Synovial fluid leukocyte cell count before versus after administration of antibiotics in patients with septic arthritis of a native joint.

BACKGROUND: Antibiotics have been shown to affect the accuracy of cultures; so antibiotics are held prior to obtaining cultures intra-operatively. No study has evaluated the effects of antibiotics on synovial fluid leukocyte cell count. The purpose of the current study is to compare the leukocyte cell count of native joints with septic arthritis when antibiotics have been given before aspiration and when no antibiotics have been given prior to aspiration. METHODS: This study was performed at a community hospital and a level 1 urban trauma hospital after IRB approval from both institutions from July 2007 to July 2017. Inclusion criteria comprised of a diagnosis of septic arthritis with positive cultures and a recorded arthrocentesis with cell count performed. Patients with septic arthritis were identified using ICD-9 codes 711.00-711.99 and ICD-10 codes M00 - M02. A retrospective chart review was performed and data was collected. Patients were placed into one of two groups. Group 1 received no antibiotics for two weeks prior to arthrocentesis, group 2 received antibiotics within 24 h prior to arthrocentesis. Demographic information, cell count number and differential, and blood lab values were collected. Timing data was also collected on timing of admission, antibiotics, joint irrigation, and discharge from the inpatient setting. RESULTS: There were 81 patients meeting final inclusion criteria. The average cell count for the group which received antibiotics (n = 30) was 40,408 ± 29,433 while the average cell count for the group receiving no antibiotics (n = 51) was 93,824 ± 73,875 (p < .0001). The average length of stay was not significantly different between the antibiotic group versus no antibiotic group (14.0 days vs 12.1 days p = .4). The time from admission to arthrocentesis and admission to washout was longer for the antibiotic group versus no antibiotic group (p = .004 and p = .002, respectively). CONCLUSION: When antibiotics are given prior to arthrocentesis of a septic joint, there is an associated lower synovial fluid leukocyte count compared to when no antibiotics are given prior. LEVEL OF EVIDENCE: Level III.

Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Downstream consequences of diagnostic error in pediatric anaphylaxis.

BACKGROUND: Pediatric anaphylaxis is commonly misdiagnosed in the Emergency Department (ED). We aimed to determine the impact of inaccurate diagnosis on the management and follow-up of pediatric anaphylaxis presenting to the ED. METHODS: Retrospective chart review of ED management of children aged 0-18 years with allergic presentations to three EDs in Melbourne, Australia in 2014. Cases were included if an ED diagnosis of anaphylaxis was recorded, or the presentation met international consensus criteria for anaphylaxis. RESULTS: Of the 60,143 pediatric ED presentations during the study period, 1551 allergy-related presentations were identified and reviewed. 187 met consensus criteria for anaphylaxis, and another 24 were diagnosed with anaphylaxis without meeting criteria. Of the 211 presentations, 105 cases were given an ED diagnosis of anaphylaxis and 106 cases were given an alternative diagnosis in ED. Those diagnosed with anaphylaxis were more likely to receive epinephrine [85.7% vs 31.1% (OR = 13.27, 95% CI: 6.09-26.3)], to be observed for the recommended four hours [56.2% vs 29.2% (OR = 3.10, 95% CI 1.76-5.48, p < 0.001)], to have an epinephrine autoinjector available on discharge [81.9% vs 35.8% (OR = 4.12, 95% CI 2.07-8.22, p < 0.001)] and to be referred to an allergist [35.2% vs 16.0% (OR = 2.85, 95% CI 1.48-5.49, p < 0.01)]. Provision of anaphylaxis action plans and allergen avoidance advice was poorly documented for all patients. CONCLUSION: Accurate diagnosis of anaphylaxis in ED has a significant impact on observation times, prescription of epinephrine autoinjectors and referral to an allergist. These factors are key to reducing mortality and the significant morbidity that results from childhood anaphylaxis.

Lack of evidence on mental health and well-being impacts of individual-level interventions for vulnerable adolescents: systematic mapping review.

OBJECTIVES: To review empirical evaluations of individual-level interventions intended to improve mental health or well-being for vulnerable adolescents. STUDY DESIGN: This is a systematic mapping review. METHODS: Thirteen databases covering academic and gray literature were searched for published reviews and randomised controlled trials, and gray literature (2005-2016) and the results quality-assessed to prioritise best available evidence. We aimed to identify well-conducted systematic reviews and trials that evaluated individual-level interventions, for mental health/well-being outcomes, where the population was adolescents aged 10-24 years in any of 12 vulnerable groups at high risk of poor health outcomes (e.g. homeless, offenders, 'looked after', carers). RESULTS: Thirty systematic reviews and 16 additional trials were identified. There was insufficient evidence to identify promising individual-level interventions that improve the mental health/well-being of any of the vulnerable groups. CONCLUSIONS: Despite Western policy to promote health and well-being among vulnerable young people, the dearth of evidence suggests a lack of interest in evaluating interventions targeting these groups in respect of their mental health/well-being outcomes.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

BACKGROUND: Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. METHODS: The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. RESULTS: Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. CONCLUSION: The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.

A new understanding of clinical patterns in post-TB lung disease.

Post-TB lung disease (PTLD) can be categorised based on physiological, radiological, and clinical abnormalities, delineating distinct clinical patterns; however, thus far the importance of this is unknown. People with PTLD have a high morbidity and increased mortality, but predictors of long-term outcomes are poorly understood.We conducted an observational study of PTLD patients attending a tertiary hospital in South Africa between 1 October 2021 and 30 September 2022. Patient demographics, risk factors, symptoms, lung function tests and outcomes were captured.A total of 185 patients were included (mean age: 45.2 years, SD ±14.3). Half of patients reported only one previous episode of Mycobacterium tuberculosis infection (n = 94, 50.8%). There was a statistically significant association between TB-associated obstructive lung disease (OLD) and dyspnoea (P = 0.002), chest pain (P = 0.014) and smoking (P = 0.005). There were significant associations between haemoptysis and both cavitation (P = 0.015) and fungal-associated disease (P < 0.001). Six patients (3.2%) died by study end.PTLD can affect young people even with only one previous episode of TB, and carries a high mortality rate. For the first time, clinical patterns have been shown to have meaningful differences; TB-related OLD is associated with dyspnoea, chest pain and smoking; while haemoptysis is associated with cavitary and fungal-associated disease..

Parenting interventions for male young offenders: a review of the evidence on what works.

Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization.

Large artery biomechanics and diastolic dysfunctionin patients with Type 2 diabetes.

AIMS: To comprehensively characterize large artery biomechanical properties and examine their relationship to cardiac function in patients with Type 2 diabetes mellitus (DM). METHODS: Fifty-five individuals with Type 2 DM were compared with 66 age- and sex-matched healthy control subjects. Arterial biomechanical properties were assessed by systemic arterial compliance (SAC; two-element Windkessel model), carotid-femoral pulse wave velocity (PWVc-f), femoral-dorsalis pedis pulse wave velocity (PWVf-d) and carotid augmentation index. Cardiac structure and function were assessed by echocardiography. RESULTS: Individuals with Type 2 DM had lower SAC and higher PWVc-f when compared with the healthy population. The PWVc-f was significantly lower than the PWVf-d in control individuals, but this difference was not evident in individuals with Type 2 DM due to higher PWVc-f. Augmentation index was similar in both groups, but the time to the first systolic inflection (time to reflection) was shorter in the individuals with Type 2 DM. The individuals with Type 2 DM had a greater prevalence of diastolic abnormalities when compared with the control group. Arterial stiffness indices, including SAC and pulse pressure, correlated with left ventricular filling pressure (defined as peak velocity during early diastolic filling divided by the velocity of movement of the mitral valve annulus in early diastole; r = -0.33 and 0.36 respectively. CONCLUSIONS: Patients with Type 2 DM on standard medication showed preferential stiffening of the large central arteries. However, carotid augmentation index was not different between the two groups and is therefore not a reliable indicator of large artery stiffening in this patient group. Diastolic dysfunction, present in a significant proportion of this population with Type 2 DM, was closely associated with arterial stiffening, suggesting a common aetiology.

Health-related quality of life assessment after breast reconstruction.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome following breast reconstruction. This study evaluated current methods of HRQL assessment in patients undergoing latissimus dorsi breast reconstruction, hypothesizing that early surgical morbidity would be reflected by poorer HRQL scores. METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and breast module (QLQ-BR23), the Functional Assessment of Cancer Therapy (FACT) general measure, and breast module and arm subscale (FACT-B + 4), and the Body Image Scale and Hospital Anxiety and Depression Scale (HADS) 3 months after surgery. They also reported additional HRQL problems not included in the questionnaires. HRQL scores were compared between patients with and without early surgical morbidity. RESULTS: Sixty women completed the questionnaires, of whom 25 (42 per cent) experienced complications. All EORTC and FACT subscale and HADS scores were similar in patients with or without morbidity. Women with complications were twice as likely to report feeling less feminine and dissatisfied with the appearance of their scar than those without problems. Thirty-two women (53 per cent) complained of problems not covered by the questionnaires, most commonly donor-site morbidity. CONCLUSION: Existing HRQL instruments are not sufficiently sensitive to detect clinically relevant problems following breast reconstruction.

Bone cement implantation syndrome.

Bone cement implantation syndrome (BCIS) is poorly understood. It is an important cause of intraoperative mortality and morbidity in patients undergoing cemented hip arthroplasty and may also be seen in the postoperative period in a milder form causing hypoxia and confusion. Hip arthroplasty is becoming more common in an ageing population. The older patient may have co-existing pathologies which can increase the likelihood of developing BCIS. This article reviews the definition, incidence, clinical features, risk factors, aetiology, pathophysiology, risk reduction, and management of BCIS. It is possible to identify high risk groups of patients in which avoidable morbidity and mortality may be minimized by surgical selection for uncemented arthroplasty. Invasive anaesthetic monitoring should be considered during cemented arthroplasty in high risk patients.

Restrictive left ventricular filling patterns are predictive of diastolic ventricular interaction in chronic heart failure.

OBJECTIVES: The purpose of this study was to determine whether restrictive left ventricular (LV) filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. BACKGROUND: We recently demonstrated a diastolic ventricular interaction in approximately 50% of a series of patients with chronic heart failure, as evidenced by paradoxic increases in LV end-diastolic volume despite reductions in right ventricular end-diastolic volume during volume unloading achieved by lower body negative pressure (LBNP). We reasoned that such an interaction would impede LV filling in mid and late diastole, but would be minimal in early diastole, resulting in a restrictive LV filling pattern. METHODS: Transmitral flow was assessed using pulsed wave Doppler echocardiography in 30 patients with chronic heart failure and an LV ejection fraction < or = 35%. Peak early (E) and atrial (A) filling velocities and E wave deceleration time were measured. Left ventricular end-diastolic volume was measured using radionuclide ventriculography before and during -30-mm Hg LBNP. RESULTS: Nine of the 11 patients with and 2 of the 16 patients without restrictive LV filling patterns (E/A > 2 or E/A 1 to 2 and E wave deceleration time < or = 140 ms) increased LV end-diastolic volume during LBNP (p = 0.001). The change in LV end-diastolic volume during LBNP was correlated with the baseline A wave velocity (r = -0.52, p = 0.005) and E/A ratio (r = 0.50, p = 0.01). CONCLUSIONS: Restrictive LV filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. Volume unloading in the setting of diastolic ventricular interaction allows for increased LV filling. Identifying patients with chronic heart failure and restrictive filling patterns may therefore indicate a group likely to benefit from additional vasodilator therapy.

Reduced cardiopulmonary baroreflex sensitivity in patients with hypertrophic cardiomyopathy.

OBJECTIVES: We sought to assess baroreflex function in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: We have previously demonstrated a specific abnormality in the afferent limb of the cardiopulmonary baroreflex in patients with vasovagal syncope. Patients with HCM exhibit abnormal control of their vasculature during exercise and upright tilt; we therefore hypothesize a similar abnormality in the afferent limb of the cardiopulmonary baroreflex arc. METHODS: We investigated 29 patients with HCM and 32 control subjects. Integrated baroreceptor sensitivity was assessed after administration of phenylephrine. Cardiopulmonary baroreceptor sensitivity was assessed by measuring forearm vascular resistance (FVR) during lower body negative pressure (LBNP). Carotid artery baroreflex sensitivity was assessed by measuring the in RR interval during manipulation of carotid artery transmural pressure. The integrity of the efferent limb of the reflex arc was determined by studying responses to both handgrip and peripheral alpha-receptor sensitivity. RESULTS: During LBNP, FVR increased by only 2.36+/-9 U in patients, compared with an increase of 123+/-8.76 U in control subjects (p=0.001). FVR paradoxically fell in eight patients, but in none of the control subjects. Furthermore, FVR fell by 4.9+/-5.6 U in patients with a history of syncope, compared with an increase of 4.7+/-7.2 U in those without syncope (p=0.014). Integrated and carotid artery baroreflex sensitivities were similar in patients and control subjects (14+/-7 vs. 14+/-6 ms/mm Hg, p=NS and -3+/-2 vs. -4+/-2 ms/mm Hg, p=NS, respectively). Similarly, handgrip responses and the dose/response ratio to phenylephrine were not significantly different. CONCLUSIONS: This study suggests that patients with HCM have a defect in the afferent limb of the cardiopulmonary reflex arc.

Atorvastatin but not L-arginine improves endothelial function in type I diabetes mellitus: a double-blind study.

OBJECTIVES: We sought to determine the effects of oral L-arginine and the hexamethylglutaryl coenzyme A reductase inhibitor atorvastatin on endothelial function in young patients with type I diabetes mellitus (DM). BACKGROUND: Endothelial dysfunction, a key early event in atherosclerosis, occurs in young patients with type I DM, and its reversal may benefit the progression of vascular disease. Cholesterol reduction in L-arginine improve endothelial function in nondiabetic subjects, but their effect in patients with type I DM is unknown. METHODS: In a double-blind, 2x2 factorial study, we investigated the effect of L-arginine (7 g twice daily) and atorvastatin (40 mg/day) on conduit artery vascular function in 84 normocholesterolemic young adults (mean+/-SD: age 34 years [range 18 to 46], low density lipoprotein [LDL] cholesterol 2.96+/-0.89 mmol/liter) with type I DM. Brachial artery dilation to flow (flow-mediated dilation [FMD]) and to the direct smooth muscle dilator glyceryl trinitrate (GTN) were assessed noninvasively using high resolution ultrasound at baseline and after six weeks of treatment. RESULTS: Atorvastatin resulted in a 48+/-10% decrease in serum LDL cholesterol levels, whereas L-arginine levels increased by 247+/-141% after L-arginine therapy. By analysis of covariance, treatment with atorvastatin resulted in a significant increase in FMD (p = 0.018. L-Arginine therapy had no significant effect on endothelial function, and there was no significant change in dilation to GTN after either intervention. CONCLUSIONS: In young patients with type I DM, improvement in endothelial dysfunction can be demonstrated after just six weeks of treatment with atorvastatin. In contrast to studies of hypercholesterolemia, however, L-arginine had no benefit. Treatment with atorvastatin at an early stage may have an impact on the progression of atherosclerosis in these high risk patients.

Effect of enalapril on endothelial function in young insulin-dependent diabetic patients: a randomized, double-blind study.

OBJECTIVES: We sought to determine whether 6 months of treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can improve conduit artery endothelial function in young subjects with insulin-dependent diabetes mellitus (IDDM). BACKGROUND: Endothelial dysfunction is an early event in atherogenesis and has been demonstrated in young subjects with IDDM. ACE inhibitors have been shown to enhance conduit artery endothelial function in animal experiments and in patients with established coronary atherosclerosis, although their effect in IDDM is not known. METHODS: Ninety-one subjects (mean age 30.9 years, range 18 to 44) with stable IDDM but no clinical evidence of vascular disease were randomized to receive enalapril (20 mg once daily) (46 subjects) or placebo (45 subjects) in a randomized, double-blind, parallel-group study. Brachial artery flow-mediated dilation (FMD), an endothelium-dependent stimulus, and response to glyceryl trinitrate (GTN), which acts directly on vascular smooth muscle, were assessed noninvasively by means of high resolution external vascular ultrasound at baseline and after 12 and 24 weeks of treatment. RESULTS: FMD was inversely correlated with total cholesterol (r=0.22, p=0.041) but not with any diabetic variables. Treatment with enalapril had no significant effect on FMD (p=0.67) or response to the endothelial-independent dilator GTN (p=0.45). CONCLUSIONS: These data suggest that impairment of endothelial-dependent dilation in young subjects with IDDM is not improved by treatment with the ACE inhibitor enalapril. This lack of improvement may reflect the complex nature of vascular disease in IDDM, which can affect both endothelial and smooth muscle function.

Contrast echocardiography improves the accuracy and reproducibility of left ventricular remodeling measurements: a prospective, randomly assigned, blinded study.

OBJECTIVES: We sought to assess the impact of contrast injection and harmonic imaging, on the measure by echocardiography of left ventricular (LV) remodeling. BACKGROUND: Left ventricular remodeling is a precursor of LV dysfunction, but the impact of contrast injection and harmonic imaging on the accuracy or reproducibility of echocardiography is unclear. METHODS: We prospectively collected LV images by using simultaneous methods. Then, LV volumes were measured off-line, in blinded manner and in random order. The accuracy of echocardiography was determined in comparison to electron beam computed tomography (EBCT) in 26 patients. The reproducibility of echocardiography was assessed by three blinded observers with different training levels in 32 patients. RESULTS: End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF), as measured by EBCT (195 +/- 55, 58 +/- 24 and 137 +/- 35 ml and 71 +/- 5%, respectively) and echocardiography with harmonic imaging and contrast injection (194 +/- 51, 55 +/- 20 and 140 +/- 35 ml and 72 +/- 4%, respectively), showed no differences (all p > 0.15) and excellent correlations (all r > 0.87). In contrast, echocardiography using harmonic imaging without contrast injection underestimated the EBCT results (all p < 0.01). Reproducibility was superior with rather than without contrast injection for intraobserver and interobserver variabilities (all p < 0.001). Values measured by different observers were different without contrast injection, but were similar with contrast injection (all p > 0.18). Consequently, intrinsic patient differences represented a larger and almost exclusive proportion of global variability with contrast injection for EDV (94 vs. 79%), ESV (93 vs. 82%), SV (87 vs. 53%) and EF (84 vs. 41%), as compared with harmonic imaging without contrast injection (all p < 0.005). CONCLUSIONS: For assessment of LV remodeling, echocardiography with harmonic imaging and contrast injection improved the accuracy and reproducibility, as compared with imaging without contrast injection. With contrast injection, variability was almost exclusively due to intrinsic patient differences. Therefore, when evaluation of LV remodeling is deemed important, assessment after contrast injection should be the preferred echocardiographic approach.

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.

Cervical cancer incidence and mortality trends in Finland and Estonia: a screened vs. an unscreened population.

Long term trends in the incidence of and mortality from invasive cervical cancer have been studied in Finland (1953-1987) and Estonia (1968-1987). The analyses are based on the data from the Finnish and Estonian Cancer Registries. An organised nationwide screening programme for cervical cancer was started in Finland in the early 1960s. In Estonia, no cytological screening programme has been introduced, and cervical malignancies are diagnosed in routine gynaecological practice. During 1968-1987, both the incidence of and mortality from cervical cancer were considerably higher in Estonia than in Finland. A decrease has taken place in the cervical cancer incidence and mortality in both countries since the mid-1960s, but whereas in Finland the decrease has been marked, in Estonia it has been less pronounced and levelled off in the 1980s. In 1987, the age-standardised (world population) incidence rate per 100,000 women was 14.0 in Estonia and 3.8 in Finland, and the age-standardised mortality rate was 6.0 and 1.6 per 100,000, respectively. The difference in the incidence of the disease in the two neighbouring countries can be partially attributed to socioeconomic factors. The main reason for the different slopes of the trend curves for cervical cancer is probably the difference in public health policies: an effective mass screening programme is being conducted in Finland but not in Estonia.

The effect of amlodipine on endothelial function in young adults with a strong family history of premature coronary artery disease: a randomised double blind study.

Endothelial dysfunction, an early event in atherogenesis, has been demonstrated in young asymptomatic subjects with a strong family history of premature coronary artery disease (CAD). In these subjects, preventive measures involving risk factor modification are not appropriate, and strategies employing novel antiatherogenic agents, such as the dihydropyridine calcium channel blocker, amlodipine, may be useful. Ninety-one subjects (mean age, 28.6 years; range, 18-40) with a strong family history of premature CAD and no other identified vascular risk factors were randomised to either 5 mg amlodipine (49 subjects) or placebo (42 subjects). Brachial artery flow mediated dilatation (FMD) (endothelium-dependent response) and response to glyceryltrinitrate (GTN) (direct smooth muscle dilator) were assessed non-invasively at baseline, and after 12 and 24 weeks using high-resolution vascular ultrasound. In those treated with amlodipine, mean FMD increased from 2.32+/-2.23% at baseline to 3.52+/-3.1% at 24 weeks (P<0.005). However, FMD also increased in the placebo group from 1.64+/-2.12 to 3.37+/-2.68% (P<0.002), and the difference between the FMD response in the amlodipine and placebo groups was not significant. Dilatation to GTN did not change in either group. Therefore, impaired endothelial function improved in family history subjects taking both amlodipine and placebo, but there is no difference between the groups.