COVID-19-Related Death in Patients with Alcohol or Substance Use Disorders.

BACKGROUND: People with substance or alcohol use disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population, but the evidence of COVID-19-related mortality in these patients is unclear. OBJECTIVES: The aim of the study was to verify whether patients with AUD and SUD have a higher mortality rate for COVID-19-related mortality compared to the general population. METHOD: We performed a follow-up study to assess mortality in 2020 in a cohort of patients diagnosed for the first time with AUDs or SUDs at the Public Health Services in the metropolitan area of Bologna (Northern Italy) from 2009 to 2019. RESULTS: SUDs/AUDs patients present an excess mortality with respect to the general population for all causes of death and for COVID-19-related mortality. CONCLUSIONS: Our data support the need for prevention strategies in SUDs/AUDs patients such as vaccinations.

Gambling Disorder in an Italian Population: Risk of Suicide Attempts and Associated Demographic-Clinical Factors using Electronic Health Records.

To identify the demographic and clinical characteristics associated with access to Emergency Departments for Suicide Attempt in a cohort of patients with Gambling disorders. We used electronic health records of inpatient and outpatient services to identify individuals who received a diagnosis of gambling disorder (ICD-9 or ICD-10 codes) in the Metropolitan area of Bologna from 2009 to 2019. In this cohort we identified accesses to Emergency Departments for suicide attempt through cross-matching with electronic records. We calculated Crude Suicide Attempt Rates; we also included the demographic-clinical variables in a multivariate Poisson regression. We identified 692 patients with a diagnosis of gambling disorder and a total of 2733 Person Years. The Crude Suicide Attempt Rate per 1000 Person Years was 9.17 (95% CI 6.20-13.58), higher for females and much higher than the general population (incidence rate ratio = 93.72). The multivariate analysis showed a higher risk of suicide attempt in the year following the first contact with a clinical service, in patients younger than 45 years, with alcohol use disorders and personality disorders. This study evidenced a high risk of access to Emergency Departments for suicide attempt in individuals with a diagnosis of gambling disorder and highlighted important demographic and clinical factors that should be considered when evaluating suicide risk in this population.

Long-term prognostic outcomes in patients with haemoptysis.

BACKGROUND: Haemoptysis is a challenging symptom that can be associated with potentially life-threatening medical conditions. Follow-up is key in these patients to promptly detect new or misdiagnosed pathologic findings. Few prospective studies have evaluated long-term prognostic outcomes in patients with haemoptysis. Furthermore, the role played by antiplatelet and anticoagulant drugs on mortality and recurrence rates is unclear. The aim of this study was to assess mortality after 18 months of follow-up. Furthermore, the incidence of recurrence and the risk factors for recurrence and death were evaluated (including the role played by anticoagulant and antiplatelet drugs). METHODS: Observational, prospective, multicentre, Italian study. RESULTS: 451/606 (74.4%) recruited patients with haemoptysis completed the 18 months follow-up. 22/604 (3.6%) diagnoses changed from baseline to the end of the follow-up. 83/604 (13.7%) patients died. In 52/83 (62.7%) patients, death was the outcome of the disease which caused haemoptysis at baseline. Only the diagnosis of lung neoplasm was associated with death (OR (95%CI): 38.2 (4.2-347.5); p-value: 0.0001). 166 recurrences were recorded in 103/604 (17%) patients. The diagnosis of bronchiectasis was significantly associated with the occurrence of a recurrence (OR (95% CI): 2.6 (1.5-4.3)); p-value < 0.0001). Anticoagulant, antiaggregant, and anticoagulant plus antiaggregant drugs were not associated with an increased risk of death and recurrence. CONCLUSIONS: Our study showed a low mortality rate in patients with haemoptysis followed-up for 18 months. Pulmonary malignancy was the main aetiology and the main predictor of death, whereas bronchiectasis was the most frequent diagnosis associated with recurrence. Antiplatelet and/or anticoagulant therapy did not change the risk of death or recurrence. Follow-up is recommended in patients initially diagnosed with lower airways infections and idiopathic bleeding. TRIAL REGISTRATION: NCT02045394.

Mortality Risk among Cocaine Users before and after the Economic Recession: Results of a Longitudinal Study.

BACKGROUND: Studies have highlighted 2 different groups of cocaine users (CUs): "socially integrated" (stable living conditions, regular employment, use cocaine alone or in combination with other psychoactive substances) and "socially marginalized" (socioeconomic and health problems, former or current heroin users, many injecting cocaine). These differences are also found in the elevated mortality risk for CUs, higher among subjects with cocaine and heroin use. This study targeted residents in Northern Italy who turned to a public treatment center for drug addiction following problems caused by primary cocaine use between 1982 and 2016. OBJECTIVES: To estimate mortality risk for subjects who have never used heroin (CUs) compared to that of subjects who have used heroin (HCUs). METHOD: Retrospective cohort study. We selected 1,993 subjects; 18,015 Person Years (PY). RESULTS: Over time, the quota of subjects injecting cocaine and using heroin decreased, while patients not using heroin increased. Both new patients and crude mortality rates (CMR) decreased during the years 2009-2012 and increased in the following period. CMRs were 5.55 per 1,000 PY, higher for HCUs, men and subjects aged over 44 years. Standardized mortality rates were 3.49, higher for women, injecting cocaine and HCUS. Among CUs, most of the deaths were from injury excluding drug related and tumors; among HCUs, from drug-related causes and diseases of the cardiovascular system. CONCLUSION: The study results show a change in the characteristics of SERD clients being treated for primary cocaine use, which are reflected both in mortality risk and causes of death. After a long period of a decrease, mortality risk increased in the period after the economic recession. Aspects concerning the effects of the economic recession on the problematic consumption of cocaine and on the risk of death are discussed.

Bronchoscopy to assess patients with hemoptysis: which is the optimal timing?

BACKGROUND: Bronchoscopy plays a key role to diagnose the etiology, to localize the site, and to identify the sources of the bleeding in patients with hemoptysis, but the ideal timing of an endoscopic examination is still unclear. METHODS: We performed a secondary analysis of an observational and multicenter study, aimed at evaluating the epidemiology of hemoptysis in Italy and the diagnostic yield of the most frequently prescribed examinations. The aim of the study was to evaluate whether an early bronchoscopy (i.e., performed during active bleeding/≤48 h after hemoptysis stopped) helps localize bleeding (i.e., site, lobe, lung) and increase diagnostic yield in comparison with a delayed examination. RESULTS: Four hundred eighty-six consecutive adult patients (69.2% males; median [IQR] age: 67 [53-76] years) with hemoptysis requiring an etiological diagnosis and undergoing bronchoscopy were recruited. Bleeding focus could be located more frequently in case of moderate-severe bleedings than in cases of mild hemoptysis (site: 70/154, 45.4%, VS. 73/330, 22.1%; p-value < 0.0001; lobe: 95/155, 61.3%, VS. 95/331, 28.7%; p-value < 0.0001; lung: 101/155, 65.1%, VS. 111/331, 33.5%; p-value < 0.0001). Early bronchoscopy showed a higher detection rate of bleeding source in comparison with delayed examination (site: 76/214, 35.5%, VS. 67/272, 24.6%; p-value = 0.01; lobe: 98/214, 45.8%, VS. 92/272, 33.8%; p-value = 0.007; lung: 110/214, 51.4%, VS. 102/272, 37.5%; p-value = 0.002). Early bronchoscopy did not provide any advantages in terms of increased diagnostic yield, in the total cohort (113/214, 52.8%, VS. 123/272, 45.2%; p-value = 0.10) and in the severity subtypes (mild: 56/128, 43.8%, VS. 88/203, 43.4%; p-value = 0.94; moderate-severe: 57/86, 66.2%, VS. 35/69, 50.7%; p-value = 0.051). CONCLUSIONS: Early bronchoscopy helps detect bleeding sources, particularly in cases of moderate-severe hemoptysis, without increasing diagnostic accuracy. TRIAL REGISTRATION: ClinicalTrials.gov (identifier: NCT02045394 ).

Epidemiology and Clinical-Demographic Characteristics of Suicide Attempts in Alcohol Use Disorders in an Italian Population.

Suicide is a leading cause of morbidity worldwide. Among the known risk factors, alcohol use disorders (AUDs) are particularly relevant, but data on the epidemiology and characteristics of suicide attempts (SA) in this group are lacking. We used electronic health records of national health services to identify individuals who received a diagnosis of AUD in the Metropolitan area of Bologna from 2009 to 2019. In this cohort we identified accesses to Emergency Departments for SA from 2009 to 2020. The Crude Suicide Rate (CSR) for 1,000 Person Years was 2.93, higher than the general population. The CSR was higher in females, within one year from receiving the diagnosis of AUD, in patients with psychiatric comorbidities, concomitant abuse of cannabis or benzodiazepines. As for Covid-19 pandemic, the risk ratio of SA was significantly higher in 2020 compared to 2019 in females. Our results are relevant to identify clinical risk factors for SA in patients with AUDs, which are strongly associated with suicide risk but with scarce data in the previous literature and paucity of evidence-based therapeutic interventions.

Mortality risk in a population of patients treated for gambling disorders: results of a follow-up study.

AIMS: To examine mortality risk and causes of death in a cohort of a population of patients treated for gambling disorders in northern Italy from 1992 to 2019. METHODS: Cohort study. RESULTS: Half of the patients were diagnosed with psychiatric disorders, substance use disorder or alcohol dependence. The excess mortality compared to the general population (SMR) was 1.16 (0.85-1.58), more elevated among females aged 40 to 59 and males aged 20 to 29. Females had higher SMRs for all cancers and suicide; males for malignant neoplasm of liver, of lung, of prostate, and of bladder. CONCLUSIONS: Despite patients increasing, subjects who most turn to the services are the most serious ones, in older age, with comorbid mental disorders and with a compromised health status. This is reflected in the high risk of death for all cancers.

Mortality Risk among Heroin Users Accessing Treatment: Natives and Non-Natives Patients Results of a Longitudinal Study.

The aim of this study was to examine mortality risk and causes of death for natives and non-natives in a cohort of heroin population of treated in Northern Italy. Crude Mortality Rates (CMRs) were 12.78 per 1,000 Person Years (PY), Standardized Mortality Rate (SMR) was 9.93. Mortality has been decreasing over time, was higher for patients who accessed the treatment services before 2001 and has been increasing with age. CMRs and SMRs were higher among natives, while non-natives were distinguished by higher CMRs and SMRs for suicide. The natives were at greater risk of death than non-natives both injecting and non-injecting, but the mortality risk was not statistically significant in the different periods of first admission. Among non-native patients, older on average, there was a lower proportion of injecting, and a higher quota of people unemployed than among Italian natives. We highlight differences between the various areas of origin concerning consumption patterns and risk of death. The results of the study highlight a particular sub-population of heroin users, the non-natives, who as compared with the Italians, have less invasive consumption styles, reach the health services later but benefit from fewer medical controls.

Ketamine abusers referring to emergency departments in northern Italy: a cross- sectional study.

INTRODUCTION: Ketamine is an essential medicine used as an anesthetic in low and middle-income countries and in veterinary medicine. Recreational use is widespread throughout the world, especially owing to its lower price compared to other substances. In Western countries its use has been mainly linked to subpopulations of young people who use drugs recreationally. Ketamine misuse is associated with amnesia, dependence, dissociation, lower urinary tract dysfunction and poor impulse control. Regular ketamine use is associated with abdominal pains. AIMS: The aims of this study are to analyze characteristics and main symptoms of ketamine abusers attending emergency departments (EDs) in the metropolitan area of Bologna, Emilia-Romagna Region, northern Italy. METHODS: We identified 74 records of ketamine-related visits: 30% female; 22% non-natives; mean age 25.6 years. Forty-two percent reported ketamine use alone, 46% reported the use of other illegal substance (cocaine 19%, heroin 18%), 26% alcohol misuse. RESULTS: The most common reported symptoms were neurological (soporous state 18%, agitation 14%, confusion 7%, panic attacks 7%, mydriasis 7%, tremors 7%), gastro-intestinal (abdominal pain 15%, vomiting 11%), urological (6.8%) and cardiac (palpitations 5%, chest pain 5%). Complications secondary to falls and cuts (7%) were the most frequent trauma complications. We highlight a significant number of visits regarding suicide attempts (10%) and overdose (4%). CONCLUSIONS: The results highlight a particular population of problematic ketamine users identified using the hospital's ICT system. In particular, poly-drug users who consume ketamine in combination with heroin or cocaine presenting to the ED represent a specific target for targeted prevention projects on non-lethal overdoses and suicide attempts.

Who Are the Subjects with Gambling-Related Problems Requiring Treatment? A Study in Northern Italy.

BACKGROUND: This study analyzes data related to Hospital (HOS), Public Treatment Service Dedicated to Drug Addicts (SERD), or Community Mental Health Center (CMHC) clients with a first diagnosis of Pathological Gambling (PG) in the period 2000/2016 in Northern Italy. The aims were to describe trends and characteristics of pathological gamblers (PGs) and to estimate the prevalence of other diagnoses before or after the diagnosis of PG. METHODS: Participants aged over 17 years with an ICD-9 or ICD-10 PG diagnosis were selected. RESULTS: 680 PGs were identified, mean age 47.4 years, 20% female, 13% non-natives, 30% had other mental disorders diagnoses, 9% had alcohol dependence syndrome, and 11% had drug dependence. Most participants with comorbid disorders were diagnosed before PG, with a more elevated prevalence regarding mental disorders. Almost seven years had elapsed on average between the first admission and the diagnosis of PG. CONCLUSIONS: The results of this study highlight a growing demand for PG treatment addressed not only to SERD, but also to psychiatric and hospital services, based on the increase in SERD attendance from 2013. Many of them had already been treated for mental health problems before, but their percentage remained costant over time.

Stimulus-response properties of motor system in patients with cerebellar ataxia.

OBJECTIVE: The aim of the study was to examine the stimulus-response properties of the excitatory and inhibitory components of corticospinal projections at rest and during voluntary contraction in cerebellar patients. METHODS: We investigated motor evoked potential (MEP) and cortical silent period recruitment curves in response to increasing intensities of transcranial magnetic stimulation in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched controls. The transcranial magnetic stimulation intensity was increased from 90 to 180% of the resting motor threshold. MEP recruitment curves were recorded at rest and during voluntary contraction in the right abductor pollicis brevis muscle. RESULTS: No statistical differences were found between patients and controls in MEP recruitment curves in either the resting or active condition. A significant difference was found between patients and controls in the cortical silent period threshold (patients: 33.2+/-3.4% of maximal stimulator output; controls 39.4+/-3.2%; P=0.01) and recruitment curve, the duration of the cortical silent period being longer in patients at transcranial magnetic stimulation intensities ranging from 90 to 130% of the resting motor threshold (patients: 135-191 ms; controls: 53-158 ms). No changes were found in the silent period evoked by peripheral nerve stimulation. CONCLUSIONS: Inhibitory components of corticospinal projections were recruited with a lower threshold in patients. No abnormalities were found in the recruitment of the excitatory networks. Our data show a prevalence of inhibitory phenomena in the motor cortex of cerebellar patients. These findings would appear to be specific to cerebellar diseases and are the opposite of those previously documented in movement disorders such as dystonia and Parkinson's disease. Our results suggest that the cerebellum and the basal ganglia may counteract each other in modulating the level of motor system excitability.

Enhanced intracortical inhibition in cerebellar patients.

OBJECTIVE: The aim of the study was to examine intracortical excitability in cerebellar patients. METHODS: Short-latency intracortical inhibition (SICI), long-latency intracortical inhibition (LICI) and intracortical facilitation (ICF) to paired transcranial magnetic stimulation (TMS) were investigated in 8 patients with 'pure' cerebellar syndromes and in 14 age-matched normal controls. The conditioning stimulus for short-latency intracortical inhibition and intracortical facilitation was set at 70% of the resting motor threshold (RMT) and preceded the test stimulus (110-120% of the resting motor threshold) by interstimulus intervals (ISIs) of 1-30 ms. For the long-latency intracortical inhibition determinations, the conditioning stimulus was set at 120% of the resting motor threshold and preceded the test stimulus (also 120% of the resting motor threshold) by interstimulus intervals of 30-500 ms. RESULTS: No statistically significant differences were found between patients and controls as regards either short-latency intracortical inhibition or intracortical facilitation. A significant prevalence of long-latency intracortical inhibition was present in cerebellar patients at interstimulus intervals of 200-500 ms (conditioned MEP amplitude=29-41% of test MEP) as compared to controls (71-96% of test MEP). The amplitude of conditioned MEPs was persistently less than 45% of the test MEP in six patients, who were studied at interstimulus intervals up to 1000 ms. CONCLUSIONS: Long-latency intracortical inhibition was prevalent and abnormally longer-lasting in patients. Tonic hyperactivation of a subpopulation of GABAergic interneurons in the motor cortex of patients may be the mechanism responsible for this abnormality. Our findings seem to be specific to cerebellar diseases and are the opposite of those found in movement disorders such as dystonia and Parkinson's disease. These data suggest that the cerebellum and the basal ganglia may have opposite influences in tuning the excitability of the motor cortex.

Emergency department admission and mortality rate for suicidal behavior. A follow-up study on attempted suicides referred to the ED between January 2004 and December 2010.

BACKGROUND: The international literature reports that for every completed suicide there are between 8 and 22 visits to an Emergency Department (ED) for attempted suicide/suicidal behavior. AIMS: To describe the characteristics of admission to emergency departments (EDs) for suicide-related presenting complaints in the metropolitan area of Bologna; to estimate the risk for all-cause mortality and for suicide; to identify the profiles of subjects most at risk. METHOD: Follow-up of patients admitted to the EDs of the metropolitan area of Bologna between January 2004 and December 2010 for attempted suicide. A Cox model was used to evaluate the association between sociodemographic variables and the general mortality risk. RESULTS: We identified 505 cases of attempted suicide, which were more frequent for female subjects, over the weekend, and at night (8:00 p.m./8:00 a.m.). The most used suicide methods were psychotropic drugs, sharp or blunt objects, and jumping from high places. In this cohort, 3.6% of subjects completed suicide (4.5% of males vs. 2.9% of females), 2.3% within 1 year of the start of follow-up. The most common causes of death were drug use and hanging. In the multivariate analysis, those who used illicit drugs 24 hr prior to admission to the ED (hazard ratio [HR] = 3.46, 95% CI = 1.23-9.73) and patients who refused the treatment (HR = 6.74, 95% CI = 1.86-24.40) showed an increased mortality risk for suicide. CONCLUSION: Deliberate self-harm patients presenting to the ED who refuse treatment represent a specific target group for setting up dedicated prevention schemes.

Ulnar nerve impairment at the wrist does not contribute to extramedian sensory symptoms in carpal tunnel syndrome.

OBJECTIVE: Extramedian spread of sensory symptoms is frequent in carpal tunnel syndrome (CTS) but its mechanisms are unclear. We explored the possible role of subtle ulnar nerve abnormalities in the pathogenesis of extramedian symptoms. METHODS: We recruited 350 CTS patients. After selection, 143 patients (225 hands) were included. The hand symptoms distribution was graded with a diagram into median (MED) and extramedian (EXTRAMED) pattern. We tested the correlation of ulnar nerve conduction measures with the distribution and the severity of symptoms involving the ulnar territory. The clinical significance of ulnar nerve conduction findings was explored with quantitative sensory testing (QST). RESULTS: EXTRAMED distribution was found in 38.7% of hands. The ulnar neurographic measures were within normal values. Ulnar nerve sensory measures were significantly better in EXTRAMED vs MED hands and not significantly correlated to ulnar symptoms severity. Ulnar and median nerve sensory measures were significantly correlated. QST showed normal function of ulnar nerve alphabeta-fibers. CONCLUSIONS: Ulnar nerve sensory abnormalities do not contribute to the spread of sensory symptoms into the ulnar territory. SIGNIFICANCE: Our data favour the hypothesis that spinal and supraspinal neuroplastic changes may underlie extramedian spread of symptoms in CTS.

Proximal pain in patients with carpal tunnel syndrome: a clinical-neurophysiological study.

Patients with carpal tunnel syndrome (CTS) usually complain of pain and paresthesia in the hand or wrist, but pain proximally to the wrist has been frequently reported in this condition. This study was aimed at understanding which clinical features are associated with the presence of proximal pain (PP) in the upper limb of CTS patients. We recruited 250 patients with clinical and neurophysiological evidence of CTS. After thorough selection to rule out concomitant upper limb painful conditions, 112 patients (175 hands) were included. PP was defined as the presence of pain in the upper limb proximally to the wrist (neck excluded) in association with sensory complaints in the hand. Patients were asked about the presence and severity of proximal sensory complaints, the distribution of sensory complaints in the hand, and underwent an objective evaluation and neurographic study. Thenar muscle strength was significantly larger, the neurophysiological measures were significantly less severe, and hand paresthesia was significantly greater in patients with PP. The neurographic score and the measures of median nerve damage were inversely correlated with the severity of PP. PP was related to extramedian spread of symptoms in the hand. None of the objective/neurographic variables was related to severity of sensory complaints restricted to the hand. PP may be found in a consistent number of CTS patients. PP may represent a clinical marker of mild median nerve damage. The presence of proximal complaints might be related to peripheral or central nervous system mechanisms.

Extra-median spread of sensory symptoms in carpal tunnel syndrome suggests the presence of pain-related mechanisms.

Patients with carpal tunnel syndrome (CTS) may complain of sensory symptoms outside the typical median nerve distribution. The study is aimed to understand which clinical features are associated with the extra-median distribution of symptoms in CTS. We recruited 241 consecutive CTS patients. After selection, 103 patients (165 hands) were included. The symptoms distribution was evaluated with a self-administered hand symptoms diagram. Patients underwent objective evaluation, neurographic study and a self-administered questionnaire on subjective complaints. No clinical or electrodiagnostic signs of ulnar nerve involvement were found in the 165 hands. Median distribution of symptoms was found in 60.6% of hands, glove distribution in 35.2% and ulnar distribution in 4.2%. Objective measures of median nerve lesion (tactile hypaesthesia and thenar muscles hypasthenia) and neurographic involvement were significantly more severe in median hands than in the other groups. Subjective complaints (nocturnal pain, numbness and tingling sensations) were significantly more severe in glove hands. Neurophysiological and objective measures were not correlated with subjective complaints. The severity of the objective examination and neurographic involvement and the intensity of sensory complaints appear to be independent factors that influence the symptoms distribution. Extra-median spread of sensory symptoms was associated with higher levels of pain and paresthesia. We suggest that central nervous system mechanisms of plasticity may underlie the spread of symptoms in CTS.

Sensorimotor integration to cutaneous afferents in humans: the effect of the size of the receptive field.

Transcranial magnetic stimulation (TMS) can be used to study sensorimotor integration in humans non-invasively. Motor excitability has been found to be inhibited when afferent stimuli are given to a peripheral nerve and precede TMS at interstimulus intervals (ISIs) of 20-50 ms. This phenomenon has been referred to as short-latency afferent inhibition (SAI). To better understand the functional meaning of these phenomena, we examined the effect of the size of the receptive field on SAI to cutaneous afferents in upper-limb sensorimotor areas in humans. We examined the effect of the stimulation of the isolated right first (D1), second (D2) and third finger (D3), the right second and third finger together (D23) and the right first three fingers together (D123) on the amplitude of motor evoked potentials (MEPs) to TMS in hand and forearm muscles. We examined the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles. Digital stimulation preceded TMS at ISIs of 20-50 ms. The effect of D2 stimulation was MEP inhibition (SAI), which was more marked and consistent in APB and FDI muscles than in ECR and FCR muscles. Similarly, D1 and D3 stimulation caused MEP reduction, while no MEP enhancement could be found to single finger stimulation. In contrast, D123 stimulation induced less effective SAI in upper-limb muscles. MEP potentiation was recorded in some muscles to D123 stimulation. A significant difference between D2 and D123 stimulation was found in APB (ISIs = 30-50 ms) and FDI (ISIs = 40-50 ms) muscles, but not in forearm muscles. The effect to D23stimulation on MEP amplitude was intermediate between those to D2 and D123 stimulation. Our data suggest that motor excitability to cutaneous afferents may be influenced by the size of the receptive fields, this effect being the result of increasing convergence between hand afferents in the somatosensory system. These phenomena appear to be topographically arranged across the representation of upper-limb muscles. These findings may help to understand the functional significance of SAI in normal physiology and pathophysiology.