Knowledge, empathy, and willingness to counsel patients with HIV among Indonesian pharmacists: a national survey of stigma.

This study aimed to assess the level of HIV treatment knowledge, empathy, and HIV stigma of pharmacy students and pharmacists working with patients as well as potential factors associated with stigma. This survey included 250 hospital pharmacists within 33 provinces and 1013 final-year pharmacy students from Java, the most populated island in Indonesia. The data were collected via Qualtrics® and distributed by WhatsApp. The mean age of the participants was (Mean ± SD) 24.68 ± 5.30 years, and 80.0% were female. The mean knowledge score of students and pharmacists were 14.14 ± 2.01 and 15.39 ± 1.87, respectively, out of the maximum score of 21. The mean empathy score of students and pharmacists was 72.06 ± 5.39 and 77.40 ± 1.35, respectively out of the maximum score of 105. The mean stigma score of students and pharmacists was 21.02 ± 4.65 and 20.66 ± 4.41, respectively, out of a maximum score of 48. Regression analysis showed that knowledge, empathy, and willingness to counsel patients were negatively associated with stigma. Working with patients was positively associated with stigma. A multi-level intervention including education may reduce stigma and strengthen the role of pharmacists in caring for patients.

Sometimes they come back: New and old spinal muscular atrophy adults in the era of nusinersen.

BACKGROUND AND PURPOSE: Following the commercial availability of nusinersen, there have been a number of new referrals of adults with spinal muscular atrophy (SMA) not regularly followed in tertiary-care centers or enrolled in any disease registry. METHODS: We compared demographics and disease characteristics, including assessment of motor and respiratory function, in regularly followed patients and newcomers subdivided according to the SMA type. RESULTS: The cohort included 166 adult patients (mean age: 37.09 years): one type I, 65 type II, 99 type III, and one type IV. Of these 166, there were 67 newcomers. There was no significant difference between newcomers and regularly followed patients in relation to age and disease duration. The Hammersmith Functional Motor Scale Expanded and Revised Upper Limb Module scores were higher in the regularly followed patients compared to newcomers in the whole cohort and in both SMA II and II. A difference was also found on ventilatory status (p = 0.013) and Cobb's angle >50° (p = 0.039) between the two subgroups. No difference was found in scoliosis surgery prevalence (p > 0.05). CONCLUSIONS: Our results showed differences between the two subgroups, even if less marked in the type III patients. In the type II patients, there was a higher proportion of newcomers who were in the severe end of the spectrum. Of the newcomers, only approximately a third initiated treatment, as opposed to the 51% in the regularly followed patients. The identification of patients who were not part of the registries will help to redefine the overall prevalence of SMA and the occurrence of different phenotypes.

Factors associated with regular counselling attendance of HIV outpatients of a national referral hospital in Jakarta, Indonesia: a cross sectional study.

BACKGROUND: Counselling has been shown to improve adherence to medication in people living with HIV (PLHIV). The aim of this study was to investigate factors associated with regular counselling attendance of patients taking antiretroviral therapy (ART). METHODS: We conducted a cross-sectional, paper-based survey among 880 PLHIV patients on ART attending outpatient clinics of a referral hospital in Jakarta. Patients on ART, above 18 years old, providing written consent were included. The primary outcome was regular counselling attendance (i.e., having attended at least 3 sessions in the previous 3 months) using records from counsellors. Factors associated with regular counselling attendance were assessed using logistic regression analysis. RESULTS: The majority of patients were male (71.1%) and had regular counselling (78.4%). Being 31 to 40 years old (odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.32-0.93, > 40 years (OR = 0.30, 95% CI = 0.16-0.55) vs < 30 years, hepatitis B/C co-infection (OR = 0.42, 95% CI = 0.24-0.75), living > 20 km from the hospital (OR = 0.55, 95% CI = 0.33-0.93), transmission male-to-male (OR = 0.13, 95% CI = 0.04-0.44), unemployment (OR = 1.88, 95% CI = 1.02-3.44), part-time employment (OR = 10.71, 95% CI = 4.09-28.02), household member with HIV (OR = 3.31, 95% CI = 1.70-6.44), and Christianity (OR = 1.82, 95% CI = 1.12-2.94) were associated with regular counselling attendance. CONCLUSION: This study suggests that counselling services should be reviewed to ensure that they are near home and fit the needs of older patients or patients with co-morbidities and minorities. Tailoring counselling may improve attendance.

Multi-strain probiotic improves subjective sleep quality with no impact on body composition, hemodynamics, and physical activity.

The objective of the study was to examine the impact of a multi-strain probiotic (MSP) on sleep, physical activity, and body composition changes. We used a randomised, double-blind, placebo-controlled approach with 70 healthy men and women (31.0 ± 9.5 years, 173.0 ± 10.4 cm, 73.9 ± 13.8 kg, 24.6 ± 3.5 kg/m2) supplemented daily with MSP (4 × 109 live cells Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01, and Bifidobacterium longum 04; Probiotical S.p.A., Novara, Italy) or placebo (PLA). In response to supplementation (after 0, 2, 4, and 6 weeks of supplementation) and 3 weeks after stopping supplementation, participants had subjective (Pittsburgh Sleep Quality Index, PSQI) and objective sleep indicators, body composition, daily physical activity and resting hemodynamics assessed. Subjective sleep quality indicators using the PSQI (sleep latency, sleep disturbance, and global PSQI score) improved ( P < 0.05) at various time points with MSP supplementation. Systolic blood pressure in PLA increased ( P < 0.05) after 6 weeks of supplementation with no change in MSP. No changes ( P > 0.05) in sleep (hours asleep, minutes awake, number of times awake) or physical activity (step count, minutes of sedentary activity, total active minutes) metrics assessed by the wearable device were observed. Additionally, no changes in resting heart rate, diastolic blood pressure, and body composition were discerned. In conclusion, MSP supplementation improved the subjective ability to fall asleep faster and disturbances experienced during sleep, which resulted in improved overall sleep quality as assessed by the PSQI. No differences in other sleep indicators, physical activity, hemodynamics, and body composition were observed during or following MSP supplementation. Registered at clinicaltrials.gov: NCT05343533.

Longitudinal data of neuropsychological profile in a cohort of Duchenne muscular dystrophy boys without cognitive impairment.

The aim of the study was to re-assess neuropsychological profile in a group of boys with Duchenne muscular dystrophy without intellectual disability and neuropsychiatric disorder three years apart from a previous evaluation, to establish possible changes over time. We were also interested in defining more in detail correlation between genotype and neuropsychological phenotype. Thirty-three of the previous 40 subjects (mean age at follow up: 10 years and 7 months) agreed to participate in the follow up study and to perform the new assessment. The results confirm a typical neuropsychological profile, with difficulty in the manipulation of stored information, poor abstract reasoning and planning capacity and impulsiveness, supporting the involvement of a cerebellar striatal cortical network for these children. The more detailed description of subgroups of subjects, according to the real expression of Dp140, let to reveal possible genotype-neuropsychological phenotype correlations, and a more general neuropsychological impairment emerged in boys without Dp140 expression.

Metabarcoding analysis of gut microbiota of healthy individuals reveals impact of probiotic and maltodextrin consumption.

In a previously published double-blind, placebo-controlled study, we showed that probiotics intake exerted a positive effect on sleep quality and a general improvement across time in different aspects of the profile of mood state, like sadness, anger, and fatigue in 33 healthy individuals. The present work investigates the impact of the probiotic product, constituted of Limosilactobacillus fermentum LF16, Lacticaseibacillus rhamnosus LR06, Lactiplantibacillus plantarum LP01 (all former members of Lactobacillus genus), and Bifidobacterium longum 04, on the gut microbiota composition of the same cohort through a metabarcoding analysis. Both the placebo and probiotic treatments had a significant impact on the microbiota composition. Statistical analysis showed that the microbiota of the individuals could be clustered into three groups, or bacteriotypes, at the baseline, and, inherently, bacterial compositions were linked to different responses to probiotic and placebo intakes. Interestingly, L. rhamnosus and L. fermentum were retrieved in the probiotic-treated cohort, while a bifidogenic effect of maltodextrin, used as placebo, was observed. The present study shed light on the importance of defining bacteriotypes to assess the impact of interventions on the gut microbiota and allowed to reveal microbial components which could be related to positive effects (i.e. sleep quality improvement) to be verified in further studies.

Duchenne muscular dystrophy: preliminary experience with sacubitril-valsartan in patients with asymptomatic left ventricular dysfunction.

OBJECTIVE: Duchenne muscular dystrophy (DMD) is an inherited X-linked recessive neuromuscular disease caused by mutations of the dystrophin gene, leading to early and progressive muscle deterioration and dilated cardiomyopathy. The aim of this investigation was to assess whether treatment with sacubitril/valsartan (S/V) is well tolerated and may have beneficial effects in DMD patients with left ventricle (LV) dysfunction. PATIENTS AND METHODS: We administered S/V to 3 DMD patients (19-29 yeard old) with LV ejection fraction <35% at echocardiography but no symptoms of heart failure. All patients were on optimal medical therapy. S/V was initiated at a very low dose of 12/13 mg/die, after withdrawal of angiotensin-converting enzyme inhibitor therapy, and slowly titrated to the dose of 49/51 mg twice daily or the maximally tolerated dose. Clinical and echocardiographic follow-up was performed after 3, 6 and 12 months. RESULTS: At baseline, the LV ejection fraction was 32±1%. A significant improvement of LV ejection fraction was observed at 3 months (44.0±6.0%; p<0.05), which was maintained at 6 (45.7±5.0%) and 12 (43.3±3.2%) months (p<0.05 for both). No relevant side effects were reported throughout the period of the study. CONCLUSIONS: Our preliminary data suggest that, in DMD patients with reduced LV ejection fraction, S/V is safe and may improve LV function.

Transcriptional behavior of DMD gene duplications in DMD/BMD males.

DMD gene exons duplications account for up to 5-10 % of Duchenne (DMD) and up to 5-19% of Becker (BMD) muscular dystrophies; as for the more common deletions, the genotype-phenotype correlation and the genetic prognosis are generally based on the "reading frame rule". Nevertheless, the transcriptional profile of duplications, abridging the genomic configuration to the eventual protein effect, has been poorly studied. We describe 26 DMD gene duplications occurring in 33 unrelated patients and detected among a cohort of 194 mutation-positive DMD/BMD patients. We have characterized at the RNA level 16 of them. Four duplications (15%) behave as exception to the reading frame rule. In three BMD cases with out-of-frame mutations, the RNA analysis revealed that exon skipping events occurring in the duplicated region represent the mechanism leading to the frame re-establishment and to the milder phenotype. Differently, in a DMD patient carrying an in-frame duplication the RNA behaviour failed to explain the clinical phenotype which is probably related to post-transcriptional-translational mechanisms. We conclude that defining the RNA profile in DMD gene duplications is mandatory both for establishing the genetic prognosis and for approaching therapeutic trials based on hnRNA modulation.

Single-Scaffold Genome Sequence of Probiotic Strain Bifidobacterium breve BR03 (DSM 16604), Obtained by Combining Hybrid Sequencing and Optical Mapping.

Bifidobacterium breve BR03 (DSM 16604) is known for its health-promoting activity. We present a single-scaffold genome obtained by using a hybrid approach combining long- and short-read sequencing techniques integrated by an optical map. This approach could be set as an industry standard for probiotic strain characterization.

POMT1 and POMT2 mutations in CMD patients: a multicentric Italian study.

Mutations in POMT1 and POMT2 genes were originally identified in Walker-Warburg syndrome (WWS) and subsequently reported in patients with milder phenotypes characterised by mental retardation with or without brain abnormalities and without ocular malformations. As part of a multicentric Italian study we screened the POMT1 and POMT2 genes in 61 congenital muscular dystrophy (CMD) patients with alpha-dystroglycan reduction on muscle biopsy and/or clinical and radiological findings suggestive of the known forms of CMD with alpha-dystroglycan deficiency. The aim of the study was to establish how frequently mutations in POMT1 and POMT2 occur in CMD patients in the Italian population and to evaluate the spectrum of associated phenotypes. Thirteen patients showed mutations in POMT1 and five harboured mutations in POMT2, accounting for a total of 20 different mutations, eight of which were novel (two in POMT1 and six in POMT2). Normal brain MRI associated with mental retardation and microcephaly was the most frequent finding in patients with mutations in POMT1 (six out of 13), but was also found in a patient with POMT2 mutations. Predominant cerebellar hypoplasia was also frequent both in patients with POMT1 (three out of 13) and POMT2 (three out of 5) mutations. A MEB phenotype with frontal cortical dysplasia and pons abnormalities was found in two patients with POMT1 and in one with POMT2 mutations, while a WWS phenotype was only found in a case with mutations in POMT1. Mutations causing frameshifts and stop codons were responsible for the more severe phenotypes. Our results provide further evidence that, as previously reported for FKRP, the array of mutations in POMT1 and POMT2 is ample and the spectrum of associated phenotypes is wider than initially thought.

Swallowing difficulties in Duchenne muscular dystrophy: indications for feeding assessment and outcome of videofluroscopic swallow studies.

Feeding difficulties are known to occur with advancing age in Duchenne muscular dystrophy (DMD). We evaluated the role of videofluoroscopy swallow study (VFSS) in a group of 30 DMD patients with feeding difficulties. Indications for feeding assessment were: respiratory infections potentially attributable to aspiration (n=10) and/or episodes of choking (n=24) subdivided into isolated choking events (n=8) and regular choking during swallowing (n=16). Indications for assessment were analysed in relation to the VFSS results. Median age at assessment was 17.13 years (range 6-31.4). Twenty-four VFSS were performed. Prolonged chewing and effortful bolus transport for solids increased with age. Swallow trigger was normal in the majority of cases. All patients had some post-swallow pharyngeal residue around the laryngeal inlet increasing in volume with age. Although this residue did not result in aspiration, it was worse in patients that were frequently choking. Three patients intermittently had penetration of the supraglottic space that did not reach the vocal folds during the swallow. Our results suggest that reported swallowing problems when assessed are not always associated with difficulties on VFSS. It is the oral phase of swallowing that is most significantly affected in DMD. The pharyngeal phase is well triggered but is weak with incomplete pharyngeal clearance leaving pharyngeal residue. Insufficient or effortful chewing coupled with weak clearance may predispose them to choking episodes either as a one off event or with increasing frequency with age. This study suggests that VFSS may not be of additional benefit to careful feeding history and observation in DMD with feeding difficulties.

2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary.

Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy.

The Hammersmith functional score correlates with the SMN2 copy number: a multicentric study.

Previous studies showed that SMN2 copy number correlates inversely with the disease severity. Our aim was to evaluate SMN2 copy numbers and the Hammersmith functional motor scale in 87 patients with SMA II in order to establish whether, within SMAII, the number of copies correlates with the severity of functional impairment. Our results showed a relative variability of functional scores, but a significant correlation between the number of SMN2 genes and the level of function.

POMT2 mutation in a patient with 'MEB-like' phenotype.

Mutations in POMT2 have so far only been reported in patients with Walker-Warburg phenotype. We report heterozygous POMT2 mutations in an a girl with a milder phenotype characterized by mental retardation, microcephaly, hypertrophy of the quadriceps and calf muscles, and structural brain changes mostly affecting the posterior fossa. Our findings suggest that, as previously reported for POMT1 and FKRP, mutations in the POMT2 can also be associated with clinical heterogeneity.

Reliability of the Hammersmith functional motor scale for spinal muscular atrophy in a multicentric study.

The aim of this study was to validate the Hammersmith functional motor scale for children with spinal muscular atrophy in a large cohort of 90 non-ambulant children with spinal muscular atrophy type 2 or 3. All had a baseline assessment (T0) and were reassessed either at 3 months (T1) (n = 66) or at 6 months (T2) (n = 24). Inter-observer reliability, tested on 13 children among 3 examiners, was > 95%. Of the 66 children examined after 3 months 4 had adverse effects in between assessments and were excluded from the analysis. Forty-two (68%) of the remaining 62 reassessed had no variation in scores between T0 and T1 and 13 (21%) were within +/- 1 point. 9 (37.5%) of the 24 children reassessed after 6 months had no variation in scores between T0 and T2 and another 9 (37.5%) had variations within +/- 1 point. Our study confirms previous observations of the reliability of the scale and helps to establish a baseline for assessing changes of functional ability over 3 and 6 month intervals. This information can be valuable in view of therapeutic trials.

Chronic lung disease in very low birth weight infants: Persistence and improvement of a quality improvement process in a tertiary level neonatal intensive care unit.

OBJECTIVE: We previously demonstrated a significant reduction in our incidence of chronic lung disease in our NICU using potentially better practices of avoiding delivery room endotracheal intubation and using early nasal CPAP. We sought to demonstrate whether these improvements were sustained and or improved over time. STUDY DESIGN: We conducted a retrospective, cross-sectional analysis of infants 501-1500 grams born at our hospital between 2005 and 2013. Infants born during the 2005-2007, 2008-2010 and 2011-2013 epochs were grouped together, respectively. Descriptive analysis was conducted to determine the number and percent of maternal and neonatal characteristics by year grouping. Chi-squared tests were used to determine whether there were any statistically significant changes in characteristics across year groupings.. Two outcome variables were assessed: a diagnosis of chronic lung disease based on the Vermont Oxford Network definition and being discharged home on supplemental oxygen. RESULTS: There was a statistically significant improvement in the incidence of chronic lung disease in infants below 27 weeks' gestation in the three year period in the 2011-2013 cohort compared with those in the 2005-2007 cohort. We also found a statistically significant improvement in the number of infants discharged on home oxygen with birth weights 751-1000 grams and infants with gestational age less than 27 weeks in the 2011-2013 cohort compared to the 2005-2007 cohort. CONCLUSIONS: We demonstrated sustained improvement in our incidence of CLD between 2005 and 2013. We speculate that a multifaceted strategy of avoiding intubation and excessive oxygen in the delivery room, the early use of CPAP, as well as the use of volume targeted ventilation, when needed, may help significantly reduce the incidence of CLD.

MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients.

BACKGROUND: Myosin heavy chain 7 (MYH7)-related myopathies are emerging as an important group of muscle diseases of childhood and adulthood, with variable clinical and histopathological expression depending on the type and location of the mutation. Mutations in the head and neck domains are a well-established cause of hypertrophic cardiomyopathy whereas mutation in the distal regions have been associated with a range of skeletal myopathies with or without cardiac involvement, including Laing distal myopathy and Myosin storage myopathy. Recently the spectrum of clinical phenotypes associated with mutations in MYH7 has increased, blurring this scheme and adding further phenotypes to the list. A broader disease spectrum could lead to misdiagnosis of different congenital myopathies, neurogenic atrophy and other neuromuscular conditions. RESULTS: As a result of a multicenter Italian study we collected clinical, histopathological and imaging data from a population of 21 cases from 15 families, carrying reported or novel mutations in MYH7. Patients displayed a variable phenotype including atypical pictures, as dropped head and bent spine, which cannot be classified in previously described groups. Half of the patients showed congenital or early infantile weakness with predominant distal weakness. Conversely, patients with later onset present prevalent proximal weakness. Seven patients were also affected by cardiomyopathy mostly in the form of non-compacted left ventricle. Muscle biopsy was consistent with minicores myopathy in numerous cases. Muscle MRI was meaningful in delineating a shared pattern of selective involvement of tibialis anterior muscles, with relative sparing of quadriceps. CONCLUSION: This work adds to the genotype-phenotype correlation of MYH7-relatedmyopathies confirming the complexity of the disorder.

Reversible aphasic disorder induced by lamotrigine in atypical benign childhood epilepsy.

PURPOSE: We studied an eleven year-old girl with atypical, benign partial epilepsy who acutely presented a severe aphasia associated with marked EEG deterioration after lamotrigine administration. A parallel monitoring of language disorders and EEG changes during the gradual withdrawal of lamotrigine was performed in order to evaluate their possible correlation with lamotrigine administration. METHODS: Detailed neuropsychological and linguistic examinations in association with awake and sleep EEG were periodically performed. RESULTS: The evolution of the aphasic disorder was closely related to the EEG abnormalities, and disappeared after the withdrawal of lamotrigine. CONCLUSIONS: We considered the hypothesis that our case could be an expression of a paradoxical reaction to lamotrigine, in which the transitory aphasic disorder was sustained by an epileptiform electric activation.