Background: Hygiene is a part of WASH Strategy which is associated with better health outcomes across the globe. Personal Hygiene practices are essential for prevention of communicable diseases like Pneumonia, Diarrhea, Influenza, COVID etc. Personal Hygiene includes Hand Hygiene, Menstrual Hygiene& Daily routine activities. Objective: To assess the knowledge and practices of population in Shimla city in relation to Personal Hygiene promotion practices. Methodology: Population based house to house survey in randomly selected households of all 34 wards using a semi structured questionnaire. Results: A total of 640 households were surveyed.Majority were (71.7%) females, Hindus (97%)& literate.Around 38% of the study participants had perception that cleaning house & household items, while 50% mopping, dusting & 41.7% daily bathing, brushing teeth, trimming nailswere the practicesto maintain good Hygiene. Almost every participant washes his hands after coming from market, 99.8% before eating, 99.8% before preparation of food. Around 71% clean the seat of public toilet before use, 17% wear trouserswhereas 15% shirt, 6% inner wear for 2 days or more in a row.13.6% of the study participants were not washing their hands at workplace. Around 10% of the study participants were still not using soap for Handwashing. Around 6% still use disposable clothes, 6% reusable cloth & 2% use cotton during menstruation. Conclusions:Most PersonalHygiene practices were found to be satisfactory in our study group. Handwashing at Workplace was still not being followed especially during COVID times also. Women were still using materials other than sanitary pads during menstruation. There are plenty who were not using both soap and water for handwashing which needs intensive IEC for benefits of handwashing. Each and every woman need to be aware of usage and also access to economical disposable sanitary pads.

Background: Menstruation or menses is the natural bodily process of releasing blood and associated matter from the uterus through the vagina as part of the menstrual cycle. Menstrual practices are influenced by taboos and socio-cultural restrictions for women. Material & method: population based Cross-sectional study involving 32 wards of Shimla city. Sampling unit was household in MC Shimla. Sample size estimated 640 stratified random sampling was done for selection of sampling unit.  Results: Perception regarding menstrual hygiene was considered by 71.4% of the respondents and 24.1% as important & only 4.5 % regarded it as slightly Regarding practices of menstrual hygiene 88.4% respondents use disposable pad for menstrual hygiene and 48.59 dispose off them in household waste. Conclusion: Menstrual hygiene perception was regarded as very important by majority of respondent as well as good practices were followed by majority.

Background: Waste poses a threat to public health and environment if it is not stored,collected and disposed of properly.The perception of waste as an unwanted with no intrinsic value has dominated attitudes towards disposal. Material and methodology: This survey was done by the from July to October 2020  to establish a baseline of the current knowledge, attitudes and behavior of population in Shimla city in relation to solid and liquid waste management and other health-related practices, to Identify specific areas where intervention is necessary to increase knowledge or lead to specific behavioural changes for better health. Results: A total of 640 households were selected for the survey. 74.7% respondents were considered solid waste management as very important. 63.59%respondents were comfortable with sanitation situation of Shimla city. 61.1 %respondents were satisfied with the waste disposal facility of Shimla city. 63.3 %respondents were satisfied with the door to door collection of waste facility of Shimla city. 96.6% had drainage system for liquid waste disposal and 95.5% had connection to waste water network.52.8% always separate their garbage, 88.3% separate dry and wet waste, 98.3% always covered their dustbin, 96.1% using door to door collection of waste service, 24.5% had abnormal presence of vectors in their households, among them 45.22 were mosquitoes.63% respondents ever seen a sanitation message, 8.6% had community health worker visit in their household informing them about sanitation and hygiene, 6.1% had ever had community meetings n sanitation and 50.5 % had ever seen message on solid waste management issues.88.4% respondents use disposable pad for menstrual hygiene and 48.59 dispose off them in household waste. Conclusion: To achieve the goal in waste management practices awareness,education and importance of safe refuse disposal program should be initiated for the public. IEC activities must be planned on waste disposal.

Hand washing is the single most effective and inexpensive way to prevent diarrhoea and acute respiratory infections, as automatic behaviour performed in homes, schools, and communities worldwide. Thus this study was carried out to see the perception and practices of hand washing in a hilly city of Shimla. Objectives of the study- To assess the perception and practices of hand washing in Shimla city. Material and methods- it is a population based cross sectional study involving all 34 wards of Shimla city. Sampling unit was households in the Municipal corporation area of Shimla city. Sample size is estimated to be 640 expecting 50% of households having adequate knowledge of WASH and solid waste management with 95% level of confidence, design effect 1.5 and 5% confidence interval and non-response rate of 5%.Stratified random Sampling was done for the selection of Households. The data collectors obtained consent from the head of Family and Pretested Standardized Questionnaire administered in every selected household. Results- Perception of hand washing was regarded as very important by 76% of the respondents and 21% regarded it as important and only 3% regarded it as slightly important. Regarding practices of hand washing 97.8% respondents wash their hands 5 or more times in a day, 79.22% respondents used water and soap for hand washing, 75.6% used clean towel after handwashing,74.7% spent 15-20 second for hand wash, 70.9% own a sanitizer, 18.8% respondent sometimes running out of water for hand wash. Conclusion- we found that hand washing was practiced by all respondents with good practices in terms of duration followed by majority of the city’s residents.

Background: Safe and Safe and readily available water is one of the important felt needs in public health. Better management of water resources and improved supply helps to boost economic growth. Depleting ground water table, deteriorating ground water, increasing population quality are threatening the sustainability of both urban and rural water supply, so this study was done to analyze water supply and consumption pattern. Material and Methods: Cross- sectional study done from July 2020 to October 2020 by residents and medical social workers of department of Community Medicine. Stratified random sampling used for selection of households. Results: 93.1% had pipe line water connection to their households, 49.2% of respondent had more than 35 liters of water per capita per day in their households, about 93.8% respondents were satisfied with the quality of water supply and 65.2% limit water usage to ensure they have sufficient water Conclusion: Majority of people are satisfied with the quality and quantity of water provided from municipal corporation Shimla.

Background: Water sanitation & Hygiene facilities are basic requirement of each individual to live socially & economically productive life as per WHO approximately 8,27000 people in low- and Middle-income countries die as a result of inadequate water, sanitation, & hygiene each year. Universal access to a basic drinking water source appears within reach, but universal access to basic sanitation will require additional efforts. This study was done to assess prevailing situation and to identify the areas of intervention. Material and Methods: Cross-sectional KAP study done by Residents & Medical Social Workers After proper training during July 2020-september 2020. Results: 97.2 % of respondents had toilet facility , 2.5% use community toilets while 0.8% went for open defecation,95.94 had all toilets functional, 4.7% had toilet related problems like flooding of toilets,17.19% share toilets with other households, and 99.2% had never went for open defecation, 92.8% had bathing facility at their homes, among them 98.4% had drainage system in the bathroom.96.3% had separate kitchen in their household,  among them 94.8 % had smoke outlet in their kitchen. 94.1% respondent used cooking gas as fuel. Conclusion: Situation of kitchen, toilet& bathroom has improved over the years compared to NFHS 4 data, Continuous efforts to sustain existing facilities and to widen the area of coverage to 100% population.

BackgroundNatural water resources in terms of bowris and handpumps are of great importance for habitants living in and around the nearby area. It can serve as a source of water borne infectious diseases like outbreaks of Hepatitia A and E. So, there is an utmost need to know the physiochemical and biological parameters of it. Material & Methods:It was a cross sectional survey to assess the quality of water consumption from natural sources done by  department of Community Medicine from July 2020 to October 2020.Results:Means of parameters for bowris and handpumps are parameter for ph = 6.69±1.59, Turbidity = 3.21NTU±4.91, Chloride = 85.38±70.69ppm, Nitrates = .488mg±2.15/L, Fluoride = .548±.14mg/L, Iron = 0.08±.12mg/L, Hardness = 177±55.63mg/L, Residual Chlorine = 0.07±.04ppm. Means of parameter for handpump areph = 7.4±.78, Turbidity = 8.53±6.02NTU, Chloride = 78.13±87.94ppm, Nitrates = 4.34±11.77mg/L, Fluoride = .540±.15mg/L, Iron = 0.160.14mg/L, Hardness = 178±47.48mg/L, Residual Chlorine = 0.00ppm.39 bowris out of 42 and 11 handpumps out of 15 turned out to be bacteriologically positive.Conclusion:Continuous  survelliance need to be done on these natural water as Shimla being a hepatitis prone area it’s a must for the situation.

With interest we read the article by Kerr et al. about the diagnostic work-up of 36 patients with confirmed mitochondrial disorder(MID) (MID-group) and 80 patients with suspected MID but yet unconfirmed diagnosis (NO-group) by means of next generation sequencing(NGS).[1] In the MID-group MID was diagnosed upon a traditional approach.[1] The authors found that bigenomic sequencing(BGS) confirmed the diagnosis in 13/36 MID-patients and detected new pathogenic variants in 3 other MID-patients. In the NO-group one new MID-patient was identified by NGS.[1] We have the following concerns.

We do not agree with the conclusions that bigenomic sequencing(BGS), consisting of nWES and optimised mtDNA analysis, should be the first step in investigating suspected MIDs.[1] BGS confirmed an already known diagnosis in only 13/36 patients, and provided a new diagnosis in only 1/80 patients with suspected MID. How do the authors explain that 20 patients with a definite MID had a negative genetic test. This is unusual particularly as the diagnosis MID was supported by different methods. 

Furthermore, we should know why only 36 of the 115 patients with confirmed MID underwent NGS. Was this due to pecuniary reasons, due to absent consent, or unavailability of invited patients? 

Of the 390 patients referred for suspected MID according to figure 1, 69 had another diagnosis according to table 1. However, “unclassified neurodegenerative disease” is no “other” diagnosis. Furthermore, it is surprising that sepsis, juvenile osteoporosis, and bronchogenic lung carcinoma, as listed in table 2, initially suggested MID. 

In table 2 the authors use the term “bilateral bulbar neurosis” [1]. We assume that this in an error and actually should be “bilateral retrobulbar optic neuritis”.

Overall, diagnosing MIDs should be based not only on NGS but also on traditional procedures. NGS not only provides false positive and false negative results but still has a low sensitivity.

With interest we read the article by Forcelledo et al. about a 50 years-old female with MELAS due to the variant m.3243A>G who predominantly manifested with intestinal pseudo-obstruction (IPO), requiring cecostomy, and lastly colectomy [1]. The further course was rapidly progressive and the patient deceased from multiorgan failure [1]. We have the following comments and concerns.

MELAS is usually a multisystem disorder affecting not only the brain, nerves, and muscles but also the ears, eyes, endocrine organs, heart, gastro-intestinal tract, kidneys, bone marrow, and the skin [2]. We should be told in which organs the reported patient manifested clinically in addition to the gastro-intestinal tract, the brain and the kidneys. Knowing the number of organs/tissues affected at onset or becoming affected during the progression is crucial for assessing the speed of progression and the outcome.

Gastro-intestinal manifestations of MELAS are well appreciated [3] and may not only include IPO, bloating, vomiting, diarrhoea, constipation, gastro-intestinal reflux, distension, but also poor appetite, sicca syndrome, gastro-intestinal sphincter dysfunction, postprandial abdominal pain, pancreatitis, hepatopathy, pancreatic cysts, diverticulosis, recurrent bowel perforations with intra-abdominal abscesses, and pneumatosis coli [3].

Interestingly, the second episode of IPO was associated with a stroke-like episode (SLE) [4]. We should be told about the clinical manifestations of this SLE and if also other episodes of IPO were associated with SLEs. Recently, it has been suspected that episodes of IPO may trigger the occurrence of SLEs [5]. Thus, we should know if other IPO episodes were also associated with SLE and if cerebral MRI showed the typical features of a stroke-like lesion (SLL) [6]. Given the fact that IPO is associated with massive stress, it is conceivable that IPO indeed triggers a SLE. 

A shortcoming of the study is that the heteroplasmy rate of the m.3243A>G variant has not been provided. Knowing heteroplasmy rates in various tissues is crucial to assess the clinical course and outcome of a patient. We should also be informed if the mtDNA copy number was reduced or normal.

Since the m.3243A>G variant is transmitted via the maternal line in 75% of the patients, we should know if the family history was positive for mitochondrial disorder (MID), in particular MELAS. Of particular interest is the mother and other first-degree relatives. We should be told if any of the first-degree relatives carried the m.3243A>G variant or manifested with a similar or variant phenotype or if the variant had occurred spontaneously in the index patient.

Overall, this interesting case has a number of shortcomings, which should be met before drawing conclusions as those provided. There is a need to report heteroplasmy rates, degree of multiorgan involvement, clinical and genetic status of first-degree relatives, and clinical manifestations of the SLE. MELAS with rare phenotypes should be thoroughly investigated and extensively described to capture the entire phenotypic spectrum of this fascinating disease. It is conceivable that IPO triggers SLEs.

We appreciated to read the article by Cohen et al. about a 45yo male suspected of having developed Parkinson’s disease (PD) due to infection with SARS-CoV-2 [1]. It was concluded that SARS-CoV-2 may trigger the development of PD [1]. We have the following comments and concerns.

Strong arguments against a causal relation between SARS-CoV-2 and PD in the index patient are that the cerebro-spinal fluid (CSF) was negative for virus-RNA and that no antibodies against the virus were detected in the CSF, Thus, it is unlikely that SARS-CoV-2 ever had entered the CSF space. The main pathways considered via which the virus enters the brain include retrograde axonal migration after invagination of SARS-CoV-2 at taste buds or olfactory epithelial cell membranes, hematogenic spread of the virus to the brain, or transmigration via the blood brain barrier (BBB) by using immune cells as transport vehicles [2]. Furthermore, there is little evidence for SARS-CoV-2 in dopaminergic neurons of the substantia nigra. Only in a single study it is mentioned that SARS-CoV-2 may enter dopaminergic neurons [3] and only a single additional case of PD due to SARS-CoV-2 has been reported [4]. Whether PD was triggered by antibodies against virus antigens which cross-reacted with cell membrane components of dopaminergic neurons, remains speculative.

More likely than the infection with SARS-CoV-2 is labetalol having triggered the development of PD. Labetalol is a combined alpha- and beta-blocker and from beta-blockers, particularly propranolol, it is well-known that they increase the risk of developing PD [5]. Also amlodipine has been reported to cause PD [6]. Since various other drugs may trigger the development of PD as well, we should know the entire medication the patient received during hospitalisation. Patients with Sjögren syndrome have an increased risk of developing PD, particularly when treated with chloroquine, a drug frequently given to COVID-19 patients. Thus, we should know if the patient received chloroquine.

Overall, the report by Cohen et al. has some shortcomings and raises doubts about the alleged causal relation between SARS-CoV-2 and PD. As long as there are not more reports suggesting that SARS-CoV-2 triggers the development of PD, as long as there are no indications from prospective studies for a causal relation between SARS-CoV-2 and PD, and as long as there is no increase in the prevalence/incidence of PD since the outbreak of the pandemic despite >30 Mill infected subjects worldwide, a causal relation between SARS-CoV-2 remains speculative.

With interest we read the review article by Margolin et al. about the causes, work-up, and treatment options of diplopia (double vision) [1]. Diplopia may be due to affection of one or both eyes. Diplopia may be permanent or transient. The author concluded that “careful history taking and basic examination skills described in the article should allow a neurologist to make an accurate diagnosis in most cases” [1]. We have the following comments and concerns.

The main shortcoming of the study is that a number of disorders manifesting with diplopia were not included in this review. The most prevalent among these disorders is myopathy of extra-ocular muscle. Myopathy is a major differential diagnosis of diplopia, which may or may not be associated with concomitant ptosis. Diplopia may occur in primary (genetic) and secondary (acquired) myopathies. 

Among the muscular dystrophies, diplopia has been particularly reported in myotonic dystrophy [2] and oculo-pharyngeal muscular dystrophy [3]. Among the congenital myopathies diplopia has been most frequently described in nemaline myopathy [4]. The most prevalent myopathic cause of diplopia is metabolic myopathy. Among the metabolic myopathies, double vision is a hallmark of mitochondrial disorders (MIDs). Diplopia occurs in syndromic and non-syndromic MIDs. Among the syndromic MIDs, diplopia occurs most frequently in patients with progressive external ophthalmoplegia (PEO), which may be due to single or multiple mtDNA deletions, mtDNA depletion, or due to point mutations in nDNA or mtDNA located genes encoding for mitochondrial proteins. Diplopia is also a frequent feature of Kearns-Sayre syndrome or Leigh syndrome. Among the hereditary transmission disorders (congenital myasthenic syndromes) diplopia has been reported in patients carrying rapsyn mutations [5]. Among the channelopathies. paramyotonia congenita may manifest with double vision.

Among the secondary myopathies diplopia may occur in sarcoid orbital myopathy [6]. Double vision may be a dominant manifestation of oculomotor, ocular neuromyotonia [7]. Double vision can be a manifestation of drug-induced myopathy, such as PD-1 myopathy which is due to programmed death inhibitors [8]. Other drugs causing diplopia include tremelimumab, durvalumab [9], or isotrenoin. 

Various subtypes of Guillain-Barre syndrome (GBS), particularly Miller- Fisher syndrome (MFS) may manifest with double vision. More rarely, acute, inflammatory, demyelinating polyneuropathy (AIDP), acute, motor, axonal neuropathy (AMAN), or Bickerstaff encephalitis may manifest   with   double   vision.   Diplopia   may   be   a   manifestation   of neuroborreliosis. Not to forget, thiamine deficiency, manifesting as Wernicke encephalopathy or beri beri, may present with double vision among other typical manifestations [10].

The author also did not consider double vision due to orbital compartment syndrome due to carotid cavernous fistula. Primary or secondary orbital tumours should be also considered as rare causes of diplopia. Neurologist and ophthalmologist should also consider benign or malign neoplasms of the cerebrum as causes of diplopia. Diplopia has been particularly reported in association with pituitary adenoma, but also in association with lipoma or lymphoma. 

Overall, work-up for diplopia should include search for primary and secondary myopathy, for immune-mediated neuropathies, for  thiamine   deficiency,  benig and malign neoplasms, traumatic brain injury, and for orbital tumours. Work-up for these neglected causes of diplopia is crucial as some of them respond favourable to treatment. Early treatment may result in a better outcome than delayed application of treatment.

With interest we read the article by Norose et al. about the histological and immune-histological findings of islet cells in two patients with mitochondrial diabetes [1]. One patient was diagnosed with mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome due to the variant m.3243A>G (patient-1) and the second patient was diagnosed with myoclonic epilepsy with ragged-red fibers (MERRF) syndrome due to the variant m.8344A>G [1]. Patient-1 required insulin, whereas patient-2 did not require any anti-diabetic treatment [1]. It was concluded that the severity of diabetes correlates with the severity of the histological and immune-histological findings on autopsy [1]. We have the following comments and concerns.

We do not agree with the conclusions that the different histological findings in the two patients correlate with the severity of diabetes. First, MELAS and MERRF are completely different disorders, why simply the genotype can explain the difference between the two patients. Second, phenotypic expression of mtDNA variants strongly depends on heteroplasmy rates, mtDNA copy number, and the haplotype [2]. Thus, it would be interesting to know if heteroplasmy rates and mtDNA copy numbers were different in islet cells or other clinically affected tissues between the two patients. We should also know if the two patients carried the same haplotype or not. Furthermore, we should know if there were alterations in the nuclear background and if the two patients had variable co-morbidities. Third, differences in histology and immune-histology could be also due to previous pancreatitis in either patient. Pancreatitis has been repeatedly reported as a clinical manifestation of mitochondrial disorder (MIDs) [3], why we should know if the previous history was positive for acute or chronic pancreatitis in either patient or if post-mortem histological findings on autopsy were indicative of previous pancreatitis. Fourth, we should know if there were any indications for affection of the cellular immune system in either patient, which has been previously reported [4], and if titers of antibodies against islet cells or mitochondria were different between the two patients.   

Furthermore, we do not agree that atrophy of islet cells necessarily means reduced production of insulin. Morphology not necessarily correlates with function. Thus, we should be informed about serum insulin levels and serum levels of the C-peptide to assess if islet cell function was truly reduced or not.

Since both MELAS and MERRF syndrome are multisystem diseases, potentially affecting liver and frequently the muscle [5], we should know if elevated blood glucose was due at least partially due to increased solution of liver or muscle glycogen or if gluconeogenesis was increased.

Since patient-2 had a HbA1c value of 6.9% (n, 4.6-6.2%) and diabetes was diagnosed, we should know why no anti- diabetic drugs or insulin were given. Was blood glucose well-controlled simply by diet?

Missing are the current blood chemical findings and the medication the two patients were taking at the time of decease. From various drugs it is known that they are potentially pancreato-toxic (e.g. valproic acid). Serum lactate may influence blood glucose levels as well and may   have    been different between the two patients.

Overall, the interesting, valuable study has some shortcomings which should be addressed before drawing final conclusions. Particularly, we need to know more about the genetic background, the current medication, and about the comorbidities of both patients before attributing different severity of diabetes only to different morphology of islet cells.

With interest we read the article by Piotrowska-Nowak et al. [1] about the influence of haplotypes and single nucleotide polymorphisms (SNPs) of the mitochondrial DNA (mtDNA) on the penetrance of the primary Leber’s hereditary optic neuropathy (LHON) mutation m.11778G>A in MT-ND4 in 47 unrelated Polish male patients. The authors concluded that haplogroup K and several mtDNA SNPs could determine the penetrance of this variant in the investigated cohort [1]. We have the following comments and concerns.

The authors are obviously not convinced about the significance of their results since the conclusions are speculative. The sample size is definitively too small to draw conclusions about the influence of the haplotype or SNPs on the penetrance of the primary LHON mutation m.11778G>A. From 5 patients carrying the haplotype K (11%) it cannot be calculated that haplotype K is responsible for the penetrance of the primary LHON mutation m.11778G>A. Furthermore, the distribution of SNPs in LHON patients and controls is not convincing as a factor determining the m.11778G> penetrance. There was no difference in the number of transitions and transversions between the two groups. The increased number of SNPs in the complex-IV regions in controls argues against causality. One would expect and increased number of SNPs in the patient group. Additionally, one would rather expect and increased number of SNPs in complex-1 regions but not complex-IV regions. 

We do not agree with the statement that “symptoms in LHON are limited to a single organ” [1]. LHON, like all other mitochondrial disorders (MIDs), is a multisystem disease, either already at onset of the disease or becomes a multisystem condition during the disease course. Though being a mono-organ condition in the vast majority of the cases at onset, several other organs or tissues become affected in LHON with progression of the disease (LHON plus) [2,3]. Only rarely, is spontaneous recovery of the abnormalities observed [4].

We do not agree with the notion that LHON is the most common MID [1]. The most common of the MIDs are the non-syndromic MIDs. Among the syndromic MIDs the most common is mitochondrial encephalopathy, lactic acidosis and stroke-like episode (MELAS) syndrome. Prevalence figures of syndromic MIDs vary largely between countries and regions.

We also do not agree with the statement that “the optic nerve is the tissue affected in LHON” [1]. The primary site of affection is the retina [5] where the primary pathophysiologic processes occur in the retinal ganglion cells (RGCs). Their neurites are secondarily affected leading degeneration and thus   secondary optic atrophy [5].

Unclear remains if all 47 included patients also manifested clinically or were asymptomatic carriers of the m.11778G>A variant. It is also unclear how many of the included patients received idebenone or not.            

Overall, the study has a number of shortcomings which need to be addressed before drawing final conclusions. The authors could not unequivocally demonstrate that haplotypes or mtDNA SNPs significantly influence the penetrance of the m.11778G>A variant. Since the vast majority of the respiratory chain complex-1 (RCC-1) subunits are nuclearly encoded, it is more likely that SNPs in nDNA genes encoding RCC-1 subunits than mtDNA SNPs influence the penetrance of the m.11778G>A variant. Warranted are more in-depth studies on the function of RCC-1 subunits and how the nuclear background influences the penetrance of mtDNA variants.

With interest we read the article by Heskamp et al. [1] about a prospective muscle MRI-study of 27 patients with myotonic dystrophy type-1 (MD1) who underwent either cognitive behavioural therapy (n = 18) or graded exercise plus behavioural therapy (n = 9). It was concluded that behavioural intervention targeting physical activity increases lower extremity muscle cross-sectional area [1]. We have the following comments and concerns.

A shortcoming of the study is that it is unclear which patients described previously [2,3] were included in the present study. In the article to which the authors refer, 33 MD1 patients were investigated [2] but the present study included only 27 patients since only these 27 underwent follow-up MRIs. Which were the 6 patients that were excluded and why? 

A further shortcoming is the application of the DM1-Activ scale to document graded exercise. Since the scale consists of 25 items describing activities of daily living, which can be assessed at three grades by the patient, the total “exercise” carried out was different in each patient, thus not standardised. We should know if a “graded exercise module” means that the patient filled in the DM1-Activ scale repeatedly. Ii is unclear which cut-offs were applied to define “exercise”. Furthermore, we should know how often during the 10 months observational period the form was filled out and how it was controlled that patients filled out the form honestly. 

Another shortcoming is that comparisons were carried out only between the standard care and the intervention group but not between the graded exercise and behavioural therapy group. This comparison is crucial to see if exercise truly had a better effect than behavioural therapy alone. 

Lastly, MD1 is a multisystem disease, affecting additionally the endocrine organs. Since muscle performance, composition, and morphology may strongly depend on endocrinologic parameters, [4] we should know if hormone levels differed between patients or groups and between inclusion and follow-up. Of particular interest are FGF-21 levels, which are increased in MD1 [5]. 

Overall, it cannot be excluded that the MRI changes reported reflect the effect of behavioural therapy alone or variable affection of endocrine organs but do not reflect graded exercise at all.