farzad fatehi

The etiology of polyneuropathies varies in the pediatric population, where hereditary or metabolic disorders are far more common than in adults. However, treatable polyneuropathies, also prevalent in these settings, are those to prioritize. Moreover, diagnosing subacute and chronic symptoms in children can be challenging compared to adults. Therefore, selecting the best and most relevant laboratory investigations and paraclinical studies is critical. This taskcan be relatively challenging in countries with limited resources or insurance coverage. This study describe the various types of polyneuropathies found in children and their characteristics and suggest an algorithm for using the best laboratory tests in the context of the Iranian healthcare system.

Muscle biopsy is commonly used to diagnose inflammatory myopathies. We evaluated the ability of muscle ultrasound, a non-invasive and simple tool, to distinguish between healthy subjects and patients with inflammatory myopathy.

This study was conducted on 17 patients recently diagnosed with biopsy inflammatory myopathies (12 dermatomyositis, 5 polymyositis) compared with 17 age- and gender-matched healthy control adults. All patients underwent clinical assessments, including manual muscle testing, hand-held dynamometry, and muscle ultrasound evaluations, including thickness and echo intensity in predefined muscle groups. 

The disease duration was seven months (interquartile range: 3 to 11 months). Except for the biceps and gastrocnemius, patients’ muscles had significantly higher echo intensity and lower thickness than the control group. The echo intensity sum-score manifested the highest area under the curve compared to the sum-scores of other variables (echo intensity vs manual muscle testing: Area under curves-difference=0.18, P<0.01; echo intensity vs dynamometry: Area under curves-difference=0.14, P=0.02; echo intensity vs thickness: Area under curves-differences-difference=0.25, P<0.01). 

The echo intensity of muscles differed significantly between healthy individuals and patients with inflammatory myopathies and may serve as a useful diagnostic biomarker.

This retrospective cohort study was conducted to evaluate the efficacy and tolerance of rituximab (RTX) for the management of myasthenia gravis (MG).

This retrospective cross-sectional study was conducted on 61 patients with refractory and non-refractory MG who received RTX. The Myasthenia Gravis Activities of Daily Living (MG-ADL) profile was used to assess MG symptoms and their effects on daily activities at the start of RTX and in the last follow-up. The Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS) scale has been used as an outcome measure after treatment with RTX in the 12th month and the last follow-up.

The mean age of the patients was 40.31 ± 13.53 years (range: 15-78 years). Of 61 patients, eight (13.1%) were double seronegative, 29 (47.5%) had anti-acetylcholine receptor (AChR+) antibody, and 24 (39.3%) had anti-muscle-specific tyrosine kinase antibody (MuSK+). According to the mean rank table, the results of this study showed that the drug was more effective in improving the symptoms of MuSK+ patients compared to the other two groups (P = 0.006). The mean MG-ADL was 4.86 ± 1.83 before treatment and 1.51 ± 2.02 in the last follow-up visit. Paired t-test showed a significant association between MG-ADL before and after treatment in the last visit [t(55): 11.30, 95% confidence interval (CI): 2.79-3.99, P = 0.001)].

This retrospective study showed a considerable effect of RTX as induction therapy in patients with MG, especially those with MuSk+ MG.

Fatigue is one of the most frequent complaints in patients with motor neuron diseases (MNDs), with a significant impact on the quality of life (QOL). Current pharmacological or non-pharmacological treatments of fatigue in this population lack enough evidence to be applied in the clinical setting. Energy conservation strategies are one of the key interventions for fatigue management in chronic diseases. In the present study, we aimed to investigate the effect of applying these techniques in the fatigue management of patients with MND.

This randomized controlled trial (RCT) study was carried out on 28 patients with MND. Participants were randomly assigned to either the intervention or control group. In addition to routine treatment, patients in the intervention group participated in 3 weekly 1-hour energy conservation programs provided by an experienced occupational therapist. The Fatigue Severity Scale (FSS) score, 36-Item Short Form Survey (SF-36), and Canadian Occupational Performance Measure (COPM) were measured at baseline, immediately after the last intervention session, and one month later.

FSS and COPM significantly changed after the course in the intervention group (P < 0.001 and P = 0.001, respectively). Both FSS and COPM improved significantly toward the final assessment only in the intervention group. The SF-36 changes were not significant in either intervention or control group.

According to the findings of the present study, using energy conservation strategies could lead to better mid-term fatigue management and occupational performance improvement, but it did not improve QOL in patients with MND.

The 8-item myasthenia gravis activity of daily living (MG-ADL) questionnaire is a valid and reliable instrument for evaluating myasthenia gravis (MG)-associated disability. This study aims to assess its validity and reliability in the Iranian population.

A total number of 58 patients with MG were qualified for the examination. All 58 patients completed the Persian translation of 15-item Myasthenia Gravis Quality of Life (MG-QOL15) and MG-ADL questionnaires initially, and 30 filled out the MG-ADL questionnaire 2 to 4 weeks after the initial visit. Pearson correlation coefficient of questionnaires, internal consistency using Cronbach's alpha (α), and test-retest repeatability of the questionnaire were evaluated.

The Pearson correlation coefficient of Persian versions of MG-QOL and MG-ADL was 0.93 (P < 0.01). The Persian MG-ADL showed satisfactory internal consistency (Cronbach’s α = 0.89) and test-retest reliability (r = 0.99, P < 0.01).

The Persian MG-ADL is a valid and reliable questionnaire for the determination of activities of daily life in Iranian patients with MG.

Myasthenia gravis (MG) is an immune-mediated potentially treatable disease in which rapid diagnosis and proper treatment can control symptoms. Treatment should be individualized in each patient according to distribution (ocular or generalized) and severity of the weakness, antibody status, thymus pathology, patient comorbidities, and preferences. A group of Iranian neuromuscular specialists have written these recommendations to treat MG based on national conditions. Four of the authors performed an extensive literature review, including PubMed, EMBASE, and Google Scholar, from 1932 to 2020 before the central meeting to define headings and subheadings. The experts held a 2-day session where the primary drafts were discussed point by point. Primary algorithms for the management of MG patients were prepared in the panel discussion. After the panel, the discussions continued in virtual group discussions, and the prepared guideline was finalized after agreement and concordance between the panel members. Finally, a total of 71 expert recommendations were included. We attempted to develop a guideline based on Iran’s local requirements. We hope that these guidelines help healthcare professionals in proper treatment and follow-up of patients with MG.

Myasthenia gravis (MG) affects the neuromuscular transmission, causing fluctuating muscle weakness and fatigue. This study is carried out with the aim to study the electrophysiologic findings of different subtypes of MG referred to our center in Tehran, Iran. All patients with MG presenting to neurology department of Shariati Hospital, Tehran University of Medical Sciences were enrolled. Clinically, patients with MG were categorized as ocular vs. generalized. The acetylcholine receptor (Ach-R) and muscle-specific receptor tyrosine kinase (anti-MuSK) antibodies were performed. Repetitive Nerve Stimulation (RNS) was performed using the standard method, with supramaximal stimulation of muscles at the 3 Hz frequency by surface electrode at rest. Abductor pollicis brevis (APB) (median nerve), anconeus (radial nerve), trapezius (accessory nerve), and nasalis (facial nerve) muscles were studied in all patients. Single fiber electromyography (SFEMG) was performed by standard method. 196 seropositive patients with MG were included in the study. In electrophysiological studies, RNS was performed for 146 patients of Ach-R-Ab positive MG, with positive results in 110 patients. In addition, SFEMG was conducted for 8 patients with negative RNS, which resulted in 7 positive tests.  Among 23 patients with anti-MuSK-positive MG, RNS was performed for 16 patients, with positive results in 11 patients. The 5 remaining patients with negative RNS test were studied by SFEMG, 4 of whom had positive results. APB compound muscle action potential (CMAP) decrementation significantly correlated with Ach-R-Ab positive MG (P < 0.03). This finding can support the hypothesis that the selection of muscles in electrodignostic study would be important. The electrodiagnostic studies are a good and non-invasive diagnostic tool for MG, and a combination of different distal, proximal, and facial muscles can increase the overall sensitivity of the test.

Guillain-Barre Syndrome (GBS) is an autoimmune acute inflammatory demyelinating polyneuropathy usually elicited by an upper respiratory tract infection. Several studies reported GBS associated with Coronavirus Disease 2019 (COVID-19) infection. In this study, we described nine GBS patients following the COVID-19 vaccine.

In this study, nine patients were introduced from six referral centers for neuromuscular disorders in Iran between April 8 and June 20, 2021. Four patients received the Sputnik V, three patients received the Sinopharm, and two cases received the AstraZeneca vaccine. All patients were diagnosed with GBS evidenced by nerve conduction studies and/or cerebrospinal fluid analysis.

The median age of the patients was 54.22 years (ranged 26-87 years), and seven patients were male. The patients were treated with Intravenous Immunoglobulin (IVIg) or Plasma Exchange (PLEX). All patients were discharged with some improvements.

The link between the COVID-19 vaccine and GBS is not well understood. Given the prevalence of GBS over the population, this association may be coincidental; therefore, more studies are needed to investigate a causal relationship.

It seems that the incidence of Guillain-Barré syndrome (GBS) has seasonal trends depending on weather as well as environmental and demographic factors such as upper respiratory tract infection (URI). The aim of this study was to evaluate seasonality of GBS and its electrophysiological subtypes.

In this cross-sectional study, the records of all admitted patients to all wards of Dr. Shariati Hospital from March 2009 to March 2019 according to ICD-10 codes for GBS and other similar neuropathies were investigated and 87 patients were registered based on fulfillment of Brighton criteria and symptom onset during the recent 4 weeks. Statistical analysis was performed by IBM SPSS version 20. A p-value < 0.05 was considered statistically significant.

Most of the patients (63.2%, n=55) were men. The mean age of them was 49.1±19.2 years, and 41.3% (n=36) and 10.3% (n=9) participants had recent URI and gastrointestinal infection, respectively. The frequency of GBS in different seasons was 35.6% (n=31) patients in the winter, 27.6% (n=24) in the autumn, 19.6% (n=17) in the spring, and 17.2% (n=15) in the summer. The most frequent electrophysiological subtype was acute inflammatory demyelinating polyneuropathy (AIDP) in all seasons. The most common GBS disability score was 1.

The highest and the lowest occurrence was seen in the winter and summer, respectively. AIDP was the most common electrophysiological subtype in all seasons. More studies are suggested to evaluate other aspects of GBS on more details.

Caregivers of patients with amyotrophic lateral sclerosis (ALS) may suffer from anxiety, depression, and reduced quality of life (QoL). Our goal was to evaluate the QoL and mood disorders in caregivers and their correlation with the patients' demographic, physical, and mental conditions.

We analyzed data from 39 patients with ALS and their caregivers. Patients completed questionnaires of anxiety assessed by Generalised Anxiety Disorder Assessment (GAD-7), depression using the Beck Depression Inventory-II (BDI-II), and QoL via 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40). Physical impairment was also measured in the patients using the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R). Caregivers were also assessed by BDI-II, GAD-7, and 36-item Short-Form Health Survey questionnaire (SF-36).

The prevalence of depression and anxiety in the patients was 82.1% and 71.8%, respectively. Caregivers also had higher rates of anxiety and depression and lower levels of QoL in comparison with the general population (anxiety: 66.7%, depression:  43.6%). Depression and anxiety were considerably associated with worsened QoL in the caregivers. None of the demographic, physical, or mental characteristics of patients with ALS were related to either mood status or QoL of the caregiver population.

Caregivers experience higher rates of anxiety and depression and lower QoL in comparison with the general population. The severity of mood disorders is inversely associated with the physical and mental domains of caregivers' QoL. Nonetheless, QoL in the caregivers is not affected by the physical or mental disability of the patients.

Myasthenia gravis (MG) is a chronic neuromuscular disease, which physically and mentally affects the patient’s life, with depression being one of the most important psychological complications in these patients. This study aims to investigate the prevalence of depression and its associated factors in a group of Iranian patients with MG. This was a cross-sectional study in which consecutive patients diagnosed with MG who referred to two referral neuromuscular clinics affiliated to the Tehran University of Medical Sciences, Tehran, Iran, were evaluated for eligibility. Patients with a previously known psychiatric disorder and those with a family history of mental disorders were excluded. Eligible patients were interviewed and screened for depression through the administration of the Hamilton Depression Rating Scale (HDRS) and the Iranian version of Beck Depression Inventory-II (BDI-II). A total of 62 patients participated in this study. The total prevalence of depression according to the HDRS and BDI-II scores was 64.5% and 53.2%, respectively. The mild depression was the most frequent level of depression based on the HDRS (33.9%) and BDI-II (22.6%) scores. None of the variables, including age, sex, duration of the disease, and dosages of prednisolone, pyridostigmine, and azathioprine, were correlated with the severity of depression. The number of academic years was the only variable associated with the lower HDRS score (P = 0.037). Based on the current findings, depression was common among Iranian patients with MG. The severity of depressive symptoms was unrelated to age, sex, marital status, duration of the disease, the daily dosage of medications, and thymectomy status. Further investigations are needed to reveal the exact burden of depression in patients with MG and address the importance of preventive interventions for improving the quality of life (QOL) in these patients.

Cerebral venous sinus thrombosis (CVST) causes significant problems for patients in the working age and may therefore negatively affect their quality of life (QOL). In the present study, we sought to evaluate the QOL and its predictors in subjects with CVST.

This observational, prospective study investigated several outcomes of 56 CVST patients after thrombosis onset. Demographic characteristics, medical history, neurological signs and symptoms during hospitalization, and the employment status of the patients were retrospectively collected. Stroke-related functional scales, including the modified Rankin Scale (mRS) and Barthel Index (BI) were employed. For physical and mental aspects of the QOL, we used the validated Persian version of the Stroke Specific Quality of Life (SS-QOL) scale.

The physical and functional outcomes in the long-term were promising according to mRS and BI tools, as well as the improved rate of return to work. Mental domains of the SS-QOL, such as energy and personality represented the lowest scores. According to the multiple linear regression analysis, lower mRS score, and longer time interval between CVST onset and interview were associated with higher physical function of the patients while their better mental function was correlated with lower mRS score and thrombosis in merely one cerebral venous.

CVST patients experience an acceptable alleviation of the primary physical disabilities, while residual symptoms, mostly in psychologic/mental domains, impair their QOL

Few studies have reported the association of Guillain-Barre syndrome (GBS) and coronavirus disease-2019 (COVID-19) infection. In this study, we reported GBS in six patients infected with COVID-19 and reviewed all existing literature about GBS in association with COVID-19.

This study was performed in three referral centers of COVID-19 in Iran, and six patients with the diagnosis of GBS were enrolled. Patients enrolled in the study with acute progressive weakness according to the demyelinating or axonal variant of GBS, according to Uncini's criteria.

Four of our patients had axonal polyneuropathy, two patients had demyelinating polyneuropathy, and one patient required mechanical ventilation. All our patients had a favorable response to treatment. In one patient, the GBS symptoms recurred four months after the first episode.

Limited case reports suggest a possible association between GBS and COVID-19. Such associations may be an incidental concurrence or a real cause-and-effect linkage; however, more patients with epidemiological studies are necessary to support a causal relationship.

Alzheimer dementia as the most common cause of dementia is a chronic, progressive, irreversible and incurable disease. The second most common cause of dementia after Alzheimer is vascular dementia. One of the systems involved in dementia is the visuospatial system and visual evoked potential (VEP) can be one of the diagnostic methods for this disease. Therefore, the present study aims to compare visual evoked potential changes in Alzheimer dementia, vascular dementia and patients with minimally conscious impairment (MCI) with healthy people.

A case-control study was performed on referred clients to Shariati Hospital, Tehran, Iran, from April 2015 to September 2016. Patients with cognitive impairment went through Montreal cognitive assessment (MOCA) test and divided into three groups of Alzheimer dementia, vascular dementia and patients with minimally conscious impairment. Subjects with normal cognition were included in the control group. The visual evoked potential test was performed on all participants in two  Methods pattern shift visual evoked potential (Ps-VEP) and flash visual evoked potential (f-VEP) and results were compared between groups.

Forty patients were studied in four groups (three patient groups and one control group). 70 percent in Alzheimer group and 60 percent in vascular dementia group had abnormal pattern shift visual evoked potential. Only in Alzheimer group visual evoked potential P100 latency was significantly higher than control group and in other groups, there was no significant difference. Also there was no significant difference between groups in the study of flash visual evoked potential variables including P1, N2, P2 and N3.

This study showed that only Alzheimer was associated with a significant increase in visual evoked potential P100 latency. On the other hand the other hand, there was no significant difference in flash visual evoked potential variables including P1, N2, P2 and N3 between different groups which shows that flash visual evoked potential cannot differentiate between Alzheimer dementia, vascular dementia, patients with minimally conscious impairment and normal people.

Burnout is prevalent in several physicians that may undermine the progress nad performance of physicians, reduced accessibility of patients to physicians, and patients’ safety. This study endeavored to determine burnout, anxiety, and depression in the specialists and attending physicians of one of the educational hospitals of Tehran University of Medical Sciences.

This cross-sectional study conducted in the academic year 2018. One-hundred twenty-three physicians filled the Malach Burnout Inventory (MBI) questionnaire, Hospital Anxiety, and Depression Survey (HADS) questionnaires.

Forty-four physicians (35.8%) had some levels of burnout. Severe Emotional Exhaustion (EE) was seen in 18 physicians (14.6%). Likewise, severe Depersonalization (DP) in 12 physicians (9.8%), and severe dysfunction in Personal Accomplishment (PA) were seen in 33 physicians (26.8%). Four physicians (3%) had an abnormal level of anxiety, and 32 subjects (26%) were in the borderline zone. Four (3.2%) had abnormal depression, and 12 subjects (9.8%) had a borderline depression. There was a significant relationship between attending teacher type (i.e., educational, research, or treatment) and dysfunction of personal accomplishment (X2 = 12.24, p = 0.02). Moreover, anxiety was higher in non-married physicians (p = 0.046); anxiety was higher in part-time physicians as well (p = 0.03).

Findings revealed that burnout is an essential issue in attending physicians of educational hospitals. Identifying and managing burnout and its adverse effects could eliminate further health complications for the physicians and under-treating patients.

Neuromuscular disorders affect physical and mental aspects of a patient and in other words alter the patients’ quality of life (QOL). In the present study, we investigated the validity and reliability of the Persian version of Individualized Neuromuscular QOL (INQOL) to provide a better insight into patients’ QOL.

Original version of the INQOL was translated backward and then forward. The resultant Persian version and a standard questionnaire, 36-Item Short Form Health Survey (SF-36), were then given to 83 participants with neuromuscular disorders. Internal consistency, known-group validity, concurrent validity, and test-retest reliability were assessed.

The scores of matched sections for QOL in the two questionnaires were favorably correlated (P < 0.05). Correlation between test and retest scores was also significant (P < 0.05). Moreover, the Cronbach’s alpha of 0.82 was representative of robust internal consistency between INQOL covering sections.

The Persian version of the INQOL can be used in clinical and research practice to detect changes in QOL which are related to neuromuscular disorders, due to its favorably reliable and valid characteristics.

Motor unit number index (MUNIX) is an electrophysiological technique to give an estimate of functioning motor neurons in a muscle. For any given neurophysiological technique for the use in clinical or research studies, reproducibility between different operators and in a single operator in different times is one of the most important qualities, which must be evaluated and approved by different examiners and centers. After its introduction, testing the reproducibility of MUNIX was the aim of many studies to show this quality of the technique. In this review, we aimed to summarize all the studies, which have been performed up to now to approve MUNIX reproducibility in amyotrophic lateral sclerosis comparing healthy individuals.

Burnout is a constellation of emotional exhaustion, depersonalization and low sense of personal accomplishment that frequently occurs in people-related professionals such as healthcare personnel. In this cross-sectional study, we proposed to evaluate burnout in one of the tertiary hospitals of Tehran University of medical sciences across different medical specialties.  Maslach Burnout Inventory (MBI) was handed out personally to 204 residents. The demographic questionnaire included age, gender, marital status, the level of residency, the field of residency. We categorized all specialties into 3 subgroups of surgery, internal medicine and paraclinical. Mean age of participants (n = 204) was 31.1 ± 4.6, and 127 (62.3%) subjects were female. Totally, 188 residents (92.2%) were burnt-out. For emotional exhaustion, 173 (84.8%) residents had a moderate or high score, for depersonalization 197 (96.6%) residents, and for low personal accomplishment 182 (89.2%). Between two genders, there was no significant difference of emotional exhaustion score (t = 0.07, p = 0.60) and personal accomplishment (t = -0.59, p = 0.15); however, depersonalization was significantly more prevalent in male reseidents (females: 21.9 ± 5.5, males: 20.6 ± 7.1; t = 1.47, p = 0.04). Regarding marital status, residency year and different specialties, we found no significant difference between male and female subjects. In this study, burnout was very frequent in residents of all groups including different genders, residency years, marital status, and specialties. Given the very high level of burnout in our residents, it is essential to conduct further studies to find the possible causes of burnout and to look for ways to alleviate the situation.

Myasthenia gravis (MG) is an autoimmune disease affecting acetylcholine postsynaptic receptor of voluntary muscles. Thymectomy is done in these patients and is a mainstay in the treatment of MG; however, the long-term result of surgery is still controversial. This study dealt with the investigation of the results of thymectomy in treatment, recovery and control of the symptoms of these patients.

This study was performed through a retrospective method in patients suffering from MG who underwent trans-sternal thymectomy between 2011 and 2016. We conducted thymectomy, excision of mediastinal mass and contents of tissues between the right and left phrenic nerves for all patients. Then, the effect of various variables including age, sex, time interval between onset of disease and surgery, thymus pathology and the dosage of drug on clinical response after surgery was determined using various statistical tests.

47 patients including 26 men and 21 women with the mean age of 33.0 ± 4.6 years have been investigated. The mean age of patients was 36.2 and 29.7 in men and women respectively (P = 0.041). Spiral chest computed tomography (CT) scan was present in 47 patients demonstrating mediastinal mass in 40 (85.1%) patients. Also, our pathological results showed thymic cells in aortopulmonary window contents of 4 patients. According to the results, the younger age of patients at the time of surgery, shorter time between diagnosis and thymectomy, being a woman and non-thymoma pathology were along with better clinical outcomes after thymectomy.

Our study shows better clinical results of thymectomy in patients with normal chest CT scan and normal or atrophic thymus in pathologic reports. Generally, it seems that performing thymectomy in a shorter time interval after diagnosis of MG is beneficial. Moreover, in MG patients who do not suffer from thymoma, it is along with positive results.

This paper introduces an inequality on vectors in $\mathbb{R}^n$ which compares vectors in $\mathbb{R}^n$ based on the $p$-norm of their projections on $\mathbb{R}^k$ ($k\leq n$).
For $p>0$, we say $x$ is $d$-projectionally less than or equal to $y$ with respect to $p$-norm if $\sum_{i=1}^k\vert x_i\vert^p$ is less than or equal to $ \sum_{i=1}^k\vert y_i\vert^p$, for every $d\leq k\leq n$. For a relation $\sim$ on a set $X$, we say a map $f:X \rightarrow X$ is a preserver of that relation, if $x\sim y$ implies $f(x)\sim f(y)$, for every $x,y\in X$. All the linear maps that preserve $d$-projectional equality and inequality are characterized in this paper.

The widespread use of internet has caused new psychological, social, and educational problems for the students. The aim of this study was to examine the quality of life in medical students who suffer from internet addiction. This cross-sectional survey was carried out in Tehran University of Medical Sciences, and a total of 174 fourth-to seventh-year undergraduate medical students were enrolled. The quality of life was assessed by WHOQOL-BREF questionnaire which covers four domains of physical health, psychological, social relationships, and the environment. For assessing internet addiction, we used Internet Addiction Test (IAT) of Young. The students with IAT score higher than 50 were considered as addicted. For evaluating academic performance, the students were requested to report their grade point average (GPA). The mean IA score (±SD) was 34.13±12.76. Twenty-eight students (16.90%) had IAT score above 50. The mean quality of life score in internet addicted group was 54.97±11.38 versus 61.65±11.21 in normal group (P=0.005). Furthermore, there was a negative correlation between IA score and physical domain (r=-0.18, P=0.02); psychological domain (r=-0.35, P=0.000); and social relation domain (r=-0.26, P=0.001). Mean GPA was significantly lower in the addicted group. It seems that quality of life is lower in the internet addicted medical students; moreover, such students academically perform poorer in comparison with non-addicts. Since internet addiction is increasing at a rapid pace which may provoke considerable academic, psychological and social implications; as a result, it may require screening programs to the immediate finding of such problem to give consultations to prevent unwanted complications.