Contact lens citation metrics: The Spanish connection

To eye care practitioners, citation metrics may seem to be a somewhat esoteric and irrelevant concept, far removed from the realities or real world, day-to-day clinical practice. However, quantitative analysis of the published literature is becoming increasingly important, and a beautiful example of this is presented in this issue of the Journal of Optometry. My former PhD student, Genís Cardona, has teamed up with Joan Sanz to undertake a thorough and telling analysis of current worldwide publishing trends in the contact lens field. When held in the mirror, this work reflects the growing contributions from Spanish researchers to the field...

Oral medication delivery in impaired swallowing: Thickening liquid medications for safe swallowing alters dissolution characteristics

Acetaminophen (paracetamol) is available in a wide range of oral formulations designed to meet the needs of the population across the age-spectrum, but for people with impaired swallowing, i.e. dysphagia, both solid and liquid medications can be difficult to swallow without modification. The effect of a commercial polysaccharide thickener, designed to be added to fluids to promote safe swallowing by dysphagic patients, on rheology and acetaminophen dissolution was tested using crushed immediate-release tablets in water, effervescent tablets in water, elixir and suspension. The inclusion of the thickener, comprised of xanthan gum and maltodextrin, had a considerable impact on dissolution; acetaminophen release from modified medications reached 12-50% in 30 minutes, which did not reflect the pharmacopeia specification for immediate release preparations. Flow curves reflect the high zero-shear viscosity and the apparent yield stress of the thickened products. The weak gel nature, in combination with high G’ values compared to G” (viscoelasticity) and high apparent yield stress, impact drug release. The restriction on drug release from these formulations is not influenced by the theoretical state of the drug (dissolved or dispersed), and the approach typically used in clinical practice (mixing crushed tablets into pre-prepared thickened fluid) cannot be improved by altering the order of incorporation or mixing method.

Assessment of conjunctival goblet cell density using laser scanning confocal microscopy versus impression cytology

Purpose To determine the association between conjunctival goblet cell density (GCD) assessed using in vivo laser scanning confocal microscopy and conjunctival impression cytology in a healthy population. Methods Ninety (90) healthy participants undertook a validated 5-item dry eye questionnaire, non-invasive tear film break-up time measurement, ocular surface fluorescein staining and phenol red thread test. These tests where undertaken to diagnose and exclude participants with dry eye. The nasal bulbar conjunctiva was imaged using laser scanning confocal microscopy (LSCM). Conjunctival impression cytology (CIC) was performed in the same region a few minutes later. Conjunctival goblet cell density was calculated as cells/mm2. Results There was a strong positive correlation of conjunctival GCD between LSCM and CIC (ρ = 0.66). Conjunctival goblet cell density was 475 ± 41 cells/mm2 and 466 ± 51 cells/mm2 measured by LSCM and CIC, respectively. Conclusions The strong association between in vivo and in vitro cellular analysis for measuring conjunctival GCD suggests that the more invasive CIC can be replaced by the less invasive LSCM in research and clinical practice.

Factors influencing hospital readmission and length of stay of Vietnamese patients with type 2 diabetes and cardiac disease

Background: Increased hospital readmission and longer stays in the hospital for patients with type 2 diabetes and cardiac disease can result in higher healthcare costs and heavier individual burden. Thus, knowledge of the characteristics and predictive factors for Vietnamese patients with type 2 diabetes and cardiac disease, at high risk of hospital readmission and longer stays in the hospital, could provide a better understanding on how to develop an effective care plan aimed at improving patient outcomes. However, information about factors influencing hospital readmission and length of stay of patients with type 2 diabetes and cardiac disease in Vietnam is limited. Aim: This study examined factors influencing hospital readmission and length of stay of Vietnamese patients with both type 2 diabetes and cardiac disease. Methods: An exploratory prospective study design was conducted on 209 patients with type 2 diabetes and cardiac disease in Vietnam. Data were collected from patient charts and patients' responses to self-administered questionnaires. Descriptive statistics, bivariate correlation, logistic and multiple regression were used to analyse the data. Results: The hospital readmission rate was 12.0% among patients with both type 2 diabetes and cardiac disease. The average length of stay in the hospital was 9.37 days. Older age (OR= 1.11, p< .05), increased duration of type 2 diabetes (OR= 1.22, p< .05), less engagement in stretching/strengthening exercise behaviours (OR= .93, p< .001) and in communication with physician (OR= .21, p< .001) were significant predictors of 30-dayhospital readmission. Increased number of additional co-morbidities (β= .33, p< .001) was a significant predictor of longer stays in the hospital. High levels of cognitive symptom management (β= .40, p< .001) significantly predicted longer stays in the hospital, indicating that the more patients practiced cognitive symptom management, the longer the stay in hospital. Conclusions: This study provides some evidence of factors influencing hospital readmission and length of stay and argues that this information may have significant implications for clinical practice in order to improve patients' health outcomes. However, the findings of this study related to the targeted hospital only. Additionally, the investigation of environmental factors is recommended for future research as these factors are important components contributing to the research model.

Infrared thermal imaging for automated detection of diabetic foot complications

Background Although thermal imaging can be a valuable technology in the prevention and management of diabetic foot disease, it is not yet widely used in clinical practice. Technological advancement in infrared imaging increases its application range. The aim was to explore the first steps in the applicability of high-resolution infrared thermal imaging for noninvasive automated detection of signs of diabetic foot disease. Methods The plantar foot surfaces of 15 diabetes patients were imaged with an infrared camera (resolution, 1.2 mm/pixel): 5 patients had no visible signs of foot complications, 5 patients had local complications (e.g., abundant callus or neuropathic ulcer), and 5 patients had difuse complications (e.g., Charcot foot, infected ulcer, or critical ischemia). Foot temperature was calculated as mean temperature across pixels for the whole foot and for specified regions of interest (ROIs). Results No diferences in mean temperature >1.5 °C between the ipsilateral and the contralateral foot were found in patients without complications. In patients with local complications, mean temperatures of the ipsilateral and the contralateral foot were similar, but temperature at the ROI was >2 °C higher compared with the corresponding region in the contralateral foot and to the mean of the whole ipsilateral foot. In patients with difuse complications, mean temperature diferences of >3 °C between ipsilateral and contralateral foot were found. Conclusions With an algorithm based on parameters that can be captured and analyzed with a high-resolution infrared camera and a computer, it is possible to detect signs of diabetic foot disease and to discriminate between no, local, or difuse diabetic foot complications. As such, an intelligent telemedicine monitoring system for noninvasive automated detection of signs of diabetic foot disease is one step closer. Future studies are essential to confirm and extend these promising early findings.

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

Objective The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3. Methods In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding. Results A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively. Conclusions CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment.

Statistical analysis of spectral data: A methodology for designing an intelligent monitoring system for the diabetic foot

Early detection of (pre-)signs of ulceration on a diabetic foot is valuable for clinical practice. Hyperspectral imaging is a promising technique for detection and classification of such (pre-)signs. However, the number of the spectral bands should be limited to avoid overfitting, which is critical for pixel classification with hyperspectral image data. The goal was to design a detector/classifier based on spectral imaging (SI) with a small number of optical bandpass filters. The performance and stability of the design were also investigated. The selection of the bandpass filters boils down to a feature selection problem. A dataset was built, containing reflectance spectra of 227 skin spots from 64 patients, measured with a spectrometer. Each skin spot was annotated manually by clinicians as "healthy" or a specific (pre-)sign of ulceration. Statistical analysis on the data set showed the number of required filters is between 3 and 7, depending on additional constraints on the filter set. The stability analysis revealed that shot noise was the most critical factor affecting the classification performance. It indicated that this impact could be avoided in future SI systems with a camera sensor whose saturation level is higher than 106, or by postimage processing.

Evaluation of haemoglobin in blister fluid as an indicator of paediatric burn wound depth

The early and accurate assessment of burns is essential to inform patient treatment regimens; however, this first critical step in clinical practice remains a challenge for specialist burns clinicians worldwide. In this regard, protein biomarkers are a potential adjunct diagnostic tool to assist experienced clinical judgement. Free circulating haemoglobin has previously shown some promise as an indicator of burn depth in a murine animal model. Using blister fluid collected from paediatric burn patients, haemoglobin abundance was measured using semi-quantitative Western blot and immunoassays. Although a trend was observed in which haemoglobin abundance increased with burn wound severity, several patient samples deviated significantly from this trend. Further, it was found that haemoglobin concentration decreased significantly when whole cells, cell debris and fibrinous matrix was removed from the blister fluid by centrifugation; although the relationship to depth was still present. Statistical analyses showed that haemoglobin abundance in the fluid was more strongly related to the time between injury and sample collection and the time taken for spontaneous re-epithelialisation. We hypothesise that prolonged exposure to the blister fluid microenvironment may result in an increased haemoglobin abundance due to erythrocyte lysis, and delayed wound healing

Heparin versus 0.9% sodium chloride intermittent flushing for the prevention of occlusion in long term central venous catheters in infants and children: A systematic review

Background Around the world, guidelines and clinical practice for the prevention of complications associated with central venous catheters (CVC) vary greatly. To prevent occlusion, most institutions recommend the use of heparin when the CVC is not in use. However, there is debate regarding the need for heparin and evidence to suggest normal saline may be as effective. The use of heparin is not without risk, may be unnecessary and is also associated with increased costs. Objectives To assess the clinical effects (benefits and harms) of heparin versus normal saline to prevent occlusion in long-term central venous catheters in infants, children and adolescents. Design A Cochrane systematic review of randomised controlled trials was undertaken. - Data sources: The Cochrane Vascular Group Specialised Register (including MEDLINE, CINAHL, EMBASE and AMED) and the Cochrane Register of Studies were searched. Hand searching of relevant journals and reference lists of retrieved articles was also undertaken. - Review Methods: Data were extracted and appraisal undertaken. We included studies that compared the efficacy of normal saline with heparin to prevent occlusion. We excluded temporary CVCs and peripherally inserted central catheters. Rate ratios per 1000 catheter days were calculated for two outcomes, occlusion of the CVC, and CVC-associated blood stream infection. Results Three trials with a total of 245 participants were included in this review. The three trials directly compared the use of normal saline and heparin. However, between studies, all used different protocols with various concentrations of heparin and frequency of flushes. The quality of the evidence ranged from low to very low. The estimated rate ratio for CVC occlusion per 1000 catheter days between the normal saline and heparin group was 0.75 (95% CI 0.10 to 5.51, two studies, 229 participants, very low quality evidence). The estimated rate ratio for CVC-associated blood stream infection was 1.48 (95% CI 0.24 to 9.37, two studies, 231 participants; low quality evidence). Conclusions It remains unclear whether heparin is necessary for CVC maintenance. More well-designed studies are required to understand this relatively simple, but clinically important question. Ultimately, if this evidence were available, the development of evidenced-based clinical practice guidelines and consistency of practice would be facilitated.

Fatigue self-management behaviors in patients with advanced cancer: A prospective longitudinal survey

Purpose: To explore the fatigue self-management behaviors and factors associated with effectiveness of these behaviors in patients with advanced cancer. Design: Prospective longitudinal interviewer-administered survey. Setting: A tertiary cancer center in Queensland Australia. Sample: One hundred fifty two outpatients with metastatic breast, lung, colorectal and prostate cancer experiencing fatigue (>3/10) were recruited. Main Research Variables: Fatigue self-management behaviors outcomes (perceived effectiveness, self-efficacy and frequency), medical/demographic characteristics (including sites of primary cancer and metastasis, comorbidity, performance status), social support, depressive, anxiety, and other symptoms were assessed. Findings: The participants reported moderate levels of fatigue at baseline (M=5.85, SD 1.44), and maintained moderate levels at 4 weeks and 8 weeks. On average, participants consistently used approximately nine behaviors at each time point. Factors significantly associated with higher levels of perceived effectiveness of fatigue self-management behaviors were higher self-efficacy (p<.001), higher education level (p=.02), and lower levels of depressive symptoms (p=.04). Conclusions: The findings of this study demonstrate that patients with cancer, even with advanced disease, still want and are able to use a number of behaviors to control their fatigue. Self-management interventions that aim to enhance self-efficacy and address any concurrent depressive symptoms have the potential to reduce fatigue severity. Implications for Nursing: Nurses are well positioned to play a key role in supporting patients in their fatigue self-management. Knowledge Translation: This study particularly focused on the perspectives of patients about fatigue self-management, highlighting a number of issues requiring further attention in clinical practice and the potential for future research.

Postmenopausal hot flushes, vascular health and hormone therapy

Vasomotor hot flushes are complained of by approximately 75% of postmenopausal women, but their frequency and severity show great individual variation. Hot flushes have been present in women attending observational studies showing cardiovascular benefit associated with hormone therapy use, whereas they have been absent or very mild in randomized hormone therapy trials showing cardiovascular harm. Therefore, if hot flushes are a factor connected with vascular health, they could perhaps be one explanation for the divergence of cardiovascular data in observational versus randomized studies. For the present study 150 healthy, recently postmenopausal women showing a large variation in hot flushes were studied in regard to cardiovascular health by way of pulse wave analysis, ambulatory blood pressure and several biochemical vascular markers. In addition, the possible impact of hot flushes on outcomes of hormone therapy was studied. This study shows that women with severe hot flushes exhibit a greater vasodilatory reactivity as assessed by pulse wave analysis than do women without vasomotor symptoms. This can be seen as a hot flush-related vascular benefit. Although severe night-time hot flushes seem to be accompanied by transient increases in blood pressure and heart rate, the diurnal blood pressure and heart rate profiles show no significant differences between women without and with mild, moderate or severe hot flushes. The levels of vascular markers, such as lipids, lipoproteins, C-reactive protein and sex hormone-binding globulin show no association with hot flush status. In the 6-month hormone therapy trial the women were classified as having either tolerable or intolerable hot flushes. These groups were treated in a randomized order with transdermal estradiol gel, oral estradiol alone or in combination with medroxyprogesterone acetate, or with placebo. In women with only tolerable hot flushes, oral estradiol leads to a reduced vasodilatory response and increases in 24-hour and daytime blood pressures as compared to women with intolerable hot flushes receiving the same therapy. No such effects were observed with the other treatment regimes or in women with intolerable hot flushes. The responses of vascular biomarkers to hormone therapy are unaffected by hot flush status. In conclusion, hot flush status contributes to cardiovascular health before and during hormone therapy. Severe hot flushes are associated with an increased vasodilatory, and thus, a beneficial vascular status. Oral estradiol leads to vasoconstrictive changes and increases in blood pressure, and thus to possible vascular harm, but only in women whose hot flushes are so mild that they would probably not lead to the initiation of hormone therapy in clinical practice. Healthy, recently postmenopausal women with moderate to severe hot flushes should be given the opportunity to use hormone therapy alleviate hot flushes, and if estrogen is prescribed for indications other than for the control of hot flushes, transdermal route of administration should be favored.

The research capacity and culture of Australian podiatrists

Background Best practice clinical health care is widely recognised to be founded on evidence based practice. Enhancing evidence based practice via the rapid translation of new evidence into every day clinical practice is fundamental to the success of health care and in turn health care professions. There is little known about the collective research capacity and culture of the podiatry profession across Australia. Thus, the aim of this study was to investigate the research capacity and culture of the podiatry profession within Australia and determine if there were any differences between podiatrists working in different health sectors and workplaces. Method All registered podiatrists were eligible to participate in a cross-sectional online survey. The Australian Podiatry Associations disseminated the survey and all podiatrists were encouraged to distribute it to colleagues. The Research Capacity and Culture (RCC) tool was used to collect all research capacity and culture item variables using a 10-point scale (1 = lowest; 10 = highest). Additional demographic, workplace and health sector data variables were also collected. Mann–Whitney-U, Kruskal–Wallis and logistic regression analyses were used to determine any difference between health sectors and workplaces. Word cloud analysis was used for qualitative responses of individual motivators and barriers to research culture. Results There were 232 fully completed surveys (6% of Australian registered podiatrists). Overall respondents reported low success or skills (Median rating < 4) on the majority of individual success or skill items. Podiatrists working in multi-practitioner workplaces reported higher individual success or skills in the majority of items compared with sole practitioners (p < 0.05). Non-clinical and public health sector podiatrists reported significantly higher post-graduate study enrolment or completion, research activity participation, provisions to undertake research and individual success or skill than those working privately. Conclusions This study suggests that podiatrists in Australia report similar low levels of research success or skill to those reported in other allied health professions. The workplace setting and health sector seem to play key roles in self reported research success and skills. This is important knowledge for podiatrists and researchers aiming to translate research evidence into clinical practice.

Determinants of outcome in critically ill patients

Assessment of the outcome of critical illness is complex. Severity scoring systems and organ dysfunction scores are traditional tools in mortality and morbidity prediction in intensive care. Their ability to explain risk of death is impressive for large cohorts of patients, but insufficient for an individual patient. Although events before intensive care unit (ICU) admission are prognostically important, the prediction models utilize data collected at and just after ICU admission. In addition, several biomarkers have been evaluated to predict mortality, but none has proven entirely useful in clinical practice. Therefore, new prognostic markers of critical illness are vital when evaluating the intensive care outcome. The aim of this dissertation was to investigate new measures and biological markers of critical illness and to evaluate their predictive value and association with mortality and disease severity. The impact of delay in emergency department (ED) on intensive care outcome, measured as hospital mortality and health-related quality of life (HRQoL) at 6 months, was assessed in 1537 consecutive patients admitted to medical ICU. Two new biological markers were investigated in two separate patient populations: in 231 ICU patients and 255 patients with severe sepsis or septic shock. Cell-free plasma DNA is a surrogate marker of apoptosis. Its association with disease severity and mortality rate was evaluated in ICU patients. Next, the predictive value of plasma DNA regarding mortality and its association with the degree of organ dysfunction and disease severity was evaluated in severe sepsis or septic shock. Heme oxygenase-1 (HO-1) is a potential regulator of apoptosis. Finally, HO-1 plasma concentrations and HO-1 gene polymorphisms and their association with outcome were evaluated in ICU patients. The length of ED stay was not associated with outcome of intensive care. The hospital mortality rate was significantly lower in patients admitted to the medical ICU from the ED than from the non-ED, and the HRQoL in the critically ill at 6 months was significantly lower than in the age- and sex-matched general population. In the ICU patient population, the maximum plasma DNA concentration measured during the first 96 hours in intensive care correlated significantly with disease severity and degree of organ failure and was independently associated with hospital mortality. In patients with severe sepsis or septic shock, the cell-free plasma DNA concentrations were significantly higher in ICU and hospital nonsurvivors than in survivors and showed a moderate discriminative power regarding ICU mortality. Plasma DNA was an independent predictor for ICU mortality, but not for hospital mortality. The degree of organ dysfunction correlated independently with plasma DNA concentration in severe sepsis and plasma HO-1 concentration in ICU patients. The HO-1 -413T/GT(L)/+99C haplotype was associated with HO-1 plasma levels and frequency of multiple organ dysfunction. Plasma DNA and HO-1 concentrations may support the assessment of outcome or organ failure development in critically ill patients, although their value is limited and requires further evaluation.

Neurological manifestations and molecular genetics of acute intermittent porphyria in North Western Russia

Acute intermittent porphyria (AIP, MIM #176000) is an inherited metabolic disease due to a partial deficiency of the third enzyme, hydroxymethylbilane synthase (HMBS, EC: 4.3.1.8), in the haem biosynthesis. Neurological symptoms during an acute attack, which is the major manifestation of AIP, are variable and relatively rare, but may endanger a patient's life. In the present study, 12 Russian and two Finnish AIP patients with severe neurological manifestations during an acute attack were studied prospectively from 1995 to 2006. Autonomic neuropathy manifested as abdominal pain (88%), tachycardia (94%), hypertension (75%) and constipation (88%). The most common neurological sign was acute motor peripheral neuropathy (PNP, 81%) often associated with neuropathic sensory loss (54%) and CNS involvement (85%). Despite heterogeneity of the neurological manifestations in our patients with acute porphyria, the major pattern of PNP associated with abdominal pain, dysautonomia, CNS involvement and mild hepatopathy could be demonstrated. If more strict inclusion criteria for biochemical abnormalities (>10-fold increase in excretion of urinary PBG) are applied, neurological manifestations in an acute attack are probably more homogeneous than described previously, which suggests that some of the neurological patients described previously may not have acute porphyria but rather secondary porphyrinuria. Screening for acute porphyria using urinary PBG is useful in a selected group of neurological patients with acute PNP or encephalopathy and seizures associated with pain and dysautonomia. Clinical manifestations and the outcome of acute attacks were used as a basis for developing a 30-score scale of the severity of an acute attack. This scale can easily be used in clinical practice and to standardise the outcome of an attack. Degree of muscle weakness scored by MRC, prolonged mechanical ventilation, bulbar paralysis, impairment of consciousness and hyponatraemia were important signs of a poor prognosis. Arrhythmia was less important and autonomic dysfunction, severity of pain and mental symptoms did not affect the outcome. The delay in the diagnosis and repeated administrations of precipitating factors were the main cause of proceeding of an acute attack into pareses and severe CNS involvement and a fatal outcome in two patients. Nerve conduction studies and needle EMG were performed in eleven AIP patients during an acute attack and/or in remission. Nine patients had severe PNP and two patients had an acute encephalopathy but no clinically evident PNP. In addition to axonopathy, features suggestive of demyelination could be demonstrated in patients with severe PNP during an acute attack. PNP with a moderate muscle weakness was mainly pure axonal. Sensory involvement was common in acute PNP and could be subclinical. Decreased conduction velocities with normal amplitudes of evoked potentials during acute attacks with no clinically evident PNP indicated subclinical polyneuropathy. Reversible symmetrical lesions comparable with posterior reversible encephalopathy syndrome (PRES) were revealed in two patients' brain CT or MRI during an acute attack. In other five patients brain MRI during or soon after the symptoms was normal. The frequency of reversible brain oedema in AIP is probably under-estimated since it may be short-lasting and often indistinguishable on CT or MRI. In the present study, nine different mutations were identified in the HMBS gene in 11 unrelated Russian AIP patients from North Western Russia and their 32 relatives. AIP was diagnosed in nine symptom-free relatives. The majority of the mutations were family-specific and confirmed allelic heterogeneity also among Russian AIP patients. Three mutations, c.825+5G>C, c.825+3_825+6del and c.770T>C, were novel. Six mutations, c.77G>A (p.R26H), c.517C>T (p.R173W), c.583C>T (p.R195C), c.673C>T (p.R225X), c.739T>C (p.C247R) and c.748G>C (p.E250A), have previously been identified in AIP patients from Western and other Eastern European populations. The effects of novel mutations were studied by amplification and sequencing of the reverse-transcribed total RNA obtained from the patients' lymphoblastoid or fibroblast cell lines. The mutations c.825+5G>C and c.770T>C resulted in varyable amounts of abnormal transcripts, r.822_825del (p.C275fsX2) and [r.770u>c, r.652_771del, r.613_771del (p.L257P, p.G218_L257del, p.I205_L257del)]. All mutations demonstrated low residual activities (0.1-1.3 %) when expressed in COS-1 cells confirming the causality of the mutations and the enzymatic defect of the disease. The clinical outcome, prognosis and correlation between the HMBS genotype and phenotype were studied in 143 Finnish and Russian AIP patients with ten mutations (c.33G>T, c.97delA, InsAlu333, p.R149X, p.R167W, p.R173W, p.R173Q, p.R225G, p.R225X, c.1073delA) and more than six patients in each group. The patients were selected from the pool of 287 Finnish AIP patients presented in a Finnish Porphyria Register (1966-2003) and 23 Russian AIP patients (diagnosed 1995-2003). Patients with the p.R167W and p.R225G mutations showed lower penetrance (19% and 11%) and the recurrence rate (33% and 0%) in comparison to the patients with other mutations (range 36 to 67% and 0 to 66%, respectively), as well as milder biochemical abnormalities [urinary porphobilinogen 47±10 vs. 163±21 mol/L, p<0.001; uroporphyrin 130±40 vs. 942±183 nmol/L, p<0.001] suggesting a milder form of AIP in these patients. Erythrocyte HMBS activity did not correlate with the porphobilinogen excretion in remission or the clinical of the disease. In all AIP severity patients, normal PBG excretion predicted freedom from acute attacks. Urinary PBG excretion together with gender, age at the time of diagnosis and mutation type could predict the likelihood of acute attacks in AIP patients.

Hay fever: An underappreciated and chronic disease

Allergic rhinitis continues to be a significant chronic disease that affects younger, usually healthier people, with considerable impacts on school performance and work productivity. Symptom-directed treatment is usually sufficient but specific immunotherapy should be considered in severely affected patients.