ames 4 exposure module, L5178Y cells were successfully exposed to a dynamic cigarette smoke aerosol, recovered and assessed for mutant frequencies, using standard assay procedures. Method development included assessment of flowing air conditions, plating efficiency and recovery of L5178Y cells from the agar-matrix surface. Positive controls MMS and B[a]P were successfully incorporated into the agar-matrix and metabolic activation was achieved by S-9 incorporation into the same agar-base-matrix. B[a]P demonstrated metabolic activation and positive response, suggesting a clear cellular interaction with the agar-matrix. Whole smoke exposed cells in the presence of metabolic activation showed a clear dose response and increasing mutant frequencies, well in excess of the controls (air and incubator) and the global evaluation factor following a 2 or 3 day expression period. This experimental concept demonstrates that L5178Y cells can be exposed to cigarette smoke aerosol, using a completely novel and a previously untested approach. Although this work successfully demonstrates the approach is viable and cells can be plated and maintained on an agar-matrix, more optimisation and robustness assessment is required before it can be considered fully adapted and used alongside other whole aerosol methodologies for the assessment of cigarette smoke and other inhaled aerosols.

Extreme testing of undiluted e-cigarette aerosol in vitro using an Ames air-agar-interface technique.

There is a growing consensus that e-cigarettes hold the potential for reducing the harm associated with cigarette smoking. Recently published studies have reported in vitro testing of e-cigarettes, demonstrating reduced toxicological and biological effects. Few studies however have reported the use of e-cigarettes under extreme testing conditions. To assess the full mutagenic potential of a commercially available electronic-cigarette (Vype ePen), this study investigated the delivery of aerosol under extreme conditions, using a scaled-down 35 mm plate Ames bacterial reverse mutagenicity assay. S. typhimurium strains TA98, TA100, TA97, TA104 and E. coli WP2 uvrA pKM101 with or without metabolic activation (S9), were employed. Using a modified Vitrocell VC 10 exposure system 0, 180, 360, 540, 720 or 900 puffs of undiluted e-cigarette aerosol was generated and delivered to bacterial cultures aligned to reported human consumption data. The results demonstrate that no mutagenic activity was observed in any strain under any test condition even when exposed to 900 puffs of undiluted e-cigarette aerosols +/- S9. Positive control responses were observed in all strains +/- S9. Nicotine assessments demonstrated an increased and consistent aerosol delivery, with calculated maximum doses of ∼1 mg/mL delivery of nicotine. These data demonstrate the validity of this unique testing approach and adds further information to the growing weight of evidence that e-cigarettes offer substantially reduced exposure when compared to conventional cigarette smoke. For future in vitro assessments of next generation tobacco and nicotine products, the generation, delivery and testing of undiluted aerosols can now be considered.

Selection and Use of Health Services for Infants' Needs by Indigenous Mothers in Canada: Integrative Literature Review.

In Canada, Indigenous infants experience significant health disparities when compared to non-Indigenous infants, including significantly higher rates of birth complications and infant mortality rates. The use of primary health care is one way to improve health outcomes; however, Indigenous children may use health services less often than non-Indigenous children. To improve health outcomes within this growing population, it is essential to understand how caregivers, defined here as mothers, select and use health services in Canada. This integrative review is the first to critique and synthesize what is known of how Indigenous mothers in Canada experience selecting and using health services to meet the health needs of their infants. Themes identified suggest both Indigenous women and infants face significant challenges; colonialism has had, and continues to have, a detrimental impact on Indigenous mothering; and very little is known about how Indigenous mothers select and use health services to meet the health of their infants. This review revealed significant gaps in the literature and a need for future research. Suggestions are made for how health providers can better support Indigenous mothers and infants in their use of health services, based on what has been explored in the literature to date.

Parents' early healthcare transition experiences with preterm and acutely ill infants: a scoping review.

BACKGROUND: Parents undergo multiple transitions following the birth of an ill infant: their infant's illness-health trajectory, neonatal intensive care unit hospitalization and transfers from one healthcare setting to another, while also transitioning to parenthood. The objective of this review was to map and synthesize evidence on the experiences and needs of parents of preterm or ill infants as they transition within and between healthcare settings following birth. METHODS: The scoping review followed Arskey and O'Malley's () framework, enhanced by Levac et al. (). Relevant studies were identified through a comprehensive search strategy of scientific and grey literature databases, online networks, Web of Science and citation lists of relevant articles. Inclusion criteria encompassed a focus on infants undergoing a healthcare transition, and the experiences and needs of parents during transition. Studies were appraised for design quality, and data relevant to parent experiences were extracted and underwent thematic analysis. RESULTS: A total of 7773 records were retrieved, 90 full texts reviewed and 11 articles synthesized that represented a total sample of 435 parents of preterm or ill infants. Parents reported on their experiences in response to their infant's transition within and between hospitals and across levels of neonatal intensive care unit, intermediate and community hospital care. Ten studies used qualitative research methods, while one employed quantitative survey methods. Four key themes were identified: that of parent distress throughout transition, parenting at a distance, sources of stress and sources of support. Parents' stress resulted from not being informed or involved in the transition decision, inadequate communication and perceived differences in cultures of care across healthcare settings. CONCLUSIONS: Opportunities to improve parents' early transition experiences include enhanced engagement, communication, information-sharing and shared decision-making between health care providers and parents. Future areas of research should focus on early transition interventions to advance parent capacity, confidence and closeness as the primary nurturer.

lncRNA/MicroRNA interactions in the vasculature.

MicroRNA (miRNA) have gained widespread attention for their role in diverse vascular processes including angiogenesis, apoptosis, proliferation, and migration. Despite great understanding of miRNA expression and function, knowledge of long noncoding RNA (lncRNA) molecular mechanisms still remains limited. The influence of miRNA on lncRNA function, and the converse, is now beginning to emerge. lncRNA may regulate miRNA function by acting as endogenous sponges to regulate gene expression and miRNA have been shown to bind and regulate lncRNA stability. A detailed understanding of the molecular and cellular effects of lncRNA-miRNA-mediated interactions in vascular pathophysiology could pave the way for new diagnostic markers and therapeutic approaches, but first there is a requirement for a more detailed understanding of the impact of such regulatory networks.

Mothers' and health care providers' perspectives of the barriers and facilitators to attendance at Canadian neonatal follow-up programs.

BACKGROUND: Despite the benefits of Neonatal Follow-Up (NFU) programs for infants at risk for developmental problems subsequent to preterm birth, non-attendance continues to be a problem within Canada and beyond. This study investigated the barriers and facilitators to attendance at Canadian NFU programs from mothers' and health care providers' (HCP) perspectives. METHODS: In this multi-site qualitative descriptive study, we conducted semi-structured individual interviews with 12 mothers, six from each of two NFU programs; and focus groups with 20 HCPs from nine NFU programs. Interviews were audio-recorded and transcribed and then subjected to thematic analysis. RESULTS: The predominant barriers represented a complex interplay of cumulative factors: mothers' isolation and feeling overwhelmed, with limited support, experiencing difficulty attending because of limited resources, who viewed NFU as not needed until problems arose for their child. Other barriers included vulnerability and fear of bad news. Mothers reported the need to protect their vulnerable child from risks, whereas HCPs reported creating vulnerability by monitoring the child's development over time. HCPs perceived fear of bad news as a barrier, whereas mothers viewed that impending bad news increased their need to attend to address the issue. The predominant facilitators were support, family centred-care and mothers with adequate resources. CONCLUSIONS: Attendance is most problematic for mothers with limited support, capacity and resources. First and foremost, targeted approaches to NFU service provision are needed to address the cumulative barriers and improve experiences for mothers who find it difficult to attend NFU. A continuous relationship with a single point of contact is needed and merits further investigation - a provider who works across the traditional silos of neonatal intensive care, NFU and community services, minimizes duplication and navigates transitions.

Maternal and infant predictors of attendance at Neonatal Follow-Up programmes.

BACKGROUND: Neonatal Follow-Up (NFU) programmes provide health services for families of infants at high risk of developmental problems following difficult or extremely premature birth: yet, up to 30% of families do not attend these programmes with their infants. METHODS: The study objective was to determine maternal and infant factors that predicted attendance at NFU programmes. Utilizing Andersen's Behavioural Model of Health Services Use, a prospective two-phase multi-site descriptive cohort study was conducted in three Canadian Neonatal Intensive Care Units (NICU) that refer to two affiliated NFU programmes. In Phase 1, 357 mothers completed standardized questionnaires that addressed maternal and infant factors, prior to their infants' NICU discharge. In Phase 2, attendance at NFU was followed at three time points over a 12-month period. Factors of interest included predisposing factors (e.g. demographic characteristics and social context); enabling factors (e.g. social support, travel distance, and income); and infant illness severity (i.e. needs factors). Multivariate logistic regression was used to estimate the odds ratio for each independent factor. RESULTS: Mothers parenting alone, experiencing higher levels of worry about maternal alcohol or drug use, or at greater distances from NFU were less likely to attend. Mothers experiencing higher maternal stress at the time of the infant's NICU hospitalization were more likely to attend NFU. No infant factors were predictive of NFU attendance. CONCLUSIONS: Mothers at risk of not attending NFU programmes with their infants require better identification, triage, referral and additional support to promote engagement with NFU programmes and improved quality of life for their high-risk infants.

The effect of long term storage on tobacco smoke particulate matter in in vitro genotoxicity and cytotoxicity assays.

Particulate matter (PM) collected from mainstream tobacco smoke is a test article commonly used for in vitro genotoxicity and cytotoxicity testing of combustible tobacco products. However, little published data exists concerning the stability of PM. We completed a 2 year study to quantify the effect of PM storage at -80 °C, on the genotoxicity and cytotoxicity of PM generated from 3R4F and M4A reference cigarettes. The Ames test, Micronucleus assay (MNvit), Mouse Lymphoma assay (MLA) and the Neutral Red Uptake assay (NRU) were used. The majority of M4A and 3R4F PMs were genotoxic and cytotoxic at the timepoints tested. Some minor but statistically significant differences were observed for stored versus freshly prepared PM, but the magnitude of changes were within the variability observed for repeat testing.

Postoperative pain assessment in the neonatal intensive care unit.

OBJECTIVES: To compare the convergent validity of two measures of pain (premature infant pain profile (PIPP) and crying, requires oxygen, increased vital signs, expression, and sleepless (CRIES)) in real life postoperative pain assessment in infants. METHODS: This study was a prospective, repeated measures, correlational design. Two staff nurses were randomly assigned either the PIPP or CRIES measure. An expert rater assessed each infant after surgery, and once a day using the visual analogue scale (VAS). SETTING: A level III neonatal intensive care unit in a metropolitan university affiliated paediatric hospital. RESULTS: Pain was assessed in 51 neonates (28-42 weeks of gestational age) after surgery. There was no significant difference in the rates of change between the pain assessment measures across time using repeated measures analysis of variance (F(50,2) = 0.62, p = 0.540), indicating correlation between the measures. Convergent validity analysis using intraclass correlation showed correlation, most evident in the first 24 hours (immediately, 4, 8, 20, and 24 hours after the operation). Correlations were more divergent at 40 and 72 hours after surgery. No significant interactions were found between gestational age and measure (F(304,4) = 0.75, p = 0.563) and surgical group and measure (F(304,2) = 0.39, p = 0.680). CONCLUSIONS: PIPP and CRIES are valid measures that correlate with pain for the first 72 hours after surgery in term and preterm infants. Both measures would provide healthcare professionals with an objective measure of a neonatal patient's pain.

Validation of the premature infant pain profile in the clinical setting.

OBJECTIVE: The Premature Infant Pain Profile (PIPP) is a 7-indicator composite measure developed to assess acute pain in preterm and term neonates. It has been validated in studies using synchronized videotaping of infants undergoing procedures. The purpose of this study was to establish (a) construct validity of the PIPP and (b) inter- and intrarater reliability of the PIPP prospectively in the clinical environment. DESIGN: A randomized, crossover design was used. SETTING: The study was conducted in a Level III outborn neonatal intensive care unit. PARTICIPANTS: A convenience sample of 43 neonates, stratified by gestational age, was studied. INTERVENTIONS: Each infant experienced three separate, randomly ordered events: baseline, a painful event, and a nonpain event. Infants were videotaped and scored at the bedside using the PIPP by the nurse caring for the infant and the clinical nurse specialist who bad expertise in infant pain. The videotapes were later reviewed by two additional experts; one in real time and one using a second-to-second stop frame technique. RESULTS: Repeated-measures analysis of the main effects and interactions yielded a statistically significant main effect for event (pain, nonpain, baseline), thus differentiating pain from nonpain and baseline events (F = 48, p = 0.0001) and establishing construct validity. Interrater reliability analysis of individual event scores of the PIPP yielded reliability coefficients of 0.93-0.96. Intrarater reliability coefficients analysis for individual events were equally high at 0.94-0.98. CONCLUSIONS: This study demonstrates that the PIPP is a pain measure with good construct validity and excellent inter- and intrarater reliability for the assessment of procedural pain of preterm and term infants in clinical settings.

Epidural analgesia for labour and delivery: informed consent issues.

OBJECTIVE: Many anaesthetists believe that informed consent for epidural analgesia during labour is inadequate. Patients are perceived to be poorly informed and unable to cope with the information given during labour for informed consent. We reviewed these two hypotheses: A) to define complications for which patients want clear information: B) to quantify the influence of pain, anxiety, opioid premedication, and the importance of level of education, on a patient's level of satisfaction with regard to the consent process: and C) to assess how satisfactory epidural pain relief correlates with satisfaction with the consent process. METHODS: Sixty patients were surveyed during the first two months after vaginal delivery by two interviewers. Questions related to demographics, severity of labour pain, level of satisfaction with the epidural anaesthetic, risk of complications and satisfaction with information received were either categorical or scored on a scale from 0 to 10. RESULTS: All epidural related complications were considered important to disclose (8.4/10). The level of satisfaction with the consent process was 8.1/10. Patient satisfaction was not affected by opioid premedication, anxiety, pain score, education group or level of pain relief. CONCLUSION: Patients indicated they should be informed of all possible complications associated with epidural analgesia, regardless of severity or risk. In contrast to reports in the literature, non disclosure of serious risks during labour was not acceptable to parturients.

Does the method of payment affect anaesthetic practice? An evaluation of an alternate payment plan.

PURPOSE: To test the null hypothesis that the method of physician payment does not influence the practice of anaesthesia. METHODS: Retrospective cohort study of anaesthetists before (Jan-June, 1994) and after (Jan-June, 1995) departure from fee-for-service practice into an alternate funding arrangement (AFP). Another group of physicians was studied as a concurrent control. Case numbers, induction times, cancellation rates, and operating hours for the department, recorded by third parties, were compared before and after AFP implementation. Using index procedures, details of individual patient decisions made by anaesthetists were compared for the two study periods, and between subscribing and non-subscribing physicians. RESULTS: Implementation of AFP resulted in a modest reduction in case numbers (7.2%) offset by an increase (5.7%) in the average case duration. Net change in time dedicated to clinical service (2% per physician) is inconsequential to the academic mission of the department. There was no change in cancellation rate and the use of invasive monitors was unchanged. An increase in the use of regional anaesthesia occurred but, since a similar increase occurred in the practice of those still on fee-for-service, it cannot be ascribed to the AFP. With respect to hip arthroplasty, the case was prolonged (P = 0.001) if the surgeon was paid via the AFP. CONCLUSION: Payment of physicians by non-fee-for-service techniques did not have a constructive influence on measures of anaesthetic practice. The goal of alternate payment arrangements, to liberate time for academic pursuits, could not be achieved in this experimental model.

Cardiac output estimation by visual inspection vs thermodilution during cardiac surgery.

PURPOSE: The objectives of this study were: 1) to compare the estimated cardiac output (CO) by visual inspection with objective measurements by thermodilution: 2) to compare the estimated systemic vascular resistance (SVR) with objective measurements by thermodilution; and 3) to assess whether management of the patient, based on subjective values, would have differed from the management of the patient based on the objective values. METHODS: A non-randomized, prospective, blinded study was conducted at a tertiary care university hospital. Following institutional ethics approval, 35 patients undergoing cardiac surgery, with pulmonary artery catheter (PAC) monitoring, were studied. Prior to the measurement of CO by thermodilution, but after separation from cardiac pulmonary bypass, the CO and SVR were estimated by the anaesthetist and the surgeon. Bland and Altman's method was used for statistical analysis. RESULTS: Surgeons' estimates of CO were comparable with the objectively measured thermodilution measures: in each case (100%), the difference between the subjective estimate and the objective measurement was less than two standard deviations from the mean difference of the two methods. Anaesthetists' estimates, by visual inspection, were also comparable with the objectively measured thermodilution values; 94.6% of cases. The surgeons' and anaesthetists' estimates of SVR were also comparable with the thermodilution measures in all cases. Management based on subjective values would have differed from those based on objective values in only 8.6% of cases. CONCLUSION: An advantage of cardiac surgery is the ability to observe the heart and assess its performance visually. This study demonstrated that estimates of CO and SVR by clinical observation are comparable with the pulmonary artery catheter's derived values.

Reduction of post-operative nausea and vomiting with the combination of morphine and droperidol in patient-controlled analgesia.

PURPOSE: To determine whether low doses of droperidol mixed with morphine in patient-controlled analgesia (PCA) would extend the duration of prophylaxis against postoperative nausea and vomiting. METHODS: Healthy women having elective open-abdominal gynaecological surgery consented to this double-blind, placebo-controlled study. Subjects were randomized to receive placebo, or 1 mg droperidol before induction followed by droperidol 0.0 (bolus group), 0.02 (0.02 group), or 0.04 (0.04 group) mg.mg-1 of PCA morphine. Study endpoints included severity of nausea, episodes of vomiting and rescue antiemetic doses, pain, and sedation and were assessed at 1, 2, 4, 8, 12, 16, 20 and 24 hr postoperatively. RESULTS: Seventy-one subjects completed the study. The groups were similar in age, weight, surgical time, pain scores, and morphine used. The 0.04 group had lower mean visual analogue scale scores for nausea (P < 0.05 vs all other groups). The incidence of vomiting was lower in all treatment groups (P < 0.05 for all groups vs placebo). The 0.04 group had lower rescue antiemetic requirements than the bolus group (P < 0.03). Mean sedation scores were low in all groups but were increased with PCA droperidol (P < 0.02). CONCLUSIONS: Droperidol 1 mg before induction of anaesthesia reduces postoperative vomiting. The addition of droperidol 0.04 mg.mg-1 of PCA morphine further reduces (i) severity of nausea and (ii) rescue antiemetic requirements postoperatively. No clinically significant side-effects were attributed to this regimen.

Argon green vs. krypton red laser photocoagulation for extrafoveal choroidal neovascularization secondary to age-related macular degeneration: 3-year results of a multicentre randomized trial. Canadian Ophthalmology Study Group.

OBJECTIVE: To determine whether argon green laser (AGL) or krypton red laser (KRL) is superior for the treatment of well-defined extrafoveal choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) after 3 years of follow-up. DESIGN: Multicentre randomized clinical trial. SETTING: University-based referral practices in Canada. PARTICIPANTS: Among 210 patients selected by ophthalmologists at 13 participating centres there were 191 eligible patients aged 50 years or more with angiographically proven CNV whose posterior edge was 200 to 2500 microns from the foveal avascular zone. Other inclusion criteria included the presence of drusen in either eye, a best corrected visual acuity in the study eye of at least 35 letters on the Early Treatment Diabetic Retinopathy Study chart (equivalent of 20/200 or better on the Snellen chart) and no prior photocoagulation in the study eye. The patients were randomly assigned to receive either AGL (96 patients) or KRL (95 patients) treatment. INTERVENTIONS: Treatment with 200-microns spots of 0.2 to 0.5 seconds' exposure to produce a homogeneous grey white lesion that completely covered the CNV. OUTCOME MEASURES: Change from baseline in visual acuity at 1, 2 and 3 years (primary measure), development of persistent or recurrent CNV (secondary measure). RESULTS: There were no significant differences between the treatment groups in drop-out rates. No significant differences were found between the two groups in loss of visual acuity or angiographic evidence of persistent or recurrent CNV. CONCLUSION: KRL is no better than AGL in preserving vision and preventing loss of visual acuity in patients with AMD with well-defined extrafoveal CNV followed for 3 years.

Association between duration of neonatal hospital stay and readmission rate.

OBJECTIVE: A recent rapid decrease in the duration of neonatal hospital stay in Ontario, Canada, enabled us to study the association between healthy infants' age at neonatal hospital discharge and subsequent readmission rates. DESIGN: (1) Population-based and (2) single hospital-based retrospective studies. SETTING AND STUDY POPULATION: (1) A total of 920,554 healthy infants with a birth weight of 2500 gm or more, born in Ontario from 1987 to 1994. (2) Infants with a birth weight of 2500 gm or more, born during the same period, and readmitted before 15 days from home to the Hospital for Sick Children for jaundice or dehydration. MEASUREMENT: Duration of neonatal stay in the hospital and readmission rates were measured, and diagnostic codes were analyzed. Severity of illness was evaluated in infants readmitted to our hospital. RESULTS: In Ontario the mean length of stay decreased from 4.5 days to 2.7 days (p = 0.000), and the readmission rate during the first 2 weeks of life increased from 12.9 to 20.7 per 1000 (p = 0.000). Increased rates of readmission were most marked for jaundice and dehydration. The infants readmitted to our hospital had evidence of increased severity of illness as indicated by higher serum bilirubin and sodium concentrations. Two deaths occurred in infants with hypernatremic dehydration, one in 1992-1993 and another in 1993-1994. CONCLUSIONS: In Ontario, shorter neonatal hospital stay was associated with increased readmission rates for conditions that may not give rise to symptoms or signs on days 1 to 3 of life. In our hospital the severity of jaundice and dehydration in readmitted infants increased. The severity-of-illness data raise the question of whether shorter neonatal hospital stay of apparently healthy infants is always safe. Decisions to discharge infants should be based on rigorous evaluation of individual infants.

Indwelling versus intermittent feeding tubes in premature neonates.

OBJECTIVE: To determine the effect of indwelling versus intermittent feeding tube placement on weight gain, apnea, and bradycardia in premature neonates. DESIGN: Eligible subjects were assigned randomly to either feeding tube method. Each subject was followed for 6 days. SETTING: The study was conducted in a secondary level neonatal intensive-care unit (NICU), a tertiary level NICU in a perinatal center, and a tertiary level NICU in a referral center. PATIENTS/PARTICIPANTS: Neonates who were 24-34 weeks gestational age, developmentally appropriate for gestational age, medically stable, on full enteral feedings through an orogastric or a nasogastric tube, and not fluid restricted. Ninety-three neonates were enrolled--49 indwelling group and 44 in the intermittent group. Nine neonates did not complete the study. INTERVENTIONS: Nasogastric indwelling feeding tubes were placed and left in site for up to 3 days. Orogastric intermittent feeding tubes were placed for each feeding and removed at completion of the feeding. MAIN OUTCOME MEASURES: Weight gain, apnea, and bradycardia. RESULTS: Members of both groups had similar demographic characteristics, clinical problems, and nutritional intake. No statistical differences were found between the two groups in weight gain or episodes of apnea and bradycardia. CONCLUSIONS: There were no statistically or clinically significant differences between the two groups. The intermittent method of feeding is more expensive. Because no clinical differences were found, the type of tube placement chosen for feeding the premature infant may be based on economics.

Chronic benign retinal pigment epithelial detachment: a subtype of central serous choroidopathy.

Between October 1983 and December 1991, 14 patients (mean age 48.1 [range 38 to 68] years) presented with single, clear, cystic-appearing juxtafoveal lesions beneath the retina, with discrete borders measuring approximately 2 mm in diameter. All patients had vision of 6/7.5 or better, which did not deteriorate over a follow-up period of 3 to 91 (mean 18.1) months. Angiographically, the lesions showed relative homogeneous hyperfluorescence with very discrete margins, the angiographic appearance of serous retinal pigment epithelial detachment. We describe the clinical and angiographic appearance on presentation and in follow-up and discuss the probable relationship of these lesions to central serous choroidopathy.

Clinical trials: where do we go from here?

Randomized clinical trials are necessary to detect a possible treatment effect of interventions for which no clear-cut answer is known. In ophthalmology, clinical trials have shown the benefit of laser therapy in several eye diseases. As smaller treatment effects are sought, sample sizes must be increased considerably to maintain statistical power. This can be done only through multicentre randomized clinical trials. Provided the question being asked is of value to society, the cost of a clinical trial is an excellent investment.