Body Mass Index and Antibody Persistence after Measles, Mumps, Rubella and Hepatitis B Vaccinations.

Overweight and obesity may cause a reduced response to vaccination. The purpose of the present research was to study the relationship between current body mass index (BMI) and antibody persistence after vaccination against measles, mumps, and rubella (MMR) and hepatitis B virus (HBV) given during childhood, as per the current vaccination schedule. The study was conducted on 2185 students at the School of Medicine, University of Padua, Italy. The mean age of the participants was 20.3 years. After adjusting for sex, age at first dose of vaccine administered, age at last dose, and age at study enrollment, no significant association was found between lack of serologic protection and BMI for either the HBV vaccine or each component of the MMR vaccine. For the first time, the absence of this relationship was demonstrated for the MMR vaccine. Given the evidence currently available, further research on BMI and vaccines in general remains desirable.

Psychological Aspect and Quality of Life in Porphyrias: A Review.

The World Health Organization (WHO) describes "health" as a state of physical, mental, and social well-being and not merely the absence of disease or infirmity. Therefore, a biopsychosocial approach should be considered as an integral part of patients' management. In this review, we summarize the available data starting from 1986 on the biological, psychological, and social aspects of porphyrias in order to provide a useful tool for clinicians about the missing knowledge within this field. Porphyrias are a group of rare metabolic disorders affecting the heme biosynthetic pathway and can be categorized into hepatic and erythropoietic. Here, a total of 20 articles reporting the psychological and the quality of life (QoL) data of porphyria patients affected by acute hepatic porphyrias (AHPs), Porphyria Cutanea Tarda (PCT), and Erythropoietic Protoporphyria (EPP) were analyzed. These 13 articles include reported quantitative methods using questionnaires, while the reaming articles employed qualitative descriptive approaches through direct interviews with patients by psychology professionals. We conclude that the use of questionnaires limits the complete description of all areas of a patient's life compared to a direct interview with specialists. However, only a combined use of these methods could be the best approach for the correct disorder management.

Rubella Serosurvey Among Future Healthcare Workers.

Objective: Rubella is a very diffusive but relatively benign infectious disease unless contracted during pregnancy, when it causes congenital rubella syndrome. The aim of this research was to determine the prevalence and titer of antirubella antibodies in a population of future healthcare workers (students at the school of medicine). Methods: The cohort consisted of 11,022 students who underwent antibody analysis after the presentation of a vaccine certificate. Results: Vaccination compliance was very high, particularly in younger students (born after 1995), reaching almost 100% (at least one dose). Unvaccinated students born before 1990 had high seropositivity (>95%), but this percentage dropped to zero among the youngest students. Variables affecting antibody titer included year of birth and sex. Considering only vaccinated students, a greater antibody response was observed if the vaccine was administered between 8 and 10 years of age. Female sex was associated with more significant (p < 0.0001) positivity and higher antibody titer after one and two doses. However, this difference appeared less consistent in relation to year of birth. Conclusions: The studied population exhibited excellent vaccination compliance, high seropositivity, and high antibody titer. Vaccine and immune coverage were higher than what is deemed necessary to achieve herd immunity.

Uptake of Non-Mandatory Vaccinations in Future Physicians in Italy.

In 2017 in Italy, a number of vaccinations became mandatory or started to be recommended and offered free of charge. In this study, we aimed at assessing the coverage rates for those vaccinations in the pre-mandatory era among students at the School of Medicine of Padua University studying the degree course in medicine and surgery (future physicians) on the basis of the vaccination certificates presented during health surveillance. The vaccinations considered were those against pertussis, rubella, mumps, measles, varicella, Haemophilus influenzae type b (which became mandatory in 2017), pneumococcus, meningococcus C and meningococcus B (only suggested and offered for free since 2017). The study enrolled 4706 students of medicine and surgery. High vaccine uptake was observed, especially in younger students (born after 1990), with vaccines against pertussis, rubella, mumps and measles. Good completion for Haemophilus influenzae type b and meningococcus C was also observed. Very low coverage rates (all under 10%) for vaccination against varicella, pneumococcus and meningococcus B were observed. In conclusion, uptake for some non-mandatory vaccines was below the recommended threshold, although younger generations showed a higher uptake, possibly as a results of policy implemented at the national level. Our findings support the idea to consider health surveillance visits also as an additional opportunity to overcome confidence and convenience barriers and offer vaccine administration.

Future Healthcare Workers and Hepatitis B Vaccination: A New Generation.

Before the introduction of universal vaccination, hepatitis B caused high morbidity and mortality, especially among healthcare workers. In the present study, the immune status against hepatitis B was assessed in a cohort of 11,188 students of the degree courses of the School of Medicine of the University of Padua (Italy) who had been subjected to mandatory vaccination in childhood or adolescence and who will be future healthcare workers. The variables that influence the antibody response to vaccination are mainly the age at which the vaccine was administered and sex. If vaccination was administered before one year of age, there is a high probability (around 50%) of having an antibody titer lower than 10 IU/L compared to those vaccinated after one year of age (12.8%). The time between vaccine and analysis is not decisive. Furthermore, female sex, but only if vaccination was administered after one year of age, shows a significant (p = 0.0008) lower percentage of anti-HBs below 10 IU/L and a greater antibody titer (p < 0.0001). In conclusion, the differences related to the age of vaccination induce more doubts than answers. The only plausible hypothesis, in addition to the different immune responses (innate and adaptive), is the type of vaccine. This is not easy to verify because vaccination certificates rarely report it.

Response to Vaccination against Mumps in Medical Students: Two Doses Are Needed.

Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p < 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p < 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

Vaccination and Immunity toward Measles: A Serosurvey in Future Healthcare Workers.

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p < 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p < 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.

Course of Metal Ions after a Revision of Malfunctioning Metal-on-Metal Total Hip Prostheses.

The present research evaluated the course of cobalt and chromium in the blood and urine after the revision of metal-on-metal with a ceramic-on-polyethylene total hip arthroplasty. Seven patients were enrolled for hip prosthesis revision owing to ascertained damage of the implant. Metals in the blood and urine were evaluated before and after the hip revision. The double measurement before the total hip revision revealed high levels of metal ions (on average, 88.1 µg/L of cobalt in the blood, 399.0 µg/g of creatinine cobalt in the urine, 46.8 µg/L of chromium in the blood, and 129.6 µg/g of creatinine chromium in the urine at the first measurements), with an increasing trend between the first and second dosage. Within a week after the hip revision, the levels of metal ions significantly decreased by approximately half. Four to six months after the operation, the cobalt levels were found near to the reference values, whereas the chromium levels reached 25% of the values measured before the revision. The revision of malfunctioning metal-on-metal implants produced a dramatic decrease of metal ions in biological fluids, although it did not completely rescue the chromium level.

In vitro Assessment of Solar Filters for Erythropoietic Protoporphyria in the Action Spectrum of Protoporphyrin IX.

Introduction: Subjects with erythropoietic protoporphyria rely on broad-spectrum sunscreens with high sun protection factor, which is not informative on efficacy in the absorption spectrum of protoporphyrin IX, spanning visible radiation and peaking around 408 nm. Photoactivation of protoporphyrin IX is responsible for painful skin photosensitivity in erythropoietic protoporphyria. The authors assessed the protective efficacy of six sunscreens in vitro in the absorption spectrum of protoporphyrin IX. Method: Transmittance measurements were performed in the 300-850 nm wavelengths on samples of six photoprotective products applied to polymethyl methacrylate plates. Porphyrin protection factor was calculated in the 300-700 nm region to provide a measurement for the efficacy of each product based on the action spectrum of protoporphyrin IX. Results: Product A showed the highest porphyrin protection factor among tested products with a median value of 4.22. Product A is a sunscreen containing organic filters, titanium dioxide and synthetic iron oxides, pigmentary grade active ingredients that absorb visible radiation. Other products showed inefficient protection in the visible, with transmittance between 75 and 95% at 500 nm. The low porphyrin protection factor of inorganic filter product B was attributed to particle micronization, as declared by the manufacturer. Conclusion: Adding porphyrin protection factor to sunscreen labeling could help patients with erythropoietic protoporphyria and other photosensitivity disorders identify products tailored on their specific needs. The development of sunscreens providing protection from visible radiation and excellent cosmetical tolerability could improve the lifestyle of patients with erythropoietic protoporphyria.

Metal Ion Release, Clinical and Radiological Outcomes in Large Diameter Metal-on-Metal Total Hip Arthroplasty at Long-Term Follow-Up.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.

Clinical and molecular epidemiology of erythropoietic protoporphyria in Italy.

BACKGROUND: Erythropoietic protoporphyria (EPP) is a rare inherited disease associated with heme metabolism, characterized by severe life-long photosensitivity and liver involvement. OBJECTIVE: To provide epidemiological data of EPP in Italy. MATERIALS & METHODS: Prospective/retrospective data of EPP patients were collected by an Italian network of porphyria specialist centres (Gruppo Italiano Porfiria, GrIP) over a 20-year period (1996-2017). RESULTS: In total, 179 patients (79 females) with a clinical and biochemical diagnosis of EPP were assessed, revealing a prevalence of 3.15 cases per million persons and an incidence of 0.13 cases per million persons/year. Incidence significantly increased after 2009 (due to the availability of alfa-melanotide, which effectively limits skin photosensitivity). Mean age at diagnosis was 28 years, with only 22 patients (12.2%) diagnosed ≤10 years old. Gene mutations were assessed in 173 (96.6%) patients; most (164; 91.3%) were FECH mutations on one allele in association with the hypomorphic variant, c.315-48C, on the other (classic EPP), and nine (5.2%) were ALAS2 mutations (X-linked EPP). Only one case of autosomal recessive EPP was observed. Of the 42 different FECH mutations, 15 are novel, three mutations collectively accounted for 45.9% (75/164) of the mutations (c.215dupT [27.2%], c.901_902delTG [11.5%] and c.67 + 5G > A [7.2%]), and frameshift mutations were prevalent (33.3%). A form of light protection was used by 109/179 (60.8%) patients, and 100 (56%) had at least one α-melanotide implant. Three cases of severe acute liver involvement, requiring OLT, were observed. CONCLUSION: These data define, for the first time, the clinical and molecular epidemiology of EPP in Italy.

Unusual Domestic Source of Lead Poisoning.

Non-occupational lead poisoning is not rare, mainly occurring in domestic situations in children, but also in adults. Lead poisoning was observed in a 65 years-old woman non-exposed to risk that caught our attention with a diagnostic suspicion of acute intermittent porphyria according to recurrent episodes of abdominal pain and neuropathy of upper limbs. Acute intermittent porphyria was excluded by a laboratory investigation that showed instead severe lead poisoning. After several thorough examinations of the domestic environment, the source of intoxication has been detected in some cooking pots that released high concentrations of lead. Ethylenediamine tetracetic acid disodium calcium therapy (three cycles) reduced consistently blood lead concentration and, after one year, neuropathy was almost entirely recovered.

Varicella seroepidemiology and immunization in a cohort of future healthcare workers in the pre-vaccination era.

OBJECTIVES: The goal of this study was to establish the seroprevalence of positive antibodies against varicella and compliance with varicella vaccination in the pre-vaccination era. METHODS: A cohort of 10 683 Italian students from Padua University Medical School (from 2004 to 2019) were enrolled and classified as unvaccinated, vaccinated once, or vaccinated twice against varicella, according to their vaccination certificate. The antibody titre was measured and the seroprevalence of positive subjects was determined. Subjects with negative or equivocal antibodies were invited for vaccination, and then the antibody titre was retested. RESULTS: Unvaccinated students were mostly seropositive (95.6%), compared with vaccinated students who were less seropositive (68.0% after one dose and 78.6% after two doses) and had significantly lower antibody titres (p < 0.0001). The post-test vaccination had a positive response rate of 85.4%: 67.4% after one dose and 91.4% after two doses. CONCLUSIONS: In the pre-vaccination era, only 3.3% of future healthcare workers were vaccinated against varicella (1.1% once and 2.2% twice). Vaccination or revaccination of negative and equivocal individuals could reduce the number of susceptible people. Implementation of varicella vaccine (two doses) in healthcare workers is of primary importance to reduce the risk of transmission.

Biological Monitoring of Metal Ions Released from Hip Prostheses.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy®, group A, 25 patients; total Met-Met System Lima®, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 µg and 21 µg, adjusted to creatinine based on the threshold in whole blood of 7 µg/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Will We Have a Cohort of Healthcare Workers Full Vaccinated against Measles, Mumps, and Rubella?

Healthcare workers are a population exposed to several infectious diseases, and an immunization programme is essential for the maintenance of good vaccination coverage to protect workers and patients. A population of 10,653 students attending degree courses at Padua Medical School (medicine and surgery, dentistry and health professions) was screened for vaccination coverage and antibody titres against rubella, mumps, and measles. The students were subdivided into five age classes according to their date of birth: those born before 1980, between 1980 and 1985, between 1986 and 1990, between 1991 and 1995, and after 1995. Vaccination coverage was very low in students born before 1980, but the rate of positive antibody titre was high due to infection in infancy. Increasing date of birth showed increased vaccination coverage. In contrast, immune coverage was high for rubella (more than 90%) but not for mumps and measles (approximately 80%). An "anomaly" was observed for mumps and measles in the cohort born between 1991 and 1995, probably due to the trivalent vaccine formulation. Students born after 1990 showed vaccination coverage that exceeded 90%. It is therefore very likely that we will have a future generation of healthcare workers with optimal vaccination coverage.

Significance of anti-HB levels below 10 IU/L after vaccination against hepatitis B in infancy or adolescence: an update in relation to sex.

Hepatitis B vaccination (three-dose series) induces long-term immunity, but it is not uncommon to find antibody levels below 10 IU/L long after vaccination. However, the majority of the subjects with low antibody levels have a prompt response to a booster dose. A population of 10,294 students at Padua University Medical School, who were subjected to hepatitis B vaccination during infancy or adolescence according to the law, was tested for the presence of anti-HBs, usually during the first year of matriculation. Among the students offered a booster dose, 1,030 were vaccinated, and the antibody titre was re-tested. The present research provides further evidence from a larger number of students (1,030) that an anti-HB level higher than 2 IU/L is predictive of a prompt response to a booster. There are also differences related to sex. The results clearly confirm that an antibody titre equal to or greater than 2 IU/L is enough to prompt a response after a booster dose, even several years after the initial vaccination cycle, and to predict effective immune protection. The length of the interval between the booster/post-booster analyses increases the probability of finding a low response to the booster; furthermore, females show a more rapid response to the booster than males. The importance for healthcare workers of measuring the antibody titre four weeks after a booster is highlighted, and the results suggest that females have a better response than males to booster vaccination.

Reliability of urinary excretion rate adjustment in measurements of hippuric acid in urine.

The urinary excretion rate is calculated based on short-term, defined time sample collections with a known sample mass, and this measurement can be used to remove the variability in urine concentrations due to urine dilution. Adjustment to the urinary excretion rate of hippuric acid was evaluated in 31 healthy volunteers (14 males and 17 females). Urine was collected as short-term or spot samples and tested for specific gravity, creatinine and hippuric acid. Hippuric acid values were unadjusted or adjusted to measurements of specific gravity, creatinine or urinary excretion rate. Hippuric acid levels were partially independent of urinary volume and urinary flow rate, in contrast to specific gravity and creatinine, which were both highly dependent on the hippuric acid level. Accordingly, hippuric acid was independent on urinary specific gravity and creatinine excretion. Unadjusted and adjusted values for specific gravity or creatinine were generally closely correlated, especially in spot samples. Values adjusted to the urinary excretion rate appeared well correlated to those unadjusted and adjusted to specific gravity or creatinine values. Thus, adjustment of crude hippuric acid values to the urinary excretion rate is a valid procedure but is difficult to apply in the field of occupational medicine and does not improve the information derived from values determined in spot urine samples, either unadjusted or adjusted to specific gravity and creatinine.

Predictivity and fate of metal ion release from metal-on-metal total hip prostheses.

Blood metal ion levels in 72 patients with large head metal-on-metal hip arthroplasty were studied to determine the correlation between the values measured in whole blood and urine. Urinary cobalt and chromium levels of 30µg and 21µg, respectively, adjusted to creatinine were found to correspond to the 7µg/l cut-off value that has been accepted in whole blood. Cobalt and chromium levels in whole blood and urine both significantly correlated with increased acetabular component inclination angle over 50 degrees and pain scores. There was no correlation with socket anteversion angle or femoral head diameter. The data support the use of urinary measurement of metal ions adjusted to creatinine to monitor patients with large head metal-on-metal total hip arthroplasty.

Hepatitis B vaccination of adolescents: significance of non-protective antibodies.

Despite hepatitis B virus (HBV) immunization, a percentage of healthy individuals display an antibody titre below the threshold for clinical protection (10 IU/L). In order to predict the existence of this inducible immunological response, the precise anti-HBs titre required to achieve protection in immunized patients with waned HBs antibodies must first be determined. A total of 4486 vaccinated students attending the University of Padova Medical, Science, and Veterinary School were recruited for study between 2004 and early 2012. The baseline concentration of anti-HBs was measured at enrolment. Participants displaying anti-HBs titre < 10 IU/L at the follow-up examination (mean 10.8 years) were given a booster vaccination and retested 20-30 days later. At enrolment, 87.6% of the 4486 vaccinated subjects showed persistence of anti-HBs higher than 10 IU/L. Of the 279 booster-vaccinated subjects, 94.6% achieved the cut-off titre. Booster-induced immunological response was correlated to the pre-booster titre level, with ≥ 2 IU/L ensuring a robust positive response and less than 2 IU/L being associated with the probability of developing insufficient levels of antibodies. Pre-booster antibody titre higher than 2 IU/L in adults might be predictive of an anamnestic response to booster vaccination, whereas titres below this value may indicate likelihood of non-response.