Rejected

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding of participants consulting healthcare due to mental illness or pain during follow-up. Regarding of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745).

Sleep disturbances are extremely common (40-86%) in children and adolescents, especially those with autism spectrum disorders (ASD) and are often among the first symptoms identified by parents at a very early stage of their child's development. These abnormalities are among the main parental concerns when having a child with ASD and have a significant impact on the quality of life of patients, their parents, and more broadly their siblings. Sleep disorders are essentially abnormalities of the sleep-wake rhythm – primarily sleep onset insomnia or nocturnal awakenings (with difficulty falling back to sleep). These disturbances can be accompanied by other sleep disorders, requiring notably a systematic elimination of the presence of a sleep apnea or restless legs syndrome – to ensure a personalized and efficient therapeutic approach. Physiologically, the determinants of these sleep disorders are poorly understood, even though several studies point to a significant decrease in melatonin synthesis in people with ASD. Melatonin is a hormone that facilitates falling asleep and maintaining sleep and is also involved in the endogenous synchronization of internal biological clocks. However, the causal factors of this decrease in melatonin synthesis are largely unknown, involving to a small extent the genes involved in melatonin synthesis pathway. The treatment of sleep disorders is relatively systematic: after eliminating other specific sleep disorders associated with the complaint of insomnia, as well as other possible associated comorbidities (such as seizures), a global and graduated therapeutic approach must be put in place. This treatment will be non-pharmacological as a first line, then pharmacological as a second line. A number of non-pharmacological treatment strategies for sleep disorders in typically developing children and adolescents, as well as those with ASD, have been shown to be effective. This treatment requires a combination of: 1) parental education to promote sleep development; 2) setting up bedtime rituals adapted to the child's age and particularities; 3) specific behavioral strategies including bedtime fading, gradual extinction and positive reinforcement of adapted behaviors. It is very essential that the parents are accompanied throughout this therapy. Sleep hygiene and behavioral care must also take into consideration the important role of the zeitgebers of sleep-wake rhythms, i.e. the external environmental factors involved in the synchronization of the biological clocks: regular exposure to light at adapted times, regular meal and wake-up times, social activities and times for going to school. The evidence for the effectiveness of behavioral interventions in the treatment of behavioral insomnia in the typical developmental child is strong, since 94% of children show clinically significant improvements in nighttime sleepiness and waking. By contrast, only about 25% of children with ASD are improved by an approach combining sleep hygiene and behavioral therapy. Melatonin has a special and prominent place in the drug management of sleep disorders associated with ASD. Several clinical trials have shown that melatonin is effective in treating sleep disorders in patients with ASD. This work led to the European Medicines Agency (EMA) granting marketing authorization in September 2018 for a sustained-release paediatric melatonin molecule (Slenyto®). This synthetic molecule is a prolonged release melatonin (PRM) which mimics the physiological pharmacokinetic and secretory characteristics of endogenous melatonin, having a very short blood half-life and prolonged secretion for several hours during the night. A recent study evaluated the efficacy and safety of pediatric PRM (mini-tablets) in 125 children, aged 2 to 17.5 years with mainly ASD. After 15 days on placebo, the children were randomized into two parallel groups, PRM or placebo in a double-blind design for 13 weeks. At endpoint, total sleep time was increased by an average of 57.5 minutes on PRM and only 9.14 minutes on placebo (P=0.034). This difference between the two groups was already significant after three weeks of treatment (P=0.006). Sleep latency was also improved in the PRM group (-39.6 minutes) compared to placebo (-12.51 minutes) (P=0.01). Consolidated sleep duration (uninterrupted by awakenings) was improved by 77.9 minutes for the PRM group and only 25.4 minutes for the placebo group (P<0.001). PRM was well tolerated, the most frequent side effects being headache and daytime drowsiness at the same level with PRM or placebo. In addition, the acceptability by the children for swallowing the mini-tablets was excellent (100% compliance). The efficacy and tolerability of PRM was maintained over the medium and long term in the open phase, over a total study duration of 2 years.

Cancer patients may have a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and abnormal secretion of cortisol. Increased cortisol levels have been associated with worse prognosis in patients with different types of tumors. Although anxiety and depression can trigger an abnormal cortisol secretion, little is known regarding the influence of these emotional disorders on HPA axis dysregulation in cancer patients when evaluating together with demographic, clinicopathological and biobehavioral variables. This cross-sectional study analyzed the pre-treatment plasma cortisol levels of 133 patients with oral squamous cell carcinoma (OSCC) and its association with demographic, clinicopathological, biobehavioral and psychological variables. Plasma cortisol levels were measured by electrochemiluminescence, and anxiety and depression symptoms were assessed using Beck Anxiety Inventory (BAI) and Depression (BDI), respectively. Demographic, clinicopathological and biobehavioral data were collected from patients' medical records. Results from multivariate analysis showed that the occurrence of cancer-induced pain was predictive for higher cortisol levels (OR = 5.388, p = 0.003). Men with OSCC were 4.5 times more likely to have higher plasma cortisol levels than women (OR = 4.472, p = 0.018). The effect of sex on cortisol concentrations was lost in the adjusted model for clinical staging (OR = 2.945, p = 0.116). The absence of chronic alcohol consumption history was a protective factor for highest hormone concentrations in oral cancer patients (OR = 0.104, p = 0.004). Anxiety symptoms measured by BAI as "hands trembling" (OR = 0.192, p = 0.016) and being "nervous" (OR = 0.207, p = 0.0004) were associated with lower cortisol levels. In contrast, the feeling of "fear of losing control" was a risk factor for highest hormone concentrations (OR = 6.508, p = 0.0004). The global score and specific symptoms of depression measured by the BDI were not predictive for plasma hormone levels (p > 0.05). Together, our results show that pain, alcohol consumption and feeling fear are independent factors for increased systemic cortisol levels in patients with oral cancer. Therefore, psychological intervention, as well as control of pain and alcohol consumption, should be considered to prevent the negative effects of cortisol secretion dysregulation in cancer patients.

Fibromyalgia and depression are frequently comorbid. We propose a hormonal system model in understanding the underlying endogenous opioid system dysregulation in fibromyalgia with the utilization of the cold pressor test (CPT) in clinical practice to monitor treatment response to low-dose naltrexone (LDN) and the subsequent remission of major depressive disorder by restoring opioid tone. A 60-year-old professional on permanent disability presented with refractory depression and chronic widespread pain after years of multiple failed medication trials. Rating scales confirmed severe depression, Hamilton Rating Scale for Depression (HAM-D) of 20, a short cold pressor test (CPT) time of 21 seconds, and a face pain scale (FPS) of 8/10. Physical examination assessing for fibromyalgia was diagnostic, with 18/18 positive tender points. LDN, a minor increase in trazodone, and transference-focused psychotherapy were employed. The patient's CPT time increased modestly. The patient achieved remission of both conditions in 10 weeks when both disorders were treated at once (FPS and HAM-D of zero), restoring the quality of life, relatedness, and motivation. Some fibromyalgia patients may achieve remission of comorbid depression with concomitant low-dose naltrexone (LDN) treatment that is widely used "off label" to treat pain. LDN is a promising alternative for the treatment of chronic pain in fibromyalgia with its safety profile, high tolerability, and absence of abuse potential. Our unique finding is that without successful LDN treatment of fibromyalgia, remission of depression may be unlikely.

Managing pain after thoracic surgery is crucial and the traditional methods have many adverse effects. We aimed to evaluate serratus anterior plane block (SAPB) and erector spinae plane block (ESPB) in acute pain control in thoracic cancer surgeries.

Background Anal fistula, or fistula-in-ano, is a chronic abnormal communication between the epithelialized surface of the anal canal and the perianal skin. Video-assisted anal fistula treatment (VAAFT) is a novel, minimally invasive, and sphincter-saving alternative to traditional seton use. This study aimed to determine the short-term and long-term outcomes of VAAFT compared with seton treatment. Material and methods This randomized control trial was conducted at the Department of Surgery, Services Hospital, Lahore, from August 2014 to July 2020. Patients were randomly assigned to either the VAAFT group or the seton group, and postoperative outcomes were assessed for up to three years. Results The study included 80 patients (64 men and 16 women) with a mean age of 39.1 ± 11.2 years. The most common type of fistula was a transsphincteric fistula (n=36, 45%). The mean duration of surgery was significantly longer in the VAAFT group (78.6 minutes) compared with the seton group (36.97 minutes; p=0.000). The mean pain score was significantly higher in the VAAFT group (4.22) compared to the seton group (2.82, p=0.000). The mean time to return to work was shorter in the VAAFT group (7.4 days) than in the seton group (9.2 days, p=0.000). The mean healing time was significantly shorter for patients treated with VAAFT (5.75 weeks) than for those treated with a seton (9.7 weeks; p=0.000). Fistula recurrence after one, two, or three years was not significantly different between groups, and neither group had incidences of anal incontinence. Conclusions VAAFT is associated with earlier healing time and earlier return to work than the traditional seton technique, with no significant difference in fistula recurrence. VAAFT is minimally invasive and, when used in patients where indicated, allows for a prompter return to routine life for the patients, which is an optimal outcome for both patients and physicians.

Programmed death-1 (PD-1) inhibitors have been approved and are currently widely used to treat lung cancer patients. However, comparative data on the adverse events (AEs) associated with different PD-1 inhibitors are very limited.

Chronic pain is one of the most common medical conditions in developed countries. The 2020 Italian National Report on Medicines shows how, in the last years, there was a light but constant increase in the prescription of pain medications. The purpose of our study was to assess the effects of long-term cannabis-based oil consumption on the distribution of patients with analgesics prescriptions for chronic pain in a Pain Medicine Unit in Northern Italy.

To translate and cross-culturally adapt the Back Beliefs Questionnaire (BBQ) and Pain Self-Efficacy Questionnaire (PSEQ) into Marathi, and to evaluate their clinimetric properties in a native Marathi speaking population with chronic low back pain.