Background and Aims

Acute hepatic porphyria (AHP) is a group of rare genetic diseases of heme biosynthesis resulting in severe neurovisceral attacks and complications that negatively impact quality of life. This study evaluated the impact of prophylactic and non-prophylactic treatment on patient-reported outcomes.

Methods

Adult patients from US, Italy, Spain, Australia, Mexico, and Brazil with AHP with >1 porphyria attack within the past 2 years or receiving intravenous hemin and/or glucose for attack prevention completed an online survey between January 19 and April 26, 2021. Descriptive analyses of demographics, health characteristics, and patient-reported outcomes (utilizing Generalized Anxiety Disorder-7 [GAD-7; scale, 0–21] and Patient Health Questionnaire [PHQ-8; scale, 0–24]) were conducted on all patients and separately among those who did and did not receive prophylactic treatment, defined as routine or scheduled hemin, routine or scheduled intravenous glucose, and/or a gonadotropin-releasing hormone agonist. Patients receiving givosiran were excluded.

Results

Ninety-two patients with AHP completed the survey (mean age, 41.1 years; 90.2% female). Prophylactic treatment was used by 38.0% of patients. Participants receiving and not receiving prophylactic treatment reported their current physical (88.6% and 71.9%), emotional (68.6% and 73.7%), cognitive (54.3% and 52.6%), financial (74.3% and 68.4%), and social health (62.9% and 49.1%) as either poor or fair, respectively. Mean GAD-7 and PHQ-8 scores for patients receiving prophylaxis were 10.3 and 12.4, respectively, and for those not receiving prophylaxis were 10.3 and 11.8, respectively.

Conclusions

Regardless of current treatment approach, AHP patients experience high disease burden and decreased quality of life.

Background and Aims

Type I autoimmune pancreatitis (AIP) is a rare form of pancreatitis that shows a brilliant response to glucocorticoids (GCs). Relapses are common and multiple courses of GCs are often required, with detrimental effects on glycemic control. To date, the prevalence of endocrine and of exocrine insufficiency at the time of diagnosis in AIP is unclear. To address this question, we performed a systematic review and meta-analysis.

Methods

The available databases were searched to identify studies reporting the incidence of endocrine and exocrine insufficiency in AIP patients. Studies involving ≥5patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. Pooled effects were calculated using a random-effect model and expressed in terms of prevalence.

Results

Fifty-four cohort studies met inclusion criteria and 2197AIP patients were included. At the time of AIP diagnosis, a total of 649 cases of diabetes (29.5%) were identified. The pooled prevalence rate of diabetes was 32%(95%CI0.26-0.39) with high heterogeneity (I^2=90). The pooled prevalence of exocrine insufficiency was 45%(95%CI 0.40-0.48). A higher pooled prevalence of diabetes was reported in study from Eastern countries (36%,95%CI 0.30-0.40) compared to Western countries(24%,95%CI 0.20-0.28). Of note, studies performed before the publication of ICDC criteria (2011)reported a higher prevalence of diabetes(43%,95%CI 32-53).

Conclusions

In this meta-analysis, we found that a large proportion of patients with AIP(>30%)display concomitant diabetes and exocrine insufficiency at the time of AIP diagnosis. Further studies on long-term outcomes are warranted to assess the impact of GCs on endocrine and exocrine pancreatic function.

Background and Aims

Medication safety at transitions of care is a focus of the Third WHO Global Patient Safety Challenge. Medication review and information transfer between health care professionals are key targets to reduce medication-related harm. We studied whether a discharge intervention combining medication review with enhanced information transfer between hospital and primary care physicians can delay readmission and impact other health-related outcomes of older inpatients with polypharmacy.

Methods

Cluster-randomized controlled trial in 21 Swiss hospitals with 6 months follow-up. In total, 68 unblinded senior physicians and their blinded junior physicians included 609 patients of ≥ 60 years taking ≥ 5 drugs. Hospitals were randomized to either integrate a checklist-guided medication review and communication stimulus into their discharge procedure, or follow usual discharge routines. Primary outcome was time-to-hospital-readmission within six months. Secondary outcomes covered health care utilization, medication, and the patients’ quality of life.

Results

Patients' characteristics were: mean age 77.5 (SD 8.6) years, 49.4% female, 9.6 (SD 4.2) drugs/patient. Time-to-first-readmission to any hospital did not differ significantly between study arms (adjusted HR 1.14 (intervention vs. control; SD 0.21), p = 0.54), nor did the 30-day readmission rates (6.7% [95% CI 3.3%-10.1%] vs. 7.0% [3.6%-10.3%]). Overall, we found no clinically relevant differences between study arms at 1, 3, and 6 months after discharge.

Conclusions

The combination of a structured medication review with enhanced information transfer did neither delay hospital readmission nor improve other health-related outcomes of older mulitmorbid inpatients. Our results may help in balancing practicality versus stringency and rigor in similar hospital discharge interventions.

Background and Aims

The aim of this study was to analyze the prevalence of malnutrition and risk of malnutrition in hospitalized patients aged ≥85 years and to evaluate the factors related to the nutritional status of these patients.

Methods

A prospective observational study that included patients aged ≥85 years admitted to Internal Medicine over March-May 2021 who underwent the Mini-Nutritional-Assessment (MNA) during admission. Sociodemographic, clinical and analytical characteristics, different scales, grip strength by dynamometry, treatment, hospital stay and in-hospital mortality were collected. Differences were evaluated according to nutritional status.

Results

Out of a total of 86 patients, 36 were male (41.9%) and the mean age was 88.7 years (SD:2.8; range:85-97). 15 patients had normal nutritional status, 44(51.2%) were at risk of malnutrition and 27(31.4%) were malnourished. Neither the risk of malnutrition nor malnutrition was related to age in these very old patients.

The presence of malnutrition (MNA≤7) was more frequent in women (p=0.003), patients with caregiver (p=0.005), frail (p<0.001) and it was also associated with the presence of cognitive impairment (p=0.005), functional impairment (p=0.017), with the Profund index (p<0.001) and it was significantly associated with a lower grip strength (p<0.001). However, no relationship was observed between malnutrition and comorbidity assessed by the Charlson index (p=0.38).

Conclusions

Four out of five hospitalized patients aged ≥85 years have altered nutritional status and almost one-third are malnourished. The risk of malnutrition and malnutrition are more frequent in women with caregivers and in frail patients. The presence of malnutrition is also related to cognitive and functional decline and muscle strength decrease.

Background and Aims

Early warning scores, as NEWS, have been recommended to detect patients at risk of clinical deterioration, but they are not adequate to define clinical complexity, not exclusively related to unstable conditions. Clinical Complexity Score (CCS) is an experimental score to quantify the burden of each patient according to the clinical relevance of any active pathology.

The aim of this study is to analyse performances of NEWS and CCS in acute medical patients.

Methods

1598 consecutive patients admitted in an Acute Medical Unit (AMU) have been considered. Clinical characteristics, main diagnoses, NEWS on admission, in AMU time-of-stay, CCS, destination wards including high-intensity (HI) transfers and in-hospital mortality were recorded and entered in a backward stepwise logistic regression analysis.

Results

Out of 1598 patients included, 18% (289) had a NEWS≥5 and 13% (207) had a CCS≥4. Patients transferred to HI-wards had higher NEWS, 4[0-13] than no-HI transfers 2[0-13], p<0.001, without differences in CCS (1[0-9] vs 1[0-10], p=0.525). Patients transferred to Internal Medicine ward had higher CCS (≥4 in 17.8%) than other wards’ transfers (≥4 in 4.4%, p<0.001) without differences in NEWS (2[0-13] vs 2[0-13], p=0.167).

NEWS but not CCS was relevant to HI transfers (OR 1.78, 95% CI 1.09-2.92, p<0.05) while both NEWS and CCS were relevant to in-hospital mortality (OR 2.72, 95% CI 1.72-4.29, p<0.0001 and OR 2.81, 95% CI 1.70-4.66, p<0.00001, respectively).

Conclusions

An integrated evaluation of clinical instability and clinical complexity supports a patient-centred and problem-oriented approach to optimize a global acute medical patients’ management.

Background and Aims

Type 2 diabetes and stuttering were linked to alterations in the hypothalamic-pituitary-adrenal axis and dopamine metabolism dysregulation. Yet, there is little data regarding the risk for incident diabetes among adolescents who stutter, possibly due to an avoidant behavior of these individuals and limited information regarding comorbidities. We investigated the association between stuttering in adolescence and incident type 2 diabetes in young adulthood in a nationwide cohort of 2.2 million adolescents.

Methods

This nationwide population-based study included 2,193,855 adolescents aged 16-20 years who were assessed for military service between 1980 and 2013. A speech-language pathologist confirmed diagnoses of stuttering in adolescence. Diabetes status for individuals as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent BMI.

Results

Analysis was stratified by sex (p_interaction=0.035). Of the 4,443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared to 25,678 (2.1%) men without stuttering (adjusted odds ratio 1.3, 95% CI 1.1–1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR=1.5, 95%CI 1.01-2.2) or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR=1.4, 95%CI 1.1-1.7). Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes (OR=2.03, 95%CI 0.48-2.20).

Conclusions

Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men.

Background and Aims

Familial Mediterranean Fever (FMF) is a known risk factor for female infertility. However, literature regarding the magnitude of the risk incurred is mixed. We aimed to estimate the risk for female infertility in patients with FMF compared to matched controls.

Methods

We used the Clalit Health Services Chronic Disease Registry to extract all female FMF patients documented between 2000-2016 and age- and sex-matched controls in a 1:1 ratio. Patients without any colchicine prescription or born outside of Israel were excluded. Logistic and Cox regression models were used to estimate the risk for female infertility.

Results

Overall, 6218 female patients were included (3109 FMF patients). The median follow-up was 32 (IQR 21 to 47) years. Infertility was diagnosed in 266 (8.6%) FMF patients and 162 (5.2%) controls. FMF patients had an OR of 1.7 (95%CI 1.39 to 2.09) for female infertility compared to controls. FMF patients had an HR of 1.66 (95%CI 1.36 to 2.01) for female infertility compared to controls.

Conclusions

This study found that FMF was associated with a significant increase in the risk for female infertility. This finding should be taken into consideration when treating female FMF patients.

Background and Aims

Early and accurate stratification risk of patients with coronavirus disease-19 (COVID-19) by using simple markers is critical to guide therapeutic strategies. Soluble interleukin-2 receptor (sIL-2R) levels have been suggested as prognostic marker for infectious and other diseases. We studied the predictive value of sIL-2R for detecting COVID-19 patients who will develop severe clinical outcomes.

Methods

sIL-2R levels were measured in 197 patients (60.9% males; median age 61-years; moderate disease, n=65; severe, n=132, intubated and/or died, n=42). All patients were treated with combined immunotherapies (anakinra ± corticosteroids ± intravenous immunoglobulin ± tocilizumab) based on initial ferritin levels and according to our local treatment algorithm (Dalekos et al. Eur J Intern Med 2021). The endpoint was the composite event of intubation due to severe respiratory failure (SRF) or COVID-19-related mortality.

Results

Median (interquartile range) sIL-2R levels were significantly higher in patients with severe disease compared to those with moderate disease [6 (6.2) ng/mL vs. 5.2 (3.4) ng/mL, p=0.017]. sIL-2R was the strongest laboratory predictive factor for intubation or death [hazard ratio 1.749, 95%CI 1.041-2.939, p=0.035] even after adjustment for other known risk factors (age, presence of diabetes or cardiovascular disease, pO₂/FiO₂ ratio, lymphocytes, ferritin, and C-reactive protein). Youden index revealed optimal sIL-2R cut-off for predicting intubation/death at 9 ng/mL (sensitivity: 67%; specificity: 86%; positive and negative predive value: 57% and 91%, respectively).

Conclusions

sIL-2R on admission may reflect disease severity and predict development of SRF and mortality.

Background and Aims

Quick Diagnosis Unit (QDU) is a form of rapid access to hospital diagnostic resources that has proven useful in the early detection of cancer. However, the effect of the COVID-19 pandemic on its access has not been well studied.

Our objective was to evaluate the impact of the pandemic on the processes management in the QDU.

Methods

Retrospective descriptive study of patients attended in a QDU 1 year before and 1 year after the first lockdown in Spain for COVID-19 (03/14/2020 - 06/21/2020). Demographic, clinical and management variables were collected. The diagnosis of malignancy and the time to diagnosis were compared and significance was established at p<0.05.

Results

A total of 234 patients were collected, 153 in the year before the first COVID-19 lockdown and 81 in the year following. The mean age was 63 years, majority of women (55.6%). Most of the medical cases came from the Emergency Room (70.9%) and the most frequent reasons for consultation were anemia (12.8%), incidental space-occupying lesion (12.4%) and fever (10.7%). The mean time to diagnosis was longer after the first quarantine than before (51.2 days vs. 41.8 days, respectively). The proportion of patients with a final cancer diagnosis was higher after lockdown (30.9%, 25/81) than before (22.7%, 34/153) (p=0.206).

Conclusions

Patients referred to QDU after the onset of the pandemic have higher rates of malignancy and they need more time for diagnosis. The health emergency has meant a break in the chain of care in the diagnosis of cancer that must be urgently guaranteed.

Background and Aims

The classical clinical picture of Herpes simplex 1(HSV-1) encephalitis (HSVE), a febrile patient with neurological impairment, is extremely non-specific and can suggest a variety of diagnoses. We aimed to identify factors on initial presentation that would aid the diagnosis of HSVE.

Methods

A single-center matched case control retrospective study in the Sheba Medical Center between the years of 1999-2017. The cases were adult patients with HSVE. The controls were patients with similar clinical pictures but with negative lumbar puncture PCR results.

Results

We identified 26 cases and 112 controls. Factors significantly associated with increased rates in HSVE when compared to controls were seizures {13 (50%), 21 (19%)}, headaches {16 (61%, 14 (12%)} and CSF pleocytosis {20 (76%), 32 (28%)}. Factors with lower rates when compared to controls were tachycardia {89.3 (±18.7), 94.7 (±13.9)}, respiratory infection signs {2 (8%), 54 (49%)} and pathological urinalysis {3 (12%), 51 (81%)}. A CHAID decision-tree analysis, performed on statistically significant variables. showed that they likelihood of a patient to have HSVE when they reported no headache and had normal CSF cell counts was 1.7% (95% CI 1.4-5.8)

Conclusions

Our study suggests that headaches are more important initial symptoms than initially thought and its absence reduces the likelihood of HSVE. However, further more robust research is needed and in the interim clinical judgement should still be the guiding factor in diagnostic and treatment decision making.

Background and Aims

To assess differences before and after SARS-Cov-2 pandemic in quality of life and coping with death strategies on a Spanish Internal Medicine service.

Methods

Descriptive study on Internal Medicine professionals through an online survey with sociodemographic variables, Coping with death scale and Quality of life scale between February-March 2019 and March-April 2021.

Results

A total of 106 professionals answered in 2019 (69.5% women, 43±11 year-old) whereas 151 did it in 2021(78.8% women, 44±12 year-old). In 2021 the mean professional experience was higher (17 versus 14 years (p<0.05)), the number of physicians who answered lower (25% vs 43%), and of nursing assistants higher (37.1% vs 21.9%, p<0.05). Accredited training to face suffering and death was significantly lower in 2021(25.5% vs 31.3%) p<0.05))

Total score on Bugen Scale in 2019 was 146.58±33.48 versus 138.95±24.67 in 2021 (p<0.05). Higher scores on Risk of burnout were found in 2021 (31.96 vs 26.79) (p<0.05). Comparing 2019 to 2021, 46.6% vs 43.7% presented low risk of burnout; 52.4% vs 56.3% medium risk and 1% vs 0% high risk (p<0.05). In addition 43.7% vs 27.2% showed low risk of Compassion Fatigue; 56.3% vs 71.5% intermediate risk and 0% vs 1.3% high risk (p<0.05).

Conclusions

After a pandemic year, the risk of Compassion Fatigue, Burnout and inadequate coping with death has increased significantly. It is necessary to develop intervention strategies to avoid a deterioration of quality of life in health-care professionals.

Background and Aims

Multi-transfused adult patients with thalassemia major (MTTΜ) are at increased risk of developing liver fibrosis due to iron overload. Transient elastography (TE) has been proved to reliably assess fibrosis stage in MTTM, but is not always available. The present study aimed to investigate the performance of non-patented serum biomarkers of liver fibrosis that have been validated in other chronic liver diseases, in thalassemic patients.

Methods

MTTΜ who were followed-up in 2 Greek academic centers (131 in Larissa, 81 in Thessaloniki) and had available TE measurements were included. AST to Platelet Ratio Index (APRI), Fibrosis-4 (FIB4), Aspartate aminotransferase and Alanine aminotransferase ratio (AAR), and Gamma-glutamyl transpeptidase to Platelet Ratio (GPR) were retrospectively calculated. The thresholds used were: >10kPa for severe fibrosis (SF)_ and >13 kPa for cirrhosis.

Results

212 MTTΜ (100 males) median age 38(19-76) years, with body mass index 23(17-35), ferritin levels 608(42-8006) ng/ml, liver iron concentration 3.2(0.3-58) mg/g dry weight were included. Thirty patients (14%) had SF and 19 (9%) cirrhosis. GPR and APRI performed better both for SF (AUC: 0.726 and 0.66, respectively) and cirrhosis (AUC: 0.756 and 0.69, respectively). GPR>0.102 showed sensitivity 63%, specificity 81% and NPV 93% for SF, while GPR>0.154 had sensitivity 68%, specificity 88% and NPV 96.6% for cirrhosis. APRI>0.37 had sensitivity 50%, specificity 82% and NPV 91% for SF, while APRI>0.28 had sensitivity 68%, specificity 70% and NPV 96% for cirrhosis.

Conclusions

Both APRI and especially GPR can safely exclude SF and cirrhosis in MTTΜ and could be used alternatively to TE for liver fibrosis assessment.